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.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract, with an estimated prevalence of 1 in 100,000 individuals. While most cases follow an autosomal dominant inheritance pattern, some are caused by de novo mutations [1].

The age of onset for JPS is typically during childhood or adolescence, with a mean age at diagnosis of 18.5 years [2]. A major concern in JPS is the increased risk of colorectal cancer (CRC), requiring close lifelong surveillance. The cumulative lifetime risk for CRC ranges from 38% to 68%, with a mean age at diagnosis between 34 and 44 years [3].

Although juvenile polyps were initially considered to have low malignant potential, studies have identified two pathways of carcinogenesis in JPS: progression from hamartomatous polyps to adenoma and then to adenocarcinoma or direct transformation of hamartomatous polyps into adenocarcinoma. The management of JPS is tailored to each patient's specific manifestations and clinical presentation. The primary treatment goal is to prevent morbidity associated with gastrointestinal polyps, such as bleeding and intestinal obstruction.

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

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.

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.

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: Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. There are conflicting reports on whether colonoscopies performed during the morning shift have higher adenoma detection rates.

Objectives: To investigate the differences in polyp detection rate (PDR) in colonoscopies between morning and afternoon shifts.

Methods: In a retrospective, multicenter study involving a large cohort, we analyzed all colonoscopies conducted between 2016 and 2023 across seven endoscopy departments. The PDR was compared between morning and afternoon shifts.

Results: We included 368,997 colonoscopies: 213,795 (57.9%) performed during the morning shift and 155,202 (42.1%) during the afternoon shift. Patients undergoing colonoscopies during the morning shift were more frequently female (53.8% vs. 51%, P < 0.001) and tended to be older compared to those in the afternoon shift (average age of 56.97 ± 12.6 vs. 55.6 ± 12.9, P < 0.001). Colonoscopies conducted during the morning shift exhibited a higher cecum intubation rate (CIR) (96.7% vs. 95.6%, P < 0.001). During the morning shift, higher rates of PDR (32.9% vs. 29.9%, P < 0.001) were observed. In the multivariate analysis, after adjusting for other variables, age, male sex, polyp follow-up, fecal occult blood test, morning shift, familial history of CRC, and rectal bleeding demonstrated statistically significant associations (P < 0.001) for PDR.

Conclusions: Colonoscopies during the morning shift yielded a higher PDR and CIR than those in the afternoon. To improve this rate, endoscopists working the afternoon shift must be provided with the right conditions.

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].

We presented the emergent development of pulmonary hypertension and right ventricular impairment in a 64-year-old woman with metastatic breast cancer undergoing carboplatin–gemcitabine combination therapy. The patient's acute decompensation, characterized by dyspnea and desaturation, occurred 2 days after chemotherapy initiation. Clinical assessments revealed right ventricular dilation and systolic dysfunction, a rare manifestation not previously associated with the administered drugs, but which may be associated with cardiopulmonary toxicity of gemcitabine therapy. Prompt discontinuation of chemotherapy and initiation of diuretic therapy resulted in clinical improvement and resolution of the right ventricular dysfunction within several weeks. While a definitive causal link to gemcitabine remains inconclusive, this report highlights a potential and under-reported side effect, emphasizing the need for increased awareness and further investigation into the cardiopulmonary effects of gemcitabine.

Background: Ascites is a product of fluid accumulation within the peritoneal cavity. Underlying etiologies include cirrhosis, congestive heart failure (CHF), nephrotic syndrome, and malignancies. Patients with cirrhotic ascites are at increased risk for infections, especially spontaneous bacterial peritonitis (SBP), which is associated with high rates of morbidity and mortality. Ascites is diagnosed both clinically and sonographically. SBP is diagnosed via abdominal paracentesis, a relatively safe and effective procedure. However, abdominal paracentesis carries risks such as bleeding, bowel perforation, and infection.

Objectives: To identify new inflammatory markers as alternative or replacement methods for accurately evaluating patients before and after abdominal paracentesis and how these new inflammatory markers can be evaluated from a simple, inexpensive, and routinely performed blood sample.

Methods: A total of 106 patients admitted with ascites were classified into three groups based on the underlying etiology of their condition: malignant ascites (30 patients), ascites secondary to CHF (30 patients), and ascites secondary to cirrhosis (46 patients). Levels of neutrophil-lymphocyte ratio (NLR), mean platelet volume, and C-reactive protein among the study groups were examined through blood samples and subsequently compared

Results: NLR values within malignant ascites and CHF ascites were significantly higher than cirrhotic ascites (P = 0.002). In addition, among risk factors for developing ascites, significant correlations were found among the three groups in hypertension (P < 0.001), diabetes mellitus (P = 0.003), hyperlipidemia (P = 0.002), CHF (P < 0.001), and ischemic heart disease (P < 0.001) variables.

Conclusions: NLR may be a prognostic tool in patient evaluation of ascites.

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.

Minocycline is a tetracycline antibiotic prescribed to treat various infections, acne vulgaris, and rosacea. In addition to its antibiotic activity, it possesses anti-inflammatory properties, including reducing the production of proinflammatory cytokines, suppressing neutrophil chemotaxis, activating superoxide dismutase, and inhibiting phagocytosis. Among its side effects are hypersensitivity syndrome reactions, drug-induced lupus, and polyarteritis nodosa (PAN) [1].

Background: Chest radiograph is a standard procedure for diagnosis of pneumonia; however, interpretation shows considerable variability among observers.

Objectives: To assess the extent of agreement between pediatric residents and board-certified radiologists in interpretation of chest radiography for detection of pneumonia. To evaluate the impact of resident experience, patient age, and signs of infection on this phenomenon.

Methods: The cohort included 935 patients with suspected pneumonia admitted to the pediatric emergency department at a non-tertiary medical center in Israel 2019–2021. All patients had chest radiographs interpreted by a resident and a radiologist. Interobserver agreement was assessed using Κ and prevalence-adjusted bias-adjusted κ (PABAK) with 95% confidence intervals (95%CI). Results were stratified by resident experience (junior or senior), patient age (≤ 3 vs. > 3 years), white blood cells (≤ 15,000 vs. > 15,000 cells/ml), C-reactive protein (≤ 5 vs. > 5.0 mg/dl), and temperature (< 38.0°C vs. ≥ 38.0°C).

Results: Moderate agreement between pediatric residents and radiologists was demonstrated for diagnosis of pneumonia (κ= 0.45). After adjustment for disease prevalence, the extent of agreement increased to near-substantial (PABAK= 0.59, 95% confidence interval 0.54–0.64). The extent of agreement was higher for children over 3 years of age and in patients without clinical or biochemical features of pneumonia, especially when diagnosis of pneumonia was ruled out.

Conclusions: A second reading of chest radiographs by an experienced radiologist should be considered, particularly for patients younger than 3 years of age and in those with signs of infection and an initial diagnosis of pneumonia.

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.