Israel Medical Association Journal

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.

Artificial Intelligence (AI), particularly large language models (LLMs) like OpenAI's ChatGPT, has shown potential in various medical fields, including pediatrics. We evaluated the utility and integration of LLMs in pediatric medicine. We conducted a search in PubMed using specific keywords related to LLMs and pediatric care. Studies were included if they assessed LLMs in pediatric settings, were published in English, peer-reviewed, and reported measurable outcomes. Sixteen studies spanning pediatric sub-specialties such as ophthalmology, cardiology, otology, and emergency medicine were analyzed. The findings indicate that LLMs provide valuable diagnostic support and information management. However, their performance varied, with limitations in complex clinical scenarios and decision-making. Despite excelling in tasks requiring data summarization and basic information delivery, the effectiveness of the models in nuanced clinical decision-making was restricted. LLMs, including ChatGPT, show promise in enhancing pediatric medical care but exhibit inconsistent performance in complex clinical situations. This finding underscores the importance of continuous human oversight. Future integration of LLMs into clinical practice should be approached with caution to ensure they supplement, rather than supplant, expert medical judgment.

Gaucher disease (GD) is an inherited autosomal recessive genetic disorder caused by mutations in the glucocerebroside (GBA1) gene [1]. These variants result in decreased activity of the lysosomal enzyme β-glucocerebrosidase (GCase), which is essential for breaking down glucocerebroside into glucose and ceramide. Consequently, activated macrophages, known as Gaucher cells, accumulate undegraded glucocerebroside. The phagocytic role and naturally high-level GCase activity of macrophages may partly explain why these cells are particularly affected in GD. The accumulation of glucocerebroside in macrophages causes an expansion in the population of these cells, leading to symptoms like hepatosplenomegaly, thrombocytopenia, anemia, bleeding tendency, growth retardation, and bone issues. Bone marrow infiltration may result in bone infarction, episodes of bone crises, and osteonecrosis, mainly of large joints and less commonly as pathological fractures. These latter skeletal complications are the most critical irreversible consequence of untreated GD, significantly impacting the quality of life of patients, and hence should be avoided by early administration of specific therapy. The accumulation of glucocerebroside in lysosomes has been linked to a pro-inflammatory state [2]. In addition, the misfolding and retention of mutant GCase within the endoplasmic reticulum (ER) has been associated with ER stress and activation of the unfolded protein response, contributing to GD phenotypic heterogeneity, inflammation, and immune dysregulation [3].

It is indisputable that internal medicine is the cornerstone of medical activities, including medical education, in hospital clinical activities, and clinical and basic medical research.

The medical landscape in Israel is exceptionally demanding, far exceeding the norms of the countries that are members of the Organisation for Economic Co-operation and Development (OECD). We have fewer hospital beds per capita, a greater workload for each physician, and in the future, we will face the challenge of teaching more medical students across our current clinical fields.

The Israeli Society of Internal Medicine has made it its mission to advance internal medicine across all dimensions of the healthcare system in Israel. As such, for the third consecutive year, we are honored to present an issue of the Israel Medical Association Journal (IMAJ) dedicated to research in the different fields of internal medicine that are conducted by physicians from various departments across the country.

This year, we emphasize even more strongly that research is an integral part of our clinical practice. At a time when the basic sciences phase of residency is under threat, it is crucial to underscore its importance. In this issue of IMAJ, we have chosen to publish various studies that were conducted during the basic sciences phase of the residency in internal medicine, highlighting how this training period can be optimally utilized to advance research while simultaneously progressing and maturing through clinical training.