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304 results on '"Otto, M"'

1. Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation:incidence and clinical implications

Author: Filipe, Wills F, Buisman, Florian E, Franssen, Stijn, Krul, Myrtle F, Grünhagen, Dirk J, Bennink, Roel J, Bolhuis, Karen, Bruijnen, Rutger C G, Buffart, Tineke E, Burgmans, Mark C, van Delden, Otto M, Doornebosch, Pascal G, Gobardhan, Paul D, Graven, Laura, de Groot, Jan Willem B, Grootscholten, Cecile, Hagendoorn, Jeroen, Harmsen, Paul, Homs, Marjolein Y V, Klompenhouwer, Elizabeth G, Kok, Niels F M, Lam, Marnix G E H, Loosveld, Olaf J L, Meier, Mark A J, Mieog, J Sven D, Oostdijk, Ad H J, Outmani, Loubna, Patijn, Gijs A, Pool, Stefan, Rietbergen, Daphne D D, Roodhart, Jeanine M L, Speetjens, Frank M, Swijnenburg, Rutger Jan, Versleijen, Michelle W J, Verhoef, Cornelis, Kuhlmann, Koert F D, Moelker, Adriaan, Groot Koerkamp, Bas, Filipe, Wills F, Buisman, Florian E, Franssen, Stijn, Krul, Myrtle F, Grünhagen, Dirk J, Bennink, Roel J, Bolhuis, Karen, Bruijnen, Rutger C G, Buffart, Tineke E, Burgmans, Mark C, van Delden, Otto M, Doornebosch, Pascal G, Gobardhan, Paul D, Graven, Laura, de Groot, Jan Willem B, Grootscholten, Cecile, Hagendoorn, Jeroen, Harmsen, Paul, Homs, Marjolein Y V, Klompenhouwer, Elizabeth G, Kok, Niels F M, Lam, Marnix G E H, Loosveld, Olaf J L, Meier, Mark A J, Mieog, J Sven D, Oostdijk, Ad H J, Outmani, Loubna, Patijn, Gijs A, Pool, Stefan, Rietbergen, Daphne D D, Roodhart, Jeanine M L, Speetjens, Frank M, Swijnenburg, Rutger Jan, Versleijen, Michelle W J, Verhoef, Cornelis, Kuhlmann, Koert F D, Moelker, Adriaan, and Groot Koerkamp, Bas
Abstract: INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy.METHODS:The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging ( 99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%.CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.
Published: 2024

2. Effect of Sarcopenia on the Increase in Liver Volume and Function After Portal Vein Embolization

Author: Arntz, Pieter J.W., Olthof, Pim B., Korenblik, Remon, Heil, Jan, Kazemier, Geert, van Delden, Otto M., Bennink, Roelof J., Damink, Steven W.M.Olde, van Dam, Ronald M., Schadde, Erik, Erdmann, Joris I., Arntz, Pieter J.W., Olthof, Pim B., Korenblik, Remon, Heil, Jan, Kazemier, Geert, van Delden, Otto M., Bennink, Roelof J., Damink, Steven W.M.Olde, van Dam, Ronald M., Schadde, Erik, and Erdmann, Joris I.
Abstract: Purpose: Sarcopenia is associated with a decreased kinetic growth rate (KGR) of the future liver remnant (FLR) after portal vein embolization (PVE). However, little is known on the increase in FLR function (FLRF) after PVE. This study evaluated the effect of sarcopenia on the functional growth rate (FGR) after PVE measured with hepatobiliary scintigraphy (HBS). Methods: All patients who underwent PVE at the Amsterdam UMC between January 2005 and August 2017 were analyzed. Functional imaging by HBS was used to determine FGR. Liver volumetry was performed using multiphase contrast computed tomography (CT). Muscle area measurement to determine sarcopenia was taken at the third lumbar level (L3). Results: Out of the 95 included patients, 9 were excluded due to unavailable data. 70/86 (81%) patients were sarcopenic. In the multivariate logistic regression analysis, sarcopenia (p = 0.009) and FLR volume (FRLV) before PVE (p = 0.021) were the only factors correlated with KGR, while no correlation was found with FGR. 90-day mortality was similar across the sarcopenic and non-sarcopenic group (4/53 [8%] versus 1/11 [9%]; p = 1.000). The resection rates were also comparable (53/70 [75%] versus 11/16 [69%]; p = 0.542). Conclusion: FGR after PVE as measured by HBS appears to be preserved in sarcopenic patients. This is in contrast to KGR after PVE as measured by liver volumetry which is decreased in sarcopenic patients. Level of Evidence: Level 3b, cohort and case control studies.
Published: 2024

3. Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Author: Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., Masellis, M., Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., and Masellis, M.
Abstract: Genetic frontotemporal dementia is most commonly attributable to mutations in the C9orf72, GRN, or MAPT genes. The disease has near-complete penetrance, making presymptomatic carriers an ideal population for ascertaining the earliest changes in disease progression and the identification of suitable biomarkers for designing therapeutic trials when minimal neuronal loss has occurred. Cerebral perfusion, as measured by arterial spin labelling (ASL) MRI, has shown promise in being one such biomarker. However, longitudinal profiles of change in perfusion over time in presymptomatic carriers across all three genetic subgroups are lacking. Using data from the multicenter GENetic Frontotemporal dementia Initiative, we investigated longitudinal profiles of cerebral perfusion using ASL-MRI in C9orf72 (n = 42), GRN (n = 70), and MAPT (n = 31) presymptomatic mutation carriers and non-carrier controls (n = 158). ASL and T1w scans were processed with the ExploreASL pipeline to produce partial volume corrected perfusion images, which were parcellated to extract mean perfusion values from whole brain grey matter and regions defined by the second version of the automated anatomical atlas (AAL2). Linear mixed effects models were used to assess longitudinal perfusion change. Mutation carrier groups and non-carriers were statistically indistinguishable by baseline demographic and clinical measures. Decline in whole brain grey matter perfusion over time was more pronounced in all three carrier subgroups relative to controls, with changes most pronounced in GRN, followed by C9orf72 and MAPT variants. Additionally, GRN and MAPT groups featured global grey matter hypoperfusion relative to non-carrier controls as early as one year after baseline measurement, with C9orf72 featuring significant hypoperfusion after two years. Region of interest analysis demonstrated that each genetic subgroup had its own regional profile in terms of longitudinal perfusion decline. Perfusion decline in C9orf72
Published: 2024

4. Ukrajinský vektor bolesti těch druhých

Author: Urban, Otto M, Šilpochová, Michaela, Urban, O M ( Otto M ), Šilpochová, M ( Michaela ), Glanc, Tomas, Urban, Otto M, Šilpochová, Michaela, Urban, O M ( Otto M ), Šilpochová, M ( Michaela ), and Glanc, Tomas
Published: 2023

5. The 2023 report of the Lancet Countdown on health and climate change: the imperative for a health-centred response in a world facing irreversible harms

Author: Romanello, M, di Napoli, C, Green, C, Kennard, H, Lampard, P, Scamman, D, Walawender, M, Ali, Z, Ameli, N, Ayeb-Karlsson, S, Beggs, PJ, Belesova, K, Ford, LB, Bowen, K, Cai, W, Callaghan, M, Campbell-Lendrum, D, Chambers, J, Cross, TJ, van Daalen, KR, Dalin, C, Dasandi, N, Dasgupta, S, Davies, M, Dominguez-Salas, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Freyberg, C, Gasparyan, O, Gordon-Strachan, G, Graham, H, Gunther, SH, Hamilton, I, Hang, Y, Hanninen, R, Hartinger, S, He, K, Heidecke, J, Hess, JJ, Hsu, S-C, Jamart, L, Jankin, S, Jay, O, Kelman, I, Kiesewetter, G, Kinney, P, Kniveton, D, Kouznetsov, R, Larosa, F, Lee, JKW, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lotto Batista, M, Lowe, R, Sewe, MO, Martinez-Urtaza, J, Maslin, M, McAllister, L, McMichael, C, Mi, Z, Milner, J, Minor, K, Minx, JC, Mohajeri, N, Momen, NC, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Obradovich, N, O'Hare, MB, Oliveira, C, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pega, F, Pershing, A, Rabbaniha, M, Rickman, J, Robinson, EJZ, Rocklov, J, Salas, RN, Semenza, JC, Sherman, JD, Shumake-Guillemot, J, Silbert, G, Sofiev, M, Springmann, M, Stowell, JD, Tabatabaei, M, Taylor, J, Thompson, R, Tonne, C, Treskova, M, Trinanes, JA, Wagner, F, Warnecke, L, Whitcombe, H, Winning, M, Wyns, A, Yglesias-Gonzalez, M, Zhang, S, Zhang, Y, Zhu, Q, Gong, P, Montgomery, H, Costello, A, Romanello, M, di Napoli, C, Green, C, Kennard, H, Lampard, P, Scamman, D, Walawender, M, Ali, Z, Ameli, N, Ayeb-Karlsson, S, Beggs, PJ, Belesova, K, Ford, LB, Bowen, K, Cai, W, Callaghan, M, Campbell-Lendrum, D, Chambers, J, Cross, TJ, van Daalen, KR, Dalin, C, Dasandi, N, Dasgupta, S, Davies, M, Dominguez-Salas, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Freyberg, C, Gasparyan, O, Gordon-Strachan, G, Graham, H, Gunther, SH, Hamilton, I, Hang, Y, Hanninen, R, Hartinger, S, He, K, Heidecke, J, Hess, JJ, Hsu, S-C, Jamart, L, Jankin, S, Jay, O, Kelman, I, Kiesewetter, G, Kinney, P, Kniveton, D, Kouznetsov, R, Larosa, F, Lee, JKW, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lotto Batista, M, Lowe, R, Sewe, MO, Martinez-Urtaza, J, Maslin, M, McAllister, L, McMichael, C, Mi, Z, Milner, J, Minor, K, Minx, JC, Mohajeri, N, Momen, NC, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Obradovich, N, O'Hare, MB, Oliveira, C, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pega, F, Pershing, A, Rabbaniha, M, Rickman, J, Robinson, EJZ, Rocklov, J, Salas, RN, Semenza, JC, Sherman, JD, Shumake-Guillemot, J, Silbert, G, Sofiev, M, Springmann, M, Stowell, JD, Tabatabaei, M, Taylor, J, Thompson, R, Tonne, C, Treskova, M, Trinanes, JA, Wagner, F, Warnecke, L, Whitcombe, H, Winning, M, Wyns, A, Yglesias-Gonzalez, M, Zhang, S, Zhang, Y, Zhu, Q, Gong, P, Montgomery, H, and Costello, A
Published: 2023

6. European Inter-Societal Delphi Consensus for the biomarker-based etiological diagnosis of neurocognitive disorders in the mild stage

Author: Massa, F., Festari, C., Cotta Ramusino, M., Orini, S., Aarsland, D., Agosta, F., Babiloni, C., Boada, M., Borroni, B., Cappa, S.F., Dubois, B., Frederiksen, K.S., Frölich, L., Garibotto, V., Georges, J., Haliassos, A., Hansson, O., Jessen, F., Kamondi, A., Kessels, R.P.C., Morbelli, S., O'Brien, J.T., Otto, M., Perret-Liaudet, A., Pizzini, F.B., Ritchie, C.W., Scheltens, P., Flier, W.M. van der, Vandenbulcke, M., Vanninen, R., Verhey, F.R.J., Vernooij, M.W., Yousry, T., Nobili, F., Frisoni, G.B., Massa, F., Festari, C., Cotta Ramusino, M., Orini, S., Aarsland, D., Agosta, F., Babiloni, C., Boada, M., Borroni, B., Cappa, S.F., Dubois, B., Frederiksen, K.S., Frölich, L., Garibotto, V., Georges, J., Haliassos, A., Hansson, O., Jessen, F., Kamondi, A., Kessels, R.P.C., Morbelli, S., O'Brien, J.T., Otto, M., Perret-Liaudet, A., Pizzini, F.B., Ritchie, C.W., Scheltens, P., Flier, W.M. van der, Vandenbulcke, M., Vanninen, R., Verhey, F.R.J., Vernooij, M.W., Yousry, T., Nobili, F., and Frisoni, G.B.
Abstract: Item does not contain fulltext, Background: CSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence-based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022. Method: A Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses. Result: In the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients’ age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient-centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first-line biomarkers according to the main clinical suspicion (i.e., FDG-PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer’s disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second-line biomarker when results of first-line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG-PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid-positive and tau-negative CSF results) or when a diagnosis remains possible despite a negative first-line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies). Conc
Published: 2023

7. The 2023 report of the Lancet Countdown on health and climate change: the imperative for a health-centred response in a world facing irreversible harms

Author: Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., Costello, A., Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., and Costello, A.
Published: 2023

8. The 2023 report of the Lancet Countdown on health and climate change: the imperative for a health-centred response in a world facing irreversible harms

Author: Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., Costello, A., Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., and Costello, A.
Published: 2023

9. The 2023 report of the Lancet Countdown on health and climate change: the imperative for a health-centred response in a world facing irreversible harms

Author: Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., Costello, A., Romanello, M., Napoli, C., Green, C., Kennard, H., Lampard, P., Scamman, D., Walawender, M., Ali, Z., Ameli, N., Ayeb-Karlsson, S., Beggs, P., Belesova, K., Berrang Ford, L., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., Cross, T., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Freyberg, C., Gasparyan, O., Gordon-Strachan, G., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Heidecke, J., Hess, J., Hsu, S., Jamart, L., Jankin, S., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kniveton, D., Kouznetsov, R., Larosa, F., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lotto Batista, M., Lowe, R., Odhiambo Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Momen, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oliveira, C., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pega, F., Pershing, A., Rabbaniha, M., Rickman, J., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Thompson, R., Tonne, C., Treskova, M., Trinanes, J., Wagner, F., Warnecke, L., Whitcombe, H., Winning, M., Wyns, A., Yglesias-González, M., Zhang, S., Zhang, Y., Zhu, Q., Gong, P., Montgomery, H., and Costello, A.
Published: 2023

10. Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC:the RALLY protocol

Author: Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, Borel Rinkes, Inne H.M., Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, and Borel Rinkes, Inne H.M.
Abstract: Background: High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. Discussion: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. Trial registration: Netherlands Trial Register NL8902 , registered on 2020–09-15.
Published: 2023

11. Transarterial Chemoembolization With Drug-Eluting Beads Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma:Outcomes From a Multicenter, Randomized, Phase 2 Trial (the TRENDY Trial)

Author: Méndez Romero, Alejandra, van der Holt, Bronno, Willemssen, Francois E.J.A., de Man, Rob A., Heijmen, Ben J.M., Habraken, Steven, Westerveld, Henrike, van Delden, Otto M., Klümpen, Heinz Josef, Tjwa, Eric T.T.L., Braam, Pètra M., Jenniskens, Sjoerd F.M., Vanwolleghem, Thomas, Weytjens, Reinhilde, d'Archambeau, Olivier, de Vos-Geelen, Judith, Buijsen, Jeroen, van der Leij, Christiaan, den Toom, Wilhelm, Sprengers, Dave, IJzermans, Jan N.M., Moelker, Adriaan, Méndez Romero, Alejandra, van der Holt, Bronno, Willemssen, Francois E.J.A., de Man, Rob A., Heijmen, Ben J.M., Habraken, Steven, Westerveld, Henrike, van Delden, Otto M., Klümpen, Heinz Josef, Tjwa, Eric T.T.L., Braam, Pètra M., Jenniskens, Sjoerd F.M., Vanwolleghem, Thomas, Weytjens, Reinhilde, d'Archambeau, Olivier, de Vos-Geelen, Judith, Buijsen, Jeroen, van der Leij, Christiaan, den Toom, Wilhelm, Sprengers, Dave, IJzermans, Jan N.M., and Moelker, Adriaan
Abstract: Purpose: To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. Methods and Materials: Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. Results: Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. Conclusions: In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.
Published: 2023

12. Evolutionary quantum feature selection

Author: Albino, Anton S., Pires, Otto M., Nooblath, Mauro Q., Nascimento, Erick G. S., Albino, Anton S., Pires, Otto M., Nooblath, Mauro Q., and Nascimento, Erick G. S.
Abstract: Effective feature selection is essential for enhancing the performance of artificial intelligence models. It involves identifying feature combinations that optimize a given metric, but this is a challenging task due to the problem's exponential time complexity. In this study, we present an innovative heuristic called Evolutionary Quantum Feature Selection (EQFS) that employs the Quantum Circuit Evolution (QCE) algorithm. Our approach harnesses the unique capabilities of QCE, which utilizes shallow depth circuits to generate sparse probability distributions. Our computational experiments demonstrate that EQFS can identify good feature combinations with quadratic scaling in the number of features. To evaluate EQFS's performance, we counted the number of times a given classical model assesses the cost function for a specific metric, as a function of the number of generations.
Published: 2023

13. Long-term efficacy of metal versus plastic stents in inoperable perihilar cholangiocarcinoma; a multicenter retrospective propensity score matched comparison

Author: Fritzsche, Jeska A, de Jong, David M, Borremans, Jasmijn J M M, Bruno, Marco J, Van Delden, Otto M, Erdmann, Joris I, Fockens, Paul, de Gooyer, Peter G M, Groot Koerkamp, Bas, Klümpen, Heinz-Josef, Moelker, Adriaan, Montazeri, Nahid S M, Nooijen, Lynn E, Ponsioen, Cyriel Y, Van Wanrooij, Roy L J, van Driel, Lydi M J W, Voermans, Rogier P, Fritzsche, Jeska A, de Jong, David M, Borremans, Jasmijn J M M, Bruno, Marco J, Van Delden, Otto M, Erdmann, Joris I, Fockens, Paul, de Gooyer, Peter G M, Groot Koerkamp, Bas, Klümpen, Heinz-Josef, Moelker, Adriaan, Montazeri, Nahid S M, Nooijen, Lynn E, Ponsioen, Cyriel Y, Van Wanrooij, Roy L J, van Driel, Lydi M J W, and Voermans, Rogier P
Abstract: BACKGROUND: For palliative drainage of inoperable perihilar cholangiocarcinoma (pCCA) uncovered metal stents are preferred over plastic stents. However, there is a lack of data on re-interventions at the long-term. The aim is to evaluate the potential difference in the number of re-interventions in patients surviving at least 6 months.METHODS: Retrospective study including patients with pCCA who underwent plastic stent placement(s) or had metal stent(s) in situ for at least 6 months. The primary outcome was the number of re-interventions per patient-year. A propensity score matching (1:1) analysis was performed using age, Bismuth classification, reason for inoperability, pathological confirmation, systemic therapy and initial approach (endoscopic vs percutaneous).RESULTS: Patients in the metal stent group (n = 87) underwent fewer re-interventions compared with the plastic stent group (n = 40) (3.0 vs. 4.7 per patient-year; IRR, 0.64; 95% CI, 0.47 to 0.88). When only non-elective re-interventions were included, there was no significant difference (2.1 vs. 2.7; IRR, 0.76; 95% CI, 0.55 to 1.08). Results were similar in the propensity score-matched dataset.CONCLUSIONS: This study shows that, also in patients with inoperable pCCA who survive at least 6 months, placement of metal stent(s) leads to fewer re-interventions in comparison with plastic stents.
Published: 2023

14. Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma

Author: Nooijen, Lynn E., Franssen, Stijn, Buis, Carlijn I., Dejong, Cornelis H.C., den Dulk, Marcel, van Delden, Otto M., Ijzermans, Jan N., Groot Koerkamp, Bas, Kazemier, Geert, van Lienden, Krijn, Klümpen, Heinz Josef, Kuipers, Hendrien, Olij, Bram, Porte, Robert J., Rauws, Erik A., Voermans, Rogier P., van Gulik, Thomas M., Erdmann, Joris I., Roos, E., Coelen, R. J., Nooijen, Lynn E., Franssen, Stijn, Buis, Carlijn I., Dejong, Cornelis H.C., den Dulk, Marcel, van Delden, Otto M., Ijzermans, Jan N., Groot Koerkamp, Bas, Kazemier, Geert, van Lienden, Krijn, Klümpen, Heinz Josef, Kuipers, Hendrien, Olij, Bram, Porte, Robert J., Rauws, Erik A., Voermans, Rogier P., van Gulik, Thomas M., Erdmann, Joris I., Roos, E., and Coelen, R. J.
Abstract: BACKGROUND AND AIMS: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.METHODS: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions.RESULTS: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77).DISCUSSION: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.
Published: 2023

15. Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol

Author: MS HOD, Lab Translational Oncology, Researchgr. Nucleaire Geneeskunde, Cancer, MS MDL 1, MS Radiologie, Regenerative Medicine and Stem Cells, MS CGO, Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, Borel Rinkes, Inne H.M., MS HOD, Lab Translational Oncology, Researchgr. Nucleaire Geneeskunde, Cancer, MS MDL 1, MS Radiologie, Regenerative Medicine and Stem Cells, MS CGO, Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, and Borel Rinkes, Inne H.M.
Published: 2023

16. Evolutionary-enhanced quantum supervised learning model

Author: Albino, Anton Simen, Bloot, Rodrigo, Pires, Otto M., Nascimento, Erick G. S., Albino, Anton Simen, Bloot, Rodrigo, Pires, Otto M., and Nascimento, Erick G. S.
Abstract: Quantum supervised learning, utilizing variational circuits, stands out as a promising technology for NISQ devices due to its efficiency in hardware resource utilization during the creation of quantum feature maps and the implementation of hardware-efficient ansatz with trainable parameters. Despite these advantages, the training of quantum models encounters challenges, notably the barren plateau phenomenon, leading to stagnation in learning during optimization iterations. This study proposes an innovative approach: an evolutionary-enhanced ansatz-free supervised learning model. In contrast to parametrized circuits, our model employs circuits with variable topology that evolves through an elitist method, mitigating the barren plateau issue. Additionally, we introduce a novel concept, the superposition of multi-hot encodings, facilitating the treatment of multi-classification problems. Our framework successfully avoids barren plateaus, resulting in enhanced model accuracy. Comparative analysis with variational quantum classifiers from the technology's state-of-the-art reveal a substantial improvement in training efficiency and precision. Furthermore, we conduct tests on a challenging dataset class, traditionally problematic for conventional kernel machines, demonstrating a potential alternative path for achieving quantum advantage in supervised learning for NISQ era.
Published: 2023

17. Protecting the Rhine-Meuse delta against sea level rise: What to do with the river's discharge?

Author: De Bruijn, Karin M., Diermanse, Ferdinand L.M., Weiler, Otto M., De Jong, Jurjen S., Haasnoot, Marjolijn, De Bruijn, Karin M., Diermanse, Ferdinand L.M., Weiler, Otto M., De Jong, Jurjen S., and Haasnoot, Marjolijn
Abstract: Sea level rise (SLR) will affect water levels and increase flood risk in river deltas. To adapt river deltas to SLR, various strategies can be followed. Many urbanised river deltas already have flood protection in place. Continuing a protection strategy under an increasing SLR, would mean higher embankments along the coast and rivers and possibly closing off the river mouths from the sea. However, closing of rivers will hamper the river flow. How to adapt river deltas and enabling rivers to discharge into the sea is a challenging question. This paper assesses impacts of SLR on flood risks in the Rhine-Meuse Delta in the Netherlands in case the current protection strategy is continued and explores two alternative protection strategies: (1) a closed system with pumps and discharge sluices and (2) an open system in which rivers are diverted to less densely populated areas. The second alternative results in a more flexible river delta, which can accommodate larger SLR. The paper shows that a systems approach and using quantitative assessments of the implications of strategies is possible. This is needed to further assess the adaptation options, so we can anticipate and adapt when needed and avoid regret of decisions.
Published: 2022

18. Look Who’s Talking: Host and pathogen drivers of staphylococcus epidermidis virulence in neonatal sepsis

Author: Joubert, I.A., Otto, M., Strunk, T., Currie, A.J., Joubert, I.A., Otto, M., Strunk, T., and Currie, A.J.
Abstract: Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.
Published: 2022

19. Personalbedarf in der hessischen Gesundheitsversorgung

Author: Geraedts, M, Ortwein, A, Otto, M, Jesberger, C, Greß, S, Geraedts, M, Ortwein, A, Otto, M, Jesberger, C, and Greß, S
Published: 2022

20. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Author: Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot-Corbel, E, Bjerke, M, Blanc-Quintin, M-C, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour-Rainfray, D, Engelborghs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau-Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska-Przybik, A, Laplanche, J-L, Lewczuk, P, Li, Q-X, Lleo, A, Malaplate, C, Marquie, M, Masters, CL, Mroczko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J-B, Paquet, C, Paoletti, FP, Parnetti, L, Perret-Liaudet, A, Peoc'h, K, Poesen, K, Puig-Pijoan, A, Quadrio, I, Quillard-Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez-Calvet, M, Tsolaki, M, Tumani, H, Udeh-Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, Lehmann, S, Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot-Corbel, E, Bjerke, M, Blanc-Quintin, M-C, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour-Rainfray, D, Engelborghs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau-Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska-Przybik, A, Laplanche, J-L, Lewczuk, P, Li, Q-X, Lleo, A, Malaplate, C, Marquie, M, Masters, CL, Mroczko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J-B, Paquet, C, Paoletti, FP, Parnetti, L, Perret-Liaudet, A, Peoc'h, K, Poesen, K, Puig-Pijoan, A, Quadrio, I, Quillard-Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez-Calvet, M, Tsolaki, M, Tumani, H, Udeh-Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, and Lehmann, S
Abstract: INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
Published: 2022

21. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Author: Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., Lehmann, S., Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., and Lehmann, S.
Abstract: Item does not contain fulltext, INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
Published: 2022

22. Trial of Deferiprone in Parkinson's Disease

Author: Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., Moreau, C., Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., and Moreau, C.
Abstract: Item does not contain fulltext, BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In parti
Published: 2022

23. Look Who’s Talking: Host and pathogen drivers of staphylococcus epidermidis virulence in neonatal sepsis

Author: Joubert, I.A., Otto, M., Strunk, T., Currie, A.J., Joubert, I.A., Otto, M., Strunk, T., and Currie, A.J.
Abstract: Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.
Published: 2022

24. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Author: Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., Lehmann, S., Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., and Lehmann, S.
Abstract: Contains fulltext : 287483.pdf (Publisher’s version ) (Open Access), INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
Published: 2022

25. Trial of Deferiprone in Parkinson's Disease

Author: Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., Moreau, C., Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., and Moreau, C.
Abstract: Contains fulltext : 287484.pdf (Publisher’s version ) (Closed access), BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In parti
Published: 2022

26. Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning Dementia Praecox Revisited

Author: Koutsouleris, N, Pantelis, C, Velakoulis, D, McGuire, P, Dwyer, DB, Urquijo-Castro, M-F, Paul, R, Sen, D, Popovic, D, Oeztuerk, O, Kambeitz, J, Salokangas, RKR, Hietala, J, Bertolino, A, Brambilla, P, Upthegrove, R, Wood, SJ, Lencer, R, Borgwardt, S, Maj, C, Nothen, M, Degenhardt, F, Polyakova, M, Mueller, K, Villringer, A, Danek, A, Fassbender, K, Fliessbach, K, Jahn, H, Kornhuber, J, Landwehrmeyer, B, Anderl-Straub, S, Prudlo, J, Synofzik, M, Wiltfang, J, Riedl, L, Diehl-Schmid, J, Otto, M, Meisenzahl, E, Falkai, P, Schroeter, ML, Koutsouleris, N, Pantelis, C, Velakoulis, D, McGuire, P, Dwyer, DB, Urquijo-Castro, M-F, Paul, R, Sen, D, Popovic, D, Oeztuerk, O, Kambeitz, J, Salokangas, RKR, Hietala, J, Bertolino, A, Brambilla, P, Upthegrove, R, Wood, SJ, Lencer, R, Borgwardt, S, Maj, C, Nothen, M, Degenhardt, F, Polyakova, M, Mueller, K, Villringer, A, Danek, A, Fassbender, K, Fliessbach, K, Jahn, H, Kornhuber, J, Landwehrmeyer, B, Anderl-Straub, S, Prudlo, J, Synofzik, M, Wiltfang, J, Riedl, L, Diehl-Schmid, J, Otto, M, Meisenzahl, E, Falkai, P, and Schroeter, ML
Abstract: IMPORTANCE: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. OBJECTIVE: To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). DESIGN, SETTING, AND PARTICIPANTS: This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. MAIN OUTCOMES AND MEASURES: Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. RESULTS: Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depressi
Published: 2022

27. Personalbedarf in der hessischen Gesundheitsversorgung

Author: Geraedts, M, Ortwein, A, Otto, M, Jesberger, C, Greß, S, Geraedts, M, Ortwein, A, Otto, M, Jesberger, C, and Greß, S
Published: 2022

28. Protecting the Rhine-Meuse delta against sea level rise: What to do with the river's discharge?

Author: Leerstoel Hout, Geomorfologie, De Bruijn, Karin M., Diermanse, Ferdinand L.M., Weiler, Otto M., De Jong, Jurjen S., Haasnoot, Marjolijn, Leerstoel Hout, Geomorfologie, De Bruijn, Karin M., Diermanse, Ferdinand L.M., Weiler, Otto M., De Jong, Jurjen S., and Haasnoot, Marjolijn
Published: 2022

29. Ultrafast electron diffraction: Visualizing dynamic states of matter

Author: Filippetto, D., Musumeci, P., Li, R. K., Siwick, B. J., Otto, M. R., Centurion, Martin, Nunes, J. P. F., Filippetto, D., Musumeci, P., Li, R. K., Siwick, B. J., Otto, M. R., Centurion, Martin, and Nunes, J. P. F.
Abstract: Since the discovery of electron-wave duality, electron scattering instrumentation has developed into a powerful array of techniques for revealing the atomic structure of matter. Beyond detecting local lattice variations in equilibrium structures with the highest possible spatial resolution, recent research efforts have been directed toward the long-sought-after dream of visualizing the dynamic evolution of matter in real time. The atomic behavior at ultrafast timescales carries critical information on phase transition and chemical reaction dynamics, the coupling of electronic and nuclear degrees of freedom in materials and molecules, and the correlation among structure, function, and previously hidden metastable or nonequilibrium states of matter. Ultrafast electron pulses play an essential role in this scientific endeavor, and their generation has been facilitated by rapid technical advances in both ultrafast laser and particle accelerator technologies. This review presents a summary of the noteworthy developments in this field in the last few decades. The physics and technology of ultrafast electron beams is presented with an emphasis on the figures of merit most relevant for ultrafast electron diffraction experiments. Recent developments in the generation, manipulation, and characterization of ultrashort electron beams aimed at improving the combined spatiotemporal resolution of these measurements are discussed. The fundamentals of electron scattering from atomic matter and the theoretical frameworks for retrieving dynamic structural information from solid-state and gas-phase samples is described. Essential experimental techniques and several landmark works that have applied these approaches are also highlighted to demonstrate the widening applicability of these methods. Ultrafast electron probes with ever-improving capabilities, combined with other complementary photon-based or spectroscopic approaches, hold tremendous potential for revolutionizing our ability t
Published: 2022

30. Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

Author: Oosterveer, Timo T.M., van Erp, Gonnie C.M., Hendriks, Pim, Broersen, Alexander, Overduin, Christiaan G., van Rijswijk, Carla S.P., van Erkel, Arian R., van der Meer, Rutger W., Tushuizen, Maarten E., Moelker, Adriaan, Meijerink, Martijn R., van Delden, Otto M., de Jong, Koert P., van der Leij, Christiaan, Smits, Maarten L.J., Urlings, Thijs A.J., Braak, Jeffrey P.B.M., Meershoek-Klein Kranenbarg, Elma, van Duijn-de Vreugd, Bianca, Zeijdner, Evelijn, Goeman, Jelle J., Fütterer, Jurgen J., Coenraad, Minneke J., Dijkstra, Jouke, Burgmans, Mark C., Oosterveer, Timo T.M., van Erp, Gonnie C.M., Hendriks, Pim, Broersen, Alexander, Overduin, Christiaan G., van Rijswijk, Carla S.P., van Erkel, Arian R., van der Meer, Rutger W., Tushuizen, Maarten E., Moelker, Adriaan, Meijerink, Martijn R., van Delden, Otto M., de Jong, Koert P., van der Leij, Christiaan, Smits, Maarten L.J., Urlings, Thijs A.J., Braak, Jeffrey P.B.M., Meershoek-Klein Kranenbarg, Elma, van Duijn-de Vreugd, Bianca, Zeijdner, Evelijn, Goeman, Jelle J., Fütterer, Jurgen J., Coenraad, Minneke J., Dijkstra, Jouke, and Burgmans, Mark C.
Abstract: Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy. Materials and Methods: This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713.
Published: 2022

31. Data-driven staging of genetic frontotemporal dementia using multi-modal MRI

Author: McCarthy, J., Borroni, B., Sanchez-Valle, R., Moreno, F., Laforce, R., Graff, C., Synofzik, M., Galimberti, D., Rowe, J. B., Masellis, M., Tartaglia, M. C., Finger, E., Vandenberghe, R., de Mendonça, A., Tagliavini, F., Santana, I., Butler, C., Gerhard, A., Danek, A., Levin, J., Otto, M., Frisoni, G., Ghidoni, R., Sorbi, S., Jiskoot, L. C., Seelaar, H., van Swieten, J. C., Rohrer, J. D., Iturria-Medina, Y., Ducharme, S., Anderl-Straub, S., Andersson, C., Antonell, A., McCarthy, J., Borroni, B., Sanchez-Valle, R., Moreno, F., Laforce, R., Graff, C., Synofzik, M., Galimberti, D., Rowe, J. B., Masellis, M., Tartaglia, M. C., Finger, E., Vandenberghe, R., de Mendonça, A., Tagliavini, F., Santana, I., Butler, C., Gerhard, A., Danek, A., Levin, J., Otto, M., Frisoni, G., Ghidoni, R., Sorbi, S., Jiskoot, L. C., Seelaar, H., van Swieten, J. C., Rohrer, J. D., Iturria-Medina, Y., Ducharme, S., Anderl-Straub, S., Andersson, C., and Antonell, A.
Abstract: Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrastive trajectory inference (cTI), an unsupervised machine learning algorithm that analyzes temporal patterns in high-dimensional large-scale population datasets to obtain individual scores of disease stage. We used cross-sectional MRI data (gray matter density, T1/T2 ratio as a proxy for myelin content, resting-state functional amplitude, gray matter fractional anisotropy, and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) and a control group of 253 noncarriers in the Genetic Frontotemporal Dementia Initiative. We compared the cTI-obtained disease scores to the estimated years to onset (age—mean age of onset in relatives), clinical, and neuropsychological test scores. The cTI based disease scores were correlated with all clinical and neuropsychological tests (measuring behavioral symptoms, attention, memory, language, and executive functions), with the highest contribution coming from mean diffusivity. Mean cTI scores were higher in the presymptomatic carriers than controls, indicating that the method may capture subtle pre-dementia cerebral changes, although this change was not replicated in a subset of subjects with complete data. This study provides a proof of concept that cTI can identify data-driven disease stages in a heterogeneous sample combining different mutations and disease stages of genetic FTD using only MRI metrics. © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
Published: 2022

32. High-Grade Glioma Treatment Response Monitoring Biomarkers:A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques

Author: Henriksen, Otto M, Del Mar Álvarez-Torres, María, Figueiredo, Patricia, Hangel, Gilbert, Keil, Vera C, Nechifor, Ruben E, Riemer, Frank, Schmainda, Kathleen M, Warnert, Esther A H, Wiegers, Evita C, Booth, Thomas C, Henriksen, Otto M, Del Mar Álvarez-Torres, María, Figueiredo, Patricia, Hangel, Gilbert, Keil, Vera C, Nechifor, Ruben E, Riemer, Frank, Schmainda, Kathleen M, Warnert, Esther A H, Wiegers, Evita C, and Booth, Thomas C
Abstract: OBJECTIVE: Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments.METHODS: Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics).RESULTS: High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motio
Published: 2022

33. High-Grade Glioma Treatment Response Monitoring Biomarkers:A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 2: Spectroscopy, Chemical Exchange Saturation, Multiparametric Imaging, and Radiomics

Author: Booth, Thomas C, Wiegers, Evita C, Warnert, Esther A H, Schmainda, Kathleen M, Riemer, Frank, Nechifor, Ruben E, Keil, Vera C, Hangel, Gilbert, Figueiredo, Patrícia, Álvarez-Torres, Maria Del Mar, Henriksen, Otto M, Booth, Thomas C, Wiegers, Evita C, Warnert, Esther A H, Schmainda, Kathleen M, Riemer, Frank, Nechifor, Ruben E, Keil, Vera C, Hangel, Gilbert, Figueiredo, Patrícia, Álvarez-Torres, Maria Del Mar, and Henriksen, Otto M
Abstract: OBJECTIVE: To summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments.METHODS: The current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging).RESULTS: The biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evide
Published: 2022

34. Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [18F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma

Author: Henriksen, Otto M., Hansen, Adam E., Muhic, Aida, Marner, Lisbeth, Madsen, Karine, Møller, Søren, Hasselbalch, Benedikte, Lundemann, Michael J., Scheie, David, Skjøth-Rasmussen, Jane, Poulsen, Hans S., Larsen, Vibeke A., Larsson, Henrik B. W., Law, Ian, Henriksen, Otto M., Hansen, Adam E., Muhic, Aida, Marner, Lisbeth, Madsen, Karine, Møller, Søren, Hasselbalch, Benedikte, Lundemann, Michael J., Scheie, David, Skjøth-Rasmussen, Jane, Poulsen, Hans S., Larsen, Vibeke A., Larsson, Henrik B. W., and Law, Ian
Abstract: Purpose: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy. Methods: A total of 76 lesions in 60 hybrid [18F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively. BV was measured from DCE MRI employing a 2-compartment exchange model (2CXM). Diagnostic performances of maximal tumour-to-background [18F]FET uptake (TBRmax), maximal BV (BVmax) and normalised BVmax (nBVmax) were determined by ROC analysis using 6-month histopathological (n = 28) or clinical/radiographical follow-up (n = 48) as reference. Sensitivity and specificity at optimal cut-offs were determined separately for enhancing and non-enhancing lesions. Results: In progressive lesions, all BV and [18F]FET metrics were higher than in non-progressive lesions. ROC analyses showed higher overall ROC AUCs for TBRmax than both BVmax and nBVmax in both lesion-wise (all lesions, p = 0.04) and in patient-wise analysis (p < 0.01). Combining TBRmax with BV metrics did not increase ROC AUC. Lesion-wise positive fraction/sensitivity/specificity at optimal cut-offs were 55%/91%/84% for TBRmax, 45%/77%/84% for BVmax and 59%/84%/72% for nBVmax. Combining TBRmax and best-performing BV cut-offs yielded lesion-wise sensitivity/specificity of 75/97%. The fraction of progressive lesions was 11% in concordant negative lesions, 33% in lesions only BV positive, 64% in les
Published: 2022

35. The 2022 report of the Lancet Countdown on health and climate change: health at the mercy of fossil fuels

Author: Romanello, M., Di Napoli, C., Drummond, P., Green, C., Kennard, H., Lampard, P., Scamman, D., Arnell, N., Ayeb-Karlsson, S., Ford, L., Belesova, K., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Escobar, L., Georgeson, L., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Hess, J., Hsu, S.-C., Jankin, S., Jamart, L., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kjellstrom, T., Kniveton, D., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Batista, M., Lowe, R., MacGuire, F., Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McGushin, A., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shi, L., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Triñanes, J., Wagner, F., Wilkinson, P., Winning, M., Yglesias-González, M., Zhang, S., Gong, P., Montgomery, H., Costello, A., Romanello, M., Di Napoli, C., Drummond, P., Green, C., Kennard, H., Lampard, P., Scamman, D., Arnell, N., Ayeb-Karlsson, S., Ford, L., Belesova, K., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Escobar, L., Georgeson, L., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Hess, J., Hsu, S.-C., Jankin, S., Jamart, L., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kjellstrom, T., Kniveton, D., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Batista, M., Lowe, R., MacGuire, F., Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McGushin, A., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shi, L., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Triñanes, J., Wagner, F., Wilkinson, P., Winning, M., Yglesias-González, M., Zhang, S., Gong, P., Montgomery, H., and Costello, A.
Published: 2022
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36. Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [18F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma

Author: Henriksen, Otto M., Hansen, Adam E., Muhic, Aida, Marner, Lisbeth, Madsen, Karine, Møller, Søren, Hasselbalch, Benedikte, Lundemann, Michael J., Scheie, David, Skjøth-Rasmussen, Jane, Poulsen, Hans S., Larsen, Vibeke A., Larsson, Henrik B. W., Law, Ian, Henriksen, Otto M., Hansen, Adam E., Muhic, Aida, Marner, Lisbeth, Madsen, Karine, Møller, Søren, Hasselbalch, Benedikte, Lundemann, Michael J., Scheie, David, Skjøth-Rasmussen, Jane, Poulsen, Hans S., Larsen, Vibeke A., Larsson, Henrik B. W., and Law, Ian
Abstract: Purpose: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy. Methods: A total of 76 lesions in 60 hybrid [18F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively. BV was measured from DCE MRI employing a 2-compartment exchange model (2CXM). Diagnostic performances of maximal tumour-to-background [18F]FET uptake (TBRmax), maximal BV (BVmax) and normalised BVmax (nBVmax) were determined by ROC analysis using 6-month histopathological (n = 28) or clinical/radiographical follow-up (n = 48) as reference. Sensitivity and specificity at optimal cut-offs were determined separately for enhancing and non-enhancing lesions. Results: In progressive lesions, all BV and [18F]FET metrics were higher than in non-progressive lesions. ROC analyses showed higher overall ROC AUCs for TBRmax than both BVmax and nBVmax in both lesion-wise (all lesions, p = 0.04) and in patient-wise analysis (p < 0.01). Combining TBRmax with BV metrics did not increase ROC AUC. Lesion-wise positive fraction/sensitivity/specificity at optimal cut-offs were 55%/91%/84% for TBRmax, 45%/77%/84% for BVmax and 59%/84%/72% for nBVmax. Combining TBRmax and best-performing BV cut-offs yielded lesion-wise sensitivity/specificity of 75/97%. The fraction of progressive lesions was 11% in concordant negative lesions, 33% in lesions only BV positive, 64% in les
Published: 2022

37. Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands:the BELIVER study

Author: Furumaya, Alicia, Haring, Martijn P.D., Van Rosmalen, Belle V., Klompenhouwer, Anne J., Besselink, Marc G., De Man, Robert A., Ijzermans, Jan N.M., Thomeer, Maarten G.J., Kramer, Matthijs, Coolsen, Mariëlle M.E., Tushuizen, Maarten E., Schaapherder, Alexander F., De Haas, Robbert J., Duiker, Evelien W., Kazemier, Geert, Van Delden, Otto M., Verheij, Joanne, Takkenberg, R. Bart, Cuperus, Frans J.C., De Meijer, Vincent E., Erdmann, Joris I., Furumaya, Alicia, Haring, Martijn P.D., Van Rosmalen, Belle V., Klompenhouwer, Anne J., Besselink, Marc G., De Man, Robert A., Ijzermans, Jan N.M., Thomeer, Maarten G.J., Kramer, Matthijs, Coolsen, Mariëlle M.E., Tushuizen, Maarten E., Schaapherder, Alexander F., De Haas, Robbert J., Duiker, Evelien W., Kazemier, Geert, Van Delden, Otto M., Verheij, Joanne, Takkenberg, R. Bart, Cuperus, Frans J.C., De Meijer, Vincent E., and Erdmann, Joris I.
Abstract: Introduction Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. Methods and analysis A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. Ethics and dissemination The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. Study registration NL8231 - 10 December 2019; Netherlands Trial Register.
Published: 2022

38. The 2022 report of the Lancet Countdown on health and climate change: health at the mercy of fossil fuels

Author: Romanello, M., Di Napoli, C., Drummond, P., Green, C., Kennard, H., Lampard, P., Scamman, D., Arnell, N., Ayeb-Karlsson, S., Ford, L., Belesova, K., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Escobar, L., Georgeson, L., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Hess, J., Hsu, S.-C., Jankin, S., Jamart, L., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kjellstrom, T., Kniveton, D., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Batista, M., Lowe, R., MacGuire, F., Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McGushin, A., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shi, L., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Triñanes, J., Wagner, F., Wilkinson, P., Winning, M., Yglesias-González, M., Zhang, S., Gong, P., Montgomery, H., Costello, A., Romanello, M., Di Napoli, C., Drummond, P., Green, C., Kennard, H., Lampard, P., Scamman, D., Arnell, N., Ayeb-Karlsson, S., Ford, L., Belesova, K., Bowen, K., Cai, W., Callaghan, M., Campbell-Lendrum, D., Chambers, J., van Daalen, K., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K., Eckelman, M., Ekins, P., Escobar, L., Georgeson, L., Graham, H., Gunther, S., Hamilton, I., Hang, Y., Hänninen, R., Hartinger, S., He, K., Hess, J., Hsu, S.-C., Jankin, S., Jamart, L., Jay, O., Kelman, I., Kiesewetter, G., Kinney, P., Kjellstrom, T., Kniveton, D., Lee, J., Lemke, B., Liu, Y., Liu, Z., Lott, M., Batista, M., Lowe, R., MacGuire, F., Sewe, M., Martinez-Urtaza, J., Maslin, M., McAllister, L., McGushin, A., McMichael, C., Mi, Z., Milner, J., Minor, K., Minx, J., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K., Neville, T., Nilsson, M., Obradovich, N., O'Hare, M., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R., Semenza, J., Sherman, J., Shi, L., Shumake-Guillemot, J., Silbert, G., Sofiev, M., Springmann, M., Stowell, J., Tabatabaei, M., Taylor, J., Triñanes, J., Wagner, F., Wilkinson, P., Winning, M., Yglesias-González, M., Zhang, S., Gong, P., Montgomery, H., and Costello, A.
Published: 2022
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39. Biliopancreatic and biliary leak after pancreatoduodenectomy treated by percutaneous transhepatic biliary drainage

Author: MS CGO, Heelkunde Opleiding, Externen Hematologie, Cancer, MS HOD, Henry, Anne Claire, Smits, F. Jasmijn, van Lienden, Krijn, van den Heuvel, Daniel A.F., Hofman, Lieke, Busch, Olivier R., van Delden, Otto M., Zijlstra, IJsbrand A., Schreuder, Sanne M., Lamers, Armand B., van Leersum, Marc, van Strijen, Marco J.L., Vos, Jan A., Te Riele, Wouter W., Molenaar, I. Quintus, Besselink, Marc G., van Santvoort, Hjalmar C., MS CGO, Heelkunde Opleiding, Externen Hematologie, Cancer, MS HOD, Henry, Anne Claire, Smits, F. Jasmijn, van Lienden, Krijn, van den Heuvel, Daniel A.F., Hofman, Lieke, Busch, Olivier R., van Delden, Otto M., Zijlstra, IJsbrand A., Schreuder, Sanne M., Lamers, Armand B., van Leersum, Marc, van Strijen, Marco J.L., Vos, Jan A., Te Riele, Wouter W., Molenaar, I. Quintus, Besselink, Marc G., and van Santvoort, Hjalmar C.
Published: 2022

40. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Author: Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot‐Corbel, E, Bjerke, M, Blanc, M, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour‐Rainfray, D, Engelborgs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau‐Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska‐Przybik, A, Laplanche, J, Lewczuk, P, Li, Q, Lleó, A, Malaplate, C, Marquié, M, Masters, CL, Mroszko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J, Paquet, C, Paoletti, FP, Parnetti, L, Perret‐Liaudet, A, Poec’h, K, Poesen, K, Puig‐Pijoan, A, Quadrio, I, Quillard‐Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez‐Calvet, M, Tsolaki, M, Tumani, H, Udeh‐Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, Lehmann, S, Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot‐Corbel, E, Bjerke, M, Blanc, M, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour‐Rainfray, D, Engelborgs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau‐Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska‐Przybik, A, Laplanche, J, Lewczuk, P, Li, Q, Lleó, A, Malaplate, C, Marquié, M, Masters, CL, Mroszko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J, Paquet, C, Paoletti, FP, Parnetti, L, Perret‐Liaudet, A, Poec’h, K, Poesen, K, Puig‐Pijoan, A, Quadrio, I, Quillard‐Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez‐Calvet, M, Tsolaki, M, Tumani, H, Udeh‐Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, and Lehmann, S
Abstract: Background The quantification of cerebrospinal fluid (CSF) biomarkers (Amyloid beta peptides [Aß1‐40 and Aß1‐42], t‐tau and p‐tau(181)) is progressively implemented in specialized laboratories as an aid for the multidisciplinary diagnosis of Alzheimer’s disease (AD). There is however a diversity of practices between centers related to pre‐analytical and analytical conditions, the calculation of ratios between analytes, the applied cut‐off, or the use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, which may raise questions about the commutability of the tests. So far, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on the profile of the quantified biomarkers. This work is an essential step towards a consensual harmonization of clinical reporting after CSF analysis in the context of AD diagnosis, as advocated by the "Biofluid Based Biomarkers PIA" working group of the Alzheimer's Association. Method We obtained, by means of a questionnaire, a description of the pre‐analytical and analytical protocols and examples of reporting from 40 centers located in 15 countries, i.e. in the majority of countries that have implemented clinical CSF tests for the diagnosis of AD. We then adopted a consensus approach to propose harmonized comments corresponding to different AD CSF biomarker profiles observed in patients. Result Pre‐analytical procedures were very similar, among the centers. Regarding the analytical part, more than 88% of the laboratories use automatized immunoassays and more than 83% measure Aß1‐40 and compute the Aß1‐42/Aß1‐40 ratio, in addition to the three core biomarkers (Aß1‐42, t‐tau and p‐tau(181)). The cut‐off values of biomarkers used by the different laboratories are widely dispersed. Delay before sending back the results is lower than 1 week in more than 34% of t
Published: 2021

41. The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future

Author: Romanello, M., McGushin, A., Di Napoli, C., Drummond, P., Hughes, N., Jamart, L., Kennard, H., Lampard, P., Solano Rodriguez, B., Arnell, N., Ayeb-Karlsson, S., Belesova, K., Cai, W., Campbell-Lendrum, D., Capstick, S., Chambers, J., Chu, L., Ciampi, L., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K.L., Eckelman, M., Ekins, P., Escobar, L.E., Georgeson, L., Grace, D., Graham, H., Gunther, S.H., Hartinger, S., He, K., Heaviside, C., Hess, J., Hsu, S.-C., Jankin, S., Jimenez, M.P., Kelman, I., Kiesewetter, G., Kinney, P.L., Kjellstrom, T., Kniveton, D., Lee, J.K.W., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lowe, R., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K.A., Neville, T., Nilsson, M., Obradovich, N., Sewe, M.O., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pencheon, D., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R.N., Semenza, J.C., Sherman, J., Shi, L., Springmann, M., Tabatabaei, M., Taylor, J., Trinanes, J., Shumake-Guillemot, J., Vu, B., Wagner, F., Wilkinson, P., Winning, M., Yglesias, M., Zhang, S., Gong, P., Montgomery, H., Costello, A., Hamilton, I., Romanello, M., McGushin, A., Di Napoli, C., Drummond, P., Hughes, N., Jamart, L., Kennard, H., Lampard, P., Solano Rodriguez, B., Arnell, N., Ayeb-Karlsson, S., Belesova, K., Cai, W., Campbell-Lendrum, D., Capstick, S., Chambers, J., Chu, L., Ciampi, L., Dalin, C., Dasandi, N., Dasgupta, S., Davies, M., Dominguez-Salas, P., Dubrow, R., Ebi, K.L., Eckelman, M., Ekins, P., Escobar, L.E., Georgeson, L., Grace, D., Graham, H., Gunther, S.H., Hartinger, S., He, K., Heaviside, C., Hess, J., Hsu, S.-C., Jankin, S., Jimenez, M.P., Kelman, I., Kiesewetter, G., Kinney, P.L., Kjellstrom, T., Kniveton, D., Lee, J.K.W., Lemke, B., Liu, Y., Liu, Z., Lott, M., Lowe, R., Martinez-Urtaza, J., Maslin, M., McAllister, L., McMichael, C., Mi, Z., Milner, J., Minor, K., Mohajeri, N., Moradi-Lakeh, M., Morrissey, K., Munzert, S., Murray, K.A., Neville, T., Nilsson, M., Obradovich, N., Sewe, M.O., Oreszczyn, T., Otto, M., Owfi, F., Pearman, O., Pencheon, D., Rabbaniha, M., Robinson, E., Rocklöv, J., Salas, R.N., Semenza, J.C., Sherman, J., Shi, L., Springmann, M., Tabatabaei, M., Taylor, J., Trinanes, J., Shumake-Guillemot, J., Vu, B., Wagner, F., Wilkinson, P., Winning, M., Yglesias, M., Zhang, S., Gong, P., Montgomery, H., Costello, A., and Hamilton, I.
Published: 2021

42. Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

Author: Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., Otto, M., Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., and Otto, M.
Abstract: Item does not contain fulltext, Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with <6 and >6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N = 65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p = 0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients' progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.
Published: 2021

43. Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia

Author: Benussi, A. (Alberto), Premi, E. (Enrico), Gazzina, S. (Stefano), Brattini, C. (Chiara), Bonomi, E. (Elisa), Alberici, P. (Paola), Jiskoot, L.C. (Lize), Swieten, J.C. (John) van, Sánchez-Valle, R. (Raquel), Moreno, F. (Fermin), Laforce, R. (Robert), Graff, C. (Caroline), Synofzik, M. (Matthis), Galimberti, D. (Daniela), Masellis, M. (Mario), Tartaglia, C. (Carmela), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), De Mendonça, A. (Alexandre), Tagliavini, F. (Fabrizio), Santana, I. (Isabel), Ducharme, S. (Simon), Butler, C.R. (Chris R.), Gerhard, A. (Alex), Levin, J. (Johannes), Danek, A. (Adrian), Otto, M. (Markus), Frisoni, G.B. (Giovanni B.), Ghidoni, R. (Roberta), Sorbi, S. (Sandro), Le Ber, I. (Isabelle), Pasquier, F. (Florence), Peakman, G. (Georgia), Todd, E. (Emily), Bocchetta, M. (Martina), Rohrer, J.D. (Jonathan), Borroni, B. (Barbara), Benussi, A. (Alberto), Premi, E. (Enrico), Gazzina, S. (Stefano), Brattini, C. (Chiara), Bonomi, E. (Elisa), Alberici, P. (Paola), Jiskoot, L.C. (Lize), Swieten, J.C. (John) van, Sánchez-Valle, R. (Raquel), Moreno, F. (Fermin), Laforce, R. (Robert), Graff, C. (Caroline), Synofzik, M. (Matthis), Galimberti, D. (Daniela), Masellis, M. (Mario), Tartaglia, C. (Carmela), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), De Mendonça, A. (Alexandre), Tagliavini, F. (Fabrizio), Santana, I. (Isabel), Ducharme, S. (Simon), Butler, C.R. (Chris R.), Gerhard, A. (Alex), Levin, J. (Johannes), Danek, A. (Adrian), Otto, M. (Markus), Frisoni, G.B. (Giovanni B.), Ghidoni, R. (Roberta), Sorbi, S. (Sandro), Le Ber, I. (Isabelle), Pasquier, F. (Florence), Peakman, G. (Georgia), Todd, E. (Emily), Bocchetta, M. (Martina), Rohrer, J.D. (Jonathan), and Borroni, B. (Barbara)
Abstract: Importance: Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. Objective: To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. Design, Setting, and Participants: This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Main Outcomes and Measures: Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of
Published: 2021
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44. Disease-related cortical thinning in presymptomatic granulin mutation carriers

Author: Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), Anderl-Straub, S. (Sarah), Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), and Anderl-Straub, S. (Sarah)
Abstract: Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an
Published: 2021
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45. The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future

Author: Romanello, M, McGushin, A, Di Napoli, C, Drummond, P, Hughes, N, Jamart, L, Kennard, H, Lampard, P, Rodriguez, BS, Arnell, N, Ayeb-Karlsson, S, Belesova, K, Cai, W, Campbell-Lendrum, D, Capstick, S, Chambers, J, Chu, L, Ciampi, L, Dalin, C, Dasandi, N, Dasgupta, S, Davies, M, Dominguez-Salas, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Escobar, LE, Georgeson, L, Grace, D, Graham, H, Gunther, SH, Hartinger, S, He, K, Heaviside, C, Hess, J, Hsu, S-C, Jankin, S, Jimenez, MP, Kelman, I, Kiesewetter, G, Kinney, PL, Kjellstrom, T, Kniveton, D, Lee, JKW, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lowe, R, Martinez-Urtaza, J, Maslin, M, McAllister, L, McMichael, C, Mi, Z, Milner, J, Minor, K, Mohajeri, N, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Obradovich, N, Sewe, MO, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pencheon, D, Rabbaniha, M, Robinson, E, Rocklov, J, Salas, RN, Semenza, JC, Sherman, J, Shi, L, Springmann, M, Tabatabaei, M, Taylor, J, Trinanes, J, Shumake-Guillemot, J, Vu, B, Wagner, F, Wilkinson, P, Winning, M, Yglesias, M, Zhang, S, Gong, P, Montgomery, H, Costello, A, Hamilton, I, Romanello, M, McGushin, A, Di Napoli, C, Drummond, P, Hughes, N, Jamart, L, Kennard, H, Lampard, P, Rodriguez, BS, Arnell, N, Ayeb-Karlsson, S, Belesova, K, Cai, W, Campbell-Lendrum, D, Capstick, S, Chambers, J, Chu, L, Ciampi, L, Dalin, C, Dasandi, N, Dasgupta, S, Davies, M, Dominguez-Salas, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Escobar, LE, Georgeson, L, Grace, D, Graham, H, Gunther, SH, Hartinger, S, He, K, Heaviside, C, Hess, J, Hsu, S-C, Jankin, S, Jimenez, MP, Kelman, I, Kiesewetter, G, Kinney, PL, Kjellstrom, T, Kniveton, D, Lee, JKW, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lowe, R, Martinez-Urtaza, J, Maslin, M, McAllister, L, McMichael, C, Mi, Z, Milner, J, Minor, K, Mohajeri, N, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Obradovich, N, Sewe, MO, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pencheon, D, Rabbaniha, M, Robinson, E, Rocklov, J, Salas, RN, Semenza, JC, Sherman, J, Shi, L, Springmann, M, Tabatabaei, M, Taylor, J, Trinanes, J, Shumake-Guillemot, J, Vu, B, Wagner, F, Wilkinson, P, Winning, M, Yglesias, M, Zhang, S, Gong, P, Montgomery, H, Costello, A, and Hamilton, I
Published: 2021

46. Assoziation zwischen Magnetresonanztomographie der Wirbelsäule und zukünftigen Rückenschmerzen

Author: Chenot, JF, Kasch, R, Nell, C, Otto, M, Schmidt, CO, Wassilew, G, Truthmann, J, Chenot, JF, Kasch, R, Nell, C, Otto, M, Schmidt, CO, Wassilew, G, and Truthmann, J
Published: 2021

47. The 2020 report of the Lancet Countdown on health and climate change: responding to converging crises

Author: Watts, N, Amann, M, Arnell, N, Ayeb-Karlsson, S, Beagley, J, Belesova, K, Boykoff, M, Byass, P, Cai, W, Campbell-Lendrum, D, Capstick, S, Chambers, J, Coleman, S, Dalin, C, Daly, M, Dasandi, N, Dasgupta, S, Davies, M, Di Napoli, C, Dominguez-Salas, P, Drummond, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Escobar, LE, Georgeson, L, Golder, S, Grace, D, Graham, H, Haggar, P, Hamilton, I, Hartinger, S, Hess, J, Hsu, S-C, Hughes, N, Mikhaylov, SJ, Jimenez, MP, Kelman, I, Kennard, H, Kiesewetter, G, Kinney, PL, Kjellstrom, T, Kniveton, D, Lampard, P, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lowe, R, Martinez-Urtaza, J, Maslin, M, McAllister, L, McGushin, A, McMichael, C, Milner, J, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Sewe, MO, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pencheon, D, Quinn, R, Rabbaniha, M, Robinson, E, Rocklov, J, Romanello, M, Semenza, JC, Sherman, J, Shi, L, Springmann, M, Tabatabaei, M, Taylor, J, Trinanes, J, Shumake-Guillemot, J, Vu, B, Wilkinson, P, Winning, M, Gong, P, Montgomery, H, Costello, A, Watts, N, Amann, M, Arnell, N, Ayeb-Karlsson, S, Beagley, J, Belesova, K, Boykoff, M, Byass, P, Cai, W, Campbell-Lendrum, D, Capstick, S, Chambers, J, Coleman, S, Dalin, C, Daly, M, Dasandi, N, Dasgupta, S, Davies, M, Di Napoli, C, Dominguez-Salas, P, Drummond, P, Dubrow, R, Ebi, KL, Eckelman, M, Ekins, P, Escobar, LE, Georgeson, L, Golder, S, Grace, D, Graham, H, Haggar, P, Hamilton, I, Hartinger, S, Hess, J, Hsu, S-C, Hughes, N, Mikhaylov, SJ, Jimenez, MP, Kelman, I, Kennard, H, Kiesewetter, G, Kinney, PL, Kjellstrom, T, Kniveton, D, Lampard, P, Lemke, B, Liu, Y, Liu, Z, Lott, M, Lowe, R, Martinez-Urtaza, J, Maslin, M, McAllister, L, McGushin, A, McMichael, C, Milner, J, Moradi-Lakeh, M, Morrissey, K, Munzert, S, Murray, KA, Neville, T, Nilsson, M, Sewe, MO, Oreszczyn, T, Otto, M, Owfi, F, Pearman, O, Pencheon, D, Quinn, R, Rabbaniha, M, Robinson, E, Rocklov, J, Romanello, M, Semenza, JC, Sherman, J, Shi, L, Springmann, M, Tabatabaei, M, Taylor, J, Trinanes, J, Shumake-Guillemot, J, Vu, B, Wilkinson, P, Winning, M, Gong, P, Montgomery, H, and Costello, A
Abstract: For the Chinese, French, German, and Spanish translations of the abstract see Supplementary Materials section.
Published: 2021

48. Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

Author: Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., Otto, M., Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., and Otto, M.
Abstract: Item does not contain fulltext, Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with <6 and >6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N = 65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p = 0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients' progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.
Published: 2021

49. Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

Author: Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., Otto, M., Steinacker, P., Feneberg, E., Halbgebauer, S., Witzel, S., Verde, F., Oeckl, P., Damme, P. van, Gaur, N., Gray, E., Grosskreutz, J., Jardel, C.G., Kachanov, M., Kuhle, J., Lamari, F., Maceski, A., Amador, M. Del Mar, Mayer, B., Morelli, C., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., Turner, M.R., Verbeek, M.M., Volk, A.E., Weishaupt, J.H., Weydt, P., Ludolph, A.C., and Otto, M.
Abstract: Item does not contain fulltext, Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with <6 and >6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N = 65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p = 0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients' progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.
Published: 2021

50. Assoziation zwischen Magnetresonanztomographie der Wirbelsäule und zukünftigen Rückenschmerzen

Author: Chenot, JF, Kasch, R, Nell, C, Otto, M, Schmidt, CO, Wassilew, G, Truthmann, J, Chenot, JF, Kasch, R, Nell, C, Otto, M, Schmidt, CO, Wassilew, G, and Truthmann, J
Published: 2021

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