Israel Medical Association Journal

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.

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.

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.

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.

I read with great interest the comprehensive and interesting paper by Hazzan and colleagues in the Israel Medical Association Journal (IMAJ) [1]. The authors examined the difference in the results between morning and afternoon shifts of colonoscopy procedures. Not to my surprise, they found that more polyps were found in the morning shifts than in those in the afternoon. I believe, as do the authors, that the higher quality of the colonoscopy, the better its efficacy in detecting polyps and preventing colorectal cancer (CRC).

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.

Background: Allergic contact dermatitis (ACD), a prevalent skin disorder marked by delayed hypersensitivity reactions to specific allergens, is commonly diagnosed through patch testing. Previous studies have indicated lower rates of positive patch tests in summer months compared to winter months.

Objectives: To investigate whether there is a difference in the proportion of positive patch test results between summer and winter months.

Methods: A retrospective study was performed on 1128 patients, with 14 individuals undergoing two tests each, resulting in a total of 1142 patch tests. The tests were conducted at a major tertiary referral center between 2016 and 2020. The data set encompassed patient demographics and comprehensive patch test results.

Results: Of the 1142 tests conducted, 808 (70.8%) yielded a positive response. The most frequently administered test series was the European standard series, conducted for 1135 (99.3%) of the tests, with 559/1135 (49.2%) showing positive results, followed by the cosmetics series (394/1120, 35.1%) and fragrances series (61/118, 51.7%). No statistically significant difference was observed in the proportion of positive patch tests between summer and winter months (313/419, 74.7% vs. 175/245, 71.4%, respectively; P-value = 0.35). There was no statistically significant difference in the rate of testing each specific series between the summer and winter months, except for the fragrances series.

Conclusions: We found no significant difference in the positive patch test rates between the summer and winter months. Therefore, patch testing can be reliably conducted during the summer without an increased risk of false-negative results.

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.

Pott’s Puffy tumor (PPT) is a rare complication of frontal sinusitis, involving a subperiosteal abscesses with associated osteomyelitis of the frontal sinus anterior table. It mainly affects children and adolescents but can also occur in adults. It presents with localized forehead swelling, pain, fever, headache, and sometimes intracranial complications like epidural or subdural abscesses [1,2]. The standard treatment for PPT typically involves surgical drainage under general anesthesia and broad-spectrum intravenous antibiotics. During the coronavirus disease 2019 (COVID-19) pandemic (March–June 2020), delayed surgeries and resource limitations led to the use of minimally invasive techniques [3] such as needle aspiration without general anesthesia. In this study, we present three adult PPT cases from Nottingham University Hospitals, United Kingdom, treated with early abscess aspiration during this period.

We conducted retrospective study of PPT cases presented during the early COVID-19 pandemic. Following patients’ consent, case notes were reviewed for baseline demographics, previous treatments, presenting symptoms, and examination findings.

Background: Prior to the coronavirus disease 2019 (COVID-19) pandemic, bronchiolitis caused by respiratory syncytial virus (RSV) was primarily observed during the winter months. Recently, however, an increase in incidence during the warmer months has been noted. This trend suggests an interaction between RSV and coronavirus, as well as the impact of public health measures, such as hand hygiene, mask-wearing, and social distancing.

Objectives: To characterize bronchiolitis cases in children under 2 years old caused by RSV during the COVID-19 pandemic in Israel from 2018 to 2022.

Methods: We conducted retrospective study by analyzing medical records of children hospitalized with bronchiolitis from January 2018 to December 2022. A comparison was made between cases before and after the first COVID-19 lockdown.

Results: A total of 922 children with bronchiolitis were studied: 276 cases occurred before the lockdown and 646 cases afterward. We found an increase in bronchiolitis frequency during the summer following the lockdown and a decrease during the winter (P < 0.0001). In addition, there was a shift in the pathogenic profile, with a notable rise in mixed infections after the lockdown (P < 0.0001). No significant differences in clinical presentation were observed between pre- and post-lockdown periods.

Conclusions: There was a change in bronchiolitis seasonality after the lockdown, with a significant increase in cases during the summer and a rise in mixed infections. Further studies are needed to assess whether this shift is a lasting consequence of the pandemic or a temporary change.

Background: Coronavirus disease-2019 (COVID-19) chest computed tomography (CT) involves ground-glass opacity (GGO) and denser consolidations, which are crucial for diagnosis.

Objectives: To determine optimal window settings for characterization and detection of GGO and dense consolidation on CT imaging in COVID-19 patients using a Simplex-based approach.

Methods: The study included 54 conventional CTs of COVID patients in two phases. First, CT images of 14 patients with GGO and 4 with dense consolidation were included. Seven radiologists evaluated representative images in different windows of varied width and center. They were graded for adequacy of characterization and detection. A Simplex algorithm was used to iteratively determine the optimal window settings. Surface response maps expressing the relationship between window settings and overall reader grades were constructed. Next, the reviewers compared manufacturer recommendations to the new optimal windows found on CT images of 40 patients.

Results: Overall, 12 different window settings were evaluated over a total of 1176 reads. Optimal characterization and detection of pure GGO was seen with a center of 630 HU and width 1460 HU, producing higher grades for both detection and characterization than the manufacturer window settings (P = 0.005). Optimal windowing for dense consolidation was like manufacturer measures (-585 HU and 1800 HU). In phase 2, an overwhelming preference of 78% favoring the optimal window compared to conventional settings was found.

Conclusions: GGO lung opacities characteristic for COVID-19 can be best seen using a lower CT windowing width than the manufacturer's recommendations, unlike denser consolidations, possibly due to differences in underlying pathophysiology.

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm² IQR [1–39] vs. 46 cm² [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Acute otitis externa (AOE) is typically a bacterial infection of the external auditory canal, which is most commonly caused by Pseudomonas aeruginosa. Although AOE occurs in all age groups, it is rarely observed in children under 2 years of age [1]. Ear drainage in a neonate is a relatively uncommon finding in the neonatal intensive care unit (NICU) population. This diagnosis requires confirmation by otoscopy [2,3].

Osteomyelitis of the temporal bone, also referred to as necrotizing otitis externa, is a severe form of infection that may develop typically in diabetic or immunocompromised patients, including premature infants. Similar to simple AOE, Pseudomonas aeruginosa is the most common pathogen [4,5]. In the NICU setting it mostly causes infection in immunocompromised hosts such as premature infants [3].

A 71-year-old man with a history of hypertension, type 2 diabetes mellitus, and dyslipidemia was admitted for unstable angina. He subsequently underwent coronary angiography. Approximately 2 hours after successful percutaneous coronary intervention (PCI), he reported a burning and itching sensation on his buttocks. The patient had no history of atopy or drug hypersensitivity. Physical examination revealed a bilateral erythematous, warm, tender, blistering rash localized to his buttocks [Figure 1A].

Background: Solid organ transplant (SOT) recipients represent a particularly vulnerable group due to their reliance on immunosuppressive therapies. Previous studies indicated a mortality rate of 20%-30% among SOT recipients with coronavirus disease 2019 (COVID-19). With the advent of the Omicron variant in November 2021, characterized by milder symptoms and lower mortality rates in the general population, safety measures relaxed, potentially impacting vulnerable populations like SOT recipients.

Objectives: To investigate mortality and morbidity among hospitalized SOT recipients with COVID-19 infection during the Omicron wave.

Methods: A retrospective, propensity-matched cohort study conducted at the Rabin Medical Center, Israel, spanned from November 2021 to June 2023. Adult SOT recipients hospitalized with COVID-19 were compared to matched controls.

Results: Among 139 hospitalized SOT recipients and 209 controls, SOT recipients hospitalized with COVID-19 displayed higher in-hospital mortality (19% vs. 11%) and 90-day all-cause mortality (30% vs. 17%). In addition, the 90-day readmission rate was significantly higher among SOT recipients (43% vs. 31%). Multivariable analysis confirmed these trends, with SOT recipients exhibiting increased risk for mortality, readmission, invasive ventilation, and intensive care unit admission.

Conclusions: The heightened vulnerability of hospitalized SOT recipients during the Omicron wave was characterized by higher mortality and readmission rates compared to matched controls. Despite the perceived milder nature of the Omicron variant, SOT recipients remain disproportionately affected. Continued vigilance and targeted interventions are necessary for this population including vaccinations and adherence to preventive measures. Investigating this population’s outcomes through the changing COVID-19 variants is still warranted.