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1. What Should I do and Who’s to blame? A cross-national study on youth’s attitudes and beliefs in times of COVID-19

Author

De Moor, Elisabeth L, Cheng, Ting-Yu, Spitzer, Jenna E, Berger, Christian, Carrizales, Alexia, Garandeau, Claire F, Gerbino, Maria, Hawk, Skyler T, Kaniušonytė, Goda, Kumru, Asiye, Malonda, Elisabeth, Rovella, Anna, Shen, Yuh-Ling, Taylor, Laura K, van Zalk, Maarten, Branje, Susan, Carlo, Gustavo, Walker, Laura Padilla, and Van der Graaff, Jolien

Subjects
Social and Personality Psychology, Psychology, Pediatric, Cancer, Good Health and Well Being, Young Adult, Humans, Adolescent, COVID-19, Attitude, Government, General Science & Technology
Abstract

The COVID-19 crisis has had a major impact on youth. This study examined factors associated with youth's attitudes towards their government's response to the pandemic and their blaming of individuals from certain risk groups, ethnic backgrounds, and countries or regions. In a sample of 5,682 young adults (Mage = 22) from 14 countries, lower perceived burden due to COVID-19, more collectivistic and less individualistic values, and more empathy were associated with more positive attitudes towards the government and less blaming of individuals of certain groups. Youth's social identification with others in the pandemic mediated these associations in the same direction, apart from the COVID-19 burden on attitudes, which had a positive indirect effect. No evidence of country-level moderation was found.

Published
2022

2. Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World

Author

Hirschfeld, Cole B, Shaw, Leslee J, Williams, Michelle C, Lahey, Ryan, Villines, Todd C, Dorbala, Sharmila, Choi, Andrew D, Shah, Nishant R, Bluemke, David A, Berman, Daniel S, Blankstein, Ron, Ferencik, Maros, Narula, Jagat, Winchester, David, Malkovskiy, Eli, Goebel, Benjamin, Randazzo, Michael J, Lopez-Mattei, Juan, Parwani, Purvi, Vitola, Joao V, Cerci, Rodrigo J, Better, Nathan, Raggi, Paolo, Lu, Bin, Sergienko, Vladimir, Sinitsyn, Valentin, Kudo, Takashi, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Cohen, Yosef A, Pascual, Thomas NB, Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, Einstein, Andrew J, Cerci, Rodrigo, Hinterleitner, Gerd, Lu, Yao, Morozova, Olga, Xu, Zhuoran, Cohen, Yosef, Randazzo, Michael, Choi, Andrew, Nasery, Mohammad Nawaz, Goda, Artan, Shirka, Ervina, Benlabgaa, Rabie, Bouyoucef, Salah, Medjahedi, Abdelkader, Nailli, Qais, Agolti, Mariela, Aguero, Roberto Nicolas, del Carmen Alak, Maria, Alberguina, Lucia Graciela, Arroñada, Guillermo, Astesiano, Andrea, Astesiano, Alfredo, Norton, Carolina Bas, Benteo, Pablo, Blanco, Juan, Bonelli, Juan Manuel, Bustos, Jose Javier, Cabrejas, Raul, Cachero, Jorge, Campisi, Roxana, Canderoli, Alejandro, Carames, Silvia, Carrascosa, Patrícia, Castro, Ricardo, Cendoya, Oscar, Cognigni, Luciano Martin, Collaud, Carlos, Cortes, Claudia, Courtis, Javier, Cragnolino, Daniel, Daicz, Mariana, De La Vega, Alejandro, De Maria, Silvia Teresa, Del Riego, Horacio, Dettori, Fernando, Deviggiano, Alejandro, and Dragonetti, Laura

Subjects
Heart Disease, Clinical Research, Health Services, Prevention, Aging, Cardiovascular, Good Health and Well Being, COVID-19, COVID-19 Testing, Humans, Pandemics, Predictive Value of Tests, SARS-CoV-2, United States, cardiovascular disease, cardiovascular imaging, coronavirus, diagnostic cardiovascular procedure, INCAPS-COVID Investigators Group, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

ObjectivesThis study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.BackgroundThe COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.MethodsData were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.ResultsReductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p

Published
2021

3. Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation

Author

Kurashima, Yosuke, Kigoshi, Takaaki, Murasaki, Sayuri, Arai, Fujimi, Shimada, Kaoru, Seki, Natsumi, Kim, Yun-Gi, Hase, Koji, Ohno, Hiroshi, Kawano, Kazuya, Ashida, Hiroshi, Suzuki, Toshihiko, Morimoto, Masako, Saito, Yukari, Sasou, Ai, Goda, Yuki, Yuki, Yoshikazu, Inagaki, Yutaka, Iijima, Hideki, Suda, Wataru, Hattori, Masahira, and Kiyono, Hiroshi

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Inflammatory Bowel Disease, Digestive Diseases, Cancer, Pancreatic Cancer, Crohn's Disease, Rare Diseases, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Acinar Cells, Animals, Colitis, Cytokines, Dextran Sulfate, Escherichia coli, Feces, Green Fluorescent Proteins, Humans, Immunoglobulin A, Inflammation, Intestinal Mucosa, Membrane Glycoproteins, Mice, Inbred C57BL, Pancreas, Recombinant Proteins, Transcription Factors, Up-Regulation, Mice
Abstract

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

Published
2021

4. International Impact of COVID-19 on the Diagnosis of Heart Disease

Author

Einstein, Andrew J, Shaw, Leslee J, Hirschfeld, Cole, Williams, Michelle C, Villines, Todd C, Better, Nathan, Vitola, Joao V, Cerci, Rodrigo, Dorbala, Sharmila, Raggi, Paolo, Choi, Andrew D, Lu, Bin, Sinitsyn, Valentin, Sergienko, Vladimir, Kudo, Takashi, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Campisi, Roxana, Milan, Elisa, Louw, Lizette, Allam, Adel H, Bhatia, Mona, Malkovskiy, Eli, Goebel, Benjamin, Cohen, Yosef, Randazzo, Michael, Narula, Jagat, Pascual, Thomas NB, Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, Hinterleitner, Gerd, Lu, Yao, Morozova, Olga, Xu, Zhuoran, Lopez-Mattei, Juan, Parwani, Purvi, Nasery, Mohammad Nawaz, Goda, Artan, Shirka, Ervina, Benlabgaa, Rabie, Bouyoucef, Salah, Medjahedi, Abdelkader, Nailli, Qais, Agolti, Mariela, Aguero, Roberto Nicolas, del Carmen Alak, Maria, Alberguina, Lucia Graciela, Arroñada, Guillermo, Astesiano, Andrea, Astesiano, Alfredo, Norton, Carolina Bas, Benteo, Pablo, Blanco, Juan, Bonelli, Juan Manuel, Bustos, Jose Javier, Cabrejas, Raul, Cachero, Jorge, Canderoli, Alejandro, Carames, Silvia, Carrascosa, Patrícia, Castro, Ricardo, Cendoya, Oscar, Cognigni, Luciano Martin, Collaud, Carlos, Cortes, Claudia, Courtis, Javier, Cragnolino, Daniel, Daicz, Mariana, De La Vega, Alejandro, De Maria, Silvia Teresa, Del Riego, Horacio, Dettori, Fernando, Deviggiano, Alejandro, Dragonetti, Laura, Embon, Mario, Enriquez, Ruben Emilio, Ensinas, Jorge, Faccio, Fernando, Facello, Adolfo, Garofalo, Diego, Geronazzo, Ricardo, Gonza, Natalia, Gutierrez, Lucas, Guzzo, Miguel Angel, Hasbani, Victor, Huerin, Melina, Jäger, Victor, Lewkowicz, Julio Manuel, De Munaín, Maria Nieves A López, Lotti, Jose Maria, Marquez, Alejandra, Masoli, Osvaldo, Mastrovito, Edgardo, Mayoraz, Matias, Melado, Graciela Eva, Mele, Anibal, Merani, Maria Fernanda, Meretta, Alejandro Horacio, and Molteni, Susana

Subjects
Heart Disease, Biomedical Imaging, Clinical Research, Cardiovascular, Heart Disease - Coronary Heart Disease, Good Health and Well Being, COVID-19, Diagnostic Techniques, Cardiovascular, Global Health, Health Care Surveys, Heart Diseases, Humans, International Agencies, the, INCAPS COVID Investigators Group, cardiac testing, cardiovascular disease, coronavirus, global health, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.ObjectivesThe study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices.MethodsThe International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.ResultsSurveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p

Published
2021

5. Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency

Author

Farmer, Jocelyn R, Foldvari, Zsofia, Ujhazi, Boglarka, De Ravin, Suk See, Chen, Karin, Bleesing, Jack JH, Schuetz, Catharina, Al-Herz, Waleed, Abraham, Roshini S, Joshi, Avni Y, Costa-Carvalho, Beatriz T, Buchbinder, David, Booth, Claire, Reiff, Andreas, Ferguson, Polly J, Aghamohammadi, Asghar, Abolhassani, Hassan, Puck, Jennifer M, Adeli, Mehdi, Cancrini, Caterina, Palma, Paolo, Bertaina, Alice, Locatelli, Franco, Di Matteo, Gigliola, Geha, Raif S, Kanariou, Maria G, Lycopoulou, Lilia, Tzanoudaki, Marianna, Sleasman, John W, Parikh, Suhag, Pinero, Gloria, Fischer, Bernard M, Dbaibo, Ghassan, Unal, Ekrem, Patiroglu, Turkan, Karakukcu, Musa, Al-Saad, Khulood Khalifa, Dilley, Meredith A, Pai, Sung-Yun, Dutmer, Cullen M, Gelfand, Erwin W, Geier, Christoph B, Eibl, Martha M, Wolf, Hermann M, Henderson, Lauren A, Hazen, Melissa M, Bonfim, Carmem, Wolska-Kuśnierz, Beata, Butte, Manish J, Hernandez, Joseph D, Nicholas, Sarah K, Stepensky, Polina, Chandrakasan, Shanmuganathan, Miano, Maurizio, Westermann-Clark, Emma, Goda, Vera, Kriván, Gergely, Holland, Steven M, Fadugba, Olajumoke, Henrickson, Sarah E, Ozen, Ahmet, Karakoc-Aydiner, Elif, Baris, Safa, Kiykim, Ayca, Bredius, Robbert, Hoeger, Birgit, Boztug, Kaan, Pashchenko, Olga, Neven, Benedicte, Moshous, Despina, Villartay, Jean-Pierre de, Bousfiha, Ahmed Aziz, Hill, Harry R, Notarangelo, Luigi D, and Walter, Jolan E

Subjects
Autoimmune Disease, Genetics, Hematology, Inflammatory and immune system, Adolescent, Adult, Autoimmunity, Child, Child, Preschool, Female, Hematopoietic Stem Cell Transplantation, Homeodomain Proteins, Humans, Immunologic Deficiency Syndromes, Immunosuppressive Agents, Infant, Inflammation, Male, Middle Aged, Treatment Outcome, Young Adult, Recombination activating gene, Severe combined immunodeficiency, Immune dysregulation, Autoimmune cytopenias, Hematopoietic stem cell transplantation
Abstract

BACKGROUND:Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE:Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS:In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS:Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS:Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

Published
2019

6. Sleep Apnea and Physical Movement During Sleep, But Not Sleep Duration, Are Independently Associated With Progression of Left Ventricular Diastolic Dysfunction: Prospective Hyogo Sleep Cardio‐Autonomic Atherosclerosis Cohort Study

Author

Yonekazu Kidawara, Manabu Kadoya, Akiko Morimoto, Takashi Daimon, Miki Kakutani‐Hatayama, Kae Kosaka‐Hamamoto, Akio Miyoshi, Kosuke Konishi, Yoshiki Kusunoki, Takuhito Shoji, Akiko Goda, Masanori Asakura, Masaharu Ishihara, and Hidenori Koyama

Subjects
actigraphy, follow‐up studies, humans, Kaplan–Meier estimate, oxygen saturation, prospective studies, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Although co‐occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four‐hundred fifty‐two subjects were followed for a mean of 34.7 months. An outcome of diastolic dysfunction was defined as increase in early inflow velocity/early diastolic tissue velocity >14. Sleep apnea‐hypopnea index, minimal oxygen saturation, sleep duration, and activity index (physical movement during sleep time, a potential parameter of poor sleep quality) were determined using apnomonitor and actigraphy findings, while heart rate variability was measured with a 24‐hour active tracer device. Sixty‐six of the patients developed diastolic dysfunction during the follow‐up period, with a median time of 25 months. Kaplan–Meier analysis results revealed that those with sleep apnea classified as moderate (apnea‐hypopnea index 15 to

Published
2022
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7. Optogenetics: 10 years after ChR2 in neurons—views from the community

Author

Adamantidis, Antoine, Arber, Silvia, Bains, Jaideep S, Bamberg, Ernst, Bonci, Antonello, Buzsáki, György, Cardin, Jessica A, Costa, Rui M, Dan, Yang, Goda, Yukiko, Graybiel, Ann M, Häusser, Michael, Hegemann, Peter, Huguenard, John R, Insel, Thomas R, Janak, Patricia H, Johnston, Daniel, Josselyn, Sheena A, Koch, Christof, Kreitzer, Anatol C, Lüscher, Christian, Malenka, Robert C, Miesenböck, Gero, Nagel, Georg, Roska, Botond, Schnitzer, Mark J, Shenoy, Krishna V, Soltesz, Ivan, Sternson, Scott M, Tsien, Richard W, Tsien, Roger Y, Turrigiano, Gina G, Tye, Kay M, and Wilson, Rachel I

Subjects
Biomedical and Clinical Sciences, Neurosciences, Genetics, Neurological, Action Potentials, Animals, Channelrhodopsins, Humans, Neurons, Optogenetics, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Published
2015

8. Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly

Author

Ohnishi, Takayuki, Yanazawa, Masako, Sasahara, Tomoya, Kitamura, Yasuki, Hiroaki, Hidekazu, Fukazawa, Yugo, Kii, Isao, Nishiyama, Takashi, Kakita, Akiyoshi, Takeda, Hiroyuki, Takeuchi, Akihide, Arai, Yoshie, Ito, Akane, Komura, Hitomi, Hirao, Hajime, Satomura, Kaori, Inoue, Masafumi, Muramatsu, Shin-ichi, Matsui, Ko, Tada, Mari, Sato, Michio, Saijo, Eri, Shigemitsu, Yoshiki, Sakai, Satoko, Umetsu, Yoshitaka, Goda, Natsuko, Takino, Naomi, Takahashi, Hitoshi, Hagiwara, Masatoshi, Sawasaki, Tatsuya, Iwasaki, Genji, Nakamura, Yu, Nabeshima, Yo-ichi, Teplow, David B, and Hoshi, Minako

Subjects
Alzheimer's Disease, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Neurosciences, Dementia, Aging, Acquired Cognitive Impairment, Aetiology, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Amino Acid Sequence, Amyloid beta-Peptides, Animals, Calcium, Cell Death, Cells, Cultured, HEK293 Cells, Homeostasis, Humans, Mass Spectrometry, Models, Biological, Models, Molecular, Molecular Imaging, Molecular Sequence Data, Molecular Weight, Neurons, Peptides, Protein Aggregates, Protein Binding, Rats, Signal Transduction, Sodium, Sodium-Potassium-Exchanging ATPase, NMR, computational modeling, abnormal protein-protein interaction in synapse, hyperexcitotoxicity, protein-protein interaction inhibitors, abnormal protein–protein interaction in synapse, protein–protein interaction inhibitors
Abstract

Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aβ-derived "thorns" responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn(879) and Trp(880) is essential for ASPD-NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD-NAKα3 interaction.

Published
2015

9. Risk of pulmonary artery dissection in adults with congenital heart disease

Author

Alexander C, Egbe, William R, Miranda, C Charles, Jain, Jason H, Anderson, Elizabeth H, Stephens, Kartik, Andi, Ahmed, Goda, Omar, Abozied, Dhanya, Ramachandran, Juan A, Crestanello, Christopher, Francois, and Heidi M, Connolly

Subjects
Adult, Male, Heart Defects, Congenital, Aortic Dissection, Hypertension, Pulmonary, Humans, Female, Pulmonary Artery, Cardiology and Cardiovascular Medicine, Aneurysm, Retrospective Studies
Abstract

There are limited data about the risk of pulmonary artery (PA) dissection in adults with congenital heart disease (CHD), and the purpose of this study was to estimate the incidence of PA dissection in this population.Retrospective cohort study of adults with CHD that underwent cross-sectional imaging (2003-2020). PA aneurysm was defined as main or branch PA diameter 40 mm or 30 mm respectively, and severe PA aneurysm was defined as main or branch PA diameter 50 mm.Of 1, 673 patients (41 ± 10 years; male 58%), 493 (24%), 286 (19%), and 306 (20%) had aneurysms of the main, right, and left PA respectively, while 66 (4%) had severe PA aneurysm. During a median follow-up of 8.2 (interquartile range 3.7-10.3) years, there was one PA dissection in a patient with Eisenmenger syndrome, thus the incidence of PA dissection was 14 per 100,000 patient-years. Of 779 females, 163 had one or more pregnancies during follow-up, and 41 (25%) of these patients had known PA aneurysm at the time of conception. There was no PA dissection during pregnancy. Of the 163 patients, 91 (56%) had cross-sectional imaging before and after pregnancy, there was no significant difference in PA dimension before versus after pregnancy (main PA 35 ± 5 versus 36 ± 4 mm, p = 0.6; right PA 21 ± 3 versus 33 ± 4 mm, p = 0.1; and left PA 23 ± 4 versus 22 ± 4 mm, p = 0.4).The risk of PA dissection was extremely low even in patients with severe PA aneurysm, or in patients with PA aneurysm that became pregnant. Collectively, these data suggest a benign natural history for patients without severe pulmonary hypertension and encourage and a conservative approach in managing patients with PA aneurysm.

Published
2023
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10. Multimodal Pain Management Protocol to Decrease Opioid Use and to Improve Pain Control After Thoracic Surgery

Author

Isabel C. Clark, Robert D. Allman, Austin L. Rogers, Tamara S. Goda, Kathryn Smith, Tyler Chanas, Aundrea L. Oliver, Mark D. Iannettoni, Carlos J. Anciano, and James E. Speicher

Subjects
Analgesics, Opioid, Pulmonary and Respiratory Medicine, Pain, Postoperative, Humans, Pain Management, Thoracic Surgery, Surgery, Opioid-Related Disorders, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract

Opioid addiction continues to be a devastating problem in our communities, and up to 40% of patients begin their addiction with legally prescribed opioids after injury or surgical procedure. An opioid-free multimodal pain regimen was developed with the goal of decreasing opioid exposure while maintaining adequate pain control.A retrospective single-institution study was conducted of 313 consecutive patients undergoing minimally invasive lobectomy before (n = 211) and after (n = 102) implementation of an opioid-free protocol from 2016 to 2020. Data analysis was conducted on preoperative characteristics, postoperative opioid use at set time points (postoperative day 0, postoperative days 1 to 7, and total stay), pain scores, discharge with opioid prescription, and postoperative outcomes.Patients on the opioid-free protocol had significantly lower average total morphine milligram equivalents at all time points. In addition, 56% of patients in the opioid-free group received no oral opioids at all, and 91% did not receive a patient-controlled analgesia pump. Average pain scores were significantly lower in the opioid-free protocol patients along with percentage of time spent with pain scores3 and6. With implementation of the protocol, 62% of patients are discharged without an opioid prescription compared with only 7% previously.Implementation of an opioid-free protocol led to a significant decrease in the use of postoperative opioids at all time points while improving overall management of pain. In addition, most patients are discharged with no home opioid prescription, decreasing a potential source of community opioid spread.

Published
2022
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11. Is music intervention effective in reducing anxiety and pain during breast biopsy procedure? A systematic review and meta-analysis of randomized controlled trials

Author

Ahmed S. A. Ashour, Mohamed Abd-ElGawad, Mariam Yohanna, Mostafa El-Nagar, Ahmed Nasser Fadl, Gehad Mohammed Goda, Yassamine Ouerdane, Hany Saad, Mona Fouad, Noura El-Nassery, Mohamed Abdelmonem Kamel, and Iman Ezahaby

Subjects
Oncology, Biopsy, Humans, Pain, Anxiety, Music Therapy, Randomized Controlled Trials as Topic
Abstract

Purpose To evaluate the evidence from randomized clinical trials (RCTs) about the effect of music intervention in reducing patients’ anxiety during breast biopsy. Methods Electronic databases including PubMed, Cochrane Library, Scopus, and Web of Science were searched using the relevant MeSH terms. The inclusion criteria were all RCTs assessing the effect of music therapy versus no music in reducing anxiety during breast biopsy. The extracted outcomes were anxiety and pain during breast biopsy. They were pooled as mean difference (MD) with a 95% confidence interval (CI) in a fixed-effects model, using Review Manager 5.3 software for windows. The quality of included studies was assessed with the Cochrane risk of bias assessment tool (RoB 1.0). Then, the outcomes of our meta-analyses were independently evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to know the grade of their evidence. Results The final analysis included five RCTs. We found a positive effect of music therapy in reducing anxiety levels compared with control group (MD = − 2.11; 95% CI (− 4.16 to − 0.06); p = 0.04). No difference between music and control groups regarding pain associated with breast biopsy (MD = 0.22; 95% CI (− 0.81 to 1.25); p = 0.68). The GRADE rating of our outcomes was low for anxiety levels and very low for pain during the biopsy. Conclusions Music therapy could be an effective, simple, non-pharmacological option in relieving anxiety during breast biopsy; however, it had no effect on procedure-associated pain. More large and high-quality studies are needed to confirm our results.

Published
2022
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12. Outcome of New-Onset Postoperative Atrial Fibrillation After Cardiac Surgery in Adults With Congenital Heart Disease

Author

Alexander C, Egbe, William R, Miranda, Jason H, Anderson, Christopher V, DeSimone, Kartik, Andi, Ahmed Y, Goda, Elizabeth H, Stephens, Joseph A, Dearani, Juan, Crestanello, Heidi M, Connolly, and Abhishek J, Deshmukh

Subjects
Male, Adult, Heart Defects, Congenital, Postoperative Complications, Atrial Fibrillation, Hypertension, Humans, Female, Prospective Studies, Middle Aged, Cardiac Surgical Procedures, Retrospective Studies
Abstract

Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery. POAF is associated with a longer hospital stay, higher healthcare resource utilization, and higher risk of morbidity and mortality. As a result, the American and European guidelines recommend the use of beta-blockers and amiodarone for the prevention of POAF, and in turn, avoid the complications associated with POAF.The purpose of this study was to determine the incidence, risk factors, and prognostic implications of new-onset POAF after cardiac surgery in adults with congenital heart disease (CHD).A retrospective study was conducted among adults with CHD who underwent cardiac surgery (2003-2019). POAF and late-onset atrial fibrillation (AF) were defined as AF occurring within and after 30 days postoperatively, respectively.Of 1,598 patients (mean age 39 ± 13 years, 51% men), 335 (21%) developed POAF. Risk factors associated with POAF were older age, hypertension, left atrial (LA) reservoir strain and right atrial (RA) dysfunction, and nonsystemic atrioventricular valve regurgitation. Of 1,291 patients (81%) with follow-up ≥12 months, the annual incidence of late-onset AF was 1.5% and was higher in patients with POAF compared with those without POAF (5.9% vs 0.4%; P 0.001). Risk factors associated with late-onset AF were POAF, older age, severe CHD, and LA and RA dysfunction. Of the 1,291 patients, 63 (5%) died during follow-up, and the risk factors associated with all-cause mortality were older age, severe CHD, hypertension, left ventricular systolic dysfunction, and LA and RA dysfunction. POAF was not associated with all-cause mortality.POAF was common in adults with CHD and was associated with late-onset AF but not all-cause mortality. Atrial dysfunction was independently associated with POAF, late-onset AF, and all-cause mortality. These risk factors can be used to identify patients at risk for POAF and provide a foundation for prospective studies assessing the efficacy of prophylactic therapies in this population.

Published
2022
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13. Non‐recovery of vancomycin‐associated nephrotoxicity is related to worsening survival outcomes: Combined retrospective analyses of two real‐world databases

Author

Masayuki Chuma, Hirofumi Hamano, Takashi Bando, Masateru Kondo, Naoto Okada, Yuki Izumi, Shunsuke Ishida, Toshihiko Yoshioka, Mizuho Asada, Takahiro Niimura, Yoshito Zamami, Kenshi Takechi, Mitsuhiro Goda, Koji Miyata, Kenta Yagi, Sachiko Kasamo, Yuki Izawa‐Ishizawa, Momoyo Azuma, Hiroaki Yanagawa, Yoshikazu Tasaki, and Keisuke Ishizawa

Subjects
Pharmacology, Drug-Related Side Effects and Adverse Reactions, Vancomycin, Risk Factors, Humans, General Medicine, Acute Kidney Injury, Toxicology, Retrospective Studies, Anti-Bacterial Agents
Abstract

There has been growing concern in worsening survival and renal outcomes following vancomycin-associated nephrotoxicity (VAN) onset, but the factors associated with these phenomena remain unclear. To examine these factors, we performed a retrospective study combining the analysis of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was used to evaluate the relationship between VAN and mortality using odds ratios (ORs) and 95% confidence intervals (CIs). Next, electronic medical records (EMRs) were examined in a more robust cohort for evaluation of the association between renal outcomes and worsening survival using Cox proportional hazards regression models. FAERS analysis revealed a significant correlation between VAN occurrence and increased mortality (OR: 1.30; 95% CI: 1.17-1.46). EMR analysis showed that non-recovery of VAN was associated with increased hospital mortality (hazard ratio [HR]: 4.05; 95% CI: 2.42-6.77) and 1-year mortality (HR: 3.03, 95% CI: 1.98-4.64). The HR for VAN recovery was lower for patients with acute kidney injury (AKI) stage ≥2 (HR: 0.09; 95% CI: 0.02-0.40). Thus, worsening survival outcomes were associated with non-recovery of VAN, whereby AKI stage ≥2 was a significant risk factor. Progression to severe VAN should be prevented for better survival outcomes.

Published
2022
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14. Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study

Author

Michael H. Albert, Tiarlan Sirait, Dirk-Jan Eikema, Katerina Bakunina, Claudia Wehr, Felipe Suarez, Maria Laura Fox, Nizar Mahlaoui, Andrew R. Gennery, Arjan C. Lankester, Rita Beier, Maria Ester Bernardo, Venetia Bigley, Caroline A. Lindemans, Siobhan O. Burns, Ben Carpenter, Jaroslaw Dybko, Tayfun Güngör, Fabian Hauck, Su Han Lum, Dmitry Balashov, Roland Meisel, Despina Moshous, Ansgar Schulz, Carsten Speckmann, Mary A. Slatter, Brigitte Strahm, Duygu Uckan-Cetinkaya, Isabelle Meyts, Tanja C. Vallée, Robert Wynn, Bénédicte Neven, Emma C. Morris, Alessandro Aiuti, Alexei Maschan, Mahmoud Aljurf, Tobias Gedde-Dahl, Gunhan Gurman, Victoria Bordon, Gergely Kriván, Franco Locatelli, Fulvio Porta, David Valcárcel, Yves Beguin, Maura Faraci, Nicolaus Kröger, Aleksandr Kulagin, Peter J. Shaw, Joan Hendrik Veelken, Cristina Diaz de Heredia, Franca Fagioli, Matthias Felber, Bernd Gruhn, Wolfgang Holter, Claudia Rössig, Petr Sedlacek, Jane Apperley, Mouhab Ayas, Ivana Bodova, Goda Choi, J.J. Cornelissen, Anne Sirvent, Anjum Khan, Alphan Kupesiz, Stig Lenhoff, Hakan Ozdogu, Nicolas von der Weid, Montserrat Rovira, Rik Schots, Donald C. Vinh, Clinical sciences, and Hematology

Subjects
Adult, Adolescent, adolescenti, Trapianto, Immunology, Graft vs Host Disease, Biochemistry, Bronchiectasis/etiology, Humans, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation/adverse effects, Child, Retrospective Studies, cellule staminali ematopoietiche, Hematopoietic Stem Cell Transplantation, Infant, Trapianto, cellule staminali ematopoietiche, adolescenti, Inborn errors of immunity, Cell Biology, Hematology, Middle Aged, Bronchiectasis, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, HSCT, young adult
Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT. ispartof: BLOOD vol:140 issue:14 pages:1635-1649 ispartof: location:United States status: published

Published
2022
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15. Improvement in hepatic and renal function following isolated heart transplant in adults with congenital heart disease

Author

Alexander C, Egbe, William R, Miranda, C Charles, Jain, Patrick S, Kamath, Renuka R, Katta, Kartik, Andi, Ahmed Y, Goda, and Heidi M, Connolly

Subjects
Adult, End Stage Liver Disease, Heart Defects, Congenital, Liver Cirrhosis, Heart Transplantation, Humans, Middle Aged, Kidney, Cardiology and Cardiovascular Medicine, Severity of Illness Index, Retrospective Studies
Abstract

There are limited data about postoperative changes in hepatic and renal function in adults with congenital heart disease (CHD) undergoing isolated heart transplant. The purpose of this study was to assess postoperative changes in hepatic and renal function in this population.Retrospective cohort study of adults with CHD undergoing isolated heart transplant at Mayo Clinic (2003-2019). Global hepatic function was assessed using the model for end-stage liver disease excluding international normalized ratio [MELD-XI]) score; hepatic fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate/platelet ratio index (APRI); and renal function was assessed using estimated glomerular filtration rate (GFR). All indices were measured preoperatively and postoperatively (at 6 months, 1 year, 2 years).Of 40 patients (age 41 ± 8 years) in the study, 35 had complete preoperative and postoperative data. There was a temporal improvement in hepatic and renal indices from preop (MELD-XI 14 ± 5, APRI 0.60 ± 0.23, FIB-4 1.44 ± 0.38, GFR 59 [44-83]) to 6 months postop (MELD-XI 12 ± 6, APRI 0.49 ± 0.17, FIB-4 1.29 ± 0.33, GFR 68 [54-96]) and 1-year postop (MELD-XI 9 ± 3, APRI 0.41 ± 0.16, FIB-4 1.12 ± 0.29, GFR 82 [69-108]), p 0.05 for all comparisons.CHD patients undergoing isolated heart transplant had significant improvement in hepatic and renal function. These data suggests that selected CHD patients may do well with isolated heart transplant despite reduced hepatic and renal function, and hepatic fibrosis preoperatively. More rigorous prospective studies are required to determine the relative outcomes of isolated versus combined heart-liver transplant in this population.

Published
2022
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16. Divergent effect of blood glucose dysregulation on long-term clinical outcome in acute decompensated heart failure: A reappraisal in contemporary practice

Author

Toshiki Chishiki, Yuji Nagatomo, Mike Saji, Makoto Takei, Ayumi Goda, Takashi Kohno, Shintaro Nakano, Yosuke Nishihata, Yukinori Ikegami, Yasuyuki Shiraishi, Shun Kohsaka, Takeshi Adachi, and Tsutomu Yoshikawa

Subjects
Blood Glucose, Glycated Hemoglobin, Heart Failure, Hospitalization, Male, Acute Disease, Humans, Prospective Studies, Prognosis, Cardiology and Cardiovascular Medicine
Abstract

The prognostic implication of elevated or decreased blood glucose (BG) level in acute decompensated heart failure (ADHF) has been still controversial. Indices of stress hyperglycemia, expressed by the ratio of BG and chronic BG control, has been reported to be associated with poor outcome in different disease population. We sought to assess BG at admission and %ΔBG, an index of BG deviation from estimated average BG calculated from glycated hemoglobin (HbA1c), on the long-term outcome in ADHF patients.The West Tokyo Heart Failure (WET-HF) Registry is a prospective multicenter registry enrolling consecutive hospitalized ADHF patients. Among the patients (N = 3078, 77 [67-84] years, male 59%), BG at admission discriminated the long-term (1000 days) incidence of ADHF rehospitalization, but not cardiac death. BG at admission showed a U-shape relationship with the long-term incidence of ADHF rehospitalization after adjustment for covariates. Especially, in patients with HbA1c ≥ 6.5%, the lowest quartile showed the highest risk of ADHF rehospitalization. On the contrary, %ΔBG showed U-shape relationship with the long-term incidence of cardiac death after discharge, rather than ADHF rehospitalization after adjustment for covariates. In addition, elevated %ΔBG was associated with the long-term risk of sudden cardiac death (SCD) even after adjustment for covariates.For ADHF patients, BG at admission and %ΔBG might be a simple, useful tool for predicting and stratifying long-term risk of cardiac events. Especially, elevated %ΔBG might be an important in predicting hard events such as cardiac death or SCD.

Published
2022
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17. Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects

Author

Hideki Nawa, Hirofumi Hamano, Takahiro Niimura, Koji Miyata, Kenta Yagi, Mitsuhiro Goda, Yoshito Zamami, and Keisuke Ishizawa

Subjects
Pharmaceutical Preparations, Drug-Related Side Effects and Adverse Reactions, Databases, Factual, Pyridones, United States Food and Drug Administration, General Neuroscience, Humans, General Medicine, General Pharmacology, Toxicology and Pharmaceutics, Lung Diseases, Interstitial, United States, Idiopathic Pulmonary Fibrosis, General Biochemistry, Genetics and Molecular Biology
Abstract

Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD.

Published
2022
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18. Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic <scp>ALL2008</scp> protocol

Author

Egnell, Christina, Närhinen, Hanna, Merker, Andrea, Jonsson, Ólafur G., Lepik, Kristi, Niinimäki, Riitta, Schmiegelow, Kjeld, Stabell, Niklas, Klug Albertsen, Birgitte, Vaitkevičienė, Goda Elizabeta, Ranta, Susanna, Harila-Saari, Arja, and Harila‐Saari, Arja

Subjects
obesity, Body Weight, support care, body mass index, acute lymphoblastic leukemia, Hematology, General Medicine, Overweight, Precursor Cell Lymphoblastic Leukemia-Lymphoma, children, overweight, Body Mass Index, Humans, Obesity, Child
Abstract

Objectives: Children with acute lymphoblastic leukemia (ALL) have a tendency to gain weight during treatment. As overweight and obesity associate with health problems, prophylactic interventions are warranted. Therefore, it is important to identify the children most prone to gain weight. Methods: Patients aged 2.0–17.9 years at ALL diagnosis were identified from the NOPHO ALL2008 registry. Registry data was complemented with height and weight at the end of therapy from questionnaires. Body mass index (BMI) was classified according to international age- and sex-adjusted International Obesity Task Force BMI cut-offs. BMI values were transformed into standard deviation scores (SDS) to calculate the difference in BMISDS during treatment. Results: Data on BMI change were available for 765 children. Overweight and obesity doubled during treatment: 9.7% were overweight and 2.1% obese at diagnosis and 21.8% and 5.4% at the end of therapy, respectively. The mean BMISDS change was +0.64. Younger (2.0–5.9 years) and healthy weight children were most prone to become overweight (mean change in BMI SDS +0.85 and + 0.65, respectively). Conclusions: Younger children (2.0–5.9 years) with healthy weight at diagnosis were most prone to becoming overweight and therefore are an important group to target while considering interventions.

Published
2022
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19. Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Author

Christoph B. Geier, Maryssa Ellison, Rachel Cruz, Sumit Pawar, Alexander Leiss-Piller, Katarina Zmajkovicova, Shannon M McNulty, Melis Yilmaz, Martin Oman Evans, Sumai Gordon, Boglarka Ujhazi, Ivana Wiest, Hassan Abolhassani, Asghar Aghamohammadi, Sara Barmettler, Saleh Bhar, Anastasia Bondarenko, Audrey Anna Bolyard, David Buchbinder, Michaela Cada, Mirta Cavieres, James A. Connelly, David C. Dale, Ekaterina Deordieva, Morna J. Dorsey, Simon B. Drysdale, Stephan Ehl, Reem Elfeky, Francesca Fioredda, Frank Firkin, Elizabeth Förster-Waldl, Bob Geng, Vera Goda, Luis Gonzalez-Granado, Eyal Grunebaum, Elzbieta Grzesk, Sarah E. Henrickson, Anna Hilfanova, Mitsuteru Hiwatari, Chihaya Imai, Winnie Ip, Soma Jyonouchi, Hirokazu Kanegane, Yuta Kawahara, Amer M. Khojah, Vy Hong-Diep Kim, Marina Kojić, Sylwia Kołtan, Gergely Krivan, Daman Langguth, Yu-Lung Lau, Daniel Leung, Maurizio Miano, Irina Mersyanova, Talal Mousallem, Mica Muskat, Flavio A. Naoum, Suzie A. Noronha, Monia Ouederni, Shuichi Ozono, G. Wendell Richmond, Inga Sakovich, Ulrich Salzer, Catharina Schuetz, Filiz Odabasi Seeborg, Svetlana O. Sharapova, Katja Sockel, Alla Volokha, Malte von Bonin, Klaus Warnatz, Oliver Wegehaupt, Geoffrey A. Weinberg, Ke-Juin Wong, Austen Worth, Huang Yu, Yulia Zharankova, Xiaodong Zhao, Lisa Devlin, Adriana Badarau, Krisztian Csomos, Marton Keszei, Joao Pereira, Arthur G Taveras, Sarah L. Beaussant-Cohen, Mei-Sing Ong, Anna Shcherbina, and Jolan E. Walter

Subjects
Receptors, CXCR4, Neutropenia, Agammaglobulinemia, Lymphopenia, Immunology, Immunologic Deficiency Syndromes, Disease Progression, Humans, Immunology and Allergy, Warts
Abstract

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

Published
2022
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20. Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds

Author

Sweety, Asija, Abhishek, Chatterjee, Sandhya, Yadav, Godhanjali, Chekuri, Atharva, Karulkar, Ankesh Kumar, Jaiswal, Jayant S, Goda, and Rahul, Purwar

Subjects
Oncolytic Virotherapy, Brain Neoplasms, Immunology, Tumor Microenvironment, Humans, Immunology and Allergy, Immunotherapy, Glioma, Glioblastoma, Immune Checkpoint Inhibitors
Abstract

The aggressive and recurrent nature of glioblastoma is multifactorial and has been attributed to its biological heterogeneity, dysfunctional metabolic signaling pathways, rigid blood-brain barrier, inherent resistance to standard therapy due to the stemness property of the gliomas cells, immunosuppressive tumor microenvironment, hypoxia and neoangiogenesis which are very well orchestrated and create the tumor's own highly pro-tumorigenic milieu. Once the relay of events starts amongst these components, eventually it becomes difficult to control the cascade using only the balanced contemporary care of treatment consisting of maximal resection, radiotherapy and chemotherapy with temozolamide. Over the past few decades, implementation of contemporary treatment modalities has shown benefit to some extent, but no significant overall survival benefit is achieved. Therefore, there is an unmet need for advanced multifaceted combinatorial strategies. Recent advances in molecular biology, development of innovative therapeutics and novel delivery platforms over the years has resulted in a paradigm shift in gliomas therapeutics. Decades of research has led to emergence of several treatment molecules, including immunotherapies such as immune checkpoint blockade, oncolytic virotherapy, adoptive cell therapy, nanoparticles, CED and BNCT, each with the unique proficiency to overcome the mentioned challenges, present research. Recent years are seeing innovative combinatorial strategies to overcome the multifactorial resistance put forth by the GBM cell and its TME. This review discusses the contemporary and the investigational combinatorial strategies being employed to treat GBM and summarizes the evidence accumulated till date.Glioblastoma is a form of brain tumor which typically leads to death in almost all patients. Over the last two decades, traditional treatment strategies such as surgery, radiotherapy and chemotherapy have been combined as standard therapy. Together, these aggressive treatment strategies have provided modest survival benefit with acceptable toxicity. However, relapse is the invariable norm resulting in death in the overwhelming majority of patients. Relapse occurs due to multiple factors such as inability of drugs to cross blood–brain barrier, immunosuppressive tumor microenvironment, stemness nature of glioma cells, tumor heterogeneity and enhanced hypoxia and angiogenic factors. Therefore, there is an urgent need to develop an innovative treatment approach to treat glioblastoma. Recently, several treatment strategies known as immunotherapies including CAR T cell therapy, dendritic cell vaccines, immune checkpoints blockade and oncolytic virus, nano particles and gene editing/silencing technology have demonstrated promising results in preclinical and few clinical trials. Furthermore, to increase the efficacy of these novel strategies, combinatorial approaches are being implemented for the treatment. This includes CAR T cell therapy in combination with small molecules, immune checkpoint inhibitors and oncolytic virus and nanoparticles plus gene editing, silencing or immune checkpoints inhibitors. These treatments have shown exciting results in preclinical settings and few of these trials are in progress. The review summarizes these combinatorial novel approaches and discusses them in detail.

Published
2022
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21. Salvage Endoscopic Submucosal Dissection for Local Recurrence of Superficial Esophageal Squamous Cell Cancer after Photodynamic Therapy

Author

Akira, Kanamori, Kenichi, Goda, Tetsuya, Nakamura, Hidetsugu, Yamagishi, Atsuko, Ohwada, Keiichiro, Abe, Tsunehiro, Suzuki, Masayuki, Kondo, Takanao, Tanaka, Akira, Yamamiya, Yoichi, Takimoto, Koki, Hoshi, Takahiro, Arisaka, Takeshi, Sugaya, Keiichi, Tominaga, Yuichi, Majima, Makoto, Iijima, and Atsushi, Irisawa

Subjects
Salvage Therapy, Endoscopic Mucosal Resection, Esophageal Neoplasms, Epithelial Cells, General Medicine, Treatment Outcome, Photochemotherapy, Carcinoma, Squamous Cell, Internal Medicine, Humans, Esophageal Squamous Cell Carcinoma, Esophagoscopy, Neoplasm Recurrence, Local, Retrospective Studies
Abstract

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Published
2022
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22. Correlation of Scoring Systems with the Requirement of an External Ventricular Drain in Intraventricular Hemorrhage

Author

Yoshinori Maki, Ryota Ishibashi, Takaya Yasuda, Hironobu Tokumasu, Yoshiharu Yamamoto, Akio Goda, Hokuto Yamashita, Takumi Morita, Hiroyuki Ikeda, Masaki Chin, and Sen Yamagata

Subjects
Treatment Outcome, Drainage, Humans, Glasgow Coma Scale, Surgery, Neurology (clinical), Child, Cerebral Hemorrhage, Hydrocephalus
Abstract

External ventricular drainage (EVD) is required to resolve acute hydrocephalus associated with intraventricular hemorrhage (IVH). The correlation of scoring systems of IVH with indications for EVD for acute hydrocephalus related to IVH is currently unknown.We identified 213 hypertensive patients with IVH and divided them into 2 groups according to treatment method: 187 patients receiving blood pressure control alone and 26 patients undergoing EVD. The following patients were excluded: pediatric patients, patients undergoing intracranial hematoma removal, patients with fetal status, and patients without sufficient clinical data. We compared the Glasgow Coma Scale score, Graeb score, LeRoux score, Evans index, and bicaudate index values between the 2 groups and determined the prognostication accuracy of each scoring system.There were significant differences in all 4 scoring systems between the 2 groups (P 0.001). The cutoff values (sensitivity and specificity) of each scoring system were as follows: Glasgow Coma Scale, 8 (65.4%, 87.7%); Graeb score, 6 (80.8%, 75.4%); LeRoux score, 9 (80.8%, 76.5%); Evans index, 0.245 (80.8%, 67.9%); and bicaudate index, 0.186 (76.9%, 76.5%). The value of the area under the curve of each scoring system (95% confidence interval) was as follows: Glasgow Coma Scale, 0.806 (0.705-0.907); Graeb score, 0.852 (0.779-0.925); LeRoux score, 0.875 (0.812-0.937); Evans index, 0.788 (0.702-0.875); and bicaudate index, 0.778 (0.673-0.883).The LeRoux score is better for identifying patients with IVH who are more likely to have EVD.

Published
2022
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23. Long-Term Clinical Outcomes and Sequelae of Therapy in Early-Stage Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

Author

Goutam Panda, Babusha Kalra, Anupam Rishi, Nehal Khanna, Sangeeta Kakoti, Epari Sridhar, Tanuja Shet, Manju Sengar, Lingaraj Nayak, Bahusaheb Bagal, Hasmukh Jain, Siddartha S Laskar, and Jayant S. Goda

Subjects
Adult, Cancer Research, Treatment Outcome, Oncology, Remission Induction, Disease Progression, Humans, Radiotherapy Dosage, Lymphoma, B-Cell, Marginal Zone, Hematology, Middle Aged, Neoplasm Recurrence, Local, Retrospective Studies
Abstract

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients.We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities.Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%).Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.

Published
2022
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24. UK National Screening Committee's approach to reviewing evidence on artificial intelligence in breast cancer screening

Author

Sian Taylor-Phillips, Farah Seedat, Goda Kijauskaite, John Marshall, Steve Halligan, Chris Hyde, Rosalind Given-Wilson, Louise Wilkinson, Alastair K Denniston, Ben Glocker, Peter Garrett, Anne Mackie, and Robert J Steele

Subjects
Health Information Management, Artificial Intelligence, Humans, Medicine (miscellaneous), Breast Neoplasms, Female, Decision Sciences (miscellaneous), Health Informatics, Early Detection of Cancer, United Kingdom, Retrospective Studies
Abstract

Artificial intelligence (AI) could have the potential to accurately classify mammograms according to the presence or absence of radiological signs of breast cancer, replacing or supplementing human readers (radiologists). The UK National Screening Committee's assessments of the use of AI systems to examine screening mammograms continues to focus on maximising benefits and minimising harms to women screened, when deciding whether to recommend the implementation of AI into the Breast Screening Programme in the UK. Maintaining or improving programme specificity is important to minimise anxiety from false positive results. When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants). Enriched, multiple-reader, multiple-case, test set laboratory studies are also biased due to the laboratory effect (ie, radiologists' performance in retrospective, laboratory, observer studies is substantially different to their performance in a clinical environment). Therefore, assessment of the effect of incorporating any AI system into the breast screening pathway in prospective studies is required as it will provide key evidence for the effect of the interaction of medical staff with AI, and the impact on women's outcomes.

Published
2022
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25. Use of short‐acting vs. long‐acting loop diuretics after heart failure hospitalization

Author

Shohei Imaeda, Yasuyuki Shiraishi, Shun Kohsaka, Nozomi Niimi, Ayumi Goda, Yuji Nagatomo, Makoto Takei, Mike Saji, Shintaro Nakano, Takashi Kohno, Keiichi Fukuda, and Tsutomu Yoshikawa

Subjects
Male, Heart Failure, Hospitalization, Sodium Potassium Chloride Symporter Inhibitors, Furosemide, Humans, Female, Cardiology and Cardiovascular Medicine, Torsemide, Aged
Abstract

Furosemide, a short-acting loop diuretic (SD), is the dominant agent prescribed for heart failure (HF) in clinical practice. However, accumulating data suggests that long-acting loop diuretics (LD), such as torsemide or azosemide, might have more favourable pharmacological profiles. This study aimed to investigate the relationship between the type of loop diuretics and long-term outcomes among patients hospitalized for acute HF enrolled in a contemporary multicentre registry.Within the West Tokyo Heart Failure Registry from 2006 to 2017, a total of 2680 patients (60.1% men with a median age of 77 years) were analysed. The patients were characterized by the type of diuretics used at the time of discharge; 2073 (77.4%) used SD, and 607 (22.6%) used LD. The primary endpoint was composite of all-cause death or HF re-admission after discharge, and the secondary endpoints were all-cause death and HF re-admission, respectively. During the median follow-up period of 2.1 years, 639 patients died [n = 519 (25.0%) in the SD group; n = 120 (19.8%) in the LD group], and 868 patients were readmitted for HF [n = 697 (33.6%) in the SD group; n = 171 (28.2%) in the LD group]. After multivariable adjustment, the LD group had lower risk for the composite outcome [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.66-0.96; P = 0.017], including all-cause death (HR; 0.73; 95% CI; 0.54-0.99; P = 0.044) and HF re-admission (HR, 0.81; 95% CI, 0.66-0.99; P = 0.038), than the SD group. Propensity score matching yielded estimates that were consistent with those of the multivariable analyses, with sub-group analyses demonstrating that use of LD was associated with favourable outcomes predominantly in younger patients with reduced ejection fraction.LD was associated with lower risk of long-term outcomes in patients with HF and a recent episode of acute decompensation.

Published
2022
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26. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author

Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.

Subjects
0301 basic medicine, Male, Pediatrics, syndromic, Sex Factor, Disease, registry, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Primary Immunodeficiency Disease, inborn error of immunity, Immunology and Allergy, warning signs, Age Factor, Registries, Family history, presenting symptom, Child, Primary immunodeficiency, Granuloma, autoimmune, immune dysregulation, inflammatory, Adult, Autoimmune Diseases, Female, Humans, Infections, Lymphoproliferative Disorders, Middle Aged, Primary Immunodeficiency Diseases, Sex Factors, Age Factors, 10177 Dermatology Clinic, Infections/epidemiology, 3. Good health, Settore MED/02, Warning signs, Lymphoproliferative Disorder, 2723 Immunology and Allergy, Infection, Human, medicine.medical_specialty, Immunology, 610 Medicine & health, Malignancy, primary immunodeficiency, Autoimmune Disease, 03 medical and health sciences, Immunity, Autoimmune Diseases/epidemiology, medicine, 2403 Immunology, business.industry, warning sign, Common variable immunodeficiency, Granuloma/epidemiology, Immune dysregulation, medicine.disease, Primary Immunodeficiency Diseases/epidemiology, 030104 developmental biology, Lymphoproliferative Disorders/epidemiology, Cohort Studie, business, 030215 immunology
Abstract

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Published
2021

27. Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Author

Romiti, Giulio Francesco, Proietti, Marco, Vitolo, Marco, Bonini, Niccolò, Fawzy, Ameenathul Mazaya, Ding, Wern Yew, Fauchier, Laurent, Marin, Francisco, Nabauer, Michael, Dan, Gheorghe Andrei, Potpara, Tatjana S., Boriani, Giuseppe, Lip, Gregory Y. H., Tavazzi, L., Maggioni, A. P., Kalarus, Z., Ferrari, R., Shantsila, A., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., García Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E. N., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K., Erglis, A., Poposka, L., Burg, M. R., Crijns, H., Erküner, Atar, D., Lenarczyk, R., Oliveira, M. Martins, Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zëra, E., Ekmekçiu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., van Genechten, G., Heidbuchel, H., Boussy, T., de Coninck, M., van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., van Hauwaert, B., Kuppens, C., Faes, D., van Lier, D., van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubíčková, M., Joensen, A. Marni, Gammelmark, A., Rasmussen, L. Hvilsted, Dinesen, P., Venø, S. Krogh, Sorensen, B., Korsgaard, A., Andersen, K., Hellum, C. Fragtrup, Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castaño, S., Cheggour, S., Poulard, J., Mouquet, V., Leparrée, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassalière, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois-Jacquey, C., Kassim, H., Marijon, E., le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden-Lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefèvre, M., Mingam, R., Haissaguerre, M., le Bidan, M., Pavin, D., le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer-Bouchard, C., da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Glöggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Köster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Förtsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Ländle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hötz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schön, B., Schön, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler-Schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V. 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K., Simantirakis E.N., Haim M., Azhari A., Najafian J., Santini M., Mirrakhimov E., Kulzida K., Erglis A., Poposka L., Burg M.R., Crijns H., Erkuner O., Atar D., Lenarczyk R., Oliveira M.M., Shah D., Serdechnaya E., Diker E., Lane D., Zera E., Ekmekciu U., Paparisto V., Tase M., Gjergo H., Dragoti J., Ciutea M., Ahadi N., el Husseini Z., Raepers M., Leroy J., Haushan P., Jourdan A., Lepiece C., Desteghe L., Vijgen J., Koopman P., Van Genechten G., Heidbuchel H., Boussy T., De Coninck M., Van Eeckhoutte H., Bouckaert N., Friart A., Boreux J., Arend C., Evrard P., Stefan L., Hoffer E., Herzet J., Massoz M., Celentano C., Sprynger M., Pierard L., Melon P., Van Hauwaert B., Kuppens C., Faes D., Van Lier D., Van Dorpe A., Gerardy A., Deceuninck O., Xhaet O., Dormal F., Ballant E., Blommaert D., Yakova D., Hristov M., Yncheva T., Stancheva N., Tisheva S., Tokmakova M., Nikolov F., Gencheva D., Kunev B., Stoyanov M., Marchov D., Gelev V., Traykov V., Kisheva A., Tsvyatkov H., Shtereva R., Bakalska-Georgieva S., Slavcheva S., Yotov Y., Kubickova M., Joensen A.M., Gammelmark A., Rasmussen L.H., Dinesen P., Veno S.K., Sorensen B., Korsgaard A., Andersen K., Hellum C.F., Svenningsen A., Nyvad O., Wiggers P., May O., Aarup A., Graversen B., Jensen L., Andersen M., Svejgaard M., Vester S., Hansen S., Lynggaard V., Ciudad M., Vettus R., Maestre A., Castano S., Cheggour S., Poulard J., Mouquet V., Leparree S., Bouet J., Taieb J., Doucy A., Duquenne H., Furber A., Dupuis J., Rautureau J., Font M., Damiano P., Lacrimini M., Abalea J., Boismal S., Menez T., Mansourati J., Range G., Gorka H., Laure C., Vassaliere C., Elbaz N., Lellouche N., Djouadi K., Roubille F., Dietz D., Davy J., Granier M., Winum P., Leperchois-Jacquey C., Kassim H., Marijon E., Le Heuzey J., Fedida J., Maupain C., Himbert C., Gandjbakhch E., Hidden-Lucet F., Duthoit G., Badenco N., Chastre T., Waintraub X., Oudihat M., Lacoste J., Stephan C., Bader H., Delarche N., Giry L., Arnaud D., Lopez C., Boury F., Brunello I., Lefevre M., Mingam R., Haissaguerre M., Le Bidan M., Pavin D., Le Moal V., Leclercq C., Beitar T., Martel I., Schmid A., Sadki N., Romeyer-Bouchard C., Da Costa A., Arnault I., Boyer M., Piat C., Lozance N., Nastevska S., Doneva A., Fortomaroska Milevska B., Sheshoski B., Petroska K., Taneska N., Bakrecheski N., Lazarovska K., Jovevska S., Ristovski V., Antovski A., Lazarova E., Kotlar I., Taleski J., Kedev S., Zlatanovik N., Jordanova S., Bajraktarova Proseva T., Doncovska S., Maisuradze D., Esakia A., Sagirashvili E., Lartsuliani K., Natelashvili N., Gumberidze N., Gvenetadze R., Gotonelia N., Kuridze N., Papiashvili G., Menabde I., Gloggler S., Napp A., Lebherz C., Romero H., Schmitz K., Berger M., Zink M., Koster S., Sachse J., Vonderhagen E., Soiron G., Mischke K., Reith R., Schneider M., Rieker W., Boscher D., Taschareck A., Beer A., Oster D., Ritter O., Adamczewski J., Walter S., Frommhold A., Luckner E., Richter J., Schellner M., Landgraf S., Bartholome S., Naumann R., Schoeler J., Westermeier D., William F., Wilhelm K., Maerkl M., Oekinghaus R., Denart M., Kriete M., Tebbe U., Scheibner T., Gruber M., Gerlach A., Beckendorf C., Anneken L., Arnold M., Lengerer S., Bal Z., Uecker C., Fortsch H., Fechner S., Mages V., Martens E., Methe H., Schmidt T., Schaeffer B., Hoffmann B., Moser J., Heitmann K., Willems S., Klaus C., Lange I., Durak M., Esen E., Mibach F., Mibach H., Utech A., Gabelmann M., Stumm R., Landle V., Gartner C., Goerg C., Kaul N., Messer S., Burkhardt D., Sander C., Orthen R., Kaes S., Baumer A., Dodos F., Barth A., Schaeffer G., Gaertner J., Winkler J., Fahrig A., Aring J., Wenzel I., Steiner S., Kliesch A., Kratz E., Winter K., Schneider P., Haag A., Mutscher I., Bosch R., Taggeselle J., Meixner S., Schnabel A., Shamalla A., Hotz H., Korinth A., Rheinert C., Mehltretter G., Schon B., Schon N., Starflinger A., Englmann E., Baytok G., Laschinger T., Ritscher G., Gerth A., Dechering D., Eckardt L., Kuhlmann M., Proskynitopoulos N., Brunn J., Foth K., Axthelm C., Hohensee H., Eberhard K., Turbanisch S., Hassler N., Koestler A., Stenzel G., Kschiwan D., Schwefer M., Neiner S., Hettwer S., Haeussler-Schuchardt M., Degenhardt R., Sennhenn S., Brendel M., Stoehr A., Widjaja W., Loehndorf S., Logemann A., Hoskamp J., Grundt J., Block M., Ulrych R., Reithmeier A., Panagopoulos V., Martignani C., Bernucci D., Fantecchi E., Diemberger I., Ziacchi M., Biffi M., Cimaglia P., Frisoni J., Giannini I., Boni S., Fumagalli S., Pupo S., Di Chiara A., Mirone P., Pesce F., Zoccali C., Malavasi V.L., Mussagaliyeva A., Ahyt B., Salihova Z., Koshum-Bayeva K., Kerimkulova A., Bairamukova A., Lurina B., Zuzans R., Jegere S., Mintale I., Kupics K., Jubele K., Kalejs O., Vanhear K., Burg M., Cachia M., Abela E., Warwicker S., Tabone T., Xuereb R., Asanovic D., Drakalovic D., Vukmirovic M., Pavlovic N., Music L., Bulatovic N., Boskovic A., Uiterwaal H., Bijsterveld N., De Groot J., Neefs J., van den Berg N., Piersma F., Wilde A., Hagens V., Van Es J., Van Opstal J., Van Rennes B., Verheij H., Breukers W., Tjeerdsma G., Nijmeijer R., Wegink D., Binnema R., Said S., Philippens S., van Doorn W., Szili-Torok T., Bhagwandien R., Janse P., Muskens A., van Eck M., Gevers R., van der Ven N., Duygun A., Rahel B., Meeder J., Vold A., Holst Hansen C., Engset I., Dyduch-Fejklowicz B., Koba E., Cichocka M., Sokal A., Kubicius A., Pruchniewicz E., Kowalik-Sztylc A., Czapla W., Mroz I., Kozlowski M., Pawlowski T., Tendera M., Winiarska-Filipek A., Fidyk A., Slowikowski A., Haberka M., Lachor-Broda M., Biedron M., Gasior Z., Kolodziej M., Janion M., Gorczyca-Michta I., Wozakowska-Kaplon B., Stasiak M., Jakubowski P., Ciurus T., Drozdz J., Simiera M., Zajac P., Wcislo T., Zycinski P., Kasprzak J., Olejnik A., Harc-Dyl E., Miarka J., Pasieka M., Zieminska-Luc M., Bujak W., Sliwinski A., Grech A., Morka J., Petrykowska K., Prasal M., Hordynski G., Feusette P., Lipski P., Wester A., Streb W., Romanek J., Wozniak P., Chlebus M., Szafarz P., Stanik W., Zakrzewski M., Kazmierczak J., Przybylska A., Skorek E., Blaszczyk H., Stepien M., Szabowski S., Krysiak W., Szymanska M., Karasinski J., Blicharz J., Skura M., Halas K., Michalczyk L., Orski Z., Krzyzanowski K., Skrobowski A., Zielinski L., Tomaszewska-Kiecana M., Dluzniewski M., Kiliszek M., Peller M., Budnik M., Balsam P., Opolski G., Tyminska A., Ozieranski K., Wancerz A., Borowiec A., Majos E., Dabrowski R., Szwed H., Musialik-Lydka A., Leopold-Jadczyk A., Jedrzejczyk-Patej E., Koziel M., Mazurek M., Krzemien-Wolska K., Starosta P., Nowalany-Kozielska E., Orzechowska A., Szpot M., Staszel M., Almeida S., Pereira H., Brandao Alves L., Miranda R., Ribeiro L., Costa F., Morgado F., Carmo P., Galvao Santos P., Bernardo R., Adragao P., Ferreira da Silva G., Peres M., Alves M., Leal M., Cordeiro A., Magalhaes P., Fontes P., Leao S., Delgado A., Costa A., Marmelo B., Rodrigues B., Moreira D., Santos J., Santos L., Terchet A., Darabantiu D., Mercea S., Turcin Halka V., Pop Moldovan A., Gabor A., Doka B., Catanescu G., Rus H., Oboroceanu L., Bobescu E., Popescu R., Dan A., Buzea A., Daha I., Dan G., Neuhoff I., Baluta M., Ploesteanu R., Dumitrache N., Vintila M., Daraban A., Japie C., Badila E., Tewelde H., Hostiuc M., Frunza S., Tintea E., Bartos D., Ciobanu A., Popescu I., Toma N., Gherghinescu C., Cretu D., Patrascu N., Stoicescu C., Udroiu C., Bicescu G., Vintila V., Vinereanu D., Cinteza M., Rimbas R., Grecu M., Cozma A., Boros F., Ille M., Tica O., Tor R., Corina A., Jeewooth A., Maria B., Georgiana C., Natalia C., Alin D., Dinu-Andrei D., Livia M., Daniela R., Larisa R., Umaar S., Tamara T., Popescu M.I., Nistor D., Sus I., Coborosanu O., Alina-Ramona N., Dan R., Petrescu L., Ionescu G., Vacarescu C., Goanta E., Mangea M., Ionac A., Mornos C., Cozma D., Pescariu S., Solodovnicova E., Soldatova I., Shutova J., Tjuleneva L., Zubova T., Uskov V., Obukhov D., Rusanova G., Isakova N., Odinsova S., Arhipova T., Kazakevich E., Zavyalova O., Novikova T., Riabaia I., Zhigalov S., Drozdova E., Luchkina I., Monogarova Y., Hegya D., Rodionova L., Nevzorova V., Lusanova O., Arandjelovic A., Toncev D., Milanov M., Sekularac N., Zdravkovic M., Hinic S., Dimkovic S., Acimovic T., Saric J., Polovina M., Vujisic-Tesic B., Nedeljkovic M., Zlatar M., Asanin M., Vasic V., Popovic Z., Djikic D., Sipic M., Peric V., Dejanovic B., Milosevic N., Stevanovic A., Andric A., Pencic B., Pavlovic-Kleut M., Celic V., Pavlovic M., Petrovic M., Vuleta M., Petrovic N., Simovic S., Savovic Z., Milanov S., Davidovic G., Iric-Cupic V., Simonovic D., Stojanovic M., Stojanovic S., Mitic V., Ilic V., Petrovic D., Deljanin Ilic M., Ilic S., Stoickov V., Markovic S., Kovacevic S., Garcia Fernandez A., Perez Cabeza A., Anguita M., Tercedor Sanchez L., Mau E., Loayssa J., Ayarra M., Carpintero M., Roldan Rabadan I., Ortega M.G., Tello Montoliu A., Orenes Pinero E., Manzano Fernandez S., Romero Aniorte A., Veliz Martinez A., Quintana Giner M., Ballesteros G., Palacio M., Alcalde O., Garcia-Bolao I., Bertomeu Gonzalez V., Otero-Ravina F., Garcia Seara J., Gonzalez Juanatey J., Dayal N., Maziarski P., Gentil-Baron P., Koc M., Onrat E., Dural I.E., Yilmaz K., Ozin B., Kurklu S.T., Atmaca Y., Canpolat U., Tokgozoglu L., Dolu A.K., Demirtas B., Sahin D., Ozcan Celebi O., Gagirci G., Turk U.O., Ari H., Polat N., Toprak N., Sucu M., Akin Serdar O., Taha Alper A., Kepez A., Yuksel Y., Uzunselvi A., Yuksel S., Sahin M., Kayapinar O., Ozcan T., Kaya H., Yilmaz M.B., Kutlu M., Demir M., Gibbs C., Kaminskiene S., Bryce M., Skinner A., Belcher G., Hunt J., Stancombe L., Holbrook B., Peters C., Tettersell S., Senoo K., Russell K., Domingos P., Hussain S., Partridge J., Haynes R., Bahadur S., Brown R., McMahon S., McDonald J., Balachandran K., Singh R., Garg S., Desai H., Davies K., Goddard W., Galasko G., Rahman I., Chua Y., Payne O., Preston S., Brennan O., Pedley L., Whiteside C., Dickinson C., Brown J., Jones K., Benham L., Brady R., Buchanan L., Ashton A., Crowther H., Fairlamb H., Thornthwaite S., Relph C., McSkeane A., Poultney U., Kelsall N., Rice P., Wilson T., Wrigley M., Kaba R., Patel T., Young E., Law J., Runnett C., Thomas H., McKie H., Fuller J., Pick S., Sharp A., Hunt A., Thorpe K., Hardman C., Cusack E., Adams L., Hough M., Keenan S., Bowring A., Watts J., Zaman J., Goffin K., Nutt H., Beerachee Y., Featherstone J., Mills C., Pearson J., Stephenson L., Grant S., Wilson A., Hawksworth C., Alam I., Robinson M., Ryan S., Egdell R., Gibson E., Holland M., Leonard D., Mishra B., Ahmad S., Randall H., Hill J., Reid L., George M., McKinley S., Brockway L., Milligan W., Sobolewska J., Muir J., Tuckis L., Winstanley L., Jacob P., Kaye S., Morby L., Jan A., Sewell T., Boos C., Wadams B., Cope C., Jefferey P., Andrews N., Getty A., Suttling A., Turner C., Hudson K., Austin R., Howe S., Iqbal R., Gandhi N., Brophy K., Mirza P., Willard E., Collins S., Ndlovu N., Subkovas E., Karthikeyan V., Waggett L., Wood A., Bolger A., Stockport J., Evans L., Harman E., Starling J., Williams L., Saul V., Sinha M., Bell L., Tudgay S., Kemp S., Frost L., Ingram T., Loughlin A., Adams C., Adams M., Hurford F., Owen C., Miller C., Donaldson D., Tivenan H., Button H., Nasser A., Jhagra O., Stidolph B., Brown C., Livingstone C., Duffy M., Madgwick P., Roberts P., Greenwood E., Fletcher L., Beveridge M., Earles S., McKenzie D., Beacock D., Dayer M., Seddon M., Greenwell D., Luxton F., Venn F., Mills H., Rewbury J., James K., Roberts K., Tonks L., Felmeden D., Taggu W., Summerhayes A., Hughes D., Sutton J., Felmeden L., Khan M., Walker E., Norris L., O'Donohoe L., Mozid A., Dymond H., Lloyd-Jones H., Saunders G., Simmons D., Coles D., Cotterill D., Beech S., Kidd S., Wrigley B., Petkar S., Smallwood A., Jones R., Radford E., Milgate S., Metherell S., Cottam V., Buckley C., Broadley A., Wood D., Allison J., Rennie K., Balian L., Howard L., Pippard L., Board S., Pitt-Kerby T., Pulmonary medicine, Rehabilitation medicine, Internal medicine, Radiology and nuclear medicine, Cardiology, Pulmonary Medicine, General Practice, ACS - Heart failure & arrhythmias, Medical Oncology, Erasmus School of Health Policy & Management, Radiotherapy, Department of Technology and Operations Management, Virology, Erasmus School of Social and Behavioural Sciences, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Tax Law, Epidemiology, Neurosciences, Rheumatology, Erasmus School of Economics, Department of Business-Society Management, Pediatrics, Erasmus MC other, Orthopedics and Sports Medicine, Intensive Care, Department of Marketing Management, Clinical Genetics, Surgery, Econometrics, Research & Education, Radiology & Nuclear Medicine, Neurosurgery, Psychiatry, Department of Psychology, Education and Child Studies, Plastic and Reconstructive Surgery and Hand Surgery, Dermatology, Public Health, Gastroenterology & Hepatology, Erasmus School of Law, and Sociology

Subjects
Registrie, Atrial Fibrillation/drug therapy, Integrated management, Risk Factor, Atrial fibrillation, Clinical complexity, Outcomes, Anticoagulants, Humans, Registries, Risk Factors, Atrial Fibrillation, Stroke, Anticoagulant, General Medicine, Anticoagulants/therapeutic use, Stroke/complications, Outcome, Human
Abstract

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Published
2022
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28. Lateral malleolar fractures Weber Type A and B: does percutaneous intramedullary screw confer a solid alternative to the traditional neutralization plate?

Author

Sherif Hamdy Zawam, Mohamed Goda Mabrouk, and Mahmoud Ahmed El-Desouky

Subjects
Fracture Fixation, Internal, Treatment Outcome, Bone Screws, Humans, Orthopedics and Sports Medicine, Surgery, Ankle Fractures, Bone Plates, Fracture Fixation, Intramedullary, Retrospective Studies
Abstract

Purpose To compare the clinical results, complication rates, and radiographic outcome between both methods of fixation of lateral malleolar fractures: lateral neutralization plates and intramedullary fully threaded screws. Patients and methods This prospective case series study involved 73 patients with fractured lateral malleolus of type A, B according to Weber classification, to whom internal fixation was performed by either lateral plate and screws construct (Group A) or intramedullary screw (Group B). All patients were followed up for 12 months at least, with an average follow-up time of 12.7 months. Results There was no significant difference in the functional outcome score between both groups. The intramedullary screw group had a significantly shorter operative time and time to full union (P Conclusion The use of intramedullary fixation is a good alternative for plate fixation in low fibular fractures (Weber A and B). Although plate fixation provides an optimal anatomic reconstruction of the fractures, intramedullary fixation may have a lower risk of complications.

Published
2022
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29. Multimorbidity, guideline‐directed medical therapies, and associated outcomes among hospitalized heart failure patients

Author

Shinsuke, Takeuchi, Takashi, Kohno, Ayumi, Goda, Yasuyuki, Shiraishi, Masataka, Kawana, Mike, Saji, Yuji, Nagatomo, Yosuke, Nishihata, Makoto, Takei, Shintaro, Nakano, Kyoko, Soejima, Shun, Kohsaka, and Tsutomu, Yoshikawa

Subjects
Heart Failure, Hypertension, Humans, Multimorbidity, Kidney Diseases, Stroke Volume, Cardiology and Cardiovascular Medicine, Ventricular Function, Left
Abstract

Multimorbidity is common among heart failure (HF) patients and may attenuate guideline-directed medical therapy (GDMT). Multimorbid patients are under-represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes.We examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (50%) in a multicentre registry (West Tokyo HF Registry: WET-HF). Ten comorbid conditions in the WET-HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0-2: n = 451; 3-4: n = 787; and ≥5: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all-cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3-4: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13-1.77, P = 0.003; ≥5: HR 2.12, 95%CI 1.69-2.65, P 0.001; and reference: 0-2] and lower GDMT prescription rate (0-2: 69.2%; 3-4: 57.7%; and ≥5: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0-2: HR 0.53, 95%CI 0.35-0.78; P = 0.001; 3-4: HR 0.82, 95%CI 0.65-1.04, P = 0.095; and ≥5: HR 0.81, 95%CI 0.65-1.00, P = 0.053; P for interaction = 0.156).Comorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients.

Published
2022
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30. Projecting prevalence of frailty and dementia and the economic cost of care in Japan from 2016 to 2043: a microsimulation modelling study

Author

Megumi, Kasajima, Karen, Eggleston, Shoki, Kusaka, Hiroki, Matsui, Tomoki, Tanaka, Bo-Kyung, Son, Katsuya, Iijima, Kazuo, Goda, Masaru, Kitsuregawa, Jay, Bhattacharya, and Hideki, Hashimoto

Subjects
Male, Aging, Frailty, Japan, Prevalence, Public Health, Environmental and Occupational Health, Humans, Dementia, Female, Middle Aged, Aged
Abstract

Dementia and frailty often accompany one another in older age, requiring complex care and resources. Available projections provide little information on their joint impact on future health-care need from different segments of society and the associated costs. Using a newly developed microsimulation model, we forecast this situation in Japan as its population ages and decreases in size.In this microsimulation modelling study, we built a model that simulates an individual's status transition across 11 chronic diseases (including diabetes, coronary heart disease, and stroke) as well as depression, functional status, and self-reported health, by age, sex, and educational strata (less than high school, high school, and college and higher), on the basis of nationally representative health surveys and existing cohort studies. Using the simulation results, we projected the prevalence of dementia and frailty, life expectancy with these conditions, and the economic cost for formal and informal care over the period 2016-43 in the population of Japan aged 60 years and older.Between 2016 and 2043, life expectancy at age 65 years will increase from 23·7 years to 24·9 years in women and from 18·7 years to 19·9 years in men. Years spent with dementia will decrease from 4·7 to 3·9 years in women and 2·2 to 1·4 years in men. By contrast, years spent with frailty will increase from 3·7 to 4·0 years for women and 1·9 to 2·1 for men, and across all educational groups. By 2043, approximately 29% of women aged 75 years and older with a less than high school education are estimated to have both dementia and frailty, and so will require complex care. The expected need for health care and formal long-term care is anticipated to reach costs of US$125 billion for dementia and $97 billion for frailty per annum in 2043 for the country.Japan's Government and policy makers should consider the potential social challenges in caring for a sizable population of older people with frailty and dementia, and a widening disparity in the burden of those conditions by sex and by educational status. The future burden of dementia and frailty should be countered not only by curative and preventive technology innovation, but also by social policies to mitigate the health gap.Japan Society for the Promotion of Science, Hitachi - the University of Tokyo Laboratory for a sustainable society, and the National Institute of Ageing.

Published
2022
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31. Myofibroblasts are increased in the dorsal layer of the hypertrophic ligamentum flavum in lumbar spinal canal stenosis

Author

Nori Sato, Koichi Sairyo, Fumio Hayashi, Kosaku Higashino, Kazuta Yamashita, Fumitake Tezuka, Masatoshi Morimoto, and Yuichiro Goda

Subjects
Pathology, medicine.medical_specialty, Constriction, Pathologic, Muscle hypertrophy, Masson's trichrome stain, Spinal Stenosis, Fibrosis, Gene expression, medicine, Humans, Orthopedics and Sports Medicine, Myofibroblasts, Heat shock protein 47, Lumbar Vertebrae, biology, business.industry, Hypertrophy, medicine.disease, Reverse transcription polymerase chain reaction, Ligamentum Flavum, biology.protein, Surgery, Neurology (clinical), business, Spinal Canal, Myofibroblast, Immunostaining
Abstract

Background context Hypertrophy of the ligamentum flavum (LF) is a major contributor to the development of lumbar spinal canal stenosis (LSS). Although previous studies have identified some factors related to hypertrophy of the LF, the etiology remains unclear. It is well known that myofibroblasts have a key role in the pathology of fibrosis in other tissues, including the skin, liver, kidney, and lung. We hypothesized that myofibroblasts were also important players in the pathology of fibrosis in the LF. Purpose To elucidate the distribution and role of myofibroblasts in the hypertrophic LF. Study design A histological, immunohistochemical, and gene expression analysis of the LF in the human lumbar spine. Patient sample Hypertrophic LF tissue samples were collected from patients with LSS. Outcome Measures Histology, immunohistochemistry, microarray, reverse transcription-quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. Methods The degree of fibrosis in the dural and dorsal layers of the LF was evaluated by Masson's trichrome tissue staining. Collagen gene expression was evaluated by quantitative reverse transcription polymerase chain reaction. Immunostaining of αSMA was performed to evaluate localization of myofibroblasts in LF tissue. The association between gene expression of alpha-smooth muscle actin (αSMA) and that of several types of collagen was investigated. The signal activated on the dorsal side of LF was examined by gene set enrichment analysis using microarray data. Expression levels of αSMA and several types of collagen in LF fibroblasts were investigated under hypoxic conditions. Results In the histological study using Masson's trichrome staining, the fibrosis score was significantly higher in the dorsal layer than in the dural layer. Gene expression levels for several types of collagen (COL1A1, COL1A2, COL3A1, COL5A1, COL6A1, and COL11A1) and heat shock protein 47 (a collagen-specific chaperone) were significantly higher in the dorsal layer. Furthermore, immunohistochemistry revealed a significantly greater number of αSMA-stained cells in the dorsal layer. There was a strong correlation of αSMA mRNA expression with COL1A-1 in LF fibroblasts. Gene set enrichment analysis showed that the set of fibrosis-related gene signals, including those for epithelial-mesenchymal transition, hypoxia, and inflammation, were significantly upregulated in the dorsal layer compared with the dural layer. Under hypoxic stimulation, expression of αSMA and several types of collagen was increased in LF fibroblasts. Conclusions This study is the first to reveal that myofibroblast expression levels are higher in the dorsal layer of the LF than in the dural layer. We confirmed that hypertrophy of the LF in LSS is associated with increased expression of myofibroblasts in the dorsal layer. Hypoxia could be a cause of expression of myofibroblasts leading to fibrosis and finally to hypertrophy of the LF. Clinical significance The results of this study partially elucidate the molecular mechanisms of LF hypertrophy and suggest that myofibroblasts may be involved in age-related degeneration of the LF.

Published
2022
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32. Trends in Investigator-Initiated Clinical Studies at a University Hospital after Enforcement of the 2018 Clinical Trials Act in Japan

Author

Yasutaka Sato, Satoshi Sakaguchi, Kenshi Takechi, Masayuki Chuma, Kenta Yagi, Chikako Kane, Mitsuhiro Goda, Hirofumi Hamano, Yuki Aoe, Hiroshi Nokihara, Yoshiaki Kubo, Ichiro Hashimoto, and Hiroaki Yanagawa

Subjects
Pharmacology, Hospitals, University, Clinical Trials as Topic, trend, clinical research, Japan, Clinical Trials Act, Pharmaceutical Science, Humans, General Medicine, investigator
Abstract

In April 2018, the Clinical Trials Act pertaining to investigator-initiated clinical trials was passed in Japan. The purpose of this study was to investigate activity in investigator-initiated clinical studies before and after enforcement of the new Clinical Trials Act. This was done by analysing the records of the Ethics Committee of Tokushima University Hospital, which reviews studies based on the Japanese government's Ethical Guidelines for Medical and Health Research Involving Human Subjects prior to the Clinical Trials Act, and records of the Certified Review Board established at Tokushima University under the Clinical Trials Act in 2018. The number of new applications to these two review boards during fiscal years 2015-2017 (pre-Act) and fiscal years 2018 and 2019 (post-Act) were used as an indicator of activity in investigator-initiated clinical studies. The number of new applications to the Ethics Committee was 303, 261, 316, 303, and 249 in 2015, 2016, 2017, 2018, and 2019, respectively. The data show that the total number of new interventional studies decreased from 50.3 in average in 2015-2017 (pre-Act) to 42 in 2018 and 40 in 2019 (post-Act), respectively. These results suggest that fewer interventional studies were started following enforcement of the new Clinical Trials Act. To confirm this trend and identify contributing factors, further studies are required. In addition, possible way, such as broader contribution of clinical research coordinators, to promote clinical studies in the new Clinical Trials Act era should be examined.

Published
2022

33. Evaluation of the analytical performance of anti-SARS-CoV-2 antibody test kits distributed or developed in Japan

Author

Hiroko Shibata, Kazuko Nishimura, Takuya Maeda, Masamitsu Honma, Yukihiro Goda, Akiko Ishii-Watabe, and Yoshiro Saito

Subjects
Automation, Laboratory, SARS-CoV-2, Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, General Medicine, Antibodies, Viral, COVID-19 Serological Testing, Analytical Chemistry, Medical Laboratory Technology, Japan, Immunoglobulin G, Humans, Reagent Kits, Diagnostic, General Pharmacology, Toxicology and Pharmaceutics
Abstract

Background: With the spread of COVID-19, anti-SARS-CoV-2 antibody tests have been utilized. Herein we evaluated the analytical performance of anti-SARS-CoV-2 antibody test kits using a new reference standard prepared from COVID-19 patient sera. Methods: Fifty-seven kits in total (16 immunochromatography types, 11 ELISA types and 30 types for automated analyzers) were examined. By measuring serially diluted reference standards, the maximum dilution factor showing a positive result and its precision were investigated. Results: The measured cut-off titers varied largely depending on the antibody kit; however, the variability was small, with the titers obtained by each kit being within twofold in most cases. Conclusion: The current results suggest that a suitable kit should be selected depending on the intended purpose.

Published
2022
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34. Impact of renal impairment on atrial fibrillation

Author

Ding W. Y., Potpara T. S., Blomstrom-Lundqvist C., Boriani G., Marin F., Fauchier L., Lip G. Y. H., Tavazzi L., Maggioni A. P., Dan G. -A., Potpara T., Nabauer M., Kalarus Z., Goda A., Mairesse G., Shalganov T., Antoniades L., Taborsky M., Riahi S., Muda P., Garcia Bolao I., Piot O., Etsadashvili K., Simantirakis E., Haim M., Azhari A., Najafian J., Santini M., Mirrakhimov E., Kulzida K., Erglis A., Poposka L., Burg M., Crijns H., Erkuner O., Atar D., Lenarczyk R., Martins Oliveira M., Shah D., Serdechnaya E., Diker E., Lane D., Zera E., Ekmekciu U., Paparisto V., Tase M., Gjergo H., Dragoti J., Ciutea M., Ahadi N., Husseini Z. E., Raepers M., Leroy J., Haushan P., Jourdan A., Lepiece C., Desteghe L., Vijgen J., Koopman P., Van Genechten G., Heidbuchel H., Boussy T., De Coninck M., Van Eeckhoutte H., Bouckaert N., Friart A., Boreux J., Arend C., Evrard P., Stefan L., Hoffer E., Herzet J., Massoz M., Celentano C., Sprynger M., Pierard L., Melon P., Van Hauwaert B., Kuppens C., Faes D., Van Lier D., Van Dorpe A., Gerardy A., Deceuninck O., Xhaet O., Dormal F., Ballant E., Blommaert D., Yakova D., Hristov M., Yncheva T., Stancheva N., Tisheva S., Tokmakova M., Nikolov F., Gencheva D., Kunev B., Stoyanov M., Marchov D., Gelev V., Traykov V., Kisheva A., Tsvyatkov H., Shtereva R., Bakalska-Georgieva S., Slavcheva S., Yotov Y., Kubickova M., Marni Joensen A., Gammelmark A., Hvilsted Rasmussen L., Dinesen P., Krogh Veno S., Sorensen B., Korsgaard A., Andersen K., Fragtrup Hellum C., Svenningsen A., Nyvad O., Wiggers P., May O., Aarup A., Graversen B., Jensen L., Andersen M., Svejgaard M., Vester S., Hansen S., Lynggaard V., Ciudad M., Vettus R., Maestre A., Castano S., Cheggour S., Poulard J., Mouquet V., Leparree S., Bouet J., Taieb J., Doucy A., Duquenne H., Furber A., Dupuis J., Rautureau J., Font M., Damiano P., Lacrimini M., Abalea J., Boismal S., Menez T., Mansourati J., Range G., Gorka H., Laure C., Vassaliere C., Elbaz N., Lellouche N., Djouadi K., Roubille F., Dietz D., Davy J., Granier M., Winum P., Leperchois-Jacquey C., Kassim H., Marijon E., Le Heuzey J., Fedida J., Maupain C., Himbert C., Gandjbakhch E., Hidden-Lucet F., Duthoit G., Badenco N., Chastre T., Waintraub X., Oudihat M., Lacoste J., Stephan C., Bader H., Delarche N., Giry L., Arnaud D., Lopez C., Boury F., Brunello I., Lefevre M., Mingam R., Haissaguerre M., Le Bidan M., Pavin D., Le Moal V., Leclercq C., Beitar T., Martel I., Schmid A., Sadki N., Romeyer-Bouchard C., Da Costa A., Arnault I., Boyer M., Piat C., Lozance N., Nastevska S., Doneva A., Fortomaroska Milevska B., Sheshoski B., Petroska K., Taneska N., Bakrecheski N., Lazarovska K., Jovevska S., Ristovski V., Antovski A., Lazarova E., Kotlar I., Taleski J., Kedev S., Zlatanovik N., Jordanova S., Bajraktarova Proseva T., Doncovska S., Maisuradze D., Esakia A., Sagirashvili E., Lartsuliani K., Natelashvili N., Gumberidze N., Gvenetadze R., Gotonelia N., Kuridze N., Papiashvili G., Menabde I., Gloggler S., Napp A., Lebherz C., Romero H., Schmitz K., Berger M., Zink M., Koster S., Sachse J., Vonderhagen E., Soiron G., Mischke K., Reith R., Schneider M., Rieker W., Boscher D., Taschareck A., Beer A., Oster D., Ritter O., Adamczewski J., Walter S., Frommhold A., Luckner E., Richter J., Schellner M., Landgraf S., Bartholome S., Naumann R., Schoeler J., Westermeier D., William F., Wilhelm K., Maerkl M., Oekinghaus R., Denart M., Kriete M., Tebbe U., Scheibner T., Gruber M., Gerlach A., Beckendorf C., Anneken L., Arnold M., Lengerer S., Bal Z., Uecker C., Fortsch H., Fechner S., Mages V., Martens E., Methe H., Schmidt T., Schaeffer B., Hoffmann B., Moser J., Heitmann K., Willems S., Klaus C., Lange I., Durak M., Esen E., Mibach F., Mibach H., Utech A., Gabelmann M., Stumm R., Landle V., Gartner C., Goerg C., Kaul N., Messer S., Burkhardt D., Sander C., Orthen R., Kaes S., Baumer A., Dodos F., Barth A., Schaeffer G., Gaertner J., Winkler J., Fahrig A., Aring J., Wenzel I., Steiner S., Kliesch A., Kratz E., Winter K., Schneider P., Haag A., Mutscher I., Bosch R., Taggeselle J., Meixner S., Schnabel A., Shamalla A., Hotz H., Korinth A., Rheinert C., Mehltretter G., Schon B., Schon N., Starflinger A., Englmann E., Baytok G., Laschinger T., Ritscher G., Gerth A., Dechering D., Eckardt L., Kuhlmann M., Proskynitopoulos N., Brunn J., Foth K., Axthelm C., Hohensee H., Eberhard K., Turbanisch S., Hassler N., Koestler A., Stenzel G., Kschiwan D., Schwefer M., Neiner S., Hettwer S., Haeussler-Schuchardt M., Degenhardt R., Sennhenn S., Brendel M., Stoehr A., Widjaja W., Loehndorf S., Logemann A., Hoskamp J., Grundt J., Block M., Ulrych R., Reithmeier A., Panagopoulos V., Martignani C., Bernucci D., Fantecchi E., Diemberger I., Ziacchi M., Biffi M., Cimaglia P., Frisoni J., Giannini I., Boni S., Fumagalli S., Pupo S., Di Chiara A., Mirone P., Pesce F., Zoccali C., Malavasi V. L., Mussagaliyeva A., Ahyt B., Salihova Z., Koshum-Bayeva K., Kerimkulova A., Bairamukova A., Lurina B., Zuzans R., Jegere S., Mintale I., Kupics K., Jubele K., Kalejs O., Vanhear K., Cachia M., Abela E., Warwicker S., Tabone T., Xuereb R., Asanovic D., Drakalovic D., Vukmirovic M., Pavlovic N., Music L., Bulatovic N., Boskovic A., Uiterwaal H., Bijsterveld N., De Groot J., Neefs J., van den Berg N., Piersma F., Wilde A., Hagens V., Van Es J., van Opstal J., Van Rennes B., Verheij H., Breukers W., Tjeerdsma G., Nijmeijer R., Wegink D., Binnema R., Said S., Philippens S., van Doorn W., Szili-Torok T., Bhagwandien R., Janse P., Muskens A., van Eck M., Gevers R., van der Ven N., Duygun A., Rahel B., Meeder J., Vold A., Holst Hansen C., Engset I., Dyduch-Fejklowicz B., Koba E., Cichocka M., Sokal A., Kubicius A., Pruchniewicz E., Kowalik-Sztylc A., Czapla W., Mroz I., Kozlowski M., Pawlowski T., Tendera M., Winiarska-Filipek A., Fidyk A., Slowikowski A., Haberka M., Lachor-Broda M., Biedron M., Gasior Z., Kolodziej M., Janion M., Gorczyca-Michta I., Wozakowska-Kaplon B., Stasiak M., Jakubowski P., Ciurus T., Drozdz J., Simiera M., Zajac P., Wcislo T., Zycinski P., Kasprzak J., Olejnik A., Harc-Dyl E., Miarka J., Pasieka M., Zieminska-Luc M., Bujak W., Sliwinski A., Grech A., Morka J., Petrykowska K., Prasal M., Hordynski G., Feusette P., Lipski P., Wester A., Streb W., Romanek J., Wozniak P., Chlebus M., Szafarz P., Stanik W., Zakrzewski M., Kazmierczak J., Przybylska A., Skorek E., Blaszczyk H., Stepien M., Szabowski S., Krysiak W., Szymanska M., Karasinski J., Blicharz J., Skura M., Halas K., Michalczyk L., Orski Z., Krzyzanowski K., Skrobowski A., Zielinski L., Tomaszewska-Kiecana M., Dluzniewski M., Kiliszek M., Peller M., Budnik M., Balsam P., Opolski G., Tyminska A., Ozieranski K., Wancerz A., Borowiec A., Majos E., Dabrowski R., Szwed H., Musialik-Lydka A., Leopold-Jadczyk A., Jedrzejczyk-Patej E., Koziel M., Mazurek M., Krzemien-Wolska K., Starosta P., Nowalany-Kozielska E., Orzechowska A., Szpot M., Staszel M., Almeida S., Pereira H., Brandao Alves L., Miranda R., Ribeiro L., Costa F., Morgado F., Carmo P., Galvao Santos P., Bernardo R., Adragao P., Ferreira da Silva G., Peres M., Alves M., Leal M., Cordeiro A., Magalhaes P., Fontes P., Leao S., Delgado A., Costa A., Marmelo B., Rodrigues B., Moreira D., Santos J., Santos L., Terchet A., Darabantiu D., Mercea S., Turcin Halka V., Pop Moldovan A., Gabor A., Doka B., Catanescu G., Rus H., Oboroceanu L., Bobescu E., Popescu R., Dan A., Buzea A., Daha I., Dan G., Neuhoff I., Baluta M., Ploesteanu R., Dumitrache N., Vintila M., Daraban A., Japie C., Badila E., Tewelde H., Hostiuc M., Frunza S., Tintea E., Bartos D., Ciobanu A., Popescu I., Toma N., Gherghinescu C., Cretu D., Patrascu N., Stoicescu C., Udroiu C., Bicescu G., Vintila V., Vinereanu D., Cinteza M., Rimbas R., Grecu M., Cozma A., Boros F., Ille M., Tica O., Tor R., Corina A., Jeewooth A., Maria B., Georgiana C., Natalia C., Alin D., Dinu-Andrei D., Livia M., Daniela R., Larisa R., Umaar S., Tamara T., Ioachim Popescu M., Nistor D., Sus I., Coborosanu O., Alina-Ramona N., Dan R., Petrescu L., Ionescu G., Vacarescu C., Goanta E., Mangea M., Ionac A., Mornos C., Cozma D., Pescariu S., Solodovnicova E., Soldatova I., Shutova J., Tjuleneva L., Zubova T., Uskov V., Obukhov D., Rusanova G., Isakova N., Odinsova S., Arhipova T., Kazakevich E., Zavyalova O., Novikova T., Riabaia I., Zhigalov S., Drozdova E., Luchkina I., Monogarova Y., Hegya D., Rodionova L., Nevzorova V., Lusanova O., Arandjelovic A., Toncev D., Vukmirovic L., Radisavljevic M., Milanov M., Sekularac N., Zdravkovic M., Hinic S., Dimkovic S., Acimovic T., Saric J., Radovanovic S., Kocijancic A., Obrenovic-Kircanski B., Kalimanovska Ostric D., Simic D., Jovanovic I., Petrovic I., Polovina M., Vukicevic M., Tomasevic M., Mujovic N., Radivojevic N., Petrovic O., Aleksandric S., Kovacevic V., Mijatovic Z., Ivanovic B., Tesic M., Ristic A., Vujisic-Tesic B., Nedeljkovic M., Karadzic A., Uscumlic A., Prodanovic M., Zlatar M., Asanin M., Bisenic B., Vasic V., Popovic Z., Djikic D., Sipic M., Peric V., Dejanovic B., Milosevic N., Backovic S., Stevanovic A., Andric A., Pencic B., Pavlovic-Kleut M., Celic V., Pavlovic M., Petrovic M., Vuleta M., Petrovic N., Simovic S., Savovic Z., Milanov S., Davidovic G., Iric-Cupic V., Djordjevic D., Damjanovic M., Zdravkovic S., Topic V., Stanojevic D., Randjelovic M., Jankovic-Tomasevic R., Atanaskovic V., Antic S., Simonovic D., Stojanovic M., Stojanovic S., Mitic V., Ilic V., Petrovic D., Deljanin Ilic M., Ilic S., Stoickov V., Markovic S., Mijatovic A., Tanasic D., Radakovic G., Peranovic J., Panic-Jelic N., Vujadinovic O., Pajic P., Bekic S., Kovacevic S., Garcia Fernandez A., Perez Cabeza A., Anguita M., Tercedor Sanchez L., Mau E., Loayssa J., Ayarra M., Carpintero M., Roldan Rabadan I., Gil Ortega M., Tello Montoliu A., Orenes Pinero E., Manzano Fernandez S., Romero Aniorte A., Veliz Martinez A., Quintana Giner M., Ballesteros G., Palacio M., Alcalde O., Garcia-Bolao I., Bertomeu Gonzalez V., Otero-Ravina F., Garcia Seara J., Gonzalez Juanatey J., Dayal N., Maziarski P., Gentil-Baron P., Koc M., Onrat E., Dural I. E., Yilmaz K., Ozin B., Tan Kurklu S., Atmaca Y., Canpolat U., Tokgozoglu L., Dolu A. K., Demirtas B., Sahin D., Ozcan Celebi O., Gagirci G., Turk U. O., Ari H., Polat N., Toprak N., Sucu M., Akin Serdar O., Taha Alper A., Kepez A., Yuksel Y., Uzunselvi A., Yuksel S., Sahin M., Kayapinar O., Ozcan T., Kaya H., Yilmaz M. B., Kutlu M., Demir M., Gibbs C., Kaminskiene S., Bryce M., Skinner A., Belcher G., Hunt J., Stancombe L., Holbrook B., Peters C., Tettersell S., Shantsila A., Senoo K., Proietti M., Russell K., Domingos P., Hussain S., Partridge J., Haynes R., Bahadur S., Brown R., McMahon S., McDonald J., Balachandran K., Singh R., Garg S., Desai H., Davies K., Goddard W., Galasko G., Rahman I., Chua Y., Payne O., Preston S., Brennan O., Pedley L., Whiteside C., Dickinson C., Brown J., Jones K., Benham L., Brady R., Buchanan L., Ashton A., Crowther H., Fairlamb H., Thornthwaite S., Relph C., McSkeane A., Poultney U., Kelsall N., Rice P., Wilson T., Wrigley M., Kaba R., Patel T., Young E., Law J., Runnett C., Thomas H., McKie H., Fuller J., Pick S., Sharp A., Hunt A., Thorpe K., Hardman C., Cusack E., Adams L., Hough M., Keenan S., Bowring A., Watts J., Zaman J., Goffin K., Nutt H., Beerachee Y., Featherstone J., Mills C., Pearson J., Stephenson L., Grant S., Wilson A., Hawksworth C., Alam I., Robinson M., Ryan S., Egdell R., Gibson E., Holland M., Leonard D., Mishra B., Ahmad S., Randall H., Hill J., Reid L., George M., McKinley S., Brockway L., Milligan W., Sobolewska J., Muir J., Tuckis L., Winstanley L., Jacob P., Kaye S., Morby L., Jan A., Sewell T., Boos C., Wadams B., Cope C., Jefferey P., Andrews N., Getty A., Suttling A., Turner C., Hudson K., Austin R., Howe S., Iqbal R., Gandhi N., Brophy K., Mirza P., Willard E., Collins S., Ndlovu N., Subkovas E., Karthikeyan V., Waggett L., Wood A., Bolger A., Stockport J., Evans L., Harman E., Starling J., Williams L., Saul V., Sinha M., Bell L., Tudgay S., Kemp S., Frost L., Ingram T., Loughlin A., Adams C., Adams M., Hurford F., Owen C., Miller C., Donaldson D., Tivenan H., Button H., Nasser A., Jhagra O., Stidolph B., Brown C., Livingstone C., Duffy M., Madgwick P., Roberts P., Greenwood E., Fletcher L., Beveridge M., Earles S., McKenzie D., Beacock D., Dayer M., Seddon M., Greenwell D., Luxton F., Venn F., Mills H., Rewbury J., James K., Roberts K., Tonks L., Felmeden D., Taggu W., Summerhayes A., Hughes D., Sutton J., Felmeden L., Khan M., Walker E., Norris L., O'Donohoe L., Mozid A., Dymond H., Lloyd-Jones H., Saunders G., Simmons D., Coles D., Cotterill D., Beech S., Kidd S., Wrigley B., Petkar S., Smallwood A., Jones R., Radford E., Milgate S., Metherell S., Cottam V., Buckley C., Broadley A., Wood D., Allison J., Rennie K., Balian L., Howard L., Pippard L., Board S., Pitt-Kerby T., UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de cardiologie, Ding W.Y., Potpara T.S., Blomstrom-Lundqvist C., Boriani G., Marin F., Fauchier L., Lip G.Y.H., Tavazzi L., Maggioni A.P., Dan G.-A., Potpara T., Nabauer M., Kalarus Z., Goda A., Mairesse G., Shalganov T., Antoniades L., Taborsky M., Riahi S., Muda P., Garcia Bolao I., Piot O., Etsadashvili K., Simantirakis E., Haim M., Azhari A., Najafian J., Santini M., Mirrakhimov E., Kulzida K., Erglis A., Poposka L., Burg M., Crijns H., Erkuner O., Atar D., Lenarczyk R., Martins Oliveira M., Shah D., Serdechnaya E., Diker E., Lane D., Zera E., Ekmekciu U., Paparisto V., Tase M., Gjergo H., Dragoti J., Ciutea M., Ahadi N., Husseini Z.E., Raepers M., Leroy J., Haushan P., Jourdan A., Lepiece C., Desteghe L., Vijgen J., Koopman P., Van Genechten G., Heidbuchel H., Boussy T., De Coninck M., Van Eeckhoutte H., Bouckaert N., Friart A., Boreux J., Arend C., Evrard P., Stefan L., Hoffer E., Herzet J., Massoz M., Celentano C., Sprynger M., Pierard L., Melon P., Van Hauwaert B., Kuppens C., Faes D., Van Lier D., Van Dorpe A., Gerardy A., Deceuninck O., Xhaet O., Dormal F., Ballant E., Blommaert D., Yakova D., Hristov M., Yncheva T., Stancheva N., Tisheva S., Tokmakova M., Nikolov F., Gencheva D., Kunev B., Stoyanov M., Marchov D., Gelev V., Traykov V., Kisheva A., Tsvyatkov H., Shtereva R., Bakalska-Georgieva S., Slavcheva S., Yotov Y., Kubickova M., Marni Joensen A., Gammelmark A., Hvilsted Rasmussen L., Dinesen P., Krogh Veno S., Sorensen B., Korsgaard A., Andersen K., Fragtrup Hellum C., Svenningsen A., Nyvad O., Wiggers P., May O., Aarup A., Graversen B., Jensen L., Andersen M., Svejgaard M., Vester S., Hansen S., Lynggaard V., Ciudad M., Vettus R., Maestre A., Castano S., Cheggour S., Poulard J., Mouquet V., Leparree S., Bouet J., Taieb J., Doucy A., Duquenne H., Furber A., Dupuis J., Rautureau J., Font M., Damiano P., Lacrimini M., Abalea J., Boismal S., Menez T., Mansourati J., Range G., Gorka H., Laure C., Vassaliere C., Elbaz N., Lellouche N., Djouadi K., Roubille F., Dietz D., Davy J., Granier M., Winum P., Leperchois-Jacquey C., Kassim H., Marijon E., Le Heuzey J., Fedida J., Maupain C., Himbert C., Gandjbakhch E., Hidden-Lucet F., Duthoit G., Badenco N., Chastre T., Waintraub X., Oudihat M., Lacoste J., Stephan C., Bader H., Delarche N., Giry L., Arnaud D., Lopez C., Boury F., Brunello I., Lefevre M., Mingam R., Haissaguerre M., Le Bidan M., Pavin D., Le Moal V., Leclercq C., Beitar T., Martel I., Schmid A., Sadki N., Romeyer-Bouchard C., Da Costa A., Arnault I., Boyer M., Piat C., Lozance N., Nastevska S., Doneva A., Fortomaroska Milevska B., Sheshoski B., Petroska K., Taneska N., Bakrecheski N., Lazarovska K., Jovevska S., Ristovski V., Antovski A., Lazarova E., Kotlar I., Taleski J., Kedev S., Zlatanovik N., Jordanova S., Bajraktarova Proseva T., Doncovska S., Maisuradze D., Esakia A., Sagirashvili E., Lartsuliani K., Natelashvili N., Gumberidze N., Gvenetadze R., Gotonelia N., Kuridze N., Papiashvili G., Menabde I., Gloggler S., Napp A., Lebherz C., Romero H., Schmitz K., Berger M., Zink M., Koster S., Sachse J., Vonderhagen E., Soiron G., Mischke K., Reith R., Schneider M., Rieker W., Boscher D., Taschareck A., Beer A., Oster D., Ritter O., Adamczewski J., Walter S., Frommhold A., Luckner E., Richter J., Schellner M., Landgraf S., Bartholome S., Naumann R., Schoeler J., Westermeier D., William F., Wilhelm K., Maerkl M., Oekinghaus R., Denart M., Kriete M., Tebbe U., Scheibner T., Gruber M., Gerlach A., Beckendorf C., Anneken L., Arnold M., Lengerer S., Bal Z., Uecker C., Fortsch H., Fechner S., Mages V., Martens E., Methe H., Schmidt T., Schaeffer B., Hoffmann B., Moser J., Heitmann K., Willems S., Klaus C., Lange I., Durak M., Esen E., Mibach F., Mibach H., Utech A., Gabelmann M., Stumm R., Landle V., Gartner C., Goerg C., Kaul N., Messer S., Burkhardt D., Sander C., Orthen R., Kaes S., Baumer A., Dodos F., Barth A., Schaeffer G., Gaertner J., Winkler J., Fahrig A., Aring J., Wenzel I., Steiner S., Kliesch A., Kratz E., Winter K., Schneider P., Haag A., Mutscher I., Bosch R., Taggeselle J., Meixner S., Schnabel A., Shamalla A., Hotz H., Korinth A., Rheinert C., Mehltretter G., Schon B., Schon N., Starflinger A., Englmann E., Baytok G., Laschinger T., Ritscher G., Gerth A., Dechering D., Eckardt L., Kuhlmann M., Proskynitopoulos N., Brunn J., Foth K., Axthelm C., Hohensee H., Eberhard K., Turbanisch S., Hassler N., Koestler A., Stenzel G., Kschiwan D., Schwefer M., Neiner S., Hettwer S., Haeussler-Schuchardt M., Degenhardt R., Sennhenn S., Brendel M., Stoehr A., Widjaja W., Loehndorf S., Logemann A., Hoskamp J., Grundt J., Block M., Ulrych R., Reithmeier A., Panagopoulos V., Martignani C., Bernucci D., Fantecchi E., Diemberger I., Ziacchi M., Biffi M., Cimaglia P., Frisoni J., Giannini I., Boni S., Fumagalli S., Pupo S., Di Chiara A., Mirone P., Pesce F., Zoccali C., Malavasi V.L., Mussagaliyeva A., Ahyt B., Salihova Z., Koshum-Bayeva K., Kerimkulova A., Bairamukova A., Lurina B., Zuzans R., Jegere S., Mintale I., Kupics K., Jubele K., Kalejs O., Vanhear K., Cachia M., Abela E., Warwicker S., Tabone T., Xuereb R., Asanovic D., Drakalovic D., Vukmirovic M., Pavlovic N., Music L., Bulatovic N., Boskovic A., Uiterwaal H., Bijsterveld N., De Groot J., Neefs J., van den Berg N., Piersma F., Wilde A., Hagens V., Van Es J., van Opstal J., Van Rennes B., Verheij H., Breukers W., Tjeerdsma G., Nijmeijer R., Wegink D., Binnema R., Said S., Philippens S., van Doorn W., Szili-Torok T., Bhagwandien R., Janse P., Muskens A., van Eck M., Gevers R., van der Ven N., Duygun A., Rahel B., Meeder J., Vold A., Holst Hansen C., Engset I., Dyduch-Fejklowicz B., Koba E., Cichocka M., Sokal A., Kubicius A., Pruchniewicz E., Kowalik-Sztylc A., Czapla W., Mroz I., Kozlowski M., Pawlowski T., Tendera M., Winiarska-Filipek A., Fidyk A., Slowikowski A., Haberka M., Lachor-Broda M., Biedron M., Gasior Z., Kolodziej M., Janion M., Gorczyca-Michta I., Wozakowska-Kaplon B., Stasiak M., Jakubowski P., Ciurus T., Drozdz J., Simiera M., Zajac P., Wcislo T., Zycinski P., Kasprzak J., Olejnik A., Harc-Dyl E., Miarka J., Pasieka M., Zieminska-Luc M., Bujak W., Sliwinski A., Grech A., Morka J., Petrykowska K., Prasal M., Hordynski G., Feusette P., Lipski P., Wester A., Streb W., Romanek J., Wozniak P., Chlebus M., Szafarz P., Stanik W., Zakrzewski M., Kazmierczak J., Przybylska A., Skorek E., Blaszczyk H., Stepien M., Szabowski S., Krysiak W., Szymanska M., Karasinski J., Blicharz J., Skura M., Halas K., Michalczyk L., Orski Z., Krzyzanowski K., Skrobowski A., Zielinski L., Tomaszewska-Kiecana M., Dluzniewski M., Kiliszek M., Peller M., Budnik M., Balsam P., Opolski G., Tyminska A., Ozieranski K., Wancerz A., Borowiec A., Majos E., Dabrowski R., Szwed H., Musialik-Lydka A., Leopold-Jadczyk A., Jedrzejczyk-Patej E., Koziel M., Mazurek M., Krzemien-Wolska K., Starosta P., Nowalany-Kozielska E., Orzechowska A., Szpot M., Staszel M., Almeida S., Pereira H., Brandao Alves L., Miranda R., Ribeiro L., Costa F., Morgado F., Carmo P., Galvao Santos P., Bernardo R., Adragao P., Ferreira da Silva G., Peres M., Alves M., Leal M., Cordeiro A., Magalhaes P., Fontes P., Leao S., Delgado A., Costa A., Marmelo B., Rodrigues B., Moreira D., Santos J., Santos L., Terchet A., Darabantiu D., Mercea S., Turcin Halka V., Pop Moldovan A., Gabor A., Doka B., Catanescu G., Rus H., Oboroceanu L., Bobescu E., Popescu R., Dan A., Buzea A., Daha I., Dan G., Neuhoff I., Baluta M., Ploesteanu R., Dumitrache N., Vintila M., Daraban A., Japie C., Badila E., Tewelde H., Hostiuc M., Frunza S., Tintea E., Bartos D., Ciobanu A., Popescu I., Toma N., Gherghinescu C., Cretu D., Patrascu N., Stoicescu C., Udroiu C., Bicescu G., Vintila V., Vinereanu D., Cinteza M., Rimbas R., Grecu M., Cozma A., Boros F., Ille M., Tica O., Tor R., Corina A., Jeewooth A., Maria B., Georgiana C., Natalia C., Alin D., Dinu-Andrei D., Livia M., Daniela R., Larisa R., Umaar S., Tamara T., Ioachim Popescu M., Nistor D., Sus I., Coborosanu O., Alina-Ramona N., Dan R., Petrescu L., Ionescu G., Vacarescu C., Goanta E., Mangea M., Ionac A., Mornos C., Cozma D., Pescariu S., Solodovnicova E., Soldatova I., Shutova J., Tjuleneva L., Zubova T., Uskov V., Obukhov D., Rusanova G., Isakova N., Odinsova S., Arhipova T., Kazakevich E., Zavyalova O., Novikova T., Riabaia I., Zhigalov S., Drozdova E., Luchkina I., Monogarova Y., Hegya D., Rodionova L., Nevzorova V., Lusanova O., Arandjelovic A., Toncev D., Vukmirovic L., Radisavljevic M., Milanov M., Sekularac N., Zdravkovic M., Hinic S., Dimkovic S., Acimovic T., Saric J., Radovanovic S., Kocijancic A., Obrenovic-Kircanski B., Kalimanovska Ostric D., Simic D., Jovanovic I., Petrovic I., Polovina M., Vukicevic M., Tomasevic M., Mujovic N., Radivojevic N., Petrovic O., Aleksandric S., Kovacevic V., Mijatovic Z., Ivanovic B., Tesic M., Ristic A., Vujisic-Tesic B., Nedeljkovic M., Karadzic A., Uscumlic A., Prodanovic M., Zlatar M., Asanin M., Bisenic B., Vasic V., Popovic Z., Djikic D., Sipic M., Peric V., Dejanovic B., Milosevic N., Backovic S., Stevanovic A., Andric A., Pencic B., Pavlovic-Kleut M., Celic V., Pavlovic M., Petrovic M., Vuleta M., Petrovic N., Simovic S., Savovic Z., Milanov S., Davidovic G., Iric-Cupic V., Djordjevic D., Damjanovic M., Zdravkovic S., Topic V., Stanojevic D., Randjelovic M., Jankovic-Tomasevic R., Atanaskovic V., Antic S., Simonovic D., Stojanovic M., Stojanovic S., Mitic V., Ilic V., Petrovic D., Deljanin Ilic M., Ilic S., Stoickov V., Markovic S., Mijatovic A., Tanasic D., Radakovic G., Peranovic J., Panic-Jelic N., Vujadinovic O., Pajic P., Bekic S., Kovacevic S., Garcia Fernandez A., Perez Cabeza A., Anguita M., Tercedor Sanchez L., Mau E., Loayssa J., Ayarra M., Carpintero M., Roldan Rabadan I., Gil Ortega M., Tello Montoliu A., Orenes Pinero E., Manzano Fernandez S., Romero Aniorte A., Veliz Martinez A., Quintana Giner M., Ballesteros G., Palacio M., Alcalde O., Garcia-Bolao I., Bertomeu Gonzalez V., Otero-Ravina F., Garcia Seara J., Gonzalez Juanatey J., Dayal N., Maziarski P., Gentil-Baron P., Koc M., Onrat E., Dural I.E., Yilmaz K., Ozin B., Tan Kurklu S., Atmaca Y., Canpolat U., Tokgozoglu L., Dolu A.K., Demirtas B., Sahin D., Ozcan Celebi O., Gagirci G., Turk U.O., Ari H., Polat N., Toprak N., Sucu M., Akin Serdar O., Taha Alper A., Kepez A., Yuksel Y., Uzunselvi A., Yuksel S., Sahin M., Kayapinar O., Ozcan T., Kaya H., Yilmaz M.B., Kutlu M., Demir M., Gibbs C., Kaminskiene S., Bryce M., Skinner A., Belcher G., Hunt J., Stancombe L., Holbrook B., Peters C., Tettersell S., Shantsila A., Senoo K., Proietti M., Russell K., Domingos P., Hussain S., Partridge J., Haynes R., Bahadur S., Brown R., McMahon S., McDonald J., Balachandran K., Singh R., Garg S., Desai H., Davies K., Goddard W., Galasko G., Rahman I., Chua Y., Payne O., Preston S., Brennan O., Pedley L., Whiteside C., Dickinson C., Brown J., Jones K., Benham L., Brady R., Buchanan L., Ashton A., Crowther H., Fairlamb H., Thornthwaite S., Relph C., McSkeane A., Poultney U., Kelsall N., Rice P., Wilson T., Wrigley M., Kaba R., Patel T., Young E., Law J., Runnett C., Thomas H., McKie H., Fuller J., Pick S., Sharp A., Hunt A., Thorpe K., Hardman C., Cusack E., Adams L., Hough M., Keenan S., Bowring A., Watts J., Zaman J., Goffin K., Nutt H., Beerachee Y., Featherstone J., Mills C., Pearson J., Stephenson L., Grant S., Wilson A., Hawksworth C., Alam I., Robinson M., Ryan S., Egdell R., Gibson E., Holland M., Leonard D., Mishra B., Ahmad S., Randall H., Hill J., Reid L., George M., McKinley S., Brockway L., Milligan W., Sobolewska J., Muir J., Tuckis L., Winstanley L., Jacob P., Kaye S., Morby L., Jan A., Sewell T., Boos C., Wadams B., Cope C., Jefferey P., Andrews N., Getty A., Suttling A., Turner C., Hudson K., Austin R., Howe S., Iqbal R., Gandhi N., Brophy K., Mirza P., Willard E., Collins S., Ndlovu N., Subkovas E., Karthikeyan V., Waggett L., Wood A., Bolger A., Stockport J., Evans L., Harman E., Starling J., Williams L., Saul V., Sinha M., Bell L., Tudgay S., Kemp S., Frost L., Ingram T., Loughlin A., Adams C., Adams M., Hurford F., Owen C., Miller C., Donaldson D., Tivenan H., Button H., Nasser A., Jhagra O., Stidolph B., Brown C., Livingstone C., Duffy M., Madgwick P., Roberts P., Greenwood E., Fletcher L., Beveridge M., Earles S., McKenzie D., Beacock D., Dayer M., Seddon M., Greenwell D., Luxton F., Venn F., Mills H., Rewbury J., James K., Roberts K., Tonks L., Felmeden D., Taggu W., Summerhayes A., Hughes D., Sutton J., Felmeden L., Khan M., Walker E., Norris L., O'Donohoe L., Mozid A., Dymond H., Lloyd-Jones H., Saunders G., Simmons D., Coles D., Cotterill D., Beech S., Kidd S., Wrigley B., Petkar S., Smallwood A., Jones R., Radford E., Milgate S., Metherell S., Cottam V., Buckley C., Broadley A., Wood D., Allison J., Rennie K., Balian L., Howard L., Pippard L., Board S., Pitt-Kerby T., Pulmonary medicine, Rehabilitation medicine, Internal medicine, and Radiology and nuclear medicine

Subjects
Male, Medicin och hälsovetenskap, Clinical Biochemistry, Hemorrhage, Medical and Health Sciences, Biochemistry, Brain Ischemia, Risk Factors, Hemorrhage/chemically induced, death, Humans, Acute Coronary Syndrome/complications, atrial fibrillation, Renal Insufficiency, Registries, Acute Coronary Syndrome, Renal Insufficiency/chemically induced, Anticoagulants, General Medicine, thromboembolism, kidney failure, Stroke, Anticoagulants/therapeutic use, major bleeding, outcome, Female, Atrial Fibrillation/complications, chronic kidney disease, Stroke/complications
Abstract

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p 2 decrease), that was most notable in patients with eGFR 2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m 2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Published
2022
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35. Monthly trends and seasonality of hemodialysis treatment and outcomes of newly initiated patients from the national database (NDB) of Japan

Author

Ryoya Tsunoda, Naohiro Mitsutake, Tomoki Ishikawa, Jumpei Sato, Kazuo Goda, Naoki Nakashima, Masaru Kitsuregawa, and Kunihiro Yamagata

Subjects
Treatment Outcome, Japan, Renal Dialysis, Nephrology, Physiology, Physiology (medical), Humans, Kidney Failure, Chronic, Retrospective Studies
Abstract

The numbers of patients treated with hemodialysis (HD) in Japan are currently quantified by manual survey. As this method requires much effort from medical institutions and cannot achieve 100% response, a more practical method is required. We aimed to establish a novel method for determining the static and dynamic numbers of patients treated with HD.This observational study used the national medical billing database (termed NDB) of Japan, based on the records of the universal healthcare insurance system. Medical billing data registered in the NDB between April 2011 and March 2015 were analyzed. From 130 billion records, we extracted and analyzed records of patients who had undergone HD at least once per month. Patients' monthly condition was classified as newly initiated HD, chronic HD, or presumed death, using conditional expressions. We also investigated renal outcome and presumed survival in newly initiated HD patients.In the last month of the study period, 274,100 patients were identified as receiving chronic HD, which is estimated as 95% of the number of these patients identified in the manual survey so far. The monthly data showed clear seasonality in the incidence of transient HD, which increased in winter and decreased in summer.Analysis of a large national database revealed a significant increase in transient HD in winter and decrease in summer. Applied to additional epidemiological exploratory studies or clinical research, this analytical technique would enable collection of the dynamics of almost all HD patients nationwide.

Published
2022
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36. Laparoscopic sleeve gastrectomy for morbid obesity improves gut microbiota balance, increases colonic mucosal-associated invariant T cells and decreases circulating regulatory T cells

Author

Naoki, Fukuda, Toshiyasu, Ojima, Keiji, Hayata, Masahiro, Katsuda, Junya, Kitadani, Akihiro, Takeuchi, Taro, Goda, Yoko, Ueda, Hiroshi, Iwakura, Masahiro, Nishi, and Hiroki, Yamaue

Subjects
Inflammation, Leptin, T-Lymphocytes, Regulatory, Mucosal-Associated Invariant T Cells, Gastrointestinal Microbiome, Obesity, Morbid, Treatment Outcome, Gastrectomy, RNA, Ribosomal, 16S, Weight Loss, Humans, Laparoscopy, Surgery, Adiponectin
Abstract

Laparoscopic sleeve gastrectomy (LSG) for morbid obesity may improve gut microbiota balance and decrease chronic inflammation. This study examines the changes in gut microbiota and immune environment, including mucosal-associated invariant T cells (MAIT cells) and regulatory T cells (Treg cells) caused by LSG.Ten morbidly obese patients underwent LSG at our institution between December 2018 and March 2020. Flow cytometry for Th1/Th2/Th17 cells, Treg cells and MAIT cells in peripheral blood and colonic mucosa and 16S rRNA analysis of gut microbiota were performed preoperatively and then 12 months postoperatively.Twelve months after LSG, the median percent total weight loss was 30.3% and the median percent excess weight loss was 66.9%. According to laboratory data, adiponectin increased, leptin decreased, and chronic inflammation improved after LSG. In the gut microbiota, Bacteroidetes and Fusobacteria increased after LSG, and indices of alpha diversity increased after LSG. In colonic mucosa, the frequency of MAIT cells increased after LSG. In peripheral blood, the frequency of Th1 cells and effector Treg cells decreased after LSG.After LSG for morbid obesity, improvement in chronic inflammation in obesity is suggested by change in the constituent bacterial species, increase in the diversity of gut microbiota, increase in MAIT cells in the colonic mucosa, and decrease in effector Treg cells in the peripheral blood.

Published
2022
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37. Hospitalizations and in-hospital outcomes in patients with ST-elevation myocardial infarction during the coronavirus disease 2019 pandemic: The Albanian experience

Author

Leonard, Simoni, Ilir, Alimehmeti, Mirald, Gina, Astrit, Ceka, Ermir, Tafaj, Alban, Dibra, and Artan, Goda

Subjects
Hospitalization, Percutaneous Coronary Intervention, SARS-CoV-2, RC666-701, Communicable Disease Control, Diseases of the circulatory (Cardiovascular) system, COVID-19, Humans, ST Elevation Myocardial Infarction, cardiovascular diseases, Pandemics, Hospitals, Original Investigation
Abstract

OBJECTIVE: Global studies report a significant decline in ST-elevation myocardial infarction (STEMI) related hospitalization rates during the coronavirus disease 2019 (COVID-19) pandemic outbreak. However, there have been several divergent reports on hospital outcomes. In this study, we aim to investigate the impact of the COVID 19 outbreak on hospitalizations because of STEMI and in-hospital outcomes in Albania. METHODS: This was a retrograde study, collecting data for hospitalizations because of STEMI from March 9, (first COVID 19 case in our country) to April 30, 2020, (period of total lockdown) compared with the same period in 2019 at our center. The incidence rate ratio (IRR) was used to compare admissions because of STEMI and procedures and the risk ratio (RR) to compare mortality and other complication rates. RESULTS: Admissions for STEMI declined during the COVID-19 period from a total of 217 in 2019 to 156 in 2020 (−28.1%) representing IRR 0.719 (p=0.033). PCIs also reduced from 168 procedures in 2019 to 113 in 2020 (−33%), representing an IRR of 0.67, p=0.021. The time from symptom onset to arrival at our intensive care unit was significantly higher in 2020 compared to 2019 (925.6±1097 vs. 438.7±385 minutes, p

Published
2022
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38. Clinical Audit of Survival Outcomes and Prognostic Factors in Adolescents and Adults with Medulloblastoma

Author

Nazia Bano, Jayant Sastri Goda, Rahul Krishnatry, Aliasgar Moiyadi, Tejpal Gupta, Neelam Shirsat, Ayushi Sahay, Girish Chinnaswamy, Roshankumar Patil, Vijay Patil, Rakesh Jalali, Abhishek Chatterjee, Archya Dasgupta, Madan Maitre, and Sridhar Epari

Subjects
Adult, Oncology, medicine.medical_specialty, Adult Medulloblastoma, Multivariate analysis, Adolescent, Disease, Internal medicine, medicine, Adjuvant therapy, Humans, Young adult, Cerebellar Neoplasms, Child, Retrospective Studies, Medulloblastoma, Clinical Audit, business.industry, Medical record, Cancer, Original Articles, Prognosis, medicine.disease, Pediatrics, Perinatology and Child Health, business
Abstract

Purpose: Medulloblastomas, comprising 20%–25% of all primary brain tumors in children are much rarer in adulthood. Disease biology varies substantially across different age groups; however, owing to rarity, adults with medulloblastoma are traditionally treated using pediatric protocols. This is a retrospective audit of adolescent and adult medulloblastoma from a comprehensive cancer center. Methods: Data regarding demography, clinical presentation, imaging characteristics, histopathological features, molecular profiling, risk stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event outcomes were analyzed using Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analysis of relevant prognostic factors was done with p value

Published
2022
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39. Measurable residual disease, FLT3‐ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1‐mutated acute myeloid leukemia

Author

Rama Al Hamed, Myriam Labopin, Etienne Daguindau, Riitta Niittyvuopio, Anne Huynh, Gerard Socié, Micha Srour, Jean Henri Bourhis, Nicolaus Kröger, Eleni Tholouli, Goda Choi, Xavier Poiré, Hans Martin, Marie‐Thérèse Rubio, Pavel Jindra, Didier Blaise, Dietrich Beelen, Hélène Labussière‐Wallet, Arnon Nagler, Ali Bazarbachi, Mohamad Mohty, Albert Einstein College of Medicine [New York], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital JeanMinjoz, Helsinki University Central Hospital [Finland] (HUCH), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, Université de Lille, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Manchester Royal Infirmary, University of Manchester [Manchester], University of Groningen [Groningen], Cliniques universitaires St Luc [Bruxelles], Goethe-Universität Frankfurt am Main, Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Medicine Charles University and General Faculty Hospital in Prague, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital [Essen, Germany], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Chaim Sheba Medical Center, American University of Beirut [Beyrouth] (AUB), Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Comprehensive Cancer Center [Helsinki, Finland], Helsinki University Hospital [Finland] (HUS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Medical Center Groningen [Groningen] (UMCG), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Charles University Hospital Pilsen, Dept. of Bone Marrow Transplantation, University Hospital, Essen, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Gestionnaire, Hal Sorbonne Université, NUNES, Jacques A, HUS Comprehensive Cancer Center, Clinicum, and Department of Oncology

Subjects
Adult, FLT3‐ITD, Cancer Research, FLT3-ITD, 3122 Cancers, Medizin, [SDV.CAN]Life Sciences [q-bio]/Cancer, acute myeloid leukemia, RELAPSE, [SDV.CAN] Life Sciences [q-bio]/Cancer, AML, Recurrence, hemic and lymphatic diseases, VERSUS-HOST-DISEASE, Humans, Radiology, Nuclear Medicine and imaging, NUCLEOPHOSMIN NPM1, RC254-282, Retrospective Studies, ACUTE MYELOGENOUS LEUKEMIA, Hematopoietic Stem Cell Transplantation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ADULTS, Prognosis, NPM-1 mutation, NPM‐1 mutation, SORAFENIB, Leukemia, Myeloid, Acute, DEFINITION, Oncology, fms-Like Tyrosine Kinase 3, Mutation, SURVIVAL, minimal residual disease, Nucleophosmin
Abstract

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age >= 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10(-5) and HR 1.71, p < 10(-5), respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score >= 90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10(-5)), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score >= 90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.

Published
2022
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40. Impact of Left Ventricular Chamber Size on Outcome in Heart Failure with Preserved Ejection Fraction

Author

Shou Ogawa, Yuji Nagatomo, Makoto Takei, Mike Saji, Ayumi Goda, Takashi Kohno, Shintaro Nakano, Yosuke Nishihata, Yukinori Ikegami, Satoshi Shoji, Yasuyuki Shiraishi, Shun Kohsaka, and Tsutomu Yoshikawa

Subjects
Aged, 80 and over, Heart Failure, Male, Heart Ventricles, Stroke Volume, General Medicine, Prognosis, Hospitalization, Japan, Echocardiography, Outcome Assessment, Health Care, Humans, Female, Registries, Cardiology and Cardiovascular Medicine, Aged
Abstract

Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heterogeneity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thoroughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF.A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm.Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e', and tricuspid regurgitation pressure gradient and greater severity of mitral regurgitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009).In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

Published
2022
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41. A Rare Case of Brain Metastasis of Thymic Carcinoma

Author

Takaaki, Mitsui, Ryosuke, Matsuda, Kazuo, Goda, Hiroe, Itami, Ichiro, Nakagawa, and Hiroyuki, Nakase

Subjects
Aged, 80 and over, Cancer Research, Thymoma, Brain Neoplasms, Thymus Neoplasms, General Medicine, Radiosurgery, Magnetic Resonance Imaging, Fatal Outcome, Japan, Oncology, Disease Progression, Humans, Female
Abstract

Thymic carcinoma is a rare cancer that often metastasizes to the liver and kidneys but rarely to the brain.We present a rare case of an 81-year-old woman with multiple cerebellar metastases of thymic carcinoma. She was initially diagnosed with stage IVb thymic carcinoma based on biopsy examination of a lesion in the anterior mediastinum. The patient refused to undergo treatment at the time. Six months later, she presented with gait disturbance and nausea. Contrast-enhanced magnetic resonance imaging revealed multiple cerebellar metastases. She underwent craniotomy and resection of the left cerebellar metastasis. Postoperative histological examination confirmed metastasis of the original thymic carcinoma. The patient underwent additional stereotactic radiotherapy for the cavity of the cerebellar metastasis and the small cerebellar metastatic lesions. Seven months after radiotherapy, she died due to progression of the thymic carcinoma.We believe that these findings add important information to the literature on this rare entity.

Published
2022
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42. Effects of S-PRG filler eluate on MMP-1 and MMP-3 secretion by human gingival fibroblasts

Author

Seiji Goda, Lan Lan, Hiroshi Inoue, Zhengjian Ke, Yan Yang, Dan Mao, and Feng Zheng

Subjects
MAPK/ERK pathway, food.ingredient, Materials science, p38 mitogen-activated protein kinases, medicine.medical_treatment, Gingiva, Fibroblasts, Matrix metalloproteinase, Molecular biology, food, Cytokine, Glass Ionomer Cements, Ceramics and Composites, medicine, Humans, Phosphorylation, Matrix Metalloproteinase 3, Secretion, Tumor necrosis factor alpha, Matrix Metalloproteinase 1, Filler (animal food), General Dentistry
Abstract

The aim of this study was to investigate the effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) filler eluate on Matrix metalloproteinase (MMP)-1 and MMP-3 secretion by human gingival fibroblasts (HGF). The S-PRG filler eluate contains 6 ions (F, Na, Al, B, Sr and Si) released from the S-PRG filler. The S-PRG filler eluate stimulation induced a slight secretion of MMP-1 and MMP-3 by HGF. It also enhanced the phosphorylation of p38 and ERK. The increase in MMP-1 and MMP-3 secretion by the inflammatory cytokine TNF-α was suppressed by the S-PRG filler eluate. TNF-α-induced increases in the phosphorylation of ERK were slightly enhanced by S-PRG filler eluate. These findings may prompt the development of new therapeutic agents for oral inflammation with materials composed of S-PRG filler eluate.

Published
2022
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43. Urine albumin-to-creatinine ratio on admission predicts early rehospitalization in patients with acute decompensated heart failure

Author

Yuki, Matsumoto, Yoshiyuki, Orihara, Masanori, Asakura, Kyung-Duk, Min, Yoshitaka, Okuhara, Kohei, Azuma, Koichi, Nishimura, Isamu, Sunayama, Kazunori, Kashiwase, Yoshiro, Naito, Akiko, Goda, and Masaharu, Ishihara

Subjects
Aged, 80 and over, Heart Failure, Male, Albumins, Creatinine, Natriuretic Peptide, Brain, Humans, Female, Prospective Studies, Urinalysis, Prognosis, Cardiology and Cardiovascular Medicine
Abstract

Detecting high-risk patients for early rehospitalization is crucial in heart failure patient care. An association of albuminuria with cardiovascular events is well known. However, its predictive impact on rehospitalization for acute decompensated heart failure (ADHF) remains unknown. In this study, 190 consecutive patients admitted due to ADHF between 2017 and April 2019 who underwent urinalysis were enrolled. Among them, 140 patients from whom urine albumin-to-creatinine ratio (UACR) was measured with spot urine samples on admission were further analyzed. The association between UACR and rehospitalization due to HF during 1 year after discharge was evaluated. The mean age of 140 participants was 77.6 years and 55% were men. Only 18% (n = 25) of patients presented with normoalbuminuria (UACR 30 mg/g∙creatinine), whereas 59% (n = 83) and 23% (n = 32) showed microalbuminuria (UACR 30-300 mg/g·creatinine) and macroalbuminuria (UACR 300 mg/g·creatinine), respectively. The level of UACR on admission was correlated with the risk of subsequent rehospitalization due to HF (p = 0.017). The receiver operating characteristic analysis indicated that the best cut-off values for the UACR and B-type natriuretic peptide (BNP) levels to predict ADHF rehospitalization were 50 mg/g·creatinine and 824 pg/ml, respectively. When the patients were divided into four groups using both cut-off values, the individual predictive impacts of UACR and BNP on rehospitalization were comparable. Patients with both elevated UACR and BNP levels had a higher rate of HF rehospitalization than those with elevated BNP levels alone (p 0.05). The combination of both values enabled more accurate prediction of HF rehospitalization than BNP levels alone. In conclusion, UACR could be a new useful biomarker to predict HF rehospitalization in patients with ADHF, especially in combination with the levels of BNP, and should be further evaluated in a prospective study.

Published
2022
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44. Power Doppler artifacts in evaluating inflammatory arthritis of small joints: comparison with a superb microvascular imaging technique

Author

Goda Seskute, Marija Montvydaite, and Irena Butrimiene

Subjects
Arthritis, Microvessels, Internal Medicine, Humans, Ultrasonography, Doppler, Radiology, Nuclear Medicine and imaging, General Medicine, Artifacts, Ultrasonography
Abstract

Conventional Doppler techniques provide clinical information about tissue vascularisation, but they have limitations in detecting low-velocity blood flow. The innovative Doppler technique called superb microvascular imaging provides visualization of microvascular flow never seen before with the ultrasound. The new tool suppresses the noise caused by motion artifacts with an innovative filter system without removing the weak signal arising from small vessel flow, hence it achieves a greater sensitivity than power Doppler. Explanation of motion artifact genesis reveals SMI imaging principles and helps to distinguish false-positive results. Due to the higher SMI sensitivity to flow, there are nuances in the interpretation of other artifacts as well as motion. The paper presents commonly encountered artifacts of power Doppler compared with a novel microvascular imaging technique focused on a small joints inflammation. The main attention is intent on the practical recommendations for ultrasound machine settings and evaluation of comparable images.

Published
2022
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46. Venous Invasion Is a Risk Factor for Recurrence of pT1 Gastric Cancer with Lymph Node Metastasis

Author

Akihiro Takeuchi, Toshiyasu Ojima, Masahiro Katsuda, Keiji Hayata, Taro Goda, Junya Kitadani, Shinta Tominaga, Naoki Fukuda, Tomoki Nakai, and Hiroki Yamaue

Subjects
Gastrectomy, Risk Factors, Stomach Neoplasms, Lymphatic Metastasis, Gastroenterology, Humans, Lymph Node Excision, Neoplasm Invasiveness, Surgery, Lymph Nodes, Prognosis, Retrospective Studies
Abstract

Postoperative adjuvant therapy for early gastric cancer (EGC) has not been widely studied, and there are differing indications for postoperative adjuvant therapy between Western and Asian countries. Japanese gastric cancer treatment guidelines do not recommend adjuvant chemotherapy for EGC, but it is unclear whether surgery alone is the most appropriate treatment.This is a single-center retrospective study of 1001 consecutive patients who underwent radical gastrectomy for pT1 gastric cancer between 1999 and 2013 at the Wakayama Medical University Hospital.Recurrence was observed in 12 patients, nine of whom as the result of hematogenous metastasis. In all patients with pT1 gastric cancer (n = 1001), lymph node metastasis was identified as an independent predictive factor for recurrence (hazard ratio [HR] = 10.910, P = 0.002). In patients with pT1N + gastric cancer, however, the 5-year disease-specific survival (DSS) rate was still high, 90.8%. In patients with pT1N + gastric cancer (n = 97), the presence of venous invasion (pT1N + v +) was identified by univariate and multivariate analyses as an independent risk factor for recurrence (HR = 4.791, P = 0.032). In patients with venous invasion, the 5-year DSS rate was significantly lower than that in those without venous invasion (79.3% vs. 95.2%, P = 0.018).Long-term prognosis of patients with EGC with lymph node metastasis is good, but venous invasion is associated with a higher risk of recurrence. Selective application of postoperative adjuvant chemotherapy for pT1N + v + gastric cancer may efficiently improve prognosis among patients with EGC.

Published
2022
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47. Deep imaging flow cytometry

Author

Kangrui Huang, Hiroki Matsumura, Yaqi Zhao, Maik Herbig, Dan Yuan, Yohei Mineharu, Jeffrey Harmon, Justin Findinier, Mai Yamagishi, Shinsuke Ohnuki, Nao Nitta, Arthur R. Grossman, Yoshikazu Ohya, Hideharu Mikami, Akihiro Isozaki, and Keisuke Goda

Subjects
Imaging, Three-Dimensional, Image Processing, Computer-Assisted, Biomedical Engineering, Humans, Cell Count, Bioengineering, General Chemistry, Flow Cytometry, Biochemistry, Algorithms, In Situ Hybridization, Fluorescence
Abstract

Imaging flow cytometry (IFC) has become a powerful tool for diverse biomedical applications by virtue of its ability to image single cells in a high-throughput manner. However, there remains a challenge posed by the fundamental trade-off between throughput, sensitivity, and spatial resolution. Here we present deep-learning-enhanced imaging flow cytometry (dIFC) that circumvents this trade-off by implementing an image restoration algorithm on a virtual-freezing fluorescence imaging (VIFFI) flow cytometry platform, enabling higher throughput without sacrificing sensitivity and spatial resolution. A key component of dIFC is a high-resolution (HR) image generator that synthesizes "virtual" HR images from the corresponding low-resolution (LR) images acquired with a low-magnification lens (10×/0.4-NA). For IFC, a low-magnification lens is favorable because of reduced image blur of cells flowing at a higher speed, which allows higher throughput. We trained and developed the HR image generator with an architecture containing two generative adversarial networks (GANs). Furthermore, we developed dIFC as a method by combining the trained generator and IFC. We characterized dIFC using

Published
2022
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48. Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children

Author

Algirdas Dagys, Goda Laucaitytė, Augusta Volkevičiūtė, Silvijus Abramavičius, Rimantas Kėvalas, Astra Vitkauskienė, and Lina Jankauskaitė

Subjects
C-Reactive Protein, Fever, Interleukin-6, Child, Preschool, Sepsis, Humans, Interleukin-2, Bacterial Infections, General Medicine, Child, Biomarkers, Interleukin-10
Abstract

While most feverish children have self-limiting diseases, 5-10% develop a serious and potentially life-threatening bacterial infection (BI). Due to potential risk, prompt recognition of BI and sepsis in the pediatric emergency department (PED) remains a clinical priority. The aim of the study was to evaluate the role of certain cytokines and chemokines separately and in combination with routine blood tests in early BI and sepsis diagnostics at PED.We prospectively studied children younger than 5 presenting to the PED with fever lasting for under 12 hours with high risk for serious illness. Clinical data, routine blood analysis, and inflammatory cytokine and chemokine panels were evaluated for their diagnostic abilities. Two separate analyses were carried out on the patients' data: one contrasting BI and viral infection (VI) groups, the other comparing septic and non-septic patients.The sample comprised 70 patients (40% with BI). IL-2 was found to be the most specific biomarker to identify BI with specificity of 100%. The best discriminative ability was demonstrated by combining IL-2, IL-6, CRP, WBC, and neutrophil count: AUC 0.942 (95% Cl 0.859-0.984). IL-10 exhibited a greater AUC (0.837. 95% CI: 0.730-0.915 p0.05) than CRP (0.807. 95% CI: 0.695-0.895 p0.05) when predicting sepsis and showed high specificity (98%) and moderate sensitivity (75%).IL-6 and IL-2 could increase the diagnostic ability of routine blood tests for predicting BI, as IL-10 raises specificity for recognizing sepsis in the early hours of disease onset.

Published
2022
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49. Inactivation of human norovirus by chlorous acid water, a novel chlorine-based disinfectant

Author

Tomomi Kuwahara, Hitoshi Yamaoka, A. Hajime Koyama, Tomohiko Fujisawa, Tamiko Nagao, Haruyuki Nakayama-Imaohji, Hisataka Goda, and Ayano Tada

Subjects
Microbiology (medical), Disinfectant, chemistry.chemical_element, medicine.disease_cause, chemistry.chemical_compound, Chlorides, medicine, Chlorine, Animals, Humans, Pharmacology (medical), Food science, Bovine serum albumin, chemistry.chemical_classification, Sheep, Chlorous acid, biology, Norovirus, Water, RNA, Amino acid, Infectious Diseases, chemistry, Sodium hypochlorite, biology.protein, Disinfectants
Abstract

Introduction Human norovirus (HuNoV) is a leading cause of infectious gastroenteritis. Since HuNoV shows resistance to alcohol, chlorine-based sanitizers are applied to decontaminate the virus on environmental surfaces. Chlorous acid water (CA) has been recently approved as a novel chlorine-based disinfectant categorized as a Type 2 OTC medicine in Japan. In this study, we aimed to evaluate the capability of CA to inactivate HuNoV. Methods HuNoV (genogroups GII.2 and GII.4) was exposed to the test disinfectants including CA and sodium hypochlorite (NaClO), and the residual RNA copy was measured by reverse transcription quantitative PCR (RT-qPCR) after pretreatment with RNase. In addition, the log10 reduction of HuNoV RNA copy number by CA and NaClO was compared in the presence of bovine serum albumin (BSA), sheep red blood cells (SRBC), polypeptone, meat extract or amino acids to evaluate the stability of these disinfectants under organic-matter-rich conditions. Results In the absence of organic substances, CA with 200 ppm free available chlorine provided >3.0 log10 reduction in the HuNoV RNA copy number within 5 min. Even under high organic matter load (0.3% each of BSA and SRBC or 0.5% polypeptone), 200 ppm CA achieved >3.0 log10 reduction in HuNoV RNA copy number while less than 1.0 log10 reduction was observed with 1,000 ppm sodium hypochlorite (NaClO) in the presence of 0.5% polypeptone. CA reacted with only cysteine, histidine and glutathione while NaClO reacted with all of the amino acids tested. Conclusions CA is an effective disinfectant to inactivate HuNoV under organic-matter-rich conditions.

Published
2022
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50. Direct inhibition of the first PDZ domain of ZO-1 by glycyrrhizin is a possible mechanism of tight junction opening of Caco-2 cells

Author

Emi Hibino, Natsuko Goda, Misaki Hisada, Takeshi Tenno, and Hidekazu Hiroaki

Subjects
Zonula Occludens-1 Protein, Humans, PDZ Domains, General Medicine, Caco-2 Cells, Glycyrrhizic Acid, Tight Junctions, Food Science
Abstract

Glycyrrhizin (GL) is known to exhibit a variety of useful pharmacological activities, including anti-inflammation, anti-hepatotoxicity, and enhancement of intestinal drug absorption. GL has been reported to modify the assembly of actin filaments, thereby modulating tight junction (TJ) integrity, but the detailed molecular mechanisms of this remain unclear. In this study, we first found that GL binds to the first PDZ domain of zonula occludens-1 (ZO-1(PDZ1)) through NMR experiments. The structure of the GL-ZO-1(PDZ1) complex was then constructed using HADDOCK with the transferred nuclear Overhauser effect-based inter-hydrogen distance constraints as well as restrictions on the interfacial residues identified from

Published
2022
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