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עמוד בית
Thu, 24.07.25

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July 2025
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.

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.

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.

Vered Nir MD, Vered Schichter-Konfino MD, Adi Klein MD

We summarized the role of lung ultrasound for diagnosing and monitoring various pediatric respiratory diseases. We began with an overview of the basics of the tool, followed by describing its use in conditions such as pneumonia, pleural effusion, bronchiolitis, atelectasis, pneumothorax, bronchiectasis, and interstitial lung disease. We highlighted the sensitivity and specificity of lung ultrasound for the various diseases described. Furthermore, we included a comparison of this modality to other commonly used imaging techniques.

June 2025
Robert Brian Schonberger MD MHCDS

The following is the text of a letter to the editor of Lancet, which the editor-in-chief recently notified us of his decision not to publish

Meital Oren-Shabtai MD, Assi Levi MD, Daniel Mimouni MD, Hadas Prag-Naveh MD, Elena Didkovsky MD, Elisheva Pokroy-Shapira MD, Emmilia Hodak MD, Iris Amitay-Laish MD

Background: Mycosis fungoides (MF) combined with photosensitive/autoimmune diseases has been reported, yet there are limited data regarding the therapeutic considerations in these patients, specifically phototherapy, a mainstay skin-directed treatment (SDT), being a relative or complete contra-indication.

Objectives: To outline therapeutic considerations for patients with MF who had also been diagnosed with photosensitive/autoimmune diseases.

Methods: We conducted a retrospective analysis of patients with MF who were treated at our center between January 2008 and December 2024with photosensitive/autoimmune diseases, especially collagen vascular diseases (CVD) or autoimmune bullous diseases (AIBD),

Results: Eight patients were diagnosed with MF at a median age of 39 years. Seven had early-stage (4-IA, 3-IB) and one had Sézary syndrome. Six early-stage MF patients were diagnosed with lupus erythematosus (LE, 4) or AIBD (2) and were treated with SDT (topical corticosteroids/chlormethine gel), systemic retinoid or methotrexate. A patient with resistant early-stage MF and discoid LE was treated with electron beam and interferon. One patient who presented with variegate porphyria and localized MF was treated with electron beam. The patient with Sézary syndrome had inclusion body myositis. He was treated with low-dose total skin electron beam, methotrexate, extracorporeal photopheresis, and subsequently with romidepsin. After a median of 8 years, no stage progression of MF was observed. The Sézary syndrome patient achieved down-staging and was at stage IB. There was no aggravation of the co-morbidity in any of the patients.

Conclusions: Effective management of MF and associated photosensitive or autoimmune co-morbidities underscore the need for individualized treatment strategies in patients with these unique dual diagnoses.

Dania Abu Assab MD, Abraham Zlotogorski MD, Vered Molho-Pessach MD

Background: Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare form of ectodermal dysplasia caused by biallelic mutations in NECTIN4 (PVRL4) gene.

Objectives: To identify new and rare mutations of the NECTIN4 gene in two unrelated families with EDSS.

Methods: Six patients from two unrelated families were diagnosed with EDSS. Next generation sequencing and Sanger sequencing were performed on DNA extracted from peripheral blood from affected and unaffected individuals from the families. We performed a literature search to identify previously reported cases of EDSS.

Results: A homozygous c.680A>G p.His227Arg mutation in NECTIN4 was found in five affected members of both families. One patient was found to be compound heterozygous for the latter mutation and for another novel missense mutation in NECTIN4 (c.79+1G>A). Both mutations affect the extracellular domain of nectin-4. A literature search identified only 13 reported families affected by this rare disorder.

Conclusions: We described two families with six affected members presenting with EDSS caused by two novel NECTIN4 mutations. We also reviewed the current available data on EDSS in the medical literature.

Lehavit Akerman MD, Baruch Kaplan MD, Daniel Mimouni MD, Adi Nosrati MD, Efrat Solomon-Cohen MD MOccH MBA

Background: Radiofrequency-skin interaction is considered self-limited for treating acquired pigmentation such as melasma. Alternatively, skin perforation with microneedling radiofrequency (MNRF) may increase skin bioavailability for depigmenting-mediated ingredients or drugs for the treatment of melasma.

Objectives: To examine the clinical feasibility of topical tranexamic acid (TA) mediated with MNRF-assisted transepidermal delivery in patients with mixed melasma.

Methods: The study protocol included 14 women with centrofacial or malar pattern of distribution of melasma (skin types II-VI; age 35–48 years). Patients underwent four treatments at 3-week intervals between treatments. Treatment protocol included non-insulated MNFR (Intensif, EndyMed Ltd, Caesarea, Israel) followed by TA (hexakapron 4%) solution application. The improvement was evaluated based on clinical photographs (Quantificare, Biot, France) and modified Melasma Area and Severity Index (mMASI) scores. Baseline Photographs were analyzed 3 months after the last treatment.

Results: In 13 patients (93%), mMASI scores were significantly lower after 3 months (mean 3.6) than at baseline (5.22). In one patient, mMASI was higher at 3 months compared to baseline. Overall, mMASI improved by 31% (P < 0.01). Physician and patient satisfaction was high. Minimal adverse reactions were recorded.

Conclusions: MNRF-assisted transepidermal delivery with topical TA is a safe and effective modality for the treatment of melasma.

Mira Hamed MD, Amir Bieber MD, Michael Ziv MD, Guy Feraru MD, Roni P Dodiuk-Gad MD, Eran Cohen-Barak MD, Daniella Kushnir-Grinbaum MD

Anifrolumab is a monoclonal antibody approved by the U.S. Food and Drug Administration in 2021 for the treatment of moderate-to-severe systemic lupus erythematosus (SLE) (excluding renal or neurological involvement). The drug inhibits the type 1 interferon receptor. Its safety and efficacy were evaluated through three placebo-controlled studies [1]. Clinical studies have demonstrated the beneficial effects of anifrolumab as an adjunct to standard therapy for SLE with cutaneous manifestations. Common side effects include upper respiratory tract infections, infusion-related reactions, herpes zoster, and hypersensitivity phenomena. Importantly, no serious skin reactions have been previously associated with the use of anifrolumab [2].

To the best of our knowledge, this is the first reported case of drug-induced bullous pemphigoid (DIBP) following treatment with anifrolumab.

Yoav C. Metzger MD, Shmuel Epshteyn MD, Mor Miodovnik MD PHD

Exercise-induced hematomas are a common condition that are caused by mechanical rupture of small blood vessels in the skin resulting in accumulation of blood in the extracellular space in the dermis. These hematomas often lead to diagnostic dilemmas in dermatological practice as they may resemble other conditions. The term talon noir (black heel) was coined to describe these hematomas as they are often blackish in appearance.

The clinical findings of subcorneal acral hematomas typically include the appearance of a bruise or a discolored purplish patch on the skin [Figure 1A] but may appear also as a black or brownish patch, raising a differential diagnosis of a melanocytic lesion. In this case series we illustrate an unusual presentation of acral hematomas that mimics melanocytic lesions.

Ayelet Ollech MD, Yizhak Confino MD, Rivka Friedland MD, Dan Ben Amitai MD, Vered Molho-Pessach MD, Michal Neumark MD, Jacob Mashiah MD, Liat Samuelov MD, Ayelet Shani-Adir MD, Hiba Zaaroura MD, Eran Cohen-Barak MD, Amir Horev MD, Yulia Valdman MD, Baruch Kaplan MD, Shoshana Greenberger MD

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. Recent advances, particularly in beta-blocker therapy, have significantly improved the management of IHs. Early identification and treatment of IH may help reduce morbidity and associated complications. In this review, experts in pediatric dermatology in Israel who have experience in treating IH formulated national guidelines for the diagnosis and treatment of IHs, providing evidence-based recommendations for selecting appropriate therapeutic approaches. These Israeli national guidelines provide a structured approach to the diagnosis and treatment of IH, emphasizing early referral, appropriate treatment selection, and careful monitoring. The guidelines serve as a critical resource for pediatricians and dermatologists, ensuring optimal patient outcomes while minimizing complications.

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