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5. Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach

Author

Fonseca, Dennyson Leandro M., Filgueiras, Igor Salerno, Marques, Alexandre H. C., Vojdani, Elroy, Halpert, Gilad, Ostrinski, Yuri, Baiocchi, Gabriela Crispim, Plaça, Desirée Rodrigues, Freire, Paula P., Pour, Shahab Zaki, Moll, Guido, Catar, Rusan, Lavi, Yael Bublil, Silverberg, Jonathan I., Zimmerman, Jason, Cabral-Miranda, Gustavo, Carvalho, Robson F., Khan, Taj Ali, Heidecke, Harald, Dalmolin, Rodrigo J. S., Luchessi, Andre Ducati, Ochs, Hans D., Schimke, Lena F., Amital, Howard, Riemekasten, Gabriela, Zyskind, Israel, Rosenberg, Avi Z., Vojdani, Aristo, Shoenfeld, Yehuda, and Cabral-Marques, Otavio

Published
2023
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16. Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

Author

Cabral-Marques, Otavio, Halpert, Gilad, Schimke, Lena F., Ostrinski, Yuri, Vojdani, Aristo, Baiocchi, Gabriela Crispim, Freire, Paula Paccielli, Filgueiras, Igor Salerno, Zyskind, Israel, Lattin, Miriam T., Tran, Florian, Schreiber, Stefan, Marques, Alexandre H. C., Plaça, Desirée Rodrigues, Fonseca, Dennyson Leandro M., Humrich, Jens Y., Müller, Antje, Giil, Lasse M., Graßhoff, Hanna, Schumann, Anja, Hackel, Alexander, Junker, Juliane, Meyer, Carlotta, Ochs, Hans D., Lavi, Yael Bublil, Scheibenbogen, Carmen, Dechend, Ralf, Jurisica, Igor, Schulze-Forster, Kai, Silverberg, Jonathan I., Amital, Howard, Zimmerman, Jason, Heidecke, Harry, Rosenberg, Avi Z., Riemekasten, Gabriela, and Shoenfeld, Yehuda

Published
2022
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18. Increased Risk for Pulmonary Embolism among Patients with Ankylosing Spondylitis—Results from a Large Database Analysis.

Author

Gendelman, Omer, Simon, Neta, Ben-Shabat, Niv, Patt, Yonatan Shneor, McGonagle, Dennis, Cohen, Arnon Dov, Amital, Howard, and Watad, Abdulla

Subjects
PULMONARY embolism, DATABASES, ANKYLOSING spondylitis, AUTOIMMUNE diseases, SACROILIITIS
Abstract

Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% (p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 (p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study

Author

Amital, Howard, Beni, Sharon, Ben-Zvi, Ilan, Blausov, Natasha, Brom, Adi, Cohen, Carmit, Feld-Simon, Olga, Fluss, Ronen, Gilboa, Mayan, Eden-Friedman, Yehudit, Halevy, Shiraz, Houri-Levi, Esther, Hupert, Amit, Jbarien, Amnah, Keller, Naty, Leibowitz, Avshalom, Mayan, Haim, Maizels, Leonid, Meltzer, Eyal, Pinas-Zade, Nani, Rahav, Galia, Raibman-Spector, Shir, Regev-Yochay (PI), Gili, Romiantsev, Marina, Shachar, Dalit, Sharif, Kassem, Segal, Gadi, Segal, Shoshi, Segev, Amitai, Smollan, Gill, Stienlauf, Shmuel, Tal, Ilana, Yonath, Hagit, Zilberman-Daniels, Tal, Zimlichman, Eyal, Gilboa, M., Houri-Levi, E., Cohen, C., Tal, I., Rubin, C., Feld-Simon, O., Brom, A., Eden-Friedman, Y., Segal, S., Rahav, G., and Regev-Yochay, G.

Published
2020
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22. Unraveling the connection: Uveitis prevalence and risk factors in psoriasis patients — a population‐based study.

Author

Patt, Yonatan Shneor, Ben‐Shabat, Niv, Sharif, Kassem, David, Paula, Patt, Chen, Elizur, Yoav, Shani, Uria, Zacay, Galia, Watad, Abdulla, and Amital, Howard

Abstract

The association between uveitis and spondyloarthropathy (SpA)‐related conditions is well‐established. However, evidence describing the link between uveitis and psoriasis, and psoriasis without concomitant SpA‐related conditions is scarce and conflicting. This large‐scale population‐based study sought to describe the prevalence and features of uveitis among psoriasis patients in Israel as well as investigating the risk for uveitis in different subgroups of psoriasis patients compared to the general population. We conducted a retrospective study utilizing the electronic database of the Meuhedet Health Maintenance Organization. The study included all patients diagnosed with psoriasis between 2000 and 2020, each patient was matched with four controls based on age, sex, place of residence, and index date. Logistic regression models were employed to assess the association between psoriasis and uveitis while adjusting for the presence of SpA‐related conditions. A total of 61 003 psoriasis patients and 244 012 matched controls were included. The prevalence of uveitis was 1.3% versus 1.1% respectively (OR 1.12; 95% CI 1.10–1.30; p < 0.001). When adjusting to psoriasis severity, concurrent SpA, and psoriasis treatment no significant association was found. The rates of uveitis among psoriasis patients with concurrent SpA‐related conditions was 3.2% compared to 1.4% in controls without psoriasis or SpA (OR 2.38; 95% CI 2.00–2.83; p < 0.001), while in psoriasis patients without SpA, the rate of uveitis was 1.0% and was similar to controls. Although crude rates of uveitis were higher in patients with severe psoriasis compared to mild psoriasis (2.1% vs. 1.1%), after adjustment, no significant association compared to controls was found in either group. Our findings suggest that the positive association between psoriasis and uveitis is primarily mediated by the coexistence of other SpA‐related conditions. These findings imply the presence of a shared pathogenetic mechanism and set the direction for a phenotypic‐targeted screening strategy. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Automated processing of thermal imaging to detect COVID-19

Author

Brzezinski, Rafael Y., Rabin, Neta, Lewis, Nir, Peled, Racheli, Kerpel, Ariel, Tsur, Avishai M., Gendelman, Omer, Naftali-Shani, Nili, Gringauz, Irina, Amital, Howard, Leibowitz, Avshalom, Mayan, Haim, Ben-Zvi, Ilan, Heller, Eyal, Shechtman, Liran, Rogowski, Ori, Shenhar-Tsarfaty, Shani, Konen, Eli, Marom, Edith M., Ironi, Avinoah, Rahav, Galia, Zimmer, Yair, Grossman, Ehud, Ovadia-Blechman, Zehava, Leor, Jonathan, and Hoffer, Oshrit

Published
2021
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37. The association between psoriasis, psoriasis severity, and inflammatory bowel disease: a population-based analysis.

Author

Shani, Uria, Ben-Shabat, Niv, Qassem, Roula, Lahat, Adi, Omar, Mahmud, Savin, Einat, Dotan, Arad, Patt, Yonatan Shneor, Fisher, Lior, Zacay, Galia, Amital, Howard, Watad, Abdulla, and Sharif, Kassem

Subjects
INFLAMMATORY bowel diseases, CROHN'S disease, HEALTH maintenance organizations, JEWISH identity, PSORIASIS, SPONDYLOARTHROPATHIES
Abstract

Background: The skin–gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37–1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01–1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03–1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2–4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86–2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5–5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02–23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis. Plain language summary: Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Increased risk for stroke in patients with familial Mediterranean fever: results from a large population-based study.

Author

Ben-Shabat, Niv, Gendelman, Omer, Fisher, Lior, Shani, Uria, Patt, Yonatan Shneor, Watad, Abdulla, Skuja, Vita, McGonagle, Dennis, and Amital, Howard

Subjects
POPULATION, STROKE, CONFIDENCE intervals, AMYLOIDOSIS, PSYCHOLOGY of cardiac patients, MULTIVARIATE analysis, INFLAMMATION, CARDIOVASCULAR diseases, RETROSPECTIVE studies, RISK assessment, ATHEROSCLEROSIS, DESCRIPTIVE statistics, AUTOINFLAMMATORY diseases, LONGITUDINAL method, DISEASE risk factors
Abstract

Objective The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. Methods A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. Results A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15–1.76; P  < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P  < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P  < 0.05). Conclusion FMF patients are at increased risk for stroke regardless of known complications. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Big data- and machine learning-based analysis of a global pharmacovigilance database enables the discovery of sex-specific differences in the safety profile of dual IL4/IL13 blockade.

Author

Sharif, Kassem, Omar, Mahmud, Lahat, Adi, Patt, Yonatan Shneor, Amital, Howard, Zoabi, Ghanem, Bragazzi, Nicola Luigi, and Watad, Abdulla

Subjects
DATABASES, DRUG side effects, BLOCKADE, DEGENERATION (Pathology), SEXUAL dimorphism, NONRELATIONAL databases
Abstract

Background: Due to its apparent efficacy and safety, dupilumab, a monoclonal antibody that blocks Interleukin 4 (IL-4) and Interleukin 13 (IL-13), has been approved for treating T-helper 2 (Th2) disorders. However, adverse effects like local injection site reactions, conjunctivitis, headaches, and nasopharyngitis have been reported. Sex differences are known to influence both adaptive and innate immune responses and, thus, may have a bearing on the occurrence of these adverse effects. Nevertheless, the literature lacks a comprehensive exploration of this influence, a gap this study aims to bridge. Materials and Methods: A comprehensive data mining of VigiBase, the World Health Organization (WHO) global pharmacovigilance database which contains case safety reports of adverse drug reactions (ADRs) was performed to test for sex -specific safety response to dual IL4/IL13 blockade by dupilumab. The information component (IC), a measure of the disproportionality of ADR occurrence, was evaluated and compared between males and females to identify potential sexual dimorphism. Results: Of the 94,065 ADRs recorded in the WHO global pharmacovigilance database, 2,001 (57.4%) were reported among female dupilumab users, and 1,768 (50.7%) were among males. Immune/autoimmune T-helper 1 (Th1)-, innate- and T-helper 17 (Th17)-driven diseases and degenerative ones were consistently reported with a stronger association with Dupilumab in males than females. Some adverse events weremore robustly associated with Dupilumab in females. Conclusion: Dupilumab has an excellent safety profile, even though some ADRs may occur. The risk is higher among male patients, further studies, including ad hoc studies, are needed to establish causality. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Vitamin D Insufficiency is Associated with Higher Incidence of Dementia, a Large Community-Based Retrospective Cohort Study.

Author

Kiderman, David, Ben-Shabat, Niv, Tsur, Avishai M., Anis, Saar, Watad, Abdulla, Cohen, Arnon D., Paz, Ziv, and Amital, Howard

Subjects
VITAMIN D, VITAMIN D deficiency, DEMENTIA, MEDICAL care, DISEASE risk factors, VASCULAR dementia
Abstract

Introduction: Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. Objectives: To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. Methods: Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. Results: Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75 nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75 nmol/l). Patients with vitamin D deficiency (<50 nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P -value = 0.05) and the insufficiency groups (77 vs. 81 P -value = 0.05) compared to the reference values (≥75 nmol/l). Conclusion: Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial

Author

Adams, Luthando, Ally, Mahmood M, du Plooy, Maria C, Louw, Ingrid C, Nayiager, Savithree, Nel, Christoffel B, Nel, Debra, Reuter, Helmuth, Soloman, Ahmed S, Spargo, Catherine E, Hall, Stephen, Rischmueller, Maureen, Sharma, Shunil D, Will, Robert K, Youssef, Peter P, Arroyo, Caroline, Baes, Rosario P, Dulos, Roger B, Hao, Llewellyn T, Lanzon, Allan E, Lichauco, Juan Javier T, Mangubat, Jill H, Ramiterre, Edgar B, Reyes, Bernadette Heizel M, Tan, Perry P, Choe, Jung-Yoon, Kang, Young Mo, Kwon, Seong Ryul, Lee, Sang-Heon, Lee, Shin-Seok, Yoo, Dae-Hyun, Lin, Hsiao-Yi, Luo, Shue-Fen, Tsai, Shih-Tzu, Tsai, Wen-Chan, Tseng, Jui-Cheng, Wei, Cheng-Chung C, Asavatanabodee, Paijit, Nantiruj, Kanokrat, Nilganuwong, Surasak, Uea-Areewongsa, Parichat, Majstorovic, Ljubinka Bozic, Bacic, Suada Mulic, Batalov, Anastas Z, Georgieva-Slavcheva, Gabriela, Mihailova, Mariyana, Nikolov, Nikolay G, Penev, Dimitar P, Spasov, Yuliy A, Stanimirova, Krasimira, Todorov, Stoyan, Toncheva, Antoaneta R, Yordanova, Nadezhda, Mosterova, Zdenka, Novosad, Libor, Prochazkova, Leona, Stehlikova, Helena, Stejfova, Zuzana, Kiseleva, Natalia, Pank, Lea, Savi, Triin, Alexandra, Balbir-Gurman, Amital, Howard, Mevorach, Dror, Rosner, Itzhak A, Mihailova, Anna, Stumbra-Stumberga, Evija, Basijokiene, Vida, Lietuvininkiene, Virginija, Unikiene, Dalia, Brzezicki, Jan, Dudek, Anna M, Glowacka-Kulesz, Maria B, Grabowicz-Wasko, Barbara, Hajduk-Kubacka, Sabina, Hilt, Joanna, Hrycaj, Pawel, Jeka, Slawomir, Kolasa, Renata, Krogulec, Marek, Mastalerz, Hanna, Olak-Popko, Anna, Owczarek, Elzbieta, Ruzga, Zofia, Walczak, Alina, Ancuta, Codrina I, Ancuta, Ioan, Balanescu, Andra R, Berghea, Florian, Bojin, Silvia, Arvunescu, Mihaela A Ianuli, Ionescu, Ruxandra M, Mociran, Eugenia, Pavel, Mariana, Rednic, Simona, Voie, Adriana, Zainea, Carmen M, Bugrova, Olga V, Demin, Alexander, Ershova, Olga B, Gavrisheva, Inna A, Krechikova, Diana G, Kuropatkin, Gennady V, Marusenko, Irina M, Menshikova, Irina V, Noskov, Sergey M, Rebrov, Andrey P, Smakotina, Svetlana A, Yakushin, Sergey S, Zhilyaev, Evgeny, Ramos, Juan Jose Amarelo, Garcia, Francisco Javier Blanco, Nebro, Antonio Fernandez, Esteban, Silvia Perez, Burson, Juan Miguel Sanchez, Sala, Raimon Sanmarti, Ataman, Sebnem, Hizmetli, Sami, Kuru, Omer, Douglas, Karen M, Emery, Paul, Moots, Robert J, Ong, Voon H, Sheeran, Thomas P, Faraawi, Rafat Y, Lessard, Clode, Mendoza, Carlos Abud, Avila-Armengol, Hilario Ernesto, Zapata, Francisco I Avila, Irazoque-Palazuelos, Fedra Consuelo, Cecena, Marco Antonio Maradiaga, Pacheco-Tena, Cesar F, Rizo-Rodriguez, Juan C, Rodriguez-Torres, Isaura M, Aelion, Jacob A, Caciolo, Barbara A, Calmes, James M, Chatpar, Prem, Dayal, Nimesh, De Jesus, Alex, Dikranian, Ara H, Diri, Erdal, Fairfax, Michael J, Fenton, Ira F, Fleischmann, Roy M, Gaylis, Norman B, George, Ronald L, Halter, Dale G, Hernandez, Paul, Hole, Susan A, Hou, Antony C, Huff, John P, Kafaja, Suzanne, Kennedy, Alastair C, Kenney, Howard, Kimmel, Steven C, Kirby, Brian S, Kivitz, Alan J, Legerton, Clarence W, Lindsey, Stephen M, Mallepalli, Jyothi R, Mathews, Steven D, Metyas, Samy K, Mizutani, Wesley T, Najam, Sabeen, Nascimento, Joao M, Pang, Shirley W, Patel, Rakesh C, Poiley, Jeffrey E, Ramirez, Carlos E, Reddy, Riteesha, Rehman, Qaiser, Schnitz, William M, Scoville, Craig D, Shergy, William J, Silverfield, Joel C, Singhal, Atul K, Smallwood-Sherrer, Yvonne R, Songcharoen, Suthin N, Stack, Michael T, Stohl, William, Su, Tien-I K, Udell, James, Waraich, Saleem, Weidmann, Charles E, Wei, Nathan, Wiesenhutter, Craig W, Winkler, Anne E, Zagar, Karen E, Berman, Alberto, Mysler, Eduardo F, Hidalgo, Rodolfo A Pardo, Venarotti, Horacio O, Sariego, Irmgadt Annelise Goecke, Calabresse, Renato E Jimenez, Ruiz-Tagle, Juan Ignacio Vargas, Vargas, Luis Fernando M Bellatin, Berrocal, Alfredo E, Portocarrero, Manuel Gustavo Leon, Jesus, Felix, Pena, Romero, Fleischmann, Roy, Mysler, Eduardo, Luo, Zhen, DeMasi, Ryan, Soma, Koshika, Zhang, Richard, Takiya, Liza, Tatulych, Svitlana, Mojcik, Christopher, Krishnaswami, Sriram, Menon, Sujatha, and Smolen, Josef S

Published
2017
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