Israel Medical Association Journal

Background: Acute myocarditis (AM) is an inflammatory cardiac condition with heterogeneous clinical manifestations that often overlap with other acute cardiac syndromes, making diagnosis challenging.

Objectives: To characterize the prevalence, clinical profile, and outcomes of AM patients with respiratory viral pathogen detection on nasopharyngeal swabs at admission.

Methods: We retrospectively analyzed all patients admitted to the Sheba Medical Center with confirmed AM between January 2005 and December 2020. Diagnosis was based on compatible presentation, elevated cardiac biomarkers, and supportive imaging findings. Nasopharyngeal swab results, when performed, were reviewed for respiratory viral detection.

Results: Among 425 identified AM cases, 146 (34%) underwent swab testing; 11 (8%) tested positive for respiratory viral pathogens, most commonly influenza A (n=5) and adenovirus (n=3). With one exception, all positive cases occurred during winter or early spring (10/77, 13%). Compared with swab-negative patients, swab-positive individuals were older (47 ± 22 vs. 35 ± 14 years, P = 0.03), more frequently female (45% vs. 14%, P = 0.007), and more often presented with dyspnea (55% vs. 25%, P = 0.036) but less commonly with ST-segment elevation (27% vs. 70%, P = 0.003). No differences were observed in inflammatory markers, imaging findings, or hospital stay.

Conclusions: Respiratory viral detection in AM is uncommon and predominantly seasonal. Nasopharyngeal swabbing is a simple, non-invasive tool that may help identify treatable viral pathogens and guide patient management. These data provide a pre-COVID-19 reference for future studies investigating the impact of viral infection on myocardial injury.

It begins with a siren, a deep, pulsating wail tearing through the night over Tel Aviv. It is 3:42 in the morning. A university student jolts awake and rushes to a reinforced room. A young couple gathers their infant and runs for the stairwell. An elderly man descends slowly toward a neighborhood shelter. They each have 90 seconds or less to get to safety. Since 7 October 2023, Israel’s Home Front Command has issued over 60,000 rocket alerts and more than 7000 UAV alerts nationwide. For much of the population, this interval, often shorter near border regions, marks the boundary between safety and danger. Beyond acute threat, these alerts impose a repeated physiological stressor that intrudes into one of the most vulnerable human states: sleep.

Background: Neurofilament light chain (NfL) is an established biomarker for detecting axonal injury in various neurological disorders. The Quanterix Single Molecule Array (Simoa) is the current standard; however, automated immunoassays, such as the Siemens Atellica and Centaur, may serve as alternatives.

Objectives: To compare NfL measurements obtained with the Centaur system to those from the Simoa-SR-X. To assess their agreement and applicability in clinical practice, research, and animal studies.

Methods: NfL levels were measured in 27 human serum, 8 plasma, and 16 cerebrospinal fluid (CSF) samples, and 9 murine serum samples, by Centaur and Simoa systems. NfL levels in concomitantly drawn serum and plasma were compared in 8 humans. The agreement between platforms was evaluated.

Results: NfL levels measured by Centaur and Simoa systems demonstrated a strong correlation in serum (Spearman r=0.97, P < 0.0001) and plasma (Pearson R²=0.95, P < 0.0001). Centaur measurements were higher (P = 0.01) than Simoa. Most importantly, system-specific Z-scores corrected these differences. Serum and plasma levels measured by the Centaur system correlated strongly (R²=0.98, P < 0.0001) and showed similar results. CSF levels measured by the Centaur system were lower (52% bias) than those measured by Simoa, with poor correlation at concentrations within the normal range (R²=0.32, P = 0.11). Mouse serum results showed a strong correlation between systems (R²=0.86, P < 0.001) with similar values.

Conclusions: The Centaur system offers an alternative to Simoa for measuring NfL in human serum, plasma, and murine serum. System-specific age-adjusted Z-scores are essential for interpretation. CSF evaluation requires further assessment.

Background: Transgender and gender diverse (TGD) adolescents often experience higher rates of psychiatric co-morbidities, autism spectrum disorder (ASD), and autistic traits. A few studies have described TGD adolescents who were referred to psychiatric clinics. To the best of our knowledge, no study has yet compared clinical characteristics of autistic vs. nonautistic TGD adolescents.

Objectives: To describe the demographic and clinical characteristics of TGD adolescents referred to a tertiary child and adolescent psychiatric clinic, and to compare the characteristics of autistic and nonautistic TGD adolescents.

Methods: We conducted a retrospective study of 28 TDG adolescents who were consecutively referred for psychiatric evaluation in a child and adolescent psychiatric clinic at a tertiary children's hospital between December 2020 and February 2023. Data were collected from electronic medical files.

Results: Of the sample, 67.9% first questioned their gender identity after the onset of secondary sex characteristics (pubertal onset) and 35.7% were identified as gifted. The gifted group had a higher rate of pubertal onset compared to the nongifted group. Our cohort exhibited a higher rate of ASD (39.3%) than the general population. Autistic compared to nonautistic TGD adolescents had a higher rate of giftedness and a lower rate of social transition.

Conclusions: TGD adolescents referred for psychiatric evaluation display distinct features, including high rates of ASD, giftedness, and pubertal onset. Autistic compared to nonautistic TGD are more likely to be gifted and less likely to have undergone social transition.

Background: Primary achalasia is a rare disorder but a significant cause of esophageal motor dysfunction. The pathophysiology of achalasia is still unknown, although an autoimmune etiology is suspected.

Objectives: To examine the presence of autoantibodies against autonomic nervous system receptors among primary achalasia patients.

Methods: In this observational cross-sectional study, we measure the levels of serum autoantibodies targeting G protein-coupled receptors of the autonomic nervous system, including adrenergic, muscarinic, endothelin, and angiotensin receptors. The study included 40 primary achalasia patients and 40 healthy controls without known history of achalasia, autoimmune diseases, or symptoms of an esophageal motility disorder.

Results: A statistically significant low level of autoantibodies against the M2 muscarinic receptor was observed in the serum of primary achalasia patients compared with the control group (P < 0.009). When exploring the two common achalasia types, a statistically significant low level of autoantibodies against type M1, M2, and M5 muscarinic receptors was observed among type 2 achalasia patients compared to patients with type 1 achalasia.

Conclusions: The finding of reduced levels of autoantibodies targeting the M2 muscarinic receptor in the serum of primary achalasia patients provides a valuable insight into the underlying pathogenesis of the disease.

Research into the genetic basis of homosexuality and broader sexual diversity has progressed from early 20th-century sexology to modern genomics. Von Krafft-Ebing and Hirschfeld first suggested heritable influences, and Kallmann’s twin studies in the 1950s introduced a systematic framework to separate genetic from environmental contributions to sexual orientation. Twin and related designs subsequently reported heritability estimates of 31–74% in males and 27–76% in females. Despite periodic critiques, the equal-environment assumption has remained broadly methodologically robust. Genome-wide association studies (GWAS) marked a major advance. Although early studies were limited by sample size, recent large-scale GWAS have identified significant single-nucleotide polymorphism associations with same-sex sexual behavior, reinforcing a complex, polygenic architecture. Polygenic scores (PGS) or polygenic risk scores (PRS) now offer quantitative estimates of individual genetic predisposition and may help build integrative models of human sexual behavior when combined with environmental and developmental data. Future work should harmonize phenotype definitions across identity, attraction, and behavior; aggregate measures to reduce noise; and adopt systems-level, multi-omics approaches that move beyond reductionism. Interdisciplinary collaboration across genetics, neuroscience, psychology, and social sciences is essential, in addition to greater attention to understudied domains (female homosexuality, sexual fluidity, bisexuality, pansexuality/polysexuality, asexuality, and transgender/trans-sexuality). Community-based participatory research can improve inclusivity and real-world relevance. Overall, the field has moved beyond a single gay gene toward models integrating genetic, epigenetic, and environmental influences, with sexogenomics together with GWAS, PGS/PRS and system biology providing a unifying framework that also engages ethical and societal dimensions.

Spinal stenosis is a progressive degenerative condition characterized by the narrowing of the spinal canal, leading to compression of the spinal cord and nerve roots [1]. While commonly associated with aging, it can also develop following traumatic injuries that induce structural damage and chronic inflammation and contribute to canal narrowing [1]. Although spinal stenosis is primarily linked to neurogenic claudication, emerging evidence suggests that it may also impact respiratory function, particularly when it involves the cervical and thoracic spine [2].

We evaluated a 77-year-old male with a longstanding history of spinal stenosis and exertional dyspnea. We explored the potential connection between his symptoms and underlying spinal pathology, particularly in the absence of cardiopulmonary disease.

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems globally, affecting chronic disease management like osteoporosis and the prevention of fragility hip fractures. We hypothesized that it led to suboptimal prevention of secondary femoral neck fractures, reduced treatment frequency, and delayed treatment initiation.

Objectives: To evaluate the treatment initiation rate for secondary prevention of femoral neck fractures, comparing pre-COVID-19, COVID-19, and post-COVID periods, considering patient demographics.

Methods: This retrospective diagnostic cohort study used automated electronic medical records database from Clalit Health Services. Data regarding patients with hip fractures from January 2017 through September 2021 were extracted from the database. Treatment for osteoporosis included one of the following treatments: alendronate, risedronate, zoledronate, abaloparatide, denosumab, romosozumab, and teriparatide. The primary outcome variable in the study is the time taken to initiate appropriate therapy for the secondary prevention of femoral neck fractures.

Results: Treatment frequency decreased over time, with rates declining from 40.4% in 2019 to 33.5% in 2021 (P-value < 0.05). However, the percentage of prompt care management (within 3 months) increased between 2020 and 2021 (47.3%–62.5%) and between 2019 and 2021 (48.7%–62.5%), P < 0.05.

Conclusions: The COVID-19 pandemic reduced the rate of appropriate treatment initiation following hip fractures. However, adherence to timely treatment within 3 months of the fracture has improved. The findings highlight the effectiveness of the health system response in managing crises and ensuring the timely delivery of critical treatment.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal metastasis from colorectal cancer (PM-CRC). The peritoneal carcinomatosis index (PCI) measures disease burden.

Objectives: To evaluate the effect of PCI on short- and long-term outcomes of patients with PM-CRC who underwent CRS-HIPEC.

Methods: We retrospectively analyzed 120 PM-CRC patients who underwent CRS-HIPEC, categorizing them into four PCI groups (PCI ≤ 3, PCI 4–6, PCI 7–11, PCI >11). We evaluated perioperative outcomes and long-term survival.

Results: Higher PCI scores were associated with increased surgical complexity, longer operative times, more organ resections, and higher blood transfusion requirements. Complete cytoreduction was achieved in 100% of the PCI ≤ 3 group, but only in 70.8% of the PCI > 11 group (P = 0.001). Postoperative outcomes showed a trend toward less major morbidity in low PCI patients (16.7% vs. 28%) and significantly shorter hospital stays (10–13 days vs. 19 days, P = 0.006). The 90-day mortality rate was 0% in the PCI ≤ 3 group compared to 11.5% in the PCI > 11 group. Long-term outcomes revealed significantly better disease-free survival (DFS) and overall survival (OS) for the PCI ≤ 3 group (DFS: 22 months vs. 4–6 months; OS: 79.6 months vs. 21–40 months, P < 0.001).

Conclusions: Patients with low PCI scores experience reduced morbidity and improved long-term survival, supporting the use of CRS-HIPEC in this subgroup. Further research is needed to enhance treatment strategies for patients with high PCI scores.

Background: Transcatheter aortic valve implantation (TAVI) has become the preferred therapeutic method for elderly patients presenting with severe symptomatic aortic stenosis (AS). Most TAVI procedures are performed in patients between 75–85 years of age. A few publications exist on TAVI in patients over 90 years, yet the outcome and complication rates are inconsistent.

Objectives: To identify all patients with AS who underwent TAVI between 2019 and 2020, specifically those age > 90 years at the time of the TAVI.

Methods: We reviewed the Maccabi Healthcare Services database for all severe/critical AS patients who underwent TAVI between 2019 and 2020, specifically those age > 90 years at the time of TAVI. These patients were compared to all patients aged 80–89 years who underwent TAVI during the same time. Follow-up ended on 31 December 2022. We compared mortality and complications rates in nonagenarians vs. those 80–89 years and evaluated the change in left ventricular ejection fraction before and after the procedure.

Results: We identified 36 nonagenarians who underwent TAVI during the study period, mean age 92.3 years, male:female ratio 15:21. During a mean follow-up period of 3 years, 44% of nonagenarians died, 26% of the control patients died (P < 0.01).

Conclusions: TAVI in nonagenarians is feasible. Total mortality during follow-up was significantly higher in nonagenarians. Overall complication rates were also higher in nonagenarians, mostly due to vascular complications. Left ventricular dysfunction appeared to improve after TAVI, even in nonagenarians.

Background: Carbohydrate counting (CC), a recommended method for managing insulin bolus in patients with Type 1 diabetes mellitus (T1DM), depends on patient cognitive ability and motivation, and often does not account for ethnic foods. We have developed a simplified, accessible, patient-specific carbohydrate counting tool (SCC) to serve our very diverse population.

Objective: To retrospectively evaluate the long-term efficacy of the SCC with an emphasis on patients with moderate to poor glycemic control.

Method: The SCC tool is tailored to each patient’s insulin:carbohydrate ratio (I:C), insulin sensitivity (IS), and dietary pattern. It includes two tables written in the patient's preferred language. The first lists the units of insulin needed to correct pre-meal blood glucose to target glucose. The second contains a list of food items derived from participant's personal eating habits, carbohydrate content, and the number of insulin units needed.

At a median follow-up period of 6 months, we examined the change in hemoglobin A1c (HbA1c) in 212 patients with T1DM who utilized the SCC.

Results: At follow-up, HbA1c in the study population decreased by 1.07% (22.43 mmol/mol) (95% confidence interval 0.8–1.3, P < 0.001). The variables sex and diabetes duration were nearly statistically significant in relation to the change in HbA1c levels (P = 0.059, P = 0.056).

Conclusions: While not influenced by age, sex, ethnicity, socioeconomic status, education, insulin delivery method, duration of diabetes, or residence, the SCC tool is designed to help adult patients with T1DM with moderate to poor glycemic control.

Background: Recent guidelines have emphasized the importance of the diagnosis and treatment of obesity in all healthcare settings. However, obesity rarely appears as a chronic diagnosis during hospitalization, and there are few reports of targeted interventions.

Objective: To assess obesity-related diagnoses and interventions during pediatric acute hospitalization.

Methods: A retrospective cohort study was conducted in a pediatric ward. Hospitalization records of all patients aged 2–18 years were retrieved during a 30-month period. Weight percentile for patient age was calculated using the U.S. Centers for Disease Control and Prevention (CDC) age- and sex-adjusted charts. Patients with a weight-percentile-for-age of ≥ 95% were classified as suspected obesity. The characteristics of obesity-diagnosed patients were compared to obesity-overlooked patients.

Results: Of the hospitalized patients, 245/2827 (8.6%) had weight-percentile-for-age of ≥ 95%. Of these, 91/245 (37.4%) had obesity-related references in their medical record; 65/245 (26.5%) had a mean body mass index of 97.66% ± 2.6. Only 38/245 (15.5%) were diagnosed with obesity; weight-related recommendations only appeared in the discharge letter for 44/245 (17.9%). Multivariate analysis indicated that obesity was significantly more overlooked in preschoolers than in adolescents (adjusted odds ratio [OR] 11.78, 95% confidence interval [95%CI] 4.71–29.42), P < 0.001) and in patients, regardless of age, whose chief complaint was not abdominal (OR 7.7, 95%CI 1.92–30.8, P = 0.004).

Conclusions: Low rates of obesity-related diagnoses during pediatric acute hospitalization, especially in younger patients, are frequent. Pediatric staff should note obesity in patients and be trained in non-stigmatizing intervention during hospitalization.

Background: Sarcoidosis is a multi-organ granulomatous inflammatory disease of unknown etiology, exhibiting significant regional and ethnic variability in disease extent and clinical features.

Objectives: To investigate the clinical characteristics of sarcoidosis among Jewish and Arab populations in Israel and to compare these findings with global data.

Methods: We conducted a retrospective review on sarcoidosis patients at Rambam Health Care Campus during 2015–2023. Patients were categorized by ethnicity. Their demographic and clinical data were collected and analysed using appropriate statistical methods.

Results: The study included 284 patients (149 Jewish, 135 Arab). Jewish patients had a higher mean age at diagnosis. Diagnosis was biopsy-proven in 82% of cases, with endobronchial ultrasound being the most common diagnostic procedure. Lung involvement was present in 88% of patients, with no significant difference between Jewish and Arab populations. No significant differences were found in pulmonary function tests, blood tests, or Scadding stage distribution between the ethnic groups. When comparing the Jewish and Arab populations to the global data, lung involvement was significantly less frequent in the Jewish population. The Israeli population, both Jewish and Arab populations, had a significantly higher rate of joint manifestations whereas eye and skin manifestations appeared to be significantly lower in the Israeli population compared to global data.

Conclusion: This study highlights the diverse clinical presentations of sarcoidosis among Israeli populations compared to world data, with notable differences between Jewish and Arab patients, and within subgroups of these populations.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a wide spectrum of clinical severity. The gold standard diagnosis of infection is reverse transcription polymerase chain reaction of nasopharyngeal swabs, which also provides a semiquantitative assessment of viral loads by measuring cycle threshold (CT) values.

Objective: To assess whether CT values at admission can predict mortality and oxygen needs among individuals hospitalized for coronavirus disease 2019 (COVID-19).

Methods: The retrospective study included adults hospitalized for COVID-19 between 1 August 2020 and 30 April 2021 at Barzilai University Medical Center. Patients were categorized according to initial CT values as high (≥ 25) or low (< 25) values. The primary outcome was the association between CT values during admission and overall mortality.

Results: The study group included 636 patients, with a mean age of 67.2 years, 54.4% males. Overall mortality of patients with CT values < 25 was significantly higher (odds ratio for mortality 1.78 vs. patients with CT ≥ 25, P = 0.002). Significantly more patients in the low CT group required oxygen support than in the high CT group, 50% vs. 31.9% (P < 0.001). An inverse association between CT values and mortality rates remained significant in multivariate regression analysis, such that a 1-unit decrease in CT was associated with a 6% increased mortality.

Conclusions: Lower CT values at admission were associated with increased mortality among patients hospitalized for COVID-19. CT values can be used to predict outcomes among such patients.

Background: The incidence of non-tuberculous mycobacterium (NTM) infections has been rising in patients with chronic lung diseases. These infections cause significant morbidity, mortality, and elevated healthcare costs due to challenges in recognition, delayed diagnosis, and treatment. While NTM infections in natural stone silicosis are documented, the incidence in artificial stone silicosis remains unexplored despite increasing exposure to silica dust.

Objectives: To describe the clinical, radiological, and pathological features of NTM infections in patients with artificial stone silicosis and emphasize the importance of early diagnosis.

Methods: We reviewed the database of a tertiary medical center in Israel from 2010 to 2024 and identified patients with occupational artificial stone silicosis diagnosed with NTM infection.

Results: We found eight patients with occupational artificial stone silicosis, all male, aged 42–74 years. Key symptoms included dyspnea, cough, weight loss, and fever. Computed tomography revealed mediastinal lymphadenopathy, progressive massive fibrosis, calcifications, pulmonary cavitations, pleural thickening, traction bronchiectasis, pulmonary nodules, and honeycombing. Biopsies showed silicotic nodules, birefringent crystals, pulmonary alveolar silico-proteinosis, fibrosis, and honeycombing. Four patients received NTM-targeted antibiotics, and six underwent lung transplantation. Four patients died.

Conclusions: Artificial stone silicosis may be associated with NTM infections. Early diagnosis requires a high degree of clinical suspicion. New or worsening respiratory or systemic symptoms in patients with silicosis should prompt further microbiological evaluation, including sputum culture or bronchoalveolar lavage. Further studies are needed to assess the incidence of NTM infections in this population.