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Background: The best first-line monotherapy for hypertension remains uncertain, as current guidelines suggest that thiazides, angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB) are appropriate in the absence of specific comorbidities. We aimed to compare the outcomes of first-line antihypertensive classes in a real-life setting with a long follow-up period., Methods: This nationwide retrospective new-user cohort study included patients insured by the largest health maintenance organization in Israel. We included patients with a new diagnosis of hypertension between 2008 and 2021 who initiated treatment with a single first-line drug for hypertension. Outcomes were assessed with and without propensity score matching for confounding factors. The primary composite outcome was the first occurrence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, or heart failure (HF)., Results: A total of 97,639 patients initiated antihypertensive treatment with a single drug as first-line therapy. The most commonly prescribed class was ACEi/ARB (66,717, 68.3%), followed by CCBs (15,922, 16.3%), beta-blockers (BBs, 12,869, 13.2%), and thiazides (2,131, 2.2%). For the primary outcome, the hazard ratios (HRs) for BBs, CCBs, and ACEi/ARBs were 1.44 (95% CI 1.25 - 1.66), 1.10 (95% CI 0.96 - 1.27), and 1.13 (95% CI 0.99 - 1.29), respectively, when compared to thiazides., Conclusion: When initiating pharmacotherapy for hypertension with a single drug, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers were associated with similar risk of MI, ACS, stroke, or HF when compared to thiazides, while beta-blockers were associated with increased risk., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The objective of this study was to assess the risk of seizures in Giant Cell Arteritis (GCA) patients in a large cohort of Israeli subjects, in comparison to matched controls., Methods: Patients diagnosed with GCA between 2002 and 2017 were included. Controls were matched based on sex, age, socioeconomic status, country of birth, diabetes mellitus, and hypertension in a 4:1 ratio. Patients with seizure records prior to the study period were excluded. Hazard ratios for seizures was obtained by cox regression models., Results: The study cohort was composed by 8,103 GCA patients and 32,412 matched controls. The GCA group included 5,535 women (68%), 2,644 patients born in Israel (33%), and 2,888 patients with low socioeconomic status (36%). The median age of this group was 71. During the followed cumulative person-years of 54,641 and 222,537 in the GCA and control group, respectively, 15.92 cases per 10,000 person-years was found in the GCA group, compared to 9.62 per 10,000 person-years in the controls. GCA was associated with seizures in the unadjusted (HR = 1.66, 95% CI [1.29 to 2.13]) and adjusted (HR = 1.67, 95% CI [1.3 to 2.14]) models. GCA was also associated with seizures after controlling for strokes (HR = 1.55, 95% CI [1.16 to 2.07])., Conclusion: According to this study, individuals with GCA are at a higher risk of developing seizures when compared to the general population. This increased risk is independent of their predisposition for stroke. One proposed mechanism is that the GCA pro-inflammatory state may decrease the neuronal threshold for depolarization.

Psoriatic arthritis (PsA) predominantly emerges in individuals previously diagnosed with psoriasis (PsO), offering a unique opportunity to study the transition from PsO to PsA. This progression provides a window to identify characteristics of PsO patients who may develop PsA, facilitating early intervention and potentially informing prevention and treatment strategies. This review evaluates a wide array of research focusing on various risk factors for PsA development. These factors span demographic characteristics, concomitant diseases and habits, characteristics of skin and nail psoriatic disease, and symptoms and imaging abnormalities associated with PsA. By summarising the existing literature, this review critically examines each risk factor, highlighting the strengths and limitations inherent in the studies. Each section of the review not only summarises the current state of knowledge but also includes an expert opinion, culminating in a final concluding remark. This integration allows physicians to utilise the confluence of established literature and ongoing clinical experience, facilitating a rationalised decision-making process that is deeply informed by both empirical evidence and practical insights.

Background and Aims: Emerging evidence suggests an arrhythmogenic effect of Anti-Ro/SSA (anti-Ro) and anti-La/SSB (anti-La) antibodies in adults, potentially involving a subclinical intracardiac inflammatory process. Despite the established association between inflammation and ischemic heart disease (IHD), it is noteworthy that as of now no study has delved into the potential link between these antibodies and IHD. This population-based study aimed to examine the association between anti-Ro/La seropositivity and IHD in the general adult population., Methods: We conducted a retrospective study using electronic medical records from the largest health maintenance organization in Israel. Patients with positive serology for either or both anti-Ro and anti-La antibodies were included, along with matched controls. Multivariate logistic regression models were utilized to assess the odds of IHD in seropositive patients compared to controls., Results: Among 17,231 seropositive patients and 84,368 controls, the rate of IHD was significantly higher in the seropositive group (9.7 % vs. 8.1 %,OR = 1.23; 95%CI 1.14-1.31; p<0.001). The association was more pronounced in younger patients [<40 years old (OR = 3.36; 95%CI 1.66-6.82; p<0.001), 40-49 years old (OR = 1.85; 95%CI 1.26-2.73; p<0.01), 50-59 years old (OR = 1.87; 95%CI 1.55-2.26; p<0.001), 60-69 years old (OR = 1.26; 95%CI 1.11-1.42; p<0.001), ≥70 years old (OR = 1.11; 95%CI 1.03-1.20; p<0.01)], as well as in patients with fewer traditional cardiovascular risk-factors (none:OR = 1.29; 95 % CI 1.09 to 1.77; p<0.01, 1-2:OR = 1.30; 95 % CI 1.19 to 1.41; p<0.001, ≥3:OR = 1.09; 95 % CI 0.99 to 1.21; p=0.076)., Conclusions: Our study demonstrates for the first time a positive association between anti-Ro/La seropositivity and IHD in the general adult population, especially among younger individuals with fewer traditional cardiovascular risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immune thrombocytopenia (ITP) is a complex autoimmune disorder characterized by thrombocytopenia and an increased bleeding risk, arising from autoantibody-mediated platelet destruction and impaired megakaryocyte function. The pathogenesis of ITP involves a multifaceted interplay of genetic predispositions, immune dysregulation, and environmental triggers, though the precise mechanisms remain uncertain. Several infectious agents, mostly viruses, have been implicated in both acute and chronic ITP through mechanisms such as molecular mimicry, direct bone marrow suppression, and immune dysregulation. Vaccinations, particularly those containing adjuvants like aluminum and those capable of inducing molecular mimicry, have also been associated with ITP, either as a new onset or as a relapse in preexisting cases. The role of drugs, particularly quinine, quinidine and certain antibiotics, in inducing ITP through various immunological pathways further illustrates the diverse etiologies of this condition. The multiple triggers of the disease raise the question of whether ITP may be classified as an autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This condition encompasses a range of autoimmune and inflammatory symptoms triggered by adjuvants, such as silicones, polypropylene meshes, metal implants, and mineral oils present in various medical materials and medications. Similar to that observed in some cases of ITP, adjuvants can trigger autoimmune or autoinflammatory responses via molecular mimicry, epitope spreading, and polyclonal activation. This narrative review explores the underlying environmental factors related to ITP and examines ITP triggers that could potentially support an association between ITP and ASIA syndrome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis., Methods: This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class., Results: The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95% CI 0.35-0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65-2.07])., Conclusion: Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor., (© 2024. The Author(s).)

Objectives: The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population., Methods: A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models., Results: A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (s.d. 12.4) vs 62.5 (s.d. 11.0) years; P = 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P < 0.05)., Conclusion: FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

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., (© 2024 Japanese Dermatological Association.)

Background: Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation in various organs, including the joints. Traditionally, the arthritis of FMF has been considered relatively harmless. However, anecdotal evidence has suggested that it may contribute to long-term joint damage, which may necessitate surgical joint replacement. This study aimed to investigate the rates of arthroplasty among FMF patients and compare it to the general population., Methods: The study used the electronic database of the largest healthcare organization in Israel to identify 9,769 FMF patients diagnosed between 2000 and 2016. A similar number of age-, gender-, and residency-matched controls were also identified. The rates of arthroplasty were compared between the two groups. A logistic regression model predicting the need for arthroplasty within the FMF group was formed to identify potential risk factors., Results: Of the 9,769 FMF patients, 114 (1.2%) underwent arthroplasty, compared with 64 (0.7%) of the control group [unadjusted odds ratio (OR)=1.79, 95% confidence interval (CI) 1.32-2.43; partially adjusted OR = 1.97, 95% CI 1.40-2.77; fully adjusted OR = 1.92, 95% CI 1.35-2.72]. Within the FMF cohort, those of North African origin had a significantly higher risk of arthroplasty (OR = 6.89, 95% CI 5.09-9.33; p< 0.001)., Conclusion: FMF patients can experience long-term joint damage that may require arthroplasty. Although this complication is relatively uncommon in FMF patients, it occurs almost twice as frequently as compared with the general population. FMF patients of North African origin are at an even higher risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Coeliac disease affects approximately 1% of the global population with the diagnosis often relying on invasive and time-demanding methods. Deep learning, a powerful tool in medical science, shows potential for non-invasive, accurate coeliac disease diagnosis, though challenges remain., Objective: This systematic review aimed to evaluate the current state of deep-learning applications in coeliac disease diagnosis and identify potential areas for future research that could enhance diagnostic accuracy, sensitivity, and specificity., Methods: A systematic review was conducted using the following databases: PubMed, Embase, Web of Science, and Scopus. PRISMA guidelines were applied. Two independent reviewers identified research articles using deep learning for coeliac disease diagnosis and severity assessment. Only original research articles with performance metrics data were included. The quality of the diagnostic accuracy studies was assessed using the QUADAS-2 tool, categorizing studies based on risk of bias and concerns about applicability. Due to heterogeneity, a narrative synthesis was conducted to describe the applications and efficacy of the deep-learning techniques (DLT) in coeliac disease diagnosis., Results: The initial search across four databases yielded 417 studies with 195 being removed due to duplicity. Finally, eight studies were found to be suitable for inclusion after rigorous evaluation. They were all published between 2017 and 2023 and focused on using DLT for coeliac disease diagnosis or assessing disease severity. Different deep-learning architectures were applied. Accuracy levels ranged from 84% to 95.94% with the GoogLeNet model achieving 100% sensitivity and specificity for video capsule endoscopy images., Conclusions: DLT hold substantial potential in coeliac disease diagnosis. They offer improved accuracy and the prospect of mitigating clinician bias. However, key challenges persist, notably the requirement for more extensive and diverse datasets, especially to detect milder forms of coeliac disease. These methods are in their nascent stages, underscoring the need of integrating multiple data sources to achieve comprehensive coeliac disease diagnosis.

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 were more 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Sharif, Omar, Lahat, Patt, Amital, Zoabi, Bragazzi and Watad.)

Celiac disease (CD) presents a complex interplay of both innate and adaptive immune responses that drive a variety of pathological manifestations. Recent studies highlight the role of immune-mediated pathogenesis, pinpointing the involvement of antibodies against tissue transglutaminases (TG2, TG3, TG6), specific HLA molecules (DQ2/8), and the regulatory role of interleukin-15, among other cellular and molecular pathways. These aspects illuminate the systemic nature of CD, reflecting its wide-reaching impact that extends beyond gastrointestinal symptoms to affect other physiological systems and giving rise to a range of pathological landscapes, including refractory CD (RCD) and, in severe cases, enteropathy-associated T cell lymphoma. The existing primary therapeutic strategy, a gluten-free diet (GFD), poses significant challenges, such as low adherence rates, necessitating alternative treatments. Emerging therapies target various stages of the disease pathology, from preventing immunogenic gluten peptide absorption to enhancing intestinal epithelial integrity and modulating the immune response, heralding potential breakthroughs in CD management. As the understanding of CD deepens, novel therapeutic avenues are emerging, paving the way for more effective and sophisticated treatment strategies with the aim of enhancing the quality of life of CD patients. This review aims to delineate the immunopathology of CD and exploring its implications on other systems, its complications and the development of novel treatments.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients., Methods: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders., Results: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47)., Conclusions: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures., (© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Acute testicular torsion is a surgical emergency that warrants prompt treatment. The diagnosis is typically confirmed by ultrasonography interpreted by a radiologist (RADUS); however, in this study, we describe the clinical course of 23 patients for whom point-of-care ultrasound (POCUS) was performed by pediatric emergency medicine physicians during the initial assessment for testicular torsion in the pediatric emergency department (PED)., Methods: A retrospective case series analysis of patients aged 0 to 18 years who were diagnosed with acute testicular torsion after undergoing scrotal POCUS through our PED., Results: Between June 2015 and December 2020, 155 boys received an International Classification of Diseases-9 code of Torsion of Testis after presenting to our PED. Seventy-three patients were imaged preoperatively, of which 50 (68.5%) were diagnosed via RADUS alone. Twenty-three patients (31.5%) underwent POCUS (median age 14.1 years [interquartile range {IQR}: 11.4-15.9 years]), of which 14 (60.9%) were imaged by POCUS alone, whereas the remaining 9 patients (39.1%) underwent POCUS before RADUS. Thirteen of the 23 patients (56.5%) who underwent POCUS had intraoperative findings consistent with acute testicular torsion, whereas another 3 patients (13.0%) required manual detorsion in the PED before orchiopexy. Six patients required orchiectomy. All patients for which POCUS findings were suggestive of acute testicular torsion were correctly classified.The median length of stay from time to admission to orchiopexy for those who received RADUS only versus POCUS only was 184 minutes (IQR: 136-255), and 121 minutes (IQR: 80-202), respectively ( P = 0.036). Among the patients who experienced POCUS, the median length of stay for those who underwent RADUS in addition to POCUS compared with those who underwent POCUS alone was 202 minutes (IQR: 136-338.4) ( P = 0.031)., Conclusions: Point-of-care ultrasound performed by pediatric emergency medicine physicians can be used to expedite surgical management and streamline the management of pediatric patients suspected of acute testicular torsion., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Smelling is a critical sense utilized daily. Consequently, smelling impairment or anosmia may lead to a reduction in life quality. Systemic diseases and particular autoimmune conditions can impair olfactory function; among others are Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis. Interactions between the olfactory process and the immune systems cause this phenomenon. Alongside autoimmune conditions, in the recent COVID-19 pandemic, anosmia was also described as a prevalent infection symptom. Nevertheless, the occurrence of anosmia is significantly less common in Omicron-infected patients. Several theories have been proposed to explain this phenomenon. One possibility is that the Omicron variant preferentially enters host cells via endocytosis, rather than plasma cell membrane fusion. This endosomal pathway is less dependent on the activation of Transmembrane serine protease 2 (TMPRSS2), expressed at the olfactory epithelium. As a result, the Omicron variant may have reduced efficiency in penetrating the olfactory epithelium, leading to a lower prevalence of anosmia. Furthermore, olfactory changes are known to be associated with inflammatory conditions. The Omicron variant elicits a less robust autoimmune and inflammatory response, believed to reduce the probability of anosmia. This review elaborates on the commonalities and differences in autoimmune and COVID-19 omicron-associated anosmia.

Aim: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother's breastmilk or to wait for breastmilk to be available., Methods: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012-2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported., Results: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group., Conclusion: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother's breastmilk.