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.

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.

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.

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.

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.

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.

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: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

Background: Acute bronchiolitis, primarily caused by respiratory syncytial virus (RSV), is the leading cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity.

Objectives: To evaluate the association between C-reactive protein (CRP) serum levels on admission and disease severity in children hospitalized due to RSV bronchiolitis.

Methods: This retrospective cohort study included children (0–24 months old) who were hospitalized due to RSV bronchiolitis (2018–2022), CRP levels taken at admission.

Results: We included 1874 children (mean age of 6.7 months, 59% males); median CRP level 1.92 mg/dl. Children with elevated CRP (> 1.92 mg/dl) were significantly older (5.1 vs. 3.8 months, P < 0.001) and had higher rates of pneumonia (9.4% vs. 4.3%, P < 0.001), urinary tract infection (UTI), (2.2% vs. 0.2%, P < 0.001), acute otitis media (AOM) (1.7% vs. 0.2%, P < 0.001), admissions to the pediatric intensive care unit (PICU) (7.4% vs. 3.7%, P < 0.001), antibiotic treatment (49.8% vs. 37.2%, P < 0.001), and longer hospitalizations (3.83 vs. 3.31 days, P < 0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk 11.6, 2.25, 1.98, 1.44, respectively, P < 0.001). CRP thresholds of 3.51, 1.9, and 2.81 mg/dl for PICU admission, UTI, and pneumonia, were calculated using Youden's index with AUC 0.72, 0.62, and 0.61, respectively.

Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Background: Giant cell arteritis (GCA) is a large vessel vasculitis predominantly affecting patients over 50 years, typically managed with glucocorticoids, with treatment varying on individual patient needs. While effective for GCA, long-term glucocorticoids use poses significant risks, including the development of osteoporosis, a metabolic bone disease common in older individuals. This overlap poses a significant clinical challenge, as the treatment for GCA inadvertently raises the risk of osteoporosis and necessitates careful balance to manage both conditions effectively.

Objectives: To investigate the occurrence of osteoporosis and other co-morbid conditions in patients with GCA treated with glucocorticoids.

Methods: A retrospective cross-sectional analysis of GCA patients examined the correlation between GCA and osteoporosis by searching the Clalit Health Service database for patients over 50 years of age from January 2002 to January 2018. In addition, we conducted a logistic regression analysis stratifying for other co-morbidities to evaluate the independent association between GCA and osteoporosis.

Results: In total, 6607 GCA patients were compared with 36,066 age- and sex-matched controls. The study revealed a higher prevalence of osteoporosis in the GCA group (43%) compared to controls (27%) (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.95–2.17). In addition, hypertension, hyperlipidemia, diabetes mellitus, and ischemic heart disease were more prevalent among GCA patients. After stratifying for cardiovascular co-morbidities, GCA remained independently associated with osteoporosis (OR 2.1, 95%CI 1.96–2.26, P < 0.001).

Conclusions: Glucocorticoid-treated GCA is independently associated with osteoporosis. Healthcare providers must consider this added aspect of GCA for the treatment and management of patients.

Background: The lifestyle of the Arab population in Israel has changed in the last few decades, and modernization and urbanization have impacted the prevalence of chronic diseases.

Objectives: To investigate the prevalence of chronic diseases in the Arab population compared to the Jewish population in Israel.

Methods: This retrospective study included Arab and Jewish people insured by Israel’s largest health maintenance organization. Demographic data and data regarding chronic diseases were collected. Crude prevalence and age group adjusted prevalence were calculated.

Results: In total, 863,116 Arab and 3,674,863 Jewish people were included in the analysis. We found that 18.3% of the Arab population had a diagnosis of diabetes mellitus and 28.8% had obesity compared to 17.5% and 22.5% in the Jewish population, P < 0.001, respectively. The prevalence of chronic heart failure, chronic ischemic heart disease, cerebrovascular accidents, hypertension, and myocardial infarction among Arabs was higher in all age groups compared to Jewish patients. Arab males had higher frequency rates of obesity and hemodialysis treatment compared to Jewish males. The proportion of women with diabetes mellitus, hemodialysis treatment, iron deficiency anemia, or obesity was greater among Arab females.

Conclusions: Significant differences were found in the prevalence of chronic diseases among Arab and Jewish patients in Israel. Culturally relevant interventions are crucial for disease prevention, early diagnosis, and management of chronic diseases among different ethnic groups.

Background: Hemodialysis requires reliable, recurrent access to the circulatory system. Central venous tunneled dialysis catheters (TDC) are frequently used for patients receiving hemodialysis as a bridge to permanent vascular access or as a final option. TDC are prone to complications such as infection and dysfunction.

Objective: To assess the prevalence and predictors of TDC dysfunction in a cohort of chronic hemodialysis patients.

Methods: This single-center, retrospective study was based on data from an electronic database of chronic hemodialysis patients during 5 years of follow-up.

Results: A total of 625 TDC were inserted in 361 patients, of which 234 (37.4%) were replaced due to dysfunction. The main insertion site was the right internal jugular vein. Diabetes mellitus was an important predictor of TDC dysfunction and was significantly correlated with TDC extraction. Chronic anticoagulation and antiplatelet treatment did not affect the rate of TDC dysfunction or replacement.

Conclusions: TDC use for chronic dialysis patients is increasing and dysfunction is a major problem. In our study, we highlighted the high prevalence of TDC dysfunction and the need for further research to improve hemodialysis access as well as TDC patency and function.

Background: Data regarding the management of adnexal torsion (AT) during the coronavirus disease 2019 (COVID-19) pandemic are scarce.

Objectives: To study the effects of actions to limit the spread of COVID-19 on AT management.

Methods: We conducted a retrospective cohort study of all women who underwent laparoscopy for suspected AT between March 2011 and February 2021. We compared the COVID-19 pandemic period, (15 March 2020–2 August 2021, group A) to a parallel period (2019–2020, group B), and a 9-year period preceding the pandemic (March 2011–February 2020, group C).

Results: We performed 97 laparoscopies in group A, 82 in group B, and 635 in group C. The proportion of women presenting following in vitro fertilization treatment was lower (odds ratio [OR] 0.22, 95% confidence interval ]95%CI] (0.06–0.86), P < 0.023). Time from admission to decision to operate was shorter (2.7 vs. 3.9 hours, P = 0.028) in group A than group B. Time from admission to surgery was shorter (9.1 vs. 12.5 hours, P = 0.005) and the rate of surgically confirmed AT was lower (59 [60.8%] vs. 455 [71.7%], P = 0.030, OR 0.61, 95%CI 0.39–0.95) in group A than group C. Among surgically confirmed AT cases only, mean time from admission to decision was shorter in group A than group B (2.6 vs. 4.6 hours, P = 0.014).

Conclusions: We identified differences in time from admission to clinical decision and from admission to surgery among women with suspected AT during the COVID-19 pandemic.

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.