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.

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: 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.

Ossifying fibroma (OF) of the jaws presents as a slow-growing, benign, fibro-osseous lesion that poses a risk for significant local destruction. Effective treatment of OF usually requires wide resection, which may lead to substantial morbidity. There are no alternative treatment options reported to date. Osteoclasts, a type of multinucleate giant cell that expresses receptor activator of nuclear factor-kappa B ligand (RANKL), play a major role in OF pathogenesis as well as in central giant cell granuloma (CGCG). CGCG is currently treated with denosumab, a human monoclonal antibody that inhibits bone lysis by binding to RANKL.

In this study, we assessed whether denosumab could be used to treat OF while avoiding surgery. Denosumab successfully treated an aggressive craniofacial ossifying fibroma, circumventing the need for invasive surgery.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

Background: Significant mitral regurgitation (MR) is associated with less spontaneous echo contrast but its effect on the occurrence of ischemic stroke in patients with atrial fibrillation (AF) is unknown.

Objectives: To examine the association of MR grade and the risk of ischemic stroke (IS) in AF patients with heart failure (HF).

Methods: We investigated 2748 patients with known AF who were hospitalized due to acute decompensated HF. All patients underwent echocardiography during hospitalization. Patients were divided into groups based on the degree of MR (high-grade MR [3–4] vs. no/low-grade MR [0–2]). The primary endpoint was IS during long term follow-up.

Results: Mean age was 79 ± 11 years, 48% were women. After 2 years of follow-up, the cumulative incidence of IS among patients with high-grade MR was significantly lower compared to patients with no/low-grade MR (6% vs. 12%, respectively; P-value = 0.0064). Multivariate Fine and Gray analysis, adjusting for CHA₂DS₂-VASc, and accounting for the competing risk of death and valve intervention, showed the presence of high-grade MR was associated with a significant 50% (P = 0.013) reduction in the risk of IS compared with no/low-grade MR. When added to the CHA₂DS₂-VASc score, MR grade allowed more accurate prediction of IS with an overall improvement of 12% (95% confidence interval 5–17%) using net reclassification index analysis.

Conclusions: Our findings suggest an inverse correlation between MR grade and the risk of stroke among AF patients with HF. These findings may be used for improved risk assessment in this population.

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.

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm² IQR [1–39] vs. 46 cm² [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Infant botulism is a rare and potentially fatal condition caused by intestinal colonization with Clostridium botulinum. Enteric toxin causes intestinal immobility and progressive descending paralysis due to the effect on acetylcholine release at the neuromuscular junction and other cholinergic nerve terminals, particularly in the gut [1].

We present a case of infant botulism, describe the characteristics of the disease, and focus on early diagnosis.

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: Little is known about audiovestibular function in psoriasis, a chronic systemic inflammatory disease that affects 2% of the world’s population.

Objective: To investigate audiovestibular function in patients with psoriasis.

Methods: In this prospective case-control trial, we enrolled 33 patients with psoriasis and 30 healthy controls. Audiologic testing included audiometry, tympanometry, and otoacoustic emissions recording. The vestibular investigation consisted of a dizziness handicap inventory questionnaire, a complete clinical vestibular examination, and video head impulse testing.

Results: The psoriasis group showed significantly higher average hearing thresholds in both ears at all frequencies. Otoacoustic measurements differed significantly at 3000 Hz in the right (P = 0.026) and left ear (P = 0.034). The average dizziness handicap score was considerably higher in the psoriasis group, with a mean difference of 7.70 (P = 0.025). The number of patients with abnormal right anterior semicircular canal gain values was significantly higher in the psoriasis group (P = 0.047). Saccade analysis in the psoriasis group showed significantly higher number of patients with covert corrective saccades of the left posterior canal (P = 0.037) and significantly higher number of patients with abnormal interaural difference of corrective saccades in the plane of the right anterior-left posterior canals (P = 0.035).

Conclusions: The study demonstrates an association between psoriasis and audiovestibular impairment, which can affect quality of life. These results suggest that patients with psoriasis may be evaluated with audiometry for possible hearing loss. Vestibular testing may be pursued as clinically indicated.

Background: Military medicine has evolved significantly over the past 50 years, advancing from basic treatments and limited evacuations to sophisticated combat casualty care. Innovations such as hemorrhage control, early blood product administration, and telemedicine have greatly improved battlefield care. Rapid evacuation systems and skilled medical teams have reduced mortality and morbidity rates.

Objectives: To review the transformation of the Israel Defense Forces Medical Corps (IDF-MC) in combat casualty care over the past 50 years, focusing on recent applications during the Iron Swords war.

Methods: Data were collected from the personal experiences of IDF-MC doctors, IDF archives, and relevant military medical literature, with an emphasis on life-saving strategies, personnel, equipment, mental health support, and civil–military cooperation.

Results: Rapid evacuation and immediate care have improved survival rates, while increased front-line deployment of medical staff has enhanced response capabilities. Modern medical tools and techniques, such as tourniquets and blood products, have been widely adopted. Improved psychological support strategies ensure better mental health outcomes for soldiers. Enhanced coordination with civilian trauma systems optimizes care and resource allocation, leading to more efficient and effective casualty treatment.

Conclusions: The IDF-MC's advancements in rapid evacuation and front-line medical support have significantly improved combat casualty outcomes. Continued innovation and collaboration with civilian systems are essential for further progress in military medicine. Future technological advancements are anticipated to further enhance military medical care.

Background: Cardiac implantable electronic devices (CIEDs) with endocardial leads crossing the tricuspid valve can lead to or worsen tricuspid regurgitation (TR), causing substantial morbidity and mortality. Despite a recent randomized controlled study revealing a low short-term incidence of device-related TR (DRT) post-CIED implantation, uncertainties persist regarding the efficacy of intra-procedural 2-dimensional transthoracic echocardiography (2DTTE) in preventing long-term TR.

Objectives: To conduct a long-term follow-up study on patients with CIED implants based on a previous study conducted at our hospital.

Methods: In a retrospective study at Assuta Ashdod Medical Center (2018–2019), patients undergoing de-novo CIED implantation with (n=39, group 1) or without (n=51, group 2) intra-procedural 2DTTE were analyzed. Clinical, demographic, and long-term (> 1 year) echocardiographic data were collected and compared.

Results: The study included 90 patients (mean age 72.3 ± 11.0 years, 63% male, 23% ICD, 50% active leads, follow-up 32.8 ± 11 months). TR aggravation was found in 25% of patients (13 in group 1, 10 in group 2), with no statistical difference between groups. Multivariate analysis identified a history of atrial fibrillation (AF) as the sole significant factor in long-term TR deterioration (OR=3.44, 95%CI 1.13–10.43, P = 0.029). Other clinical, demographic, echocardiographic, and device-related factors did not significantly contribute to long-term DRT.

Conclusions: After one-year post-CIED implantation, the incidence of DRT significantly increases. Intra-procedural 2DTTE does not effectively reduce long-term DRT, suggesting that implantation-related mechanisms are less likely the primary cause. AF likely plays a major role in the pathogenesis of long-term TR in this subset post-CIED implantation.

Background: Cardiac implantable electronic devices (CIEDs) are associated with risks of device-related infections (DRI) impacting major adverse outcomes. Staphylococcus aureus (SA) is a leading cause of early pocket infection and bacteremia. While studies in other surgical contexts have suggested that nasal mupirocin treatment and chlorhexidine skin washing may reduce colonization and infection risk, limited data exist for CIED interventions.

Objectives: To assess the impact of SA decolonization on DRI rates.

Methods: We conducted a retrospective, single-center observational study on consecutive patients undergoing CIED interventions (March 2020–March 2022). All patients received pre-procedure antibiotics and chlorhexidine skin washing. Starting in March 2021, additional pre-treatment with mupirocin for SA decolonization was administered. DRI rates within 6 months post-implantation were compared between patients treated according to guidelines (Group 1) and those receiving mupirocin in addition to the recommended guidelines (Group 2).

Results: The study comprised 276 patients (age 77 ± 10 years; 60% male). DRI occurred in five patients (1.8%);80% underwent cardiac resynchronization therapy procedures. In Group 1 (n=177), four patients (2.2%) experienced DRI 11–48 days post-procedure; three with pocket infection (two with negative cultures and one with local Pseudomonas) and one with methicillin-sensitive SA endocarditis necessitating device extraction. In Group 2 (n=99), only one patient (1%) had DRI (Strep. dysgalactiae endocarditis) 135 days post-procedure (P = NS).

Conclusions: The routine decolonization of SA with mupirocin, in addition to guideline-directed protocols, did not significantly affect DRI rates. Larger prospective studies are needed to evaluate the preventive role of routine SA decolonization in CIED procedures.

In the last hundred years, the science of fracture repair has significantly changed. Management has moved from a simple metabolic and hormonal concept of bone regeneration to an inflammatory concept and now to a more complicated immunological description. Fracture repair has been considered age-dependent and related to diabetes, nutrition, hormone connection, autoimmune diseases, rheumatic arthritis, and nicotine. Recently a new branch of medicine, osteoimmunology, which deals with the mechanism of fracture repair, has been introduced.