Israel Medical Association Journal

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: Gangrenous appendicitis falls to the midpoint of the continuum between uncomplicated and complicated appendicitis. We present an eight-year single-center retrospective review of uncomplicated, complicated and gangrenous appendicitis.

Objectives: To analyze the presentation of gangrenous appendicitis in our population.

Methods: We reviewed the presentation, as well as the laboratory, surgical, and pathological findings for complicated, uncomplicated, and gangrenous appendicitis. Logistic regression analysis was conducted to identify predictors of gangrenous and of complicated appendicitis.

Results: During the study period, 865 children had uncomplicated appendicitis and 134 had complicated appendicitis. Younger age, duration of illness as well as vomiting, diarrhea, and fever were more common in complicated than uncomplicated appendicitis. White blood cell count, neutrophil count and C-reactive protein were higher in complicated appendicitis. Logistic regression showed that vomiting and presence of fever occurred more frequently in children with non-perforated gangrenous appendicitis than with other uncomplicated appendicitis. Laboratory results for non-perforated gangrenous appendicitis were comparable to those of complicated appendicitis, as was usage of radiography and computed tomography.

Conclusion: Gangrenous appendicitis shares similar historical elements with complicated appendicitis and has a similar laboratory. These children, like those with complicated appendicitis, may not be optimal candidates for non-operative management.

Background: Mass honeybee envenomation (MHE) is a rare occurrence, with possible life-threatening or fatal consequences.

Objectives: To present the first description of multiple simultaneous casualties in a single incident of MHE.

Methods: Nine young men were simultaneously attacked by a large honeybee swarm. All patients were hemodynamically stable on arrival to Sheba Medical Center. One had fiberoptic evidence of laryngeal edema. Eight (89%) of the patients had leukocytosis and laboratory evidence of rhabdomyolysis. Eight patients were hospitalized in an internal medicine ward. The patient who had the most (over 300) stings removed presented with severe rhabdomyolysis and acute renal failure (ARF) and was admitted to the intensive care unit.

Results: Most patients had a benign clinical course and were discharged within 2 days. One patient developed severe rhabdomyolysis and was treated with fluids and urine alkalinization with significant improvement. The clinical course of another patient was complicated by ARF consistent with acute tubular necrosis. His creatinine peaked at 3.04 mg/dl and improved over several days until his discharge.

Conclusions: In our case series, we demonstrated the spectrum of clinical presentations associated with MHE and highlighted the importance of stings load as a prognostic factor, which may dictate early therapeutic intervention.

Pleural effusion is a common finding after coronary bypass graft surgery. Rarely, patients may develop loculated effusions, which may potentially lead to cardiac chamber compression. We report a rare case of loculated right pleural effusion (LRPE) that resulted in right atrial compression, leading to cardiac tamponade physiology, which resolved completely after emergent surgical drainage of the pleural effusion. This case underscores the need for early implementation of echocardiography in the postoperative management of hemodynamically unstable patients following cardiac surgery.

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: Lung cancer is a major cause of death worldwide. Accurate diagnosis and staging are essential for effective treatment. Mediastinal lymph node involvement determines the disease stage and influences treatment decisions, especially with new biological and immunotherapy options. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main minimally invasive procedure for evaluating mediastinal and hilar adenopathy. It offers high sensitivity, specificity, and fewer complications than mediastinoscopy or video-assisted thoracic surgery. It also retrieves crucial molecular markers for guiding therapeutic decisions in non-small cell lung cancer.

Objectives: To evaluate the diagnostic yield of EBUS-TBNA in patients with mediastinal lymphadenopathy.

Methods: This retrospective study included patients who underwent bronchoscopy with EBUS and had lymph node malignancy between 2018 and 2023. Crossmatching was conducted by pathology and genomic study results. No informed consent was required as the study was based on the hospital database.

Results Next generation sequencing was performed on 57 specimens (83%) collected via EBUS from patients with primary non-small cell lung cancer. However, 12 of the specimens (17%) were insufficient for pathological analysis. Among these, 7 (58%) were from adenocarcinomas and 5 (42%) were from squamous cell carcinoma patients.

Conclusions: The utilization of EBUS-TBNA is an effective tool for obtaining genetically profiled diagnoses by minimally invasive means. As more genetic mutations are discovered, we expect that multigene mutation analysis will gain importance in tailoring individualized treatment plans.

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: Pediatric urinary tract infections (UTIs) are a significant health concern, with rising antibiotic resistance complicating treatment decisions. We investigated pathogen distribution, antibiotic susceptibility patterns, and the cost-effectiveness of treatment options among hospitalized children at a tertiary medical center in Israel.

Objectives: To assess antibiotic susceptibility patterns of UTI pathogens in hospitalized children and evaluate cost-effective alternatives to gentamicin.

Methods: A retrospective analysis of 1649 pediatric UTI cases (January 2010–May 2022) at Galilee Medical Center examined patient demographics, urine culture results, and antibiotic susceptibility. A cost-effectiveness analysis was performed using incremental cost-effectiveness ratios (ICERs), based on susceptibility rates from the study and antibiotic costs from the Israel Ministry of Health, with gentamicin as the comparator.

Results: Escherichia coli was the most common pathogen (63.7%). High susceptibility rates were observed for carbapenems and amikacin (> 99%), with lower rates for gentamicin (91.7%) and ceftriaxone (87.6%). Treatment costs ranged from US$2.54 (trimethoprim/sulfamethoxazole) to US$307.80 (ertapenem). Fosfomycin demonstrated higher susceptibility than gentamicin (94.2% vs 91.7%) and lower cost (US$3.77 vs US$8.05), dominating gentamicin in cost-effectiveness analysis. Piperacillin/tazobactam and ceftriaxone were dominated by gentamicin in terms of cost-effectiveness.

Conclusions: E. coli was the predominant pathogen in pediatric UTIs among hospitalized children. Carbapenems and amikacin showed high susceptibility but were costly. Fosfomycin demonstrated high susceptibility, favorable cost-effectiveness, and the advantage of oral administration, making it a promising option for empiric treatment. Empiric antibiotic selection should integrate susceptibility patterns, clinical context, and economic considerations.

Background: Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is an emerging residual risk factor for atherosclerotic cardiovascular disease. Data on the prognostic significance after an ischemic stroke are limited.

Objectives: To investigate the association between RC and risk for cardiac events following hospitalization for an ischemic stroke.

Methods: Data were collected for 5697 patients (39.5% women) affiliated with Clalit Health Services and hospitalized with an acute ischemic stroke. Adjusted Cox-regression models were used to estimate the association between RC percentiles, calculated using a routine post-discharge lipid profile, and risk for future myocardial infarction (MI) or coronary revascularization.

Results: Mean age was 69 ± 10 years; 78% were treated by lipid-lowering therapies. During median follow-up of 22 months, a MI or coronary revascularization event occurred in 243 patients. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI or revascularization risk: hazard ratio (95% confidence interval): 1.42 (1.10–1.85), 1.50 (1.11–2.02), 1.62 (1.09–2.40), and 1.93 (1.22–3.06), in those with RC percentiles ≥ 50th (23.3 mg/dl), ≥ 75th (31.8 mg/dl), ≥ 90th (42.1 mg/dl), and ≥ 95th (49.1 mg/dl), compared to < 50th percentile. When RC and non-HDL-C levels were discordant, the level of RC better reflected higher risk for adverse cardiac events.

Conclusions: Elevated RC following acute ischemic stroke is a risk factor for MI or coronary revascularization, independent of lipid-lowering therapies and non-HDL-C and may serve as a residual cardiovascular risk marker and potential treatment target in patients with ischemic stroke.

Background: Laparoscopic right hemicolectomy is considered the gold standard surgical treatment for patients with right colon malignancies. The restoration of bowel continuity can be performed by intracorporal (ICA) or extracorporal (ECA) techniques.

Objectives: To evaluate a single-center experience in laparoscopic right colectomy, comparing patients with ICA and ECA.

Methods: This is a case-control retrospective study included all patients who underwent laparoscopic right colectomy between the years 2016–2022 at our medical center. Patients were divided according to the operative technique. The study database included demographics as well as intraoperative and postoperative parameters.

Results: Overall, 125 patients were included in the study, which included 98 patients (78.4%) from the ICA group included and 27 patients in the ECA group. Both groups were comparable in demographics and co-morbidities. No significant differences were observed between the groups in intraoperative complications, length of surgery, return to the oral diet, and length of hospital stay. The incidence of postoperative ventral hernia was significantly higher in patients from the ECA group (18.5% vs. 3.1%, P = 0.012).

Conclusions: Laparoscopic right colectomy with ICA is associated with a lower rate of postoperative ventral hernias.

In the 1950s, ionizing radiation to the scalp was commonly used in Israel as a treatment for tinea capitis. Decades later, epidemiological studies identified an increased incidence of head and neck malignancies, particularly basal cell carcinoma, as well as intracranial tumors such as meningiomas among individuals who underwent this therapy in childhood. In addition to the oncologic risk, irradiated scalp skin presents significant reconstructive challenges due to chronic skin atrophy, hypovascularity, fibrosis, and impaired wound healing. In this study, we present our clinical experience with a modified, skin-sparing surgical protocol for managing reconstruction post excision of non-melanoma skin cancer of the scalp in patients previously irradiated for tinea capitis. The surgical strategy is tailored according to lesion size, depth, periosteal involvement, and scalp tissue quality. It incorporates components of the reconstructive ladder as appropriate. We present three representative cases highlighting key surgical challenges and considerations in this complex population.

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.

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: Hyponatremia is common among hospitalized children, including those with community acquired pneumonia. The prevalence and severity of hyponatremia were reported to correlate with disease. However, data regarding the association between hyponatremia and causative infectious pathogens are limited and results are inconsistent.

Objectives: To investigate the associations between sodium levels, severity and causative pathogen in children with pneumonia.

Methods: A retrospective study of all children (< 18 years) hospitalized with pneumonia from 1 January 2018 to 31 December 2020. Admission sodium levels were compared to the presumed etiological pathogens, clinical parameters, and inflammatory markers.

Results: Among 751 (52% males) children, 10 (1%) had sodium levels < 130 mEq/L, 187 (25%) had mildly decreased levels 130–134 mEq/L, and the remaining 554 (74%) had normal levels 135–145 mEq/L. Sodium levels < 130 mEq/L were found in 7/236 (3%) of the patients with presumed bacterial pneumonia, in 0/20 of patients with presumed atypical-bacterial, and in only 3/495 (0.6%) of the patients with a presumed viral infection, P < 0.001. Sodium levels < 135 mEq/L conferred an odds ratio of 3.1 (95% confidence interval [95%CI] 2.1–4.3) and levels < 130 mEq/L an odds ratio of 6.8 (95%CI 1.8–33.0) for bacterial infection, P < 0.001 for both. Hyponatremia was also inversely associated with high white blood cell counts, absolute neutrophil cell counts, and C-reactive protein levels.

Conclusions: Hyponatremia was common among children hospitalized with pneumonia and was associated with elevated inflammatory markers and presumed bacterial pneumonia.