Yossi Steier MD, Eyal Cohen-Sela MD, Shay Averbauch BSc, Asaf Oren MD, Ori Eyal MD, Yael Lebenthal MD, Avivit Brener MD
Background: The Iron Swords war created stressful circumstances that could negatively impact glycemic control in individuals with type 1 diabetes (T1D).
Objectives: To evaluate changes in continuous glucose monitoring (CGM) metrics in pediatric T1D patients during the war.
Methods: This retrospective study included T1D patients monitored by CGM. Metrics from three selected 2-week periods were compared (before the war, after the war outbreak, and 4 months later). Study variables included time-in-range (70–180 mg/dl; 3.9–10 mmol/L), time-in-tight-range (70–140 mg/dl; 3.9–7.8 mmol/L), time-in-marked-hypoglycemia (< 54 mg/dl; < 3 mmol/liter), and time-in-severe-hyperglycemia (> 250 mg/dl; >13.3 mmol/liter). Patients were treated with either a multiple daily insulin (MDI) regimen or insulin pump, with or without an open-source automated insulin delivery (OS-AID) system.
Results: Data of 99 patients were analyzed (mean age 12.2 ± 4.0 years, mean diabetes duration 4.6 ± 3.9 years, 52.5% males). No significant changes in CGM metrics were observed across the entire cohort at any time point. Patients with higher socioeconomic position (SEP; cluster > 7) had better CGM metrics, with an increase in time-in-tight-range in the lower SEP group and in time-in-severe-hyperglycemia in the higher SEP group (P = 0.003). OS-AID users (n=20) had superior pre-war CGM metrics and maintained stable glycemia during the war, MDI users showed increased time-in-severe-hyperglycemia post-outbreak (P = 0.05).
Conclusions: Throughout the war, children and adolescents with T1D treated with insulin pumps maintained relatively stable glycemic control. Susceptibility to change following the onset of war was influenced by SEP and mode of insulin therapy.
Adam Folman MD, Maguli S. Barel MD, Ariel Roguin MD PhD
We report a case of true syncope with documented vasovagal syncope which occurred at the time of an alarm due to missile attack. This case shows a severe vasovagal reaction to emotional stress and fear.
The vasovagal response (neurocardiogenic response) involves an abnormal interplay of bradycardia and paradoxical vasodilation. This intense vagal stimulation can result in syncope, which may have dramatic consequences, especially in elderly patients. Such an event was triggered during a missile alarm in an 80-year-old man. To the best of our knowledge, no similar case has been previously reported [1,2]. A sinus pause is a temporary cessation of electrical impulses from the sinus node, resulting in a brief but complete halt of heart contraction. The excessive vagal input diminishes sinus node automaticity, potentially causing pauses that vary in duration from seconds to even longer periods, depending on individual susceptibility and the length and intensity of the vagal response.
Although typically transient, sinus pauses may also result in significant symptoms like lightheadedness or syncope. In severe cases, they can compromise cerebral perfusion, necessitating immediate intervention. Recognizing the risk of sinus pause in susceptible patients is essential for preventing potential complications, particularly during procedures that may provoke a strong vasovagal reaction.
Keren Zloto MD, Gad Segal MD, Lital Shaham MD PhD, Shlomit Blumenfeld MD, Noa Brenner MD, Shani Steinberg MD, Roy Mashiah MD, Dahlia Admon MD, Eyal Sivan MD, Alina Weissmann-Brenner MD
Background: In times of war, healthcare systems face the dual challenge of attending to the medical needs of injured soldiers and civilians as well as struggling to meet the everyday healthcare demands of civilians.
Objectives: To assess the correlation between exposure to war and the likelihood of spontaneous abortion (SAB) and to compare it to a similar period in previous years.
Methods: We conducted a retrospective study comparing the rate of SAB during war to the previous years.
Results: During the Iron Swords war, 381 patients out of 3245 (11.74%) were diagnosed with SAB, compared to 530 of 4080 (13%) in 2022, 536 of 3387 (13.8%) in 2021, and 516 of 3798 (13.6%) in 2020. The median gestational age at diagnosis was similar between the groups, with most cases identified during the first trimester. The study group exhibited a significantly higher prevalence of smoking (18.47% vs. 7.75% vs. 6.3% vs. 9.3%, P = 0.03), with no differences in the prevalence of chronic diseases and in the method of pregnancy termination.
Conclusions: Exposure to stress due to war during early pregnancy appears to have no significant impact on the rate of SAB.
Ron Yaniv MD MHA Mderm, Baruch Kaplan MD
Acne vulgaris is a common dermatological condition, affecting up to 85% of adolescents and increasingly observed in adults, particularly women. Its chronic nature and visible manifestations impose significant psychological and social burdens. This review provides an updated examination of acne pathogenesis that explores emerging therapeutic approaches informed by recent molecular, genetic, and microbiome research. Findings from clinical studies, molecular biology, and immunological research published in the past decade are presented in a comprehensive overview of current advancements in acne treatment. Key databases and recent consensus guidelines have been utilized to identify novel mechanisms and therapeutic innovations. Current understanding emphasizes the role of innate immunity (e.g., toll-like receptors, inflammasomes), sebocyte biology via peroxisome proliferator-activated receptors (PPAR) signaling, and strain-specific Cutibacterium acnes dynamics. Environmental and genetic factors, including androgen receptor gene polymorphisms and lifestyle contributors, influence disease expression. Emerging treatments include selective retinoids (trifarotene), PPAR modulators, interleukin-targeting biologics, probiotics, bacteriophages, and hormonal therapies with improved safety profiles. Microbiome modulation and narrow-spectrum antibiotics are gaining attention for precision management. Integrating molecular insights with clinical practice fosters a personalized, multidisciplinary approach to acne care. Future research should prioritize microbiome restoration, novel biologics, and strategies to minimize antimicrobial resistance.
Marwan Dawood MD, Itay Cohen MD, Salih Mishlab MD, Emily Avitan-Hersh MD PHD
Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].
Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].
The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].
These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.
Lia Mazur, Avishai M. Tsur MD MHA, Harald Heidecke PhD, Kai Schulze-Forster PhD, Abdulla Watad MD, Howard Amital MD MHA, Yehuda Shoenfeld MD FRCP MaACR, Gilad Halpert PhD
Background: Silicone breast implants (SBIs) are associated with subjective and autoimmune related manifestations, ranging from reported symptoms such as depression and fatigue to diseases such as Sjögren's syndrome and systemic sclerosis.
Objectives: To examine whether autoantibodies directed against autonomic nervous system receptors are associated with reported symptoms of dry mouth and eyes in patients with SBIs.
Methods: ELISA assays were used to evaluate a panel of 11 autoantibodies in the sera of patients with SBIs and age-matched healthy controls.
Results: Four autoantibodies (anti-angiotensin II type 1 receptor, anti-β1 adrenergic receptor, anti-muscarinic receptors M2, and anti-muscarinic receptors MR) had significantly lower median titers in SBI recipients who reported dry mouth compared to the control group (9.9 vs. 15.7, P < 0.001; 8.8 vs. 23.3, P < 0.001; 3.2 vs. 4.7, P < 0.001; and 6 vs. 8.8, P = 0.0011, respectively). Anti-muscarinic receptor M4 had significantly lower median titers in patients with SBIs who reported dry eyes compared to the control group (5.9 vs. 8.8, P = 0.0039).
Conclusions: A dysregulation of the autonomic nervous system in SBI recipients was correlated with the presence of dry mouth and dry eyes. Our results emphasize the need to further investigate the proposed involvement of the autonomic nervous system in subjective symptoms reported by SBI recipients.
Fadi Hassan MD, Firas Sabbah MD, Rula Daood MD, Helana Jeries MD, Tamar Hareuveni MD, Mohammad E. Naffaa MD
Background: Behcet's syndrome (BS) is a multisystem syndrome that typically manifests as recurrent oral and genital ulcers, as well as other systemic manifestations. Few studies describing the characteristics of BS among Israeli patients have been published.
Objectives: To describe the characteristics of BS patients and to compare Jewish and Arab subpopulations.
Methods: We retrospectively reviewed electronic medical records and extracted demographic, clinical, laboratory, and medication data for each patient. We compared the Jewish and Arabic BS patients.
Results: The cohort included 98 patients. Males constituted 49 (50%); mean age at the time of diagnosis was 29.9 years; 71 (72.4%) were Arab and 27 (27.6%) were Jewish. Oral ulcers were evident in 93 patients (94.9%) and genital ulcers in 54 (55.1%). Involvement of the skin, joints, eyes, gastrointestinal tract, and neurologic and vascular systems were demonstrated among 42 (42.9%), 57 (58.2%), 47 (48.0%), 8 (8.2%), 10 (10.2%), and 15 (15.3%), respectively. HLA B51 was positive in 24 of 37 (64.9%). Pathergy was positive in 8 of 12 (66.7%). Colchicine was used in 82 (83.7%), azathioprine 47 (48%), methotrexate 16 (16.3%), apremilast 10 (10.2%), cyclosporine-A 8 (8.2%), adalimumab 26 (26.5%), infliximab 12 (12.2%), cyclophosphamide 1 (1.0%), tocilizumab 2 (2.0%), and anti-coagulation 6 (6.1%). The Arab and Jewish subpopulations were significantly different regarding male proportion, 40 (56.3%) vs. 9 (33.3%), P = 0.042.
Conclusions: BS is more common among Arabs in northern Israel, but no significant clinical or demographic differences were found except for a higher proportion of male patients among Arabs.
Nir Roguin, Amir Cohen MD, Ella Yahud MD, Gabriel Bryk PhD, Michal Cipok PhD, Nadav Sorek PhD, Eyal Ben-Assa MD, Eli I. Lev MD
Background: Inflammatory and thrombotic markers play crucial roles in risk stratification for various diseases.
Objectives: To investigate the relative importance of inflammation, measured by C-reactive protein (CRP), and platelet turnover, indicated by immature platelet fraction (IPF), in predicting outcomes for patients with cardiovascular disease, coronavirus disease 2019 (COVID-19), and bacterial infections.
Methods: In this retrospective observational study, we analyzed data from 1473 individuals admitted to the Samson Assuta Ashdod University Hospital between 2018 and 2022. Patients were categorized based on CRP and IPF levels, with a focus on 280 patients in the high CRP/low IPF or high IPF/low CRP tertiles.
Results: The high CRP low IPF group demonstrated significantly higher mortality rates compared to the low CRP high IPF group (13.5% vs. 0.8%, P < 0.001). Logistic regression analysis revealed that the high CRP and low IPF combination was the strongest predictor of mortality (odds ratio 12.951, 95% confidence interval 1.409–119.020, P = 0.024).
Conclusions: The combination of inflammatory (CRP) and thrombotic (IPF) markers provides superior prognostic information compared to individual disease diagnoses in patients with cardiovascular disease, COVID-19, and bacterial infections.
Saleh Sharif MD, Emran El Ukbi MD, Herschel Horowitz MD, Eran Kalmanovich MD, Dror Cantrell MD
Background: Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).
Objectives: To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).
Methods: We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.
Results: Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.
Conclusions: In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.
Mor Amital MD, Yehuda Shoenfeld MD FRCP MaACR, Arkadi Yakirevitch MD
Chronic cough is a common clinical symptom with a broad differential diagnosis, including respiratory, gastrointestinal, and neurological causes. A rare yet important cause is Arnold’s nerve reflex (ear-cough reflex) and triggered by stimulation of the auricular branch of the vagus nerve. We present the case of a 77-year-old man with a persistent dry cough and no significant medical history other than mild hypertension. The patient reported paresthesia in his left ear and noted that his cough was often triggered by touching the ear. A comprehensive physical and neurological examination, including otoscopy, was performed. Examination revealed cerumen impaction covering the posterior wall of the left external ear canal. Removal of the cerumen immediately triggered a cough but resulted in complete resolution of symptoms within one day. This case emphasizes the importance of considering Arnold’s nerve reflex as an underlying cause of chronic cough. A thorough physical examination, particularly otoscopy, is essential for accurate diagnosis. Understanding the neuropathic basis of the ear-cough reflex provides insights into targeted management including neuromodulator therapy.