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עמוד בית
Sat, 25.05.24

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April 2024
Kassem Sharif MD, Adi Lahat MD, Yonatan Shneor Patt MD, Niv Ben-Shabat MD, Mahmud Omar MD, Abdulla Watad MD, Howard Amital MD MHA, Omer Gendelman MD

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

July 2023
Yonatan Shneor Patt MD, Niv Ben-Shabat MD, Lior Fisher MD, Howard Amital MD MHA, Abdulla Watad MD, Kassem Sharif MD

Background: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases.

Objectives: To investigate the association between dementia and PM/DM.

Methods: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort.

Results: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77–1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57–2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67–17.67, P = 0.005).

Conclusions: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.

November 2022
Rivka Sheinin MD, Ana Rita Nogueira MD, Nicola L. Bragazzi MD PhD, Abdulla Watad MD, Shmuel Tiosano MD, Tal Gonen MD, Kassem Sharif MD, Yehuda Kameri MD PhD, Howard Amital MD MHA, Daniela Amital MD MHA, Hofit Cohen MD

Background: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia.

Objectives: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not.

Methods: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population.

Results: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia.

Conclusions: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

Bar Pitaro Alter MD, Shmuel Tiosano MD, Yuval Kuntzman MD, Omer Gendelman MD, Guy Shalom MD, Abdulla Watad MD, Howard Amital MD MHA, Arnon D. Cohen MD MPH, Daniela Amital MD MHA

Backgrounds: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression.

Objectives: To evaluate the association between BD and depression, adjusting for established risk factors for depression.

Methods: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex.

Results: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37–2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39–2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18–39 years of age), low and high socioeconomical status, and non-smokers.

Conclusions: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

January 2022
Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD, and Yehuda Shoenfeld MD FRCP MaACR
June 2021
Naim Mahroum MD, Magdi Zoubi MD, Abdulla Watad MD, Howard Amital MD MHA, Josef Haik MD MPH, and Yehuda Shoenfeld MD FRCP MaACR

Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.

October 2020
Khalaf Kridin MD, Mouhammad Kridin MD, Howard Amital MD, Abdulla Watad MD and Mogher Khamaisi MD

Background: The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population.

Objectives: To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center.

Methods: In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated.

Results: Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5–9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8–12.3) and dermatomyositis (7.2, 95%CI 5.0–10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis.

Conclusions: The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.

June 2020
Charlie Bridgewood PhD, Giovanni Damiani MD, Kassem Sharif MD, Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD MPH, Luca Quartuccio MD, Sinisa Savic and Dennis McGonagle FRCPI PhD

In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients

 

August 2019
Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD MPH, Howard Amital MD MHA and Yehuda Shoenfeld MD FRCP MACR
May 2019
Mahmud Mahamid MD, Amir Mari MD, Tawfik Khoury MD, Nicola Luigi Bragazzi MD PhD, Majeed Ghantous MD, Omar Abu-Elhija MD and Abdulla Watad MD

Background: The prevalence of Helicobacter pylori varies geographically by age, race, and socioeconomic status (SES). However, the impact of ethnicity on endoscopic outcomes in infected individuals is not well known.

Objectives: To assess the impact of ethnicity among Israelis with biopsy-proven H. pylori infection.

Methods: A retrospective study, including patients who underwent gastroscopy and were diagnosed histologically with H. pylori infection, was conducted. Information on demographics, SES, medications, and co-morbidities were extracted from medical records. Univariate (Student's t-test, chi-square test) and multivariate (multinomial and logistic) regression analysis were conducted to examine the predictors of the clinical outcome.

Results: The study included 100 Israeli Jews and 100 Israeli Arabs diagnosed with biopsy-proven H. pylori infection. At univariate analysis, the number of households was higher among Arabs (P < 0.001), whose family income and parental education were lower than among Jews (P < 0.001 for both variables). The response to amoxicillin and clarithromycin differed between the two groups, being higher among Jews (P < 0.001).In clinical outcomes (gastritis severity, gastric and duodenal ulcer, intestinal metaplasia, atrophic gastritis, and MALT), no statistically significant differences could be detected between Jews and Arabs. Concerning intestinal metaplasia, lack of consumption of nonsteroidal anti-inflammatory drugs resulted a statistically significant protective factor (odds ratio 0.128, 95% confidence interval 0.024–0.685, P = 0.016).

Conclusions: Although in the literature ethnicity seems to be a risk factor for H. pylori colonization, no statistical significance was detected in various endoscopic and histological findings related to H. Pylori infection between Israeli Arabs and Jews.

October 2018
Adi Guy MD, Kassem Sharif MD, Nicola Luigi Bragazzi MD PhD, Alec Krosser MD, Boris Gilburd PhD, Eleanor Zeruya MD, Ora Shovman MD, Abdulla Watad MD and Howard Amital MD MHA

Background: Patients with rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS), encounter significantly higher rates of cardiovascular morbidity and mortality. The renin-angiotensin-aldosterone system maintains hemodynamic stability through blood pressure regulation. When dysregulated, this system has been implicated in various pathological conditions, including cardiovascular events.

Objectives: To investigate the levels of renin and aldosterone in RA and AS patients.

Methods: Three groups were recruited: patients with RA, patients with AS, and healthy controls. Subjects were excluded if they had a diagnosis of hypertension, hyperaldosteronism, or renal artery stenosis, or were taking drugs that might have affected renin levels. Renin and aldosterone levels were measured using commercially available kits. Data were analyzed using univariate analyses and multivariate regression analyses.

Results: Fifty-one subjects were enrolled in the study: 15 with RA, 4 with AS, and 32 healthy controls. At the univariate analysis, the three groups differed in age (P = 0.005), renin levels (P = 0.013), and aldosterone-to-renin ratio (P = 0.019). At the post-hoc tests, both AS and RA patients differed from controls for renin levels and the aldosterone-to-renin ratio. At the multivariate regression analysis, AS patients had lower renin values than controls (beta standardized regression coefficient -0.323, P = 0.022).

Conclusion: Patients with RA tended to have lower levels of plasma renin compared to healthy subjects. This finding indicates that the renin-angiotensin-aldosterone system might not be directly involved in the process that results in increased cardiovascular events in rheumatoid arthritis.

November 2017
Abdulla Watad MD, Iris Eshed MD and Dennis McGonagle MD FRCPI PhD

Enthesitis is a term that refers to inflammation at tendon, ligament, or joint capsule insertions. The entheses are increasinlgly considered to be the primary site of joint inflammation in the spondyloarthropathies including psoriatic arthritis (PsA). Great advances have occurred in the understanding of enthesopathy, which has resulted in a better understanding of the etiopathogenesis of PsA. Enthesitis is difficult to assess on both clinical examination and on imaging because of the overlap in features between mechanical, degenerative, and inflammatory pathologies. Ultrasonography frequently detects entheseal abnormalities in patients with psoriasis, despite the absence of clinical symptoms of arthropathy and the longitudinal value of such lesions for PsA prediction remains unknown. The role of magnetic resonance imaging (MRI) in the assessment and monitoring of enthesitis is not fully agreed on but it is clearly superior for the assessment of spinal polyenthesitis and for diffuse peri-enthseal osteitis that can occur anywhere in the skeleton. Nuclear medicine, including conventional positron-emission tomography (PET) and high-resolution PET scan (hrPET), is more of a research tool for enthesitis and can, for example, help distinguish between PsA and osteoarthritis. Entheseal abnormalities are common in osteoarthritis, which creates diagnostic difficulty from PsA. Entheseal changes, especially on imaging, may also occur in rheumatoid arthritis (RA) and likely reflect the extension of the inflammatory process from the adjacent synovium. The nail is anatomically anchored to the skeleton via a mini-enthesis network. An association between ultrasonography determined distal interphalageal joint (DIP) extensor tendon enthesopathy and clinical nail disease was found, which highlights the pivotal role of the enthesis in this PsA risk factor. This review summarizes the relevant insights and implication of imaging for enthesitis, primarily in PsA but also in other arthropathies.

 

October 2017
Chen Ben David MS, Kassem Sharif MD, Abdulla Watad MD, Nicola Luigi Bragazzi MD MPH PhD and Mohammad Adawi MD MHA
July 2017
Nicola Luigi Bragazzi MD PhD, Abdulla Watad MD, Mohammad Adawi MD, Howard Amital MD MHA, Gali Aljadeff BSc and Yehuda Shoenfeld MD FRCP MaACR
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