Author: "Konrad M." / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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106 results on '"Konrad M."'

1. A Thirteen-Year Analysis of Facial Fractures among Professional Soccer Players.

Author: Kozlowski, Konrad M, Kozlowski, Konrad M, Rosston, Peter A, Park, Asher C, Hakimi, Amir A, Socolovsky, Leandro, Wong, Brian J-F, Kozlowski, Konrad M, Kozlowski, Konrad M, Rosston, Peter A, Park, Asher C, Hakimi, Amir A, Socolovsky, Leandro, and Wong, Brian J-F
Abstract: This study aims to identify the epidemiology and effects of facial fractures on return to play (RTP) in Major League Soccer (MLS) and the English Premier League (EPL). A total of 39 MLS players and 40 EPL players who sustained facial fractures from 2007 to 2019 were identified. Data on player demographics, the injury, and the impact of their injury on RTP were collected. Elbow-to-head was the most common mechanism of injury (20.3%). The most common fracture involved the nasal bone (48.3%). Most players (90%) RTP the same season. Players who sustained nasal fractures missed significantly fewer games (p < 0.001) than those who suffered other craniofacial fractures. Players treated surgically missed significantly more games (3.21 vs. 0.71, p = 0.006) and days (30.1 vs. 8.70, p = 0.002) than those managed nonoperatively. Significantly more EPL players who sustained facial fractures wore headgear upon RTP compared to MLS players (82% vs. 56%, p <0 .01). Most professional soccer players who sustain a facial fracture RTP the same season, but their recovery time can vary depending on the type of fracture, injury management, or injury severity. Our findings can help inform future craniofacial injury management as well as guidelines on player safety and fracture prevention.
Published: 2023

2. Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome.

Author: Viering, D.H.H.M., Hureaux, M., Neveling, K., Latta, F., Kwint, M.P., Blanchard, A., Konrad, M., Bindels, R.J.M., Schlingmann, K.P., Vargas-Poussou, R., Baaij, J.H.F. de, Viering, D.H.H.M., Hureaux, M., Neveling, K., Latta, F., Kwint, M.P., Blanchard, A., Konrad, M., Bindels, R.J.M., Schlingmann, K.P., Vargas-Poussou, R., and Baaij, J.H.F. de
Abstract: Item does not contain fulltext, BACKGROUND: Gitelman syndrome is a salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. It is caused by homozygous recessive or compound heterozygous pathogenic variants in SLC12A3 , which encodes the Na + -Cl - cotransporter (NCC). In up to 10% of patients with Gitelman syndrome, current genetic techniques detect only one specific pathogenic variant. This study aimed to identify a second pathogenic variant in introns, splice sites, or promoters to increase the diagnostic yield. METHODS: Long-read sequencing of SLC12A3 was performed in 67 DNA samples from individuals with suspected Gitelman syndrome in whom a single likely pathogenic or pathogenic variant was previously detected. In addition, we sequenced DNA samples from 28 individuals with one variant of uncertain significance or no candidate variant. Midigene splice assays assessed the pathogenicity of novel intronic variants. RESULTS: A second likely pathogenic/pathogenic variant was identified in 45 (67%) patients. Those with two likely pathogenic/pathogenic variants had a more severe electrolyte phenotype than other patients. Of the 45 patients, 16 had intronic variants outside of canonic splice sites (nine variants, mostly deep intronic, six novel), whereas 29 patients had an exonic variant or canonic splice site variant. Midigene splice assays of the previously known c.1670-191C>T variant and intronic candidate variants demonstrated aberrant splicing patterns. CONCLUSION: Intronic pathogenic variants explain an important part of the missing heritability in Gitelman syndrome. Long-read sequencing should be considered in diagnostic workflows for Gitelman syndrome.
Published: 2023

3. Withdrawn as duplicate: Expanding the phenotypic spectrum of Kenny-Caffey syndrome: a case series and systematic literature review.

Author: Schigt, H., Bald, M., Eerden, B.C.J. van der, Gal, Lars, Ilenwabor, B.P., Konrad, M., Levine, M.A., Li, D., Mache, C.J., Mackin, S., Perry, C., Rios, F.J., Schlingmann, K.P., Storey, B., Trapp, C.M., Verkerk, A.J.M.H., Zillikens, M.C., Touyz, R.M., Hoorn, E.J., Hoenderop, J.G.J., Baaij, J.H.F. de, Schigt, H., Bald, M., Eerden, B.C.J. van der, Gal, Lars, Ilenwabor, B.P., Konrad, M., Levine, M.A., Li, D., Mache, C.J., Mackin, S., Perry, C., Rios, F.J., Schlingmann, K.P., Storey, B., Trapp, C.M., Verkerk, A.J.M.H., Zillikens, M.C., Touyz, R.M., Hoorn, E.J., Hoenderop, J.G.J., and Baaij, J.H.F. de
Abstract: Item does not contain fulltext, This article has been withdrawn due to a publisher error that caused it to be duplicated. The definitive version of this article is published under https://doi.org/10.1210/clinem/dgad147.
Published: 2023

4. Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome.

Author: Viering, D.H.H.M., Hureaux, M., Neveling, K., Latta, F., Kwint, M.P., Blanchard, A., Konrad, M., Bindels, R.J.M., Schlingmann, K.P., Vargas-Poussou, R., Baaij, J.H.F. de, Viering, D.H.H.M., Hureaux, M., Neveling, K., Latta, F., Kwint, M.P., Blanchard, A., Konrad, M., Bindels, R.J.M., Schlingmann, K.P., Vargas-Poussou, R., and Baaij, J.H.F. de
Abstract: Item does not contain fulltext, BACKGROUND: Gitelman syndrome is a salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. It is caused by homozygous recessive or compound heterozygous pathogenic variants in SLC12A3 , which encodes the Na + -Cl - cotransporter (NCC). In up to 10% of patients with Gitelman syndrome, current genetic techniques detect only one specific pathogenic variant. This study aimed to identify a second pathogenic variant in introns, splice sites, or promoters to increase the diagnostic yield. METHODS: Long-read sequencing of SLC12A3 was performed in 67 DNA samples from individuals with suspected Gitelman syndrome in whom a single likely pathogenic or pathogenic variant was previously detected. In addition, we sequenced DNA samples from 28 individuals with one variant of uncertain significance or no candidate variant. Midigene splice assays assessed the pathogenicity of novel intronic variants. RESULTS: A second likely pathogenic/pathogenic variant was identified in 45 (67%) patients. Those with two likely pathogenic/pathogenic variants had a more severe electrolyte phenotype than other patients. Of the 45 patients, 16 had intronic variants outside of canonic splice sites (nine variants, mostly deep intronic, six novel), whereas 29 patients had an exonic variant or canonic splice site variant. Midigene splice assays of the previously known c.1670-191C>T variant and intronic candidate variants demonstrated aberrant splicing patterns. CONCLUSION: Intronic pathogenic variants explain an important part of the missing heritability in Gitelman syndrome. Long-read sequencing should be considered in diagnostic workflows for Gitelman syndrome.
Published: 2023

5. Expanding the Phenotypic Spectrum of Kenny-Caffey Syndrome.

Author: Schigt, H., Bald, M., Eerden, B.C.J. van der, Gal, Lars, Ilenwabor, B.P., Konrad, M., Levine, M.A., Li, D., Mache, C.J., Mackin, S., Perry, C., Rios, F.J., Schlingmann, K.P., Storey, B., Trapp, C.M., Verkerk, A.J.M.H., Zillikens, M.C., Touyz, R.M., Hoorn, E.J., Hoenderop, J.G.J., Baaij, J.H.F. de, Schigt, H., Bald, M., Eerden, B.C.J. van der, Gal, Lars, Ilenwabor, B.P., Konrad, M., Levine, M.A., Li, D., Mache, C.J., Mackin, S., Perry, C., Rios, F.J., Schlingmann, K.P., Storey, B., Trapp, C.M., Verkerk, A.J.M.H., Zillikens, M.C., Touyz, R.M., Hoorn, E.J., Hoenderop, J.G.J., and Baaij, J.H.F. de
Abstract: Contains fulltext : 295983.pdf (Publisher’s version ) (Open Access), CONTEXT: Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish. OBJECTIVE: The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders. METHODS: We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers. RESULTS: Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common. CONCLUSION: Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Published: 2023

6. Spielen Umweltkriterien in der öffentlichen Arzneimittelbeschaffung eine Rolle? Status-Quo und Erfahrungen in 32 europäischen Ländern

Author: Vogler, S, Salcher-Konrad, M, Habimana, K, Vogler, S, Salcher-Konrad, M, and Habimana, K
Published: 2023

7. Spielen Umweltkriterien in der öffentlichen Arzneimittelbeschaffung eine Rolle? Status-Quo und Erfahrungen in 32 europäischen Ländern

Author: Vogler, S, Salcher-Konrad, M, Habimana, K, Vogler, S, Salcher-Konrad, M, and Habimana, K
Published: 2023

8. What are validated questionnaires and which ones measure quality of life?

Author: Szymanski, Konrad M., Kaefer, Martin, Fossum, Magdalena, Kalfa, Nicolas, Herbst, Katherine W., Braga, Luis H., Cascio, Salvatore, Garriboli, Massimo, Nelson, Caleb P., Nieuwhoff-Leppink, Anka, Bagli, Darius, Harper, Luke, Szymanski, Konrad M., Kaefer, Martin, Fossum, Magdalena, Kalfa, Nicolas, Herbst, Katherine W., Braga, Luis H., Cascio, Salvatore, Garriboli, Massimo, Nelson, Caleb P., Nieuwhoff-Leppink, Anka, Bagli, Darius, and Harper, Luke
Published: 2023

9. Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA

Author: Viering, D.H., Schlingmann, K.P., Hureaux, M., Nijenhuis, T., Mallett, A., Chan, M.M., Beek, Andre van, Eerde, A.M. van, Coulibaly, J.M., Vallet, M., Decramer, S., Pelletier, S., Klaus, G., Kömhoff, M., Beetz, R., Patel, C., Shenoy, M., Steenbergen, E.J., Anderson, G., Bongers, E.M.H.F., Bergmann, C., Panneman, D., Rodenburg, R.J.T., Kleta, R., Houillier, P., Konrad, M., Vargas-Poussou, R., Knoers, N.V.A.M., Bockenhauer, D., Baaij, J.H.F. de, Viering, D.H., Schlingmann, K.P., Hureaux, M., Nijenhuis, T., Mallett, A., Chan, M.M., Beek, Andre van, Eerde, A.M. van, Coulibaly, J.M., Vallet, M., Decramer, S., Pelletier, S., Klaus, G., Kömhoff, M., Beetz, R., Patel, C., Shenoy, M., Steenbergen, E.J., Anderson, G., Bongers, E.M.H.F., Bergmann, C., Panneman, D., Rodenburg, R.J.T., Kleta, R., Houillier, P., Konrad, M., Vargas-Poussou, R., Knoers, N.V.A.M., Bockenhauer, D., and Baaij, J.H.F. de
Abstract: Item does not contain fulltext, BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na(+)-Cl(-) cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in three families with Gitelman-like electrolyte abnormalities, then investigated 156 families for variants in MT-TI and MT-TF, which encode the transfer RNAs for phenylalanine and isoleucine. Mitochondrial respiratory chain function was assessed in patient fibroblasts. Mitochondrial dysfunction was induced in NCC-expressing HEK293 cells to assess the effect on thiazide-sensitive (22)Na(+) transport. RESULTS: Genetic investigations revealed four mtDNA variants in 13 families: m.591C>T (n=7), m.616T>C (n=1), m.643A>G (n=1) (all in MT-TF), and m.4291T>C (n=4, in MT-TI). Variants were near homoplasmic in affected individuals. All variants were classified as pathogenic, except for m.643A>G, which was classified as a variant of uncertain significance. Importantly, affected members of six families with an MT-TF variant additionally suffered from progressive chronic kidney disease. Dysfunction of oxidative phosphorylation complex IV and reduced maximal mitochondrial respiratory capacity were found in patient fibroblasts. In vitro pharmacological inhibition of complex IV, mimicking the effect of the mtDNA variants, inhibited NCC phosphorylation and NCC-mediated sodium uptake. CONCLUSION: Pathogenic mtDNA variants in MT-TF and MT-TI can cause a Gitelman-like syndrome. Genetic investigation of mtDNA should be considered in patients with unexplained Gitelman syndro
Published: 2022

10. Frontiers of the Roman Empire. The Eastern Frontiers = Frontières de l'Empire Romain. Les frontières orientales

Author: Breeze, D.J., Abudanah, F., Braund, D., Driessen, M., James, S., Konrad, M., Polak, M., Breeze, D.J., Abudanah, F., Braund, D., Driessen, M., James, S., Konrad, M., and Polak, M.
Abstract: Item does not contain fulltext
Published: 2022

11. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Author: Verploegen, M.F.A., Vargas-Poussou, R., Walsh, S.B., Alpay, H., Amouzegar, A., Ariceta, G., Atmis, B., Bacchetta, J., Bárány, P., Baron, S., Bayrakci, U.S., Belge, H., Besouw, M., Blanchard, A., Bökenkamp, A., Boyer, O., Burgmaier, K., Calò, L.A., Decramer, S., Devuyst, O., Dyck, M. van, Ferraro, P.M., Fila, M., Francisco, T., Ghiggeri, G.M., Gondra, L., Guarino, S., Hooman, N., Hoorn, E.J., Houillier, P., Kamperis, K., Kari, J.A., Konrad, M., Levtchenko, E., Lucchetti, L., Lugani, F., Marzuillo, P., Mohidin, B., Neuhaus, T.J., Osman, A., Papizh, S., Perelló, M., Rookmaaker, M.B., Conti, V.S., Santos, F., Sawaf, G., Serdaroglu, E., Szczepanska, M., Taroni, F., Topaloglu, R., Trepiccione, F., Vidal, E., Wan, E.R., Weber, L., Yildirim, Z.Y., Yüksel, S., Zlatanova, G., Bockenhauer, D., Emma, F., Nijenhuis, T., Verploegen, M.F.A., Vargas-Poussou, R., Walsh, S.B., Alpay, H., Amouzegar, A., Ariceta, G., Atmis, B., Bacchetta, J., Bárány, P., Baron, S., Bayrakci, U.S., Belge, H., Besouw, M., Blanchard, A., Bökenkamp, A., Boyer, O., Burgmaier, K., Calò, L.A., Decramer, S., Devuyst, O., Dyck, M. van, Ferraro, P.M., Fila, M., Francisco, T., Ghiggeri, G.M., Gondra, L., Guarino, S., Hooman, N., Hoorn, E.J., Houillier, P., Kamperis, K., Kari, J.A., Konrad, M., Levtchenko, E., Lucchetti, L., Lugani, F., Marzuillo, P., Mohidin, B., Neuhaus, T.J., Osman, A., Papizh, S., Perelló, M., Rookmaaker, M.B., Conti, V.S., Santos, F., Sawaf, G., Serdaroglu, E., Szczepanska, M., Taroni, F., Topaloglu, R., Trepiccione, F., Vidal, E., Wan, E.R., Weber, L., Yildirim, Z.Y., Yüksel, S., Zlatanova, G., Bockenhauer, D., Emma, F., and Nijenhuis, T.
Abstract: Item does not contain fulltext, BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
Published: 2022

12. Comment to 'Recommendation on an updated standardization of serum magnesium reference ranges'.

Author: Baaij, J.H.F. de, Bockenhauer, D., Claverie-Martin, F., Hoenderop, J.G.J., Hoorn, E.J., Houillier, P., Knoers, N.V.A.M., Konrad, M., Müller, D., Nijenhuis, T., Schlingmann, K.P., Vargas Poussou, R., Baaij, J.H.F. de, Bockenhauer, D., Claverie-Martin, F., Hoenderop, J.G.J., Hoorn, E.J., Houillier, P., Knoers, N.V.A.M., Konrad, M., Müller, D., Nijenhuis, T., Schlingmann, K.P., and Vargas Poussou, R.
Abstract: Item does not contain fulltext
Published: 2022

13. Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA

Author: Viering, D.H., Schlingmann, K.P., Hureaux, M., Nijenhuis, T., Mallett, A., Chan, M.M., Beek, Andre van, Eerde, A.M. van, Coulibaly, J.M., Vallet, M., Decramer, S., Pelletier, S., Klaus, G., Kömhoff, M., Beetz, R., Patel, C., Shenoy, M., Steenbergen, E.J., Anderson, G., Bongers, E.M.H.F., Bergmann, C., Panneman, D., Rodenburg, R.J.T., Kleta, R., Houillier, P., Konrad, M., Vargas-Poussou, R., Knoers, N.V.A.M., Bockenhauer, D., Baaij, J.H.F. de, Viering, D.H., Schlingmann, K.P., Hureaux, M., Nijenhuis, T., Mallett, A., Chan, M.M., Beek, Andre van, Eerde, A.M. van, Coulibaly, J.M., Vallet, M., Decramer, S., Pelletier, S., Klaus, G., Kömhoff, M., Beetz, R., Patel, C., Shenoy, M., Steenbergen, E.J., Anderson, G., Bongers, E.M.H.F., Bergmann, C., Panneman, D., Rodenburg, R.J.T., Kleta, R., Houillier, P., Konrad, M., Vargas-Poussou, R., Knoers, N.V.A.M., Bockenhauer, D., and Baaij, J.H.F. de
Abstract: Item does not contain fulltext, BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na(+)-Cl(-) cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in three families with Gitelman-like electrolyte abnormalities, then investigated 156 families for variants in MT-TI and MT-TF, which encode the transfer RNAs for phenylalanine and isoleucine. Mitochondrial respiratory chain function was assessed in patient fibroblasts. Mitochondrial dysfunction was induced in NCC-expressing HEK293 cells to assess the effect on thiazide-sensitive (22)Na(+) transport. RESULTS: Genetic investigations revealed four mtDNA variants in 13 families: m.591C>T (n=7), m.616T>C (n=1), m.643A>G (n=1) (all in MT-TF), and m.4291T>C (n=4, in MT-TI). Variants were near homoplasmic in affected individuals. All variants were classified as pathogenic, except for m.643A>G, which was classified as a variant of uncertain significance. Importantly, affected members of six families with an MT-TF variant additionally suffered from progressive chronic kidney disease. Dysfunction of oxidative phosphorylation complex IV and reduced maximal mitochondrial respiratory capacity were found in patient fibroblasts. In vitro pharmacological inhibition of complex IV, mimicking the effect of the mtDNA variants, inhibited NCC phosphorylation and NCC-mediated sodium uptake. CONCLUSION: Pathogenic mtDNA variants in MT-TF and MT-TI can cause a Gitelman-like syndrome. Genetic investigation of mtDNA should be considered in patients with unexplained Gitelman syndro
Published: 2022

14. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Author: Verploegen, M.F.A., Vargas-Poussou, R., Walsh, S.B., Alpay, H., Amouzegar, A., Ariceta, G., Atmis, B., Bacchetta, J., Bárány, P., Baron, S., Bayrakci, U.S., Belge, H., Besouw, M., Blanchard, A., Bökenkamp, A., Boyer, O., Burgmaier, K., Calò, L.A., Decramer, S., Devuyst, O., Dyck, M. van, Ferraro, P.M., Fila, M., Francisco, T., Ghiggeri, G.M., Gondra, L., Guarino, S., Hooman, N., Hoorn, E.J., Houillier, P., Kamperis, K., Kari, J.A., Konrad, M., Levtchenko, E., Lucchetti, L., Lugani, F., Marzuillo, P., Mohidin, B., Neuhaus, T.J., Osman, A., Papizh, S., Perelló, M., Rookmaaker, M.B., Conti, V.S., Santos, F., Sawaf, G., Serdaroglu, E., Szczepanska, M., Taroni, F., Topaloglu, R., Trepiccione, F., Vidal, E., Wan, E.R., Weber, L., Yildirim, Z.Y., Yüksel, S., Zlatanova, G., Bockenhauer, D., Emma, F., Nijenhuis, T., Verploegen, M.F.A., Vargas-Poussou, R., Walsh, S.B., Alpay, H., Amouzegar, A., Ariceta, G., Atmis, B., Bacchetta, J., Bárány, P., Baron, S., Bayrakci, U.S., Belge, H., Besouw, M., Blanchard, A., Bökenkamp, A., Boyer, O., Burgmaier, K., Calò, L.A., Decramer, S., Devuyst, O., Dyck, M. van, Ferraro, P.M., Fila, M., Francisco, T., Ghiggeri, G.M., Gondra, L., Guarino, S., Hooman, N., Hoorn, E.J., Houillier, P., Kamperis, K., Kari, J.A., Konrad, M., Levtchenko, E., Lucchetti, L., Lugani, F., Marzuillo, P., Mohidin, B., Neuhaus, T.J., Osman, A., Papizh, S., Perelló, M., Rookmaaker, M.B., Conti, V.S., Santos, F., Sawaf, G., Serdaroglu, E., Szczepanska, M., Taroni, F., Topaloglu, R., Trepiccione, F., Vidal, E., Wan, E.R., Weber, L., Yildirim, Z.Y., Yüksel, S., Zlatanova, G., Bockenhauer, D., Emma, F., and Nijenhuis, T.
Abstract: Contains fulltext : 287287.pdf (Publisher’s version ) (Open Access), BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
Published: 2022

15. Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: Post-hoc analysis of LAS VEGAS study

Author: Robba, C, Hemmes, S, Serpa Neto, A, Bluth, T, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Putensen, C, Jaber, S, Schmid, W, Severgnini, P, Wrigge, H, Battaglini, D, Ball, L, Gama De Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Van Mossevelde, V, Van Malderen, M, Dylst, D, Van Melkebeek, J, Beran, M, De Hert, S, De Baerdemaeker, L, Heyse, B, Van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, Van De Velde, S, Leva, B, Damster, S, Plichon, B, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Saric, J, Erceg, G, Dvorscak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Hasan, W, Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, De Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, In 'T Veld, B, Werger, A, Dennesen, P, Severijns, C, De Jong, J, Hering, J, Van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, De Lurdes Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, De Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, De Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Alvares-Santullano, C, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Melo, M, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Robba C., Hemmes S. N. T., Serpa Neto A., Bluth T., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Putensen C., Jaber S., Schmid W., Severgnini P., Wrigge H., Battaglini D., Ball L., Gama De Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Van Mossevelde V., Van Malderen M. -C., Dylst D., Van Melkebeek J., Beran M., De Hert S., De Baerdemaeker L., Heyse B., Van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., Van De Velde S., Leva B., Damster S., Plichon B., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Saric J. P., Erceg G., Dvorscak M. B., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Abdelwahab H. H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., De Abreu M. G., Uhlig C., Kiss T., Bundy A., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. -K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'Antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., In 'T Veld B., Werger A., Dennesen P., Severijns C., De Jong J., Hering J., Van Beek R., Ivars S., Jammer I., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., De Lurdes Goncalves Castro M., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Garotescu I. P., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. -T., Gherghina I., Costea D., Cindea I., Copotoiu S. -M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., De Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., De Andres Ibanez J. A., Pastor E., Soro M., Ferrando C., Defez M., Alvares-Santullano C. A., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., Tze Y., Robba, C, Hemmes, S, Serpa Neto, A, Bluth, T, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Putensen, C, Jaber, S, Schmid, W, Severgnini, P, Wrigge, H, Battaglini, D, Ball, L, Gama De Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Van Mossevelde, V, Van Malderen, M, Dylst, D, Van Melkebeek, J, Beran, M, De Hert, S, De Baerdemaeker, L, Heyse, B, Van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, Van De Velde, S, Leva, B, Damster, S, Plichon, B, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Saric, J, Erceg, G, Dvorscak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Hasan, W, Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, De Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, In 'T Veld, B, Werger, A, Dennesen, P, Severijns, C, De Jong, J, Hering, J, Van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, De Lurdes Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, De Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, De Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Alvares-Santullano, C, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Melo, M, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Robba C., Hemmes S. N. T., Serpa Neto A., Bluth T., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Putensen C., Jaber S., Schmid W., Severgnini P., Wrigge H., Battaglini D., Ball L., Gama De Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Van Mossevelde V., Van Malderen M. -C., Dylst D., Van Melkebeek J., Beran M., De Hert S., De Baerdemaeker L., Heyse B., Van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., Van De Velde S., Leva B., Damster S., Plichon B., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Saric J. P., Erceg G., Dvorscak M. B., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Abdelwahab H. H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., De Abreu M. G., Uhlig C., Kiss T., Bundy A., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. -K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'Antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., In 'T Veld B., Werger A., Dennesen P., Severijns C., De Jong J., Hering J., Van Beek R., Ivars S., Jammer I., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., De Lurdes Goncalves Castro M., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Garotescu I. P., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. -T., Gherghina I., Costea D., Cindea I., Copotoiu S. -M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., De Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., De Andres Ibanez J. A., Pastor E., Soro M., Ferrando C., Defez M., Alvares-Santullano C. A., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., and Tze Y.
Abstract: Background: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs.
Published: 2020

16. Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: Post-hoc analysis of LAS VEGAS study

Author: Robba, C, Hemmes, S, Serpa Neto, A, Bluth, T, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Putensen, C, Jaber, S, Schmid, W, Severgnini, P, Wrigge, H, Battaglini, D, Ball, L, Gama De Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Van Mossevelde, V, Van Malderen, M, Dylst, D, Van Melkebeek, J, Beran, M, De Hert, S, De Baerdemaeker, L, Heyse, B, Van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, Van De Velde, S, Leva, B, Damster, S, Plichon, B, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Saric, J, Erceg, G, Dvorscak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Hasan, W, Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, De Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, In 'T Veld, B, Werger, A, Dennesen, P, Severijns, C, De Jong, J, Hering, J, Van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, De Lurdes Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, De Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, De Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Alvares-Santullano, C, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Melo, M, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Robba C., Hemmes S. N. T., Serpa Neto A., Bluth T., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Putensen C., Jaber S., Schmid W., Severgnini P., Wrigge H., Battaglini D., Ball L., Gama De Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Van Mossevelde V., Van Malderen M. -C., Dylst D., Van Melkebeek J., Beran M., De Hert S., De Baerdemaeker L., Heyse B., Van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., Van De Velde S., Leva B., Damster S., Plichon B., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Saric J. P., Erceg G., Dvorscak M. B., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Abdelwahab H. H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., De Abreu M. G., Uhlig C., Kiss T., Bundy A., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. -K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'Antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., In 'T Veld B., Werger A., Dennesen P., Severijns C., De Jong J., Hering J., Van Beek R., Ivars S., Jammer I., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., De Lurdes Goncalves Castro M., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Garotescu I. P., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. -T., Gherghina I., Costea D., Cindea I., Copotoiu S. -M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., De Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., De Andres Ibanez J. A., Pastor E., Soro M., Ferrando C., Defez M., Alvares-Santullano C. A., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., Tze Y., Robba, C, Hemmes, S, Serpa Neto, A, Bluth, T, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Putensen, C, Jaber, S, Schmid, W, Severgnini, P, Wrigge, H, Battaglini, D, Ball, L, Gama De Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Van Mossevelde, V, Van Malderen, M, Dylst, D, Van Melkebeek, J, Beran, M, De Hert, S, De Baerdemaeker, L, Heyse, B, Van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, Van De Velde, S, Leva, B, Damster, S, Plichon, B, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Saric, J, Erceg, G, Dvorscak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Hasan, W, Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, De Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, In 'T Veld, B, Werger, A, Dennesen, P, Severijns, C, De Jong, J, Hering, J, Van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, De Lurdes Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, De Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, De Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Alvares-Santullano, C, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Melo, M, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Robba C., Hemmes S. N. T., Serpa Neto A., Bluth T., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Putensen C., Jaber S., Schmid W., Severgnini P., Wrigge H., Battaglini D., Ball L., Gama De Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Van Mossevelde V., Van Malderen M. -C., Dylst D., Van Melkebeek J., Beran M., De Hert S., De Baerdemaeker L., Heyse B., Van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., Van De Velde S., Leva B., Damster S., Plichon B., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Saric J. P., Erceg G., Dvorscak M. B., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Abdelwahab H. H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., De Abreu M. G., Uhlig C., Kiss T., Bundy A., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. -K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'Antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., In 'T Veld B., Werger A., Dennesen P., Severijns C., De Jong J., Hering J., Van Beek R., Ivars S., Jammer I., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., De Lurdes Goncalves Castro M., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Garotescu I. P., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. -T., Gherghina I., Costea D., Cindea I., Copotoiu S. -M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., De Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., De Andres Ibanez J. A., Pastor E., Soro M., Ferrando C., Defez M., Alvares-Santullano C. A., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., and Tze Y.
Abstract: Background: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs.
Published: 2020

17. Dynamic programming and automated segmentation of optical coherence tomography images of the neonatal subglottis: enabling efficient diagnostics to manage subglottic stenosis.

Author: Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, Wong, Brian J-F, Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, and Wong, Brian J-F
Abstract: Subglottic stenosis (SGS) is a challenging disease to diagnose in neonates. Long-range optical coherence tomography (OCT) is an optical imaging modality that has been described to image the subglottis in intubated neonates. A major challenge associated with OCT imaging is the lack of an automated method for image analysis and micrometry of large volumes of data that are acquired with each airway scan (1 to 2 Gb). We developed a tissue segmentation algorithm that identifies, measures, and conducts image analysis on tissue layers within the mucosa and submucosa and compared these automated tissue measurements with manual tracings. We noted small but statistically significant differences in thickness measurements of the mucosa and submucosa layers in the larynx (p < 0.001), subglottis (p = 0.015), and trachea (p = 0.012). The automated algorithm was also shown to be over 8 times faster than the manual approach. Moderate Pearson correlations were found between different tissue texture parameters and the patient's gestational age at birth, age in days, duration of intubation, and differences with age (mean age 17 days). Automated OCT data analysis is necessary in the diagnosis and monitoring of SGS, as it can provide vital information about the airway in real time and aid clinicians in making management decisions for intubated neonates..
Published: 2019

18. Dynamic programming and automated segmentation of optical coherence tomography images of the neonatal subglottis: enabling efficient diagnostics to manage subglottic stenosis.

Author: Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, Wong, Brian J-F, Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, and Wong, Brian J-F
Abstract: Subglottic stenosis (SGS) is a challenging disease to diagnose in neonates. Long-range optical coherence tomography (OCT) is an optical imaging modality that has been described to image the subglottis in intubated neonates. A major challenge associated with OCT imaging is the lack of an automated method for image analysis and micrometry of large volumes of data that are acquired with each airway scan (1 to 2 Gb). We developed a tissue segmentation algorithm that identifies, measures, and conducts image analysis on tissue layers within the mucosa and submucosa and compared these automated tissue measurements with manual tracings. We noted small but statistically significant differences in thickness measurements of the mucosa and submucosa layers in the larynx (p < 0.001), subglottis (p = 0.015), and trachea (p = 0.012). The automated algorithm was also shown to be over 8 times faster than the manual approach. Moderate Pearson correlations were found between different tissue texture parameters and the patient’s gestational age at birth, age in days, duration of intubation, and differences with age (mean age 17 days). Automated OCT data analysis is necessary in the diagnosis and monitoring of SGS, as it can provide vital information about the airway in real time and aid clinicians in making management decisions for intubated neonates.
Published: 2019

19. Dynamic programming and automated segmentation of optical coherence tomography images of the neonatal subglottis: enabling efficient diagnostics to manage subglottic stenosis.

Author: Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, Wong, Brian J-F, Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, and Wong, Brian J-F
Abstract: Subglottic stenosis (SGS) is a challenging disease to diagnose in neonates. Long-range optical coherence tomography (OCT) is an optical imaging modality that has been described to image the subglottis in intubated neonates. A major challenge associated with OCT imaging is the lack of an automated method for image analysis and micrometry of large volumes of data that are acquired with each airway scan (1 to 2 Gb). We developed a tissue segmentation algorithm that identifies, measures, and conducts image analysis on tissue layers within the mucosa and submucosa and compared these automated tissue measurements with manual tracings. We noted small but statistically significant differences in thickness measurements of the mucosa and submucosa layers in the larynx (p < 0.001), subglottis (p = 0.015), and trachea (p = 0.012). The automated algorithm was also shown to be over 8 times faster than the manual approach. Moderate Pearson correlations were found between different tissue texture parameters and the patient's gestational age at birth, age in days, duration of intubation, and differences with age (mean age 17 days). Automated OCT data analysis is necessary in the diagnosis and monitoring of SGS, as it can provide vital information about the airway in real time and aid clinicians in making management decisions for intubated neonates..
Published: 2019

20. Dynamic programming and automated segmentation of optical coherence tomography images of the neonatal subglottis: enabling efficient diagnostics to manage subglottic stenosis.

Author: Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, Wong, Brian J-F, Kozlowski, Konrad M, Kozlowski, Konrad M, Sharma, Giriraj K, Chen, Jason J, Qi, Li, Osann, Kathryn, Jing, Joseph C, Ahuja, Gurpreet S, Heidari, Andrew E, Chung, Phil-Sang, Kim, Sehwan, Chen, Zhongping, and Wong, Brian J-F
Abstract: Subglottic stenosis (SGS) is a challenging disease to diagnose in neonates. Long-range optical coherence tomography (OCT) is an optical imaging modality that has been described to image the subglottis in intubated neonates. A major challenge associated with OCT imaging is the lack of an automated method for image analysis and micrometry of large volumes of data that are acquired with each airway scan (1 to 2 Gb). We developed a tissue segmentation algorithm that identifies, measures, and conducts image analysis on tissue layers within the mucosa and submucosa and compared these automated tissue measurements with manual tracings. We noted small but statistically significant differences in thickness measurements of the mucosa and submucosa layers in the larynx (p < 0.001), subglottis (p = 0.015), and trachea (p = 0.012). The automated algorithm was also shown to be over 8 times faster than the manual approach. Moderate Pearson correlations were found between different tissue texture parameters and the patient’s gestational age at birth, age in days, duration of intubation, and differences with age (mean age 17 days). Automated OCT data analysis is necessary in the diagnosis and monitoring of SGS, as it can provide vital information about the airway in real time and aid clinicians in making management decisions for intubated neonates.
Published: 2019

21. Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications

Author: Cortegiani, A, Gregoretti, C, Neto, A, Hemmes, S, Ball, L, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Melo, M, Putensen, C, Schmid, W, Severgnini, P, Wrigge, H, Gama de Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Mossevelde, V, van Malderen, M, Dylst, D, Melkebeek, J, Beran, M, Hert, S, Baerdemaeker, L, Heyse, B, Limmen, J, Wyffels, P, Jacobs, T, Roels, N, Bruyne, A, Velde, S, Marina, J, Dejana, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Darija, A, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Saric, J, Erceg, G, Dvorscak, M, Branka, M, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Inga, M, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, Kafrawy, S, Abdelwahab, H, Metwally, T, Ahmed, A, Ahmed Mostafa, E, Hasan, W, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Jaber, S, Prades, A, Krassler, J, Merzky, S, Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Bluth, T, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodorak, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, Michele, M, Bona, F, Giacoletto, G, Sardo, E, Sottosanti, L, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Agreta, G, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, Veld, B, Werger, A, Dennesen, P, Severijns, C, Jong, J, Hering, J, Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Jannicke, M, Andersson, E, Amir, S, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Popescu Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Barbka, N, Ana, P, Jovanov, M, Strazisar, B, Jasmina, M, Vesna, N, Voje, M, Grynyuk, A, Kostadinov, I, Alenka, S, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Cesar Aldecoa, A, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Ben, C, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Ana, F, Luzier, E, Almagro, A, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Cortegiani A., Gregoretti C., Neto A. S., Hemmes S. N. T., Ball L., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Melo M. F. V., Putensen C., Schmid W., Severgnini P., Wrigge H., Gama de Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Mossevelde V., van Malderen M. C., Dylst D., Melkebeek J. V., Beran M., Hert S. D., Baerdemaeker L. D., Heyse B., Limmen J. V., Wyffels P., Jacobs T., Roels N., Bruyne A. D., Velde S. V. D., Marina J. Z., Dejana D. O., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Darija A. V., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Saric J. P., Erceg G., Dvorscak M. B., Branka M. S., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Inga M. B., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., Kafrawy S. E., Abdelwahab H. H., Metwally T., Ahmed A. R., Ahmed Mostafa E. S., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Jaber S., Prades A., Krassler J., Merzky S., Abreu M. G. D., Uhlig C., Kiss T., Bundy A., Bluth T., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodorak K., Gkiokas G., Tasoulis M. K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., Michele M. D., Bona F., Giacoletto G., Sardo E., Sottosanti L. G. V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., Bella D. L., Mirabella L., D'antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Parma A. L. D., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Agreta G. G., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., Veld B. I. '., Werger A., Dennesen P., Severijns C., Jong J. D., Hering J., Beek R. V., Ivars S., Jammer I. B., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Jannicke M. O., Andersson E., Amir S. K., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., Castro M. D. L. G., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Popescu Garotescu I., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. T., Gherghina I., Costea D., Cindea I., Copotoiu S. M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Barbka N. S., Ana P. G., Jovanov M., Strazisar B., Jasmina M. B., Vesna N. J., Voje M., Grynyuk A., Kostadinov I., Alenka S. V., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., Larriba A. D. A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., Andres Ibanez J. A. D., Pastor E., Soro M., Ferrando C., Defez M., Cesar Aldecoa A. S., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Ben C. B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Ana F. B., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., Tze Y., Cortegiani, A, Gregoretti, C, Neto, A, Hemmes, S, Ball, L, Canet, J, Hiesmayr, M, Hollmann, M, Mills, G, Melo, M, Putensen, C, Schmid, W, Severgnini, P, Wrigge, H, Gama de Abreu, M, Schultz, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, Mossevelde, V, van Malderen, M, Dylst, D, Melkebeek, J, Beran, M, Hert, S, Baerdemaeker, L, Heyse, B, Limmen, J, Wyffels, P, Jacobs, T, Roels, N, Bruyne, A, Velde, S, Marina, J, Dejana, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Darija, A, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Saric, J, Erceg, G, Dvorscak, M, Branka, M, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Inga, M, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, Kafrawy, S, Abdelwahab, H, Metwally, T, Ahmed, A, Ahmed Mostafa, E, Hasan, W, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Jaber, S, Prades, A, Krassler, J, Merzky, S, Abreu, M, Uhlig, C, Kiss, T, Bundy, A, Bluth, T, Gueldner, A, Spieth, P, Scharffenberg, M, Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodorak, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, Michele, M, Bona, F, Giacoletto, G, Sardo, E, Sottosanti, L, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Agreta, G, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Binnekade, J, Bos, L, Boer, C, Duvekot, A, Veld, B, Werger, A, Dennesen, P, Severijns, C, Jong, J, Hering, J, Beek, R, Ivars, S, Jammer, I, Breidablik, A, Hodt, K, Fjellanger, F, Avalos, M, Jannicke, M, Andersson, E, Amir, S, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Popescu Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, S, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Barbka, N, Ana, P, Jovanov, M, Strazisar, B, Jasmina, M, Vesna, N, Voje, M, Grynyuk, A, Kostadinov, I, Alenka, S, Moral, V, Unzueta, M, Puigbo, C, Fava, J, Moret, E, Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Martinez, F, Temino, M, Simon, A, Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Vivo, J, Ruiz, C, Andres Ibanez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Cesar Aldecoa, A, Perez, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Bengisun, Z, Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Ben, C, Watt, P, Raymode, P, Pearse, R, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Ana, F, Luzier, E, Almagro, A, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Cortegiani A., Gregoretti C., Neto A. S., Hemmes S. N. T., Ball L., Canet J., Hiesmayr M., Hollmann M. W., Mills G. H., Melo M. F. V., Putensen C., Schmid W., Severgnini P., Wrigge H., Gama de Abreu M., Schultz M. J., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., Mossevelde V., van Malderen M. C., Dylst D., Melkebeek J. V., Beran M., Hert S. D., Baerdemaeker L. D., Heyse B., Limmen J. V., Wyffels P., Jacobs T., Roels N., Bruyne A. D., Velde S. V. D., Marina J. Z., Dejana D. O., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Darija A. V., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Saric J. P., Erceg G., Dvorscak M. B., Branka M. S., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Inga M. B., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., Kafrawy S. E., Abdelwahab H. H., Metwally T., Ahmed A. R., Ahmed Mostafa E. S., Hasan W. F., Ahmed A. G., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Jaber S., Prades A., Krassler J., Merzky S., Abreu M. G. D., Uhlig C., Kiss T., Bundy A., Bluth T., Gueldner A., Spieth P., Scharffenberg M., Thiem D. T., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodorak K., Gkiokas G., Tasoulis M. K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., Michele M. D., Bona F., Giacoletto G., Sardo E., Sottosanti L. G. V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., Bella D. L., Mirabella L., D'antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Parma A. L. D., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Agreta G. G., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Hemmes S., Schultz M., Hollmann M., Wiersma I., Binnekade J., Bos L., Boer C., Duvekot A., Veld B. I. '., Werger A., Dennesen P., Severijns C., Jong J. D., Hering J., Beek R. V., Ivars S., Jammer I. B., Breidablik A., Hodt K. S., Fjellanger F., Avalos M. V., Jannicke M. O., Andersson E., Amir S. K., Molina R., Wutai S., Morais E., Tareco G., Ferreira D., Amaral J., Castro M. D. L. G., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Popescu Garotescu I., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. T., Gherghina I., Costea D., Cindea I., Copotoiu S. M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan S. G., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Barbka N. S., Ana P. G., Jovanov M., Strazisar B., Jasmina M. B., Vesna N. J., Voje M., Grynyuk A., Kostadinov I., Alenka S. V., Moral V., Unzueta M. C., Puigbo C., Fava J., Moret E., Nunez M. R., Sendra M., Brunelli A., Rodenas F., Monedero P., Martinez F. H., Temino M. J. Y., Simon A. M., Larriba A. D. A., Lisi A., Perez G., Martinez R., Granell M., Vivo J. T., Ruiz C. S., Andres Ibanez J. A. D., Pastor E., Soro M., Ferrando C., Defez M., Cesar Aldecoa A. S., Perez R., Rico J., Jawad M., Saeed Y., Gillberg L., Bengisun Z. K., Kazbek B. K., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ozgen S. U., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Karaman F. M., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Ben C. B., Watt P., Raymode P., Pearse R., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Mills G., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Ana F. B., Luzier E., Almagro A., Melo M. V., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., and Tze Y.
Abstract: Background: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). Methods: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during ‘daytime’ when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as ‘night-time’ when induction was between 8:00 PM and 7:59 AM. Results: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09–1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89–1.90; P=0.15). Conclusions: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients’ clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. Clinical trial registration: NCT0160122
Published: 2019

22. mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.

Author: Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., Baaij, J.H.F. de, Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., and Baaij, J.H.F. de
Abstract: 01 november 2021, Item does not contain fulltext, BACKGROUND: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis. METHODS: We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). RESULTS: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Published: 2021

23. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results

Author: Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., Schaefer, F., Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., and Schaefer, F.
Abstract: Contains fulltext : 235691.pdf (Publisher’s version ) (Open Access), BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4
Published: 2021

24. Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders

Author: Konrad, M., Nijenhuis, T., Ariceta, G., Bertholet-Thomas, A., Calo, L.A., Capasso, G., Emma, F., Schlingmann, K.P., Singh, M., Trepiccione, F., Walsh, S.B., Whitton, K., Vargas-Poussou, R., Bockenhauer, D., Konrad, M., Nijenhuis, T., Ariceta, G., Bertholet-Thomas, A., Calo, L.A., Capasso, G., Emma, F., Schlingmann, K.P., Singh, M., Trepiccione, F., Walsh, S.B., Whitton, K., Vargas-Poussou, R., and Bockenhauer, D.
Abstract: Item does not contain fulltext, Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date. Despite considerable phenotypic overlap, correlations of specific clinical characteristics with the underlying molecular defects have been demonstrated, generating gene-specific phenotypes. As with many other rare disease conditions, there is a paucity of clinical studies that could guide diagnosis and therapeutic interventions. In this expert consensus document, the authors have summarized the currently available knowledge and propose clinical indicators to assess and improve quality of care.
Published: 2021

25. Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness

Author: Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., Konrad, M., Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., and Konrad, M.
Abstract: Item does not contain fulltext, BACKGROUND: The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na(+),K(+)-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness. METHODS: A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. RESULTS: We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents. CONCLUSIONS: Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
Published: 2021

26. The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).

Author: Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., Baaij, J.H.F. de, Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., and Baaij, J.H.F. de
Abstract: 01 april 2021, Contains fulltext : 238837.pdf (Publisher’s version ) (Open Access), Hypomagnesemia, seizures, and intellectual disability (HSMR) syndrome is a rare disorder caused by mutations in the cyclin M2 (CNNM2) gene. Due to the limited number of cases, extensive phenotype analyses of these patients have not been performed, hindering early recognition of patients. In this study, we established the largest cohort of HSMR to date, aiming to improve recognition and diagnosis of this complex disorder. Eleven novel variants in CNNM2 were identified in nine single sporadic cases and in two families with suspected HSMR syndrome. (25) Mg(2+) uptake assays demonstrated loss-of-function in seven out of nine variants in CNNM2. Interestingly, the pathogenic mutations resulted in decreased plasma membrane expression. The phenotype of those affected by pathogenic CNNM2 mutations was compared with five previously reported cases of HSMR. All patients suffered from hypomagnesemia (0.44-0.72 mmol/L), which could not be fully corrected by Mg(2+) supplementation. The majority of patients (77%) experienced generalized seizures and exhibited mild to moderate intellectual disability and speech delay. Moreover, severe obesity was present in most patients (89%). Our data establish hypomagnesemia, seizures, intellectual disability, and obesity as hallmarks of HSMR syndrome. The assessment of these major features offers a straightforward tool for the clinical diagnosis of HSMR.
Published: 2021

27. Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness

Author: Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., Konrad, M., Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., and Konrad, M.
Abstract: Contains fulltext : 238760.pdf (Publisher’s version ) (Closed access), BACKGROUND: The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na(+),K(+)-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness. METHODS: A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. RESULTS: We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents. CONCLUSIONS: Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
Published: 2021

28. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results

Author: Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., Schaefer, F., Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., and Schaefer, F.
Abstract: Contains fulltext : 235691.pdf (Publisher’s version ) (Open Access), BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4
Published: 2021

29. The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).

Author: Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., Baaij, J.H.F. de, Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., and Baaij, J.H.F. de
Abstract: 01 april 2021, Contains fulltext : 238837.pdf (Publisher’s version ) (Open Access), Hypomagnesemia, seizures, and intellectual disability (HSMR) syndrome is a rare disorder caused by mutations in the cyclin M2 (CNNM2) gene. Due to the limited number of cases, extensive phenotype analyses of these patients have not been performed, hindering early recognition of patients. In this study, we established the largest cohort of HSMR to date, aiming to improve recognition and diagnosis of this complex disorder. Eleven novel variants in CNNM2 were identified in nine single sporadic cases and in two families with suspected HSMR syndrome. (25) Mg(2+) uptake assays demonstrated loss-of-function in seven out of nine variants in CNNM2. Interestingly, the pathogenic mutations resulted in decreased plasma membrane expression. The phenotype of those affected by pathogenic CNNM2 mutations was compared with five previously reported cases of HSMR. All patients suffered from hypomagnesemia (0.44-0.72 mmol/L), which could not be fully corrected by Mg(2+) supplementation. The majority of patients (77%) experienced generalized seizures and exhibited mild to moderate intellectual disability and speech delay. Moreover, severe obesity was present in most patients (89%). Our data establish hypomagnesemia, seizures, intellectual disability, and obesity as hallmarks of HSMR syndrome. The assessment of these major features offers a straightforward tool for the clinical diagnosis of HSMR.
Published: 2021

30. Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders

Author: Konrad, M., Nijenhuis, T., Ariceta, G., Bertholet-Thomas, A., Calo, L.A., Capasso, G., Emma, F., Schlingmann, K.P., Singh, M., Trepiccione, F., Walsh, S.B., Whitton, K., Vargas-Poussou, R., Bockenhauer, D., Konrad, M., Nijenhuis, T., Ariceta, G., Bertholet-Thomas, A., Calo, L.A., Capasso, G., Emma, F., Schlingmann, K.P., Singh, M., Trepiccione, F., Walsh, S.B., Whitton, K., Vargas-Poussou, R., and Bockenhauer, D.
Abstract: Contains fulltext : 235621.pdf (Publisher’s version ) (Open Access), Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date. Despite considerable phenotypic overlap, correlations of specific clinical characteristics with the underlying molecular defects have been demonstrated, generating gene-specific phenotypes. As with many other rare disease conditions, there is a paucity of clinical studies that could guide diagnosis and therapeutic interventions. In this expert consensus document, the authors have summarized the currently available knowledge and propose clinical indicators to assess and improve quality of care.
Published: 2021

31. mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.

Author: Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., Baaij, J.H.F. de, Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., and Baaij, J.H.F. de
Abstract: 01 november 2021, Item does not contain fulltext, BACKGROUND: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis. METHODS: We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). RESULTS: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Published: 2021

32. The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).

Author: Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., Baaij, J.H.F. de, Franken, G.A.C., Müller, D., Mignot, C., Keren, B., Lévy, J., Tabet, A.C., Germanaud, D., Tejada, M.I., Kroes, H.Y., Nievelstein, R.A., Brimble, E., Ruzhnikov, M., Claverie-Martin, F., Szczepańska, M., Ćuk, M., Latta, F., Konrad, M., Martínez-Cruz, L.A., Bindels, R.J.M., Hoenderop, J.G.J., Schlingmann, K.P., and Baaij, J.H.F. de
Abstract: 01 april 2021, Contains fulltext : 238837.pdf (Publisher’s version ) (Open Access), Hypomagnesemia, seizures, and intellectual disability (HSMR) syndrome is a rare disorder caused by mutations in the cyclin M2 (CNNM2) gene. Due to the limited number of cases, extensive phenotype analyses of these patients have not been performed, hindering early recognition of patients. In this study, we established the largest cohort of HSMR to date, aiming to improve recognition and diagnosis of this complex disorder. Eleven novel variants in CNNM2 were identified in nine single sporadic cases and in two families with suspected HSMR syndrome. (25) Mg(2+) uptake assays demonstrated loss-of-function in seven out of nine variants in CNNM2. Interestingly, the pathogenic mutations resulted in decreased plasma membrane expression. The phenotype of those affected by pathogenic CNNM2 mutations was compared with five previously reported cases of HSMR. All patients suffered from hypomagnesemia (0.44-0.72 mmol/L), which could not be fully corrected by Mg(2+) supplementation. The majority of patients (77%) experienced generalized seizures and exhibited mild to moderate intellectual disability and speech delay. Moreover, severe obesity was present in most patients (89%). Our data establish hypomagnesemia, seizures, intellectual disability, and obesity as hallmarks of HSMR syndrome. The assessment of these major features offers a straightforward tool for the clinical diagnosis of HSMR.
Published: 2021

33. mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.

Author: Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., Baaij, J.H.F. de, Schlingmann, K.P., Jouret, F., Shen, K., Nigam, A., Arjona, F.J., Dafinger, C., Houillier, P., Jones, D.P., Kleinerüschkamp, F., Oh, J., Godefroid, N., Eltan, M., Güran, T., Burtey, S., Parotte, M.C., König, J., Braun, A., Bos, C., Ibars Serra, M., Rehmann, H., Zwartkruis, F.J., Renkema, K.Y., Klingel, K., Schulze-Bahr, E., Schermer, B., Bergmann, C., Altmüller, J., Thiele, H., Beck, B.B., Dahan, K., Sabatini, D., Liebau, M.C., Vargas-Poussou, R., Knoers, N.V.A.M., Konrad, M., and Baaij, J.H.F. de
Abstract: 01 november 2021, Item does not contain fulltext, BACKGROUND: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis. METHODS: We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). RESULTS: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Published: 2021

34. Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness

Author: Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., Konrad, M., Schlingmann, K.P., Renigunta, A., Hoorn, E.J., Forst, A.L., Renigunta, V., Atanasov, V., Mahendran, S., Barakat, T.S., Gillion, V., Godefroid, N., Brooks, A.S., Lugtenberg, D., Lake, J., Debaix, H., Rudin, C., Knebelmann, B., Tellier, S., Rousset-Rouvière, C., Viering, D., Baaij, J.H.F. de, Weber, S., Palygin, O., Staruschenko, A., Kleta, R., Houillier, P., Bockenhauer, D., Devuyst, O., Vargas-Poussou, R., Warth, R., Zdebik, A.A., and Konrad, M.
Abstract: Contains fulltext : 238760.pdf (Publisher’s version ) (Closed access), BACKGROUND: The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na(+),K(+)-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness. METHODS: A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. RESULTS: We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents. CONCLUSIONS: Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
Published: 2021

35. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results

Author: Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., Schaefer, F., Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E.N., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, P.M., Montini, G., Oh, J., Decramer, S., Levart, T.K., Wetzels, J., Cornelissen, E.A., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Varda, N. Marcun, Ghiggeri, G.M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J.W., and Schaefer, F.
Abstract: Contains fulltext : 235691.pdf (Publisher’s version ) (Open Access), BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4
Published: 2021

36. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results

Author: Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, Pietro Manuel, Montini, G., Oh, J., Decramer, S., Levart, T. K., Wetzels, J., Cornelissen, E., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Marcun Varda, N., Ghiggeri, G. M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J. W., Schaefer, F., Ferraro P. M. (ORCID:0000-0002-1379-022X), Bassanese, G., Wlodkowski, T., Servais, A., Heidet, L., Roccatello, D., Emma, F., Levtchenko, E., Ariceta, G., Bacchetta, J., Capasso, G., Jankauskiene, A., Miglinas, M., Ferraro, Pietro Manuel, Montini, G., Oh, J., Decramer, S., Levart, T. K., Wetzels, J., Cornelissen, E., Devuyst, O., Zurowska, A., Pape, L., Buescher, A., Haffner, D., Marcun Varda, N., Ghiggeri, G. M., Remuzzi, G., Konrad, M., Longo, G., Bockenhauer, D., Awan, A., Andersone, I., Groothoff, J. W., Schaefer, F., and Ferraro P. M. (ORCID:0000-0002-1379-022X)
Abstract: Background: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient’s outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. Results: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathi
Published: 2021

37. Mitochondrial Dysfunction Combined with High Calcium Load Leads to Impaired Antioxidant Defense Underlying the Selective Loss of Nigral Dopaminergic Neurons

Author: Ricke, Konrad M., Pass, Thomas, Kimoloi, Sammy, Faehrmann, Kai, Juengst, Christian, Schauss, Astrid, Baris, Olivier R., Aradjanski, Marijana, Trifunovic, Aleksandra, Faelker, Therese M. Eriksson, Bergami, Matteo, Wiesner, Rudolf J., Ricke, Konrad M., Pass, Thomas, Kimoloi, Sammy, Faehrmann, Kai, Juengst, Christian, Schauss, Astrid, Baris, Olivier R., Aradjanski, Marijana, Trifunovic, Aleksandra, Faelker, Therese M. Eriksson, Bergami, Matteo, and Wiesner, Rudolf J.
Abstract: Mitochondrial dysfunction is critically involved in Parkinson's disease, characterized by loss of dopaminergic neurons (DaNs) in the substantia nigra (SNc), whereas DaNs in the neighboring ventral tegmental area (VTA) are much less affected. In contrast to VTA, SNc DaNs engage calcium channels to generate action potentials, which lead to oxidant stress by yet unknown pathways. To determine the molecular mechanisms linking calcium load with selective cell death in the presence of mitochondrial deficiency, we analyzed the mitochondrial redox state and the mitochondrial membrane potential in mice of both sexes with genetically induced, severe mitochondrial dysfunction in DaNs (MitoPark mice), at the same time expressing a redox-sensitive GFP targeted to the mitochondrial matrix. Despite mitochondrial insufficiency in all DaNs, exclusively SNc neurons showed an oxidized redox-system, i.e., a low reduced/oxidized glutathione (GSH-GSSG) ratio. This was mimicked by cyanide, but not by rotenone or antimycin A, making the involvement of reactive oxygen species rather unlikely. Surprisingly, a high mitochondrial inner membrane potential was maintained in MitoPark SNc DaNs. Antagonizing calcium influx into the cell and into mitochondria, respectively, rescued the disturbed redox ratio and induced further hyperpolarization of the inner mitochondrial membrane. Our data therefore show that the constant calcium load in SNc DaNs is counterbalanced by a high mitochondrial inner membrane potential, even under conditions of severe mitochondrial dysfunction, but triggers a detrimental imbalance in the mitochondrial redox system, which will lead to neuron death. Our findings thus reveal a new mechanism, redox imbalance, which underlies the differential vulnerability of DaNs to mitochondrial defects.
Published: 2020

38. The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection

Author: Pass, Thomas, Assfalg, Marlene, Tolve, Marianna, Blaess, Sandra, Rothermel, Markus, Wiesner, Rudolf J., Ricke, Konrad M., Pass, Thomas, Assfalg, Marlene, Tolve, Marianna, Blaess, Sandra, Rothermel, Markus, Wiesner, Rudolf J., and Ricke, Konrad M.
Abstract: Understanding non-motor symptoms of Parkinson's disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson's disease patients. Mitochondrial dysfunction is a key feature in Parkinson's disease and importantly contributes to the selective loss of dopaminergic neurons thesubstantia nigra pars compacta. The olfactory bulb, the first olfactory processing station, also contains dopaminergic neurons, which modulate odor information and thereby enable odor detection as well as odor discrimination. MitoPark mice are a genetic model for Parkinson's disease with severe mitochondrial dysfunction, reproducing the differential vulnerability of dopaminergic neurons in the midbrain. These animals were used to investigate the impact of mitochondrial dysfunction on olfactory-related behavior and olfactory bulb dopaminergic neuron survival. Odor detection was severely impaired in MitoPark mice. Interestingly, only the small anaxonic dopaminergic subpopulation, which is continuously replenished by neurogenesis, was moderately reduced in number, much less compared with dopaminergic neurons in the midbrain. As a potential compensatory response, an enhanced mobilization of progenitor cells was found in the subventricular zone. These results reveal a high robustness of dopaminergic neurons located in the olfactory bulb towards mitochondrial impairment, in striking contrast to their midbrain counterparts.
Published: 2020

39. Assoziation von körperlichen und psychiatrischen Erkrankungen und dem chronischen Erschöpfungssysndrom in Deutschland

Author: Kostev, K, Konrad, M, Kostev, K, and Konrad, M
Published: 2020

40. Assoziation von körperlichen und psychiatrischen Erkrankungen und dem chronischen Erschöpfungssysndrom in Deutschland

Author: Kostev, K, Konrad, M, Kostev, K, and Konrad, M
Published: 2020

41. Mitochondrial Dysfunction Combined with High Calcium Load Leads to Impaired Antioxidant Defense Underlying the Selective Loss of Nigral Dopaminergic Neurons

Author: Ricke, Konrad M., Pass, Thomas, Kimoloi, Sammy, Faehrmann, Kai, Juengst, Christian, Schauss, Astrid, Baris, Olivier R., Aradjanski, Marijana, Trifunovic, Aleksandra, Faelker, Therese M. Eriksson, Bergami, Matteo, Wiesner, Rudolf J., Ricke, Konrad M., Pass, Thomas, Kimoloi, Sammy, Faehrmann, Kai, Juengst, Christian, Schauss, Astrid, Baris, Olivier R., Aradjanski, Marijana, Trifunovic, Aleksandra, Faelker, Therese M. Eriksson, Bergami, Matteo, and Wiesner, Rudolf J.
Abstract: Mitochondrial dysfunction is critically involved in Parkinson's disease, characterized by loss of dopaminergic neurons (DaNs) in the substantia nigra (SNc), whereas DaNs in the neighboring ventral tegmental area (VTA) are much less affected. In contrast to VTA, SNc DaNs engage calcium channels to generate action potentials, which lead to oxidant stress by yet unknown pathways. To determine the molecular mechanisms linking calcium load with selective cell death in the presence of mitochondrial deficiency, we analyzed the mitochondrial redox state and the mitochondrial membrane potential in mice of both sexes with genetically induced, severe mitochondrial dysfunction in DaNs (MitoPark mice), at the same time expressing a redox-sensitive GFP targeted to the mitochondrial matrix. Despite mitochondrial insufficiency in all DaNs, exclusively SNc neurons showed an oxidized redox-system, i.e., a low reduced/oxidized glutathione (GSH-GSSG) ratio. This was mimicked by cyanide, but not by rotenone or antimycin A, making the involvement of reactive oxygen species rather unlikely. Surprisingly, a high mitochondrial inner membrane potential was maintained in MitoPark SNc DaNs. Antagonizing calcium influx into the cell and into mitochondria, respectively, rescued the disturbed redox ratio and induced further hyperpolarization of the inner mitochondrial membrane. Our data therefore show that the constant calcium load in SNc DaNs is counterbalanced by a high mitochondrial inner membrane potential, even under conditions of severe mitochondrial dysfunction, but triggers a detrimental imbalance in the mitochondrial redox system, which will lead to neuron death. Our findings thus reveal a new mechanism, redox imbalance, which underlies the differential vulnerability of DaNs to mitochondrial defects.
Published: 2020

42. The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection

Author: Pass, Thomas, Assfalg, Marlene, Tolve, Marianna, Blaess, Sandra, Rothermel, Markus, Wiesner, Rudolf J., Ricke, Konrad M., Pass, Thomas, Assfalg, Marlene, Tolve, Marianna, Blaess, Sandra, Rothermel, Markus, Wiesner, Rudolf J., and Ricke, Konrad M.
Abstract: Understanding non-motor symptoms of Parkinson's disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson's disease patients. Mitochondrial dysfunction is a key feature in Parkinson's disease and importantly contributes to the selective loss of dopaminergic neurons thesubstantia nigra pars compacta. The olfactory bulb, the first olfactory processing station, also contains dopaminergic neurons, which modulate odor information and thereby enable odor detection as well as odor discrimination. MitoPark mice are a genetic model for Parkinson's disease with severe mitochondrial dysfunction, reproducing the differential vulnerability of dopaminergic neurons in the midbrain. These animals were used to investigate the impact of mitochondrial dysfunction on olfactory-related behavior and olfactory bulb dopaminergic neuron survival. Odor detection was severely impaired in MitoPark mice. Interestingly, only the small anaxonic dopaminergic subpopulation, which is continuously replenished by neurogenesis, was moderately reduced in number, much less compared with dopaminergic neurons in the midbrain. As a potential compensatory response, an enhanced mobilization of progenitor cells was found in the subventricular zone. These results reveal a high robustness of dopaminergic neurons located in the olfactory bulb towards mitochondrial impairment, in striking contrast to their midbrain counterparts.
Published: 2020

43. Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - An observational study in 29 countries

Author: Schultz, M, Hemmes, S, Neto, A, Binnekade, J, Canet, J, Hedenstierna, G, Jaber, S, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Pearse, R, Putensen, C, Schmid, W, Severgnini, P, Wrigge, H, De Abreu, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Leva, B, Damster, S, Plichon, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, van Mossevelde, V, van Malderen, M, Dylst, D, van Melkebeek, J, Beran, M, de Hert, S, De Baerdemaeker, L, Heyse, B, van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, van de Velde, S, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Pavicic-Saric, J, Erceg, G, Bogdanovic Dvorcak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Hosny Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Fathy Hasan, W, Gouda Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, Uhlig, C, Kiss, T, Bundy, A, Bluth, T, Guldner, A, Spieth, P, Scharffenberg, M, Tran Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Bos, L, Boer, C, Duvekot, A, In't Veld, B, Werger, A, Dennesen, P, Severijns, C, de Jong, J, Hering, J, van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Skirstad Hodt, K, Fjellanger, F, Vicoavalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Popescu Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, G, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, C, Puigbo, C, Fava, J, Moret, E, Rodriguez Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Hidalgo Martinez, F, Yepes Temino, M, Marti Nez Simon, A, de Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Tatay Vivo, J, Saiz Ruiz, C, de Andre S Iban Ez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Aldecoa Alvares-Santullano, C, Pere, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Kazak Bengisun, Z, Kansu Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ustalar Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Mine Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Schultz M. J., Hemmes S. N. T., Neto A. S., Binnekade J. M., Canet J., Hedenstierna G., Jaber S., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Pearse R., Putensen C., Schmid W., Severgnini P., Wrigge H., De Abreu M. G., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Leva B., Damster S., Plichon B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., van Mossevelde V., van Malderen M. C., Dylst D., van Melkebeek J., Beran M., de Hert S., De Baerdemaeker L., Heyse B., van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., van de Velde S., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Pavicic-Saric J., Erceg G., Bogdanovic Dvorcak M., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Hosny Abdelwahab H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Fathy Hasan W., Gouda Ahmed A., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., Uhlig C., Kiss T., Bundy A., Bluth T., Guldner A., Spieth P., Scharffenberg M., Tran Thiem D., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Wiersma I., Bos L., Boer C., Duvekot A., In't Veld B., Werger A., Dennesen P., Severijns C., de Jong J., Hering J., van Beek R., Ivars S., Jammer I., Breidablik A., Skirstad Hodt K., Fjellanger F., VicoAvalos M., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G. R., Ferreira D., Amaral J., Goncalves Castro M. L., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Popescu Garotescu I., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. T., Gherghina I., Costea D., Cindea I., Copotoiu S. M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan G. S., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta C., Puigbo C., Fava J., Moret E., Rodriguez Nunez M. N., Sendra M., Brunelli A., Rodenas F., Monedero P., Hidalgo Martinez F., Yepes Temino M. J., Marti Nez Simon A., de Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Tatay Vivo J., Saiz Ruiz C., de Andre S Iban Ez J. A., Pastor E., Soro M., Ferrando C., Defez M., Aldecoa Alvares-Santullano C., Pere R., Rico J., Jawad M., Saeed Y., Gillberg L., Kazak Bengisun Z., Kansu Kazbek B., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ustalar Ozgen S., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S. U., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Mine Karaman F., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., Tze Y., Schultz, M, Hemmes, S, Neto, A, Binnekade, J, Canet, J, Hedenstierna, G, Jaber, S, Hiesmayr, M, Hollmann, M, Mills, G, Vidal Melo, M, Pearse, R, Putensen, C, Schmid, W, Severgnini, P, Wrigge, H, De Abreu, M, Pelosi, P, Kroell, W, Metzler, H, Struber, G, Wegscheider, T, Gombotz, H, Urbanek, B, Leva, B, Damster, S, Plichon, B, Kahn, D, Momeni, M, Pospiech, A, Lois, F, Forget, P, Grosu, I, Poelaert, J, van Mossevelde, V, van Malderen, M, Dylst, D, van Melkebeek, J, Beran, M, de Hert, S, De Baerdemaeker, L, Heyse, B, van Limmen, J, Wyffels, P, Jacobs, T, Roels, N, De Bruyne, A, van de Velde, S, Juros-Zovko, M, Djonovic-Omanovic, D, Pernar, S, Zunic, J, Miskovic, P, Zilic, A, Kvolik, S, Ivic, D, Azenic-Venzera, D, Skiljic, S, Vinkovic, H, Oputric, I, Juricic, K, Frkovic, V, Kopic, J, Mirkovic, I, Karanovic, N, Carev, M, Dropulic, N, Pavicic-Saric, J, Erceg, G, Bogdanovic Dvorcak, M, Mazul-Sunko, B, Pavicic, A, Goranovic, T, Maldini, B, Radocaj, T, Gavranovic, Z, Mladic-Batinica, I, Sehovic, M, Stourac, P, Harazim, H, Smekalova, O, Kosinova, M, Kolacek, T, Hudacek, K, Drab, M, Brujevic, J, Vitkova, K, Jirmanova, K, Volfova, I, Dzurnakova, P, Liskova, K, Dudas, R, Filipsky, R, El Kafrawy, S, Hosny Abdelwahab, H, Metwally, T, Abdel-Razek, A, El-Shaarawy, A, Fathy Hasan, W, Gouda Ahmed, A, Yassin, H, Magdy, M, Abdelhady, M, Mahran, M, Herodes, E, Kivik, P, Oganjan, J, Aun, A, Sormus, A, Sarapuu, K, Mall, M, Karjagin, J, Futier, E, Petit, A, Gerard, A, Marret, E, Solier, M, Prades, A, Krassler, J, Merzky, S, Uhlig, C, Kiss, T, Bundy, A, Bluth, T, Guldner, A, Spieth, P, Scharffenberg, M, Tran Thiem, D, Koch, T, Treschan, T, Schaefer, M, Bastin, B, Geib, J, Weiss, M, Kienbaum, P, Pannen, B, Gottschalk, A, Konrad, M, Westerheide, D, Schwerdtfeger, B, Simon, P, Reske, A, Nestler, C, Valsamidis, D, Stroumpoulis, K, Antholopoulos, G, Andreou, A, Karapanos, D, Theodoraki, K, Gkiokas, G, Tasoulis, M, Sidiropoulou, T, Zafeiropoulou, F, Florou, P, Pandazi, A, Tsaousi, G, Nouris, C, Pourzitaki, C, Bystritski, D, Pizov, R, Eden, A, Pesce, C, Campanile, A, Marrella, A, Grasso, S, De Michele, M, Bona, F, Giacoletto, G, Sardo, E, Giancarlo, L, Sottosanti, V, Solca, M, Volta, C, Spadaro, S, Verri, M, Ragazzi, R, Zoppellari, R, Cinnella, G, Raimondo, P, La Bella, D, Mirabella, L, D'Antini, D, Molin, A, Brunetti, I, Gratarola, A, Pellerano, G, Sileo, R, Pezzatto, S, Montagnani, L, Pasin, L, Landoni, G, Zangrillo, A, Beretta, L, Di Parma, A, Tarzia, V, Dossi, R, Sassone, M, Sances, D, Tredici, S, Spano, G, Castellani, G, Delunas, L, Peradze, S, Venturino, M, Arpino, I, Sher, S, Tommasino, C, Rapido, F, Morelli, P, Vargas, M, Servillo, G, Cortegiani, A, Raineri, S, Montalto, F, Russotto, V, Giarratano, A, Baciarello, M, Generali, M, Cerati, G, Leykin, Y, Bressan, F, Bartolini, V, Zamidei, L, Brazzi, L, Liperi, C, Sales, G, Pistidda, L, Brugnoni, E, Musella, G, Bacuzzi, A, Muhardri, D, Gecaj-Gashi, A, Sada, F, Bytyqi, A, Karbonskiene, A, Aukstakalniene, R, Teberaite, Z, Salciute, E, Tikuisis, R, Miliauskas, P, Jurate, S, Kontrimaviciute, E, Tomkute, G, Xuereb, J, Bezzina, M, Borg, F, Wiersma, I, Bos, L, Boer, C, Duvekot, A, In't Veld, B, Werger, A, Dennesen, P, Severijns, C, de Jong, J, Hering, J, van Beek, R, Ivars, S, Jammer, I, Breidablik, A, Skirstad Hodt, K, Fjellanger, F, Vicoavalos, M, Mellin-Olsen, J, Andersson, E, Shafi-Kabiri, A, Molina, R, Wutai, S, Morais, E, Tareco, G, Ferreira, D, Amaral, J, Goncalves Castro, M, Cadilha, S, Appleton, S, Parente, S, Correia, M, Martins, D, Monteirosa, A, Ricardo, A, Rodrigues, S, Horhota, L, Grintescu, I, Mirea, L, Corneci, D, Negoita, S, Dutu, M, Popescu Garotescu, I, Filipescu, D, Prodan, A, Droc, G, Fota, R, Popescu, M, Tomescu, D, Petcu, A, Tudoroiu, M, Moise, A, Guran, C, Gherghina, I, Costea, D, Cindea, I, Copotoiu, S, Copotoiu, R, Barsan, V, Tolcser, Z, Riciu, M, Moldovan, G, Veres, M, Gritsan, A, Kapkan, T, Gritsan, G, Korolkov, O, Kulikov, A, Lubnin, A, Ovezov, A, Prokoshev, P, Lugovoy, A, Anipchenko, N, Babayants, A, Komissarova, I, Zalina, K, Likhvantsev, V, Fedorov, S, Lazukic, A, Pejakovic, J, Mihajlovic, D, Kusnierikova, Z, Zelinkova, M, Bruncakova, K, Polakovicova, L, Sobona, V, Novak-Supe, B, Pekle-Golez, A, Jovanov, M, Strazisar, B, Markovic-Bozic, J, Novak-Jankovic, V, Voje, M, Grynyuk, A, Kostadinov, I, Spindler-Vesel, A, Moral, V, Unzueta, C, Puigbo, C, Fava, J, Moret, E, Rodriguez Nunez, M, Sendra, M, Brunelli, A, Rodenas, F, Monedero, P, Hidalgo Martinez, F, Yepes Temino, M, Marti Nez Simon, A, de Abajo Larriba, A, Lisi, A, Perez, G, Martinez, R, Granell, M, Tatay Vivo, J, Saiz Ruiz, C, de Andre S Iban Ez, J, Pastor, E, Soro, M, Ferrando, C, Defez, M, Aldecoa Alvares-Santullano, C, Pere, R, Rico, J, Jawad, M, Saeed, Y, Gillberg, L, Kazak Bengisun, Z, Kansu Kazbek, B, Coskunfirat, N, Boztug, N, Sanli, S, Yilmaz, M, Hadimioglu, N, Senturk, N, Camci, E, Kucukgoncu, S, Sungur, Z, Sivrikoz, N, Ustalar Ozgen, S, Toraman, F, Selvi, O, Senturk, O, Yildiz, M, Kuvaki, B, Gunenc, F, Kucukguclu, S, Ozbilgin, S, Maral, J, Canli, S, Arun, O, Saltali, A, Aydogan, E, Akgun, F, Sanlikarip, C, Mine Karaman, F, Mazur, A, Vorotyntsev, S, Rousseau, G, Barrett, C, Stancombe, L, Shelley, B, Scholes, H, Limb, J, Rafi, A, Wayman, L, Deane, J, Rogerson, D, Williams, J, Yates, S, Rogers, E, Pulletz, M, Moreton, S, Jones, S, Venkatesh, S, Burton, M, Brown, L, Goodall, C, Rucklidge, M, Fuller, D, Nadolski, M, Kusre, S, Lundberg, M, Everett, L, Nutt, H, Zuleika, M, Carvalho, P, Clements, D, Creagh-Brown, B, Watt, P, Raymode, P, Mohr, O, Raj, A, Creary, T, Chishti, A, Bell, A, Higham, C, Cain, A, Gibb, S, Mowat, S, Franklin, D, West, C, Minto, G, Boyd, N, Calton, E, Walker, R, Mackenzie, F, Ellison, B, Roberts, H, Chikungwa, M, Jackson, C, Donovan, A, Foot, J, Homan, E, Montgomery, J, Portch, D, Mercer, P, Palmer, J, Paddle, J, Fouracres, A, Datson, A, Andrew, A, Welch, L, Rose, A, Varma, S, Simeson, K, Rambhatla, M, Susarla, J, Marri, S, Kodaganallur, K, Das, A, Algarsamy, S, Colley, J, Davies, S, Szewczyk, M, Smith, T, Fernandez-Bustamante, A, Luzier, E, Almagro, A, Fernando, L, Sulemanji, D, Sprung, J, Weingarten, T, Kor, D, Scavonetto, F, Tze, Y, Schultz M. J., Hemmes S. N. T., Neto A. S., Binnekade J. M., Canet J., Hedenstierna G., Jaber S., Hiesmayr M., Hollmann M. W., Mills G. H., Vidal Melo M. F., Pearse R., Putensen C., Schmid W., Severgnini P., Wrigge H., De Abreu M. G., Pelosi P., Kroell W., Metzler H., Struber G., Wegscheider T., Gombotz H., Urbanek B., Leva B., Damster S., Plichon B., Kahn D., Momeni M., Pospiech A., Lois F., Forget P., Grosu I., Poelaert J., van Mossevelde V., van Malderen M. C., Dylst D., van Melkebeek J., Beran M., de Hert S., De Baerdemaeker L., Heyse B., van Limmen J., Wyffels P., Jacobs T., Roels N., De Bruyne A., van de Velde S., Juros-Zovko M., Djonovic-Omanovic D., Pernar S., Zunic J., Miskovic P., Zilic A., Kvolik S., Ivic D., Azenic-Venzera D., Skiljic S., Vinkovic H., Oputric I., Juricic K., Frkovic V., Kopic J., Mirkovic I., Karanovic N., Carev M., Dropulic N., Pavicic-Saric J., Erceg G., Bogdanovic Dvorcak M., Mazul-Sunko B., Pavicic A. M., Goranovic T., Maldini B., Radocaj T., Gavranovic Z., Mladic-Batinica I., Sehovic M., Stourac P., Harazim H., Smekalova O., Kosinova M., Kolacek T., Hudacek K., Drab M., Brujevic J., Vitkova K., Jirmanova K., Volfova I., Dzurnakova P., Liskova K., Dudas R., Filipsky R., El Kafrawy S., Hosny Abdelwahab H., Metwally T., Abdel-Razek A., El-Shaarawy A. M., Fathy Hasan W., Gouda Ahmed A., Yassin H., Magdy M., Abdelhady M., Mahran M., Herodes E., Kivik P., Oganjan J., Aun A., Sormus A., Sarapuu K., Mall M., Karjagin J., Futier E., Petit A., Gerard A., Marret E., Solier M., Prades A., Krassler J., Merzky S., Uhlig C., Kiss T., Bundy A., Bluth T., Guldner A., Spieth P., Scharffenberg M., Tran Thiem D., Koch T., Treschan T., Schaefer M., Bastin B., Geib J., Weiss M., Kienbaum P., Pannen B., Gottschalk A., Konrad M., Westerheide D., Schwerdtfeger B., Simon P., Reske A., Nestler C., Valsamidis D., Stroumpoulis K., Antholopoulos G., Andreou A., Karapanos D., Theodoraki K., Gkiokas G., Tasoulis M. K., Sidiropoulou T., Zafeiropoulou F., Florou P., Pandazi A., Tsaousi G., Nouris C., Pourzitaki C., Bystritski D., Pizov R., Eden A., Pesce C. V., Campanile A., Marrella A., Grasso S., De Michele M., Bona F., Giacoletto G., Sardo E., Giancarlo L., Sottosanti V., Solca M., Volta C. A., Spadaro S., Verri M., Ragazzi R., Zoppellari R., Cinnella G., Raimondo P., La Bella D., Mirabella L., D'antini D., Molin A., Brunetti I., Gratarola A., Pellerano G., Sileo R., Pezzatto S., Montagnani L., Pasin L., Landoni G., Zangrillo A., Beretta L., Di Parma A. L., Tarzia V., Dossi R., Sassone M. E., Sances D., Tredici S., Spano G., Castellani G., Delunas L., Peradze S., Venturino M., Arpino I., Sher S., Tommasino C., Rapido F., Morelli P., Vargas M., Servillo G., Cortegiani A., Raineri S. M., Montalto F., Russotto V., Giarratano A., Baciarello M., Generali M., Cerati G., Leykin Y., Bressan F., Bartolini V., Zamidei L., Brazzi L., Liperi C., Sales G., Pistidda L., Brugnoni E., Musella G., Bacuzzi A., Muhardri D., Gecaj-Gashi A., Sada F., Bytyqi A., Karbonskiene A., Aukstakalniene R., Teberaite Z., Salciute E., Tikuisis R., Miliauskas P., Jurate S., Kontrimaviciute E., Tomkute G., Xuereb J., Bezzina M., Borg F. J., Wiersma I., Bos L., Boer C., Duvekot A., In't Veld B., Werger A., Dennesen P., Severijns C., de Jong J., Hering J., van Beek R., Ivars S., Jammer I., Breidablik A., Skirstad Hodt K., Fjellanger F., VicoAvalos M., Mellin-Olsen J., Andersson E., Shafi-Kabiri A., Molina R., Wutai S., Morais E., Tareco G. R., Ferreira D., Amaral J., Goncalves Castro M. L., Cadilha S., Appleton S., Parente S., Correia M., Martins D., Monteirosa A., Ricardo A., Rodrigues S., Horhota L., Grintescu I. M., Mirea L., Grintescu I. C., Corneci D., Negoita S., Dutu M., Popescu Garotescu I., Filipescu D., Prodan A. B., Droc G., Fota R., Popescu M., Tomescu D., Petcu A. M., Tudoroiu M. I., Moise A., Guran C. T., Gherghina I., Costea D., Cindea I., Copotoiu S. M., Copotoiu R., Barsan V., Tolcser Z., Riciu M., Moldovan G. S., Veres M., Gritsan A., Kapkan T., Gritsan G., Korolkov O., Kulikov A., Lubnin A., Ovezov A., Prokoshev P., Lugovoy A., Anipchenko N., Babayants A., Komissarova I., Zalina K., Likhvantsev V., Fedorov S., Lazukic A., Pejakovic J., Mihajlovic D., Kusnierikova Z., Zelinkova M., Bruncakova K., Polakovicova L., Sobona V., Novak-Supe B., Pekle-Golez A., Jovanov M., Strazisar B., Markovic-Bozic J., Novak-Jankovic V., Voje M., Grynyuk A., Kostadinov I., Spindler-Vesel A., Moral V., Unzueta C., Puigbo C., Fava J., Moret E., Rodriguez Nunez M. N., Sendra M., Brunelli A., Rodenas F., Monedero P., Hidalgo Martinez F., Yepes Temino M. J., Marti Nez Simon A., de Abajo Larriba A., Lisi A., Perez G., Martinez R., Granell M., Tatay Vivo J., Saiz Ruiz C., de Andre S Iban Ez J. A., Pastor E., Soro M., Ferrando C., Defez M., Aldecoa Alvares-Santullano C., Pere R., Rico J., Jawad M., Saeed Y., Gillberg L., Kazak Bengisun Z., Kansu Kazbek B., Coskunfirat N., Boztug N., Sanli S., Yilmaz M., Hadimioglu N., Senturk N. M., Camci E., Kucukgoncu S., Sungur Z., Sivrikoz N., Ustalar Ozgen S., Toraman F., Selvi O., Senturk O., Yildiz M., Kuvaki B., Gunenc F., Kucukguclu S., Ozbilgin S. U., Maral J., Canli S., Arun O., Saltali A., Aydogan E., Akgun F. N., Sanlikarip C., Mine Karaman F., Mazur A., Vorotyntsev S., Rousseau G., Barrett C., Stancombe L., Shelley B., Scholes H., Limb J., Rafi A., Wayman L., Deane J., Rogerson D., Williams J., Yates S., Rogers E., Pulletz M., Moreton S., Jones S., Venkatesh S., Burton M., Brown L., Goodall C., Rucklidge M., Fuller D., Nadolski M., Kusre S., Lundberg M., Everett L., Nutt H., Zuleika M., Carvalho P., Clements D., Creagh-Brown B., Watt P., Raymode P., Mohr O., Raj A., Creary T., Chishti A., Bell A., Higham C., Cain A., Gibb S., Mowat S., Franklin D., West C., Minto G., Boyd N., Calton E., Walker R., Mackenzie F., Ellison B., Roberts H., Chikungwa M., Jackson C., Donovan A., Foot J., Homan E., Montgomery J., Portch D., Mercer P., Palmer J., Paddle J., Fouracres A., Datson A., Andrew A., Welch L., Rose A., Varma S., Simeson K., Rambhatla M., Susarla J., Marri S., Kodaganallur K., Das A., Algarsamy S., Colley J., Davies S., Szewczyk M., Smith T., Fernandez-Bustamante A., Luzier E., Almagro A., Fernando L., Sulemanji D., Sprung J., Weingarten T., Kor D., Scavonetto F., and Tze Y.
Abstract: Background: Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. Objectives: To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. Design: This was a prospective international 1-week observational study using the 'Assess Respiratory Risk in Surgical Patients in Catalonia risk score' (ARISCAT score) for PPC for risk stratification. Patients and Setting: Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. Main Outcome Measures: The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. Results: A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg-1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH 2 O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. Conclusion: The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at i
Published: 2017

44. Treatment and long-term outcome in primary distal renal tubular acidosis

Author: Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., Bockenhauer, D., Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., and Bockenhauer, D.
Abstract: Contains fulltext : 204259.pdf (publisher's version ) (Closed access), BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (+/-1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage >/=2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.
Published: 2019

45. Treatment and long-term outcome in primary distal renal tubular acidosis

Author: Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., Bockenhauer, D., Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., and Bockenhauer, D.
Abstract: Contains fulltext : 204259.pdf (publisher's version ) (Closed access), BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (+/-1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage >/=2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.
Published: 2019

46. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Author: Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., Devuyst, O., Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., and Devuyst, O.
Abstract: 1 januari 2018, Contains fulltext : 184156.pdf (publisher's version ) (Closed access), Magnesium (Mg(2+)) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg(2+), which is crucial for Mg(2+) homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg(2+) homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4x10(-13)) near TRPM6, which encodes an epithelial Mg(2+) channel, and rs35929 (P=2.1x10(-11)), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg(2+) regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg(2+) wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg(2+) deficiency to insulin resistance and obesity.
Published: 2018

47. Dauer der Arbeitsunfähigkeit von Depressionspatienten, die in hausärztlichen und psychiatrischen Praxen behandelt werden

Author: Kostev, K, Konrad, M, Bohlken, J, Kostev, K, Konrad, M, and Bohlken, J
Published: 2018

48. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Author: Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., Devuyst, O., Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., and Devuyst, O.
Abstract: 01 januari 2018, Contains fulltext : 184156.pdf (publisher's version ) (Closed access), Magnesium (Mg(2+)) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg(2+), which is crucial for Mg(2+) homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg(2+) homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4x10(-13)) near TRPM6, which encodes an epithelial Mg(2+) channel, and rs35929 (P=2.1x10(-11)), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg(2+) regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg(2+) wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg(2+) deficiency to insulin resistance and obesity.
Published: 2018

49. Zeit zwischen Verdachtsdiagnose und bestätigter Diagnose eines Morbus Crohn oder einer Colitis ulcerosa bei Patienten in gastroenterologischen Praxen in Deutschland

Author: Kostev, K, Dombrowski, S, Konrad, M, Kostev, K, Dombrowski, S, and Konrad, M
Published: 2018

50. Zeit zwischen Verdachtsdiagnose und bestätigter Diagnose eines Morbus Crohn oder einer Colitis ulcerosa bei Patienten in gastroenterologischen Praxen in Deutschland

Author: Kostev, K, Dombrowski, S, Konrad, M, Kostev, K, Dombrowski, S, and Konrad, M
Published: 2018

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