Israel Medical Association Journal

Background: Continuous-flow left ventricular assist devices (CF-LVADs) have yielded improved outcomes compared with pulsatile-flow devices; however, significant rates of gastrointestinal bleeding (GIB) have been observed. The HeartMate 3 left ventricular assist device (HM3-LVAD) (Abbott, Inc., Chicago, IL, USA) includes new features, such as an artificial pulse, which may decrease GIB prevalence compared to the HeartMate 2 left ventricular assist device (HM2-LVAD).

Objectives: To evaluate the incidence, predictors, and clinical outcomes of GIB in patients supported by the HM3-LVAD.

Methods: From 2016 until 2024, 180 patients with chronic heart failure underwent HM3-LVAD implantation. Records were reviewed to determine the post-implant GIB prevalence, location of the bleeding, and associated morbidity and mortality. Univariate and multivariate analyses were conducted to identify independent predictors of GIB.

Results: GIB occurred in 25 patients (14%) with a duration of support ranging from 1 to 1821 days. Sources of GIB included the small bowel and rectum in eight patients each, large bowel in one, and stomach in two. No clear source was identified in 11 patients. Recurrent GIB occurred in 16 patients (64%). There were no deaths attributable to GIB. None of the historical or demographic parameters were found to be independent predictors of GIB.

Conclusions: GIB is a frequent source of morbidity for patients on HM3-LVAD support but does not significantly impact survival. As the implantation of CF-LVADs with non-pulsatile flow gains popularity for both bridge-to-transplant and destination therapy, a better understanding of the pathophysiology of GIB in these patients will reduce the prevalence of this complication.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease leading to end-stage lung disease (ESLD). Single lung transplantation (SLT) is the primary treatment option for IPF; however, the native lung continues to influence post-transplant outcomes.

Objective: To determine whether the native lung continues to deteriorate under post-transplantation immunosuppression treatment by assessing chest computed tomography (CT) and perfusion scans.

Methods: We conducted a single-center retrospective analysis of patients who underwent SLT for IPF between 2016 and 2023. Serial chest CT scans assessed native lung changes. CT signs of fibrosis were scored for severity according to published criteria for defining pulmonary fibrosis disease progression. Lung volumes and perfusion were calculated.

Results: Among 57 patients (mean age 57 years; 33% female), 42% died during follow-up (median survival 95 months). The most common immunosuppressive regimen (54% of patients) included prednisone, calcineurin inhibitor, and mycophenolate mofetil. CT analysis demonstrated that in 41/57 (72%) patients, fibrosis signs continued to deteriorate. There was also a significant correlation decline in native lung volume and perfusion scans over time (P = 0.0003, P < 0.0001, respectively) (r = 0.82, P = 0.03).

Conclusions: Fibrotic progression in the native lung persists after SLT as demonstrated by both chest CT and nuclear perfusion scan, thus highlighting the importance of ongoing monitoring for accuracy and complications assessment, integrating it into routine surveillance, and ensuring it is consistently considered in post-transplant assessments.

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.

Pulmonary medicine, a major subspecialty of internal medicine, has advanced dramatically over the past decade and continues to grow at an impressive pace. The subspeciality is a uniquely multifaceted field, requiring thoughtful integration of the patient’s history, physical findings, laboratory data, and imaging to reach an accurate diagnosis and suggest proper treatment. This clinical depth is complemented by a rapidly expanding therapeutic arsenal for complex lung diseases. At the same time, technological progress has transformed our practice. Innovations in imaging and in both diagnostic and therapeutic bronchoscopy–central components of interventional pulmonology–have evolved so rapidly that tools used only a decade or two ago now seem outdated [1]. All these advancements offer meaningful opportunities to enhance the health outcomes of our patients. What a fascinating specialty and what an exciting time to be a pulmonologist.

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: 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: Epidemiological studies have demonstrated an association between sleep deprivation (SD) and ischemic heart disease.

Objectives: To determine the effect of SD on the endothelial function and on the inflammatory profile of young healthy men following 24 hours of work without sleep.

Methods: Fourteen healthy men (age 31.3 ± 2.4 years) participated in our prospective study. Endothelial function was evaluated by the brachial artery method, measuring flow medicated percent change (FMD%) of the brachial artery by a linear array ultrasound early in the morning. Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured in saliva by ELISA.

Results: Basic FMD% was 6.7 ± 6.8%, and following SD 1.7 ± 3.3% (P = 0.009). A 5.0 ± 6.1% decrease was measured after SD. IL-1 levels increased after SD from 36 ± 21 pg/ml to 47 ± 24 pg/ml (P = 0.004), and IL-6 levels increased from 22 ± 07 pg/ml to 36 ± 11 pg/ml (P = 0.0005). A negative correlation was found between the change (decrease) in FMD% and the change (increase) in IL-1 level (r = -0.813; P = 0.001). A negative correlation was found between the decrease in FMD% and the increase in IL-6 level (r = -0.735; P = 0.003).

Conclusions: SD led to endothelial dysfunction with increase in markers of inflammation (IL-1 and IL-6), with an inverse correlation between the change (decrease) in endothelial function and the change (increase) in IL-1 and in IL-6.

Background: The management of chronic hepatitis C virus (HCV) infection in patients with concurrent severe mental illness and substance use disorder poses significant challenges to treatment initiation, adherence, and completion. Multiple barriers impede successful treatment outcomes in this population, including cognitive impairments associated with mental illness, ongoing psychoactive substance use, and inadequate social and environmental support systems.

Objectives: To implement a treatment program for HCV-infected patients during their psychiatric hospitalization. To establish a multidisciplinary task force comprising a hepatologist, psychiatric ward team (psychiatrists, nurses, social workers), and a project administrator.

Methods: We conducted a retrospective cohort study of patients hospitalized with dual diagnosis (DD) of severe mental illness and substance use disorder who tested positive for HCV antibodies. Patients underwent clinical evaluations and received treatment with direct antiviral agents during hospitalization under the supervision of the joint team. Demographic and clinical characteristics were analyzed.

Results: Between January 2018 and June 2023, 694 DD patients were hospitalized, of whom 119 tested positive for HCV antibodies (prevalence 17.1%). Twenty-seven patients (23%) completed treatment; 17 (63%) achieved confirmed sustained virologic response. Treatment discontinuation occurred primarily post-discharge from the mental health facility. Significant efforts were made to engage community caregivers to maintain continuity of care.

Conclusions: Our findings demonstrate that treating HCV in patients with concurrent severe mental illness and substance use disorder requires collaborative efforts across medical disciplines. This integrated approach during psychiatric hospitalization provides a unique opportunity for initiating and monitoring HCV treatment in this complex patient population.

Background: Identifying drug–drug interactions (DDIs) in dermatology can be cumbersome and time-consuming using traditional methods.

Objectives: To explore the potential of ChatGPT-4o, an artificial intelligence (AI)-based chatbot, to streamline the identification process.

Methods: ChatGPT-4o was tasked with assessing DDIs among commonly prescribed dermatological medications. The accuracy and reliability of the chatbot's outputs were compared against established references for 43 interactions.

Results: ChatGPT-4o successfully identified all evaluated interactions. It accurately described the interaction effects in 42 cases, with only one example of misdescription.

Conclusions: The findings highlight the potential of ChatGPT to serve as an effective and efficient alternative for identifying and understanding DDIs in dermatology, despite one noted error that emphasizes the need for ongoing verification against trusted references. Further research is needed to validate its use across a broader range of medications and clinical scenarios.

Psoriasis is a chronic, immune-mediated skin disease characterized by inflammatory lesions and systemic co-morbidities. Emerging evidence highlights the significant role of the microbiome in psoriasis pathogenesis. Dysbiosis of the skin and gut microbiota has been linked to increased disease severity and co-morbidities such as psoriatic arthritis and cardiovascular disease. In this review, we explored the microbiome's influence on immune responses in psoriasis and its potential as a therapeutic target. Microbial therapies, such as probiotics and fecal microbiota transplantation, hold promise for restoring microbial balance and improving outcomes. We also discuss how the microbiome modulates drug efficacy and toxicity, offering insights for personalized treatment approaches. While challenges remain in establishing causality and translating findings into clinical practice, leveraging the gut-skin axis may optimize psoriasis management and improve patient outcomes.

Background: BRCA1/BRCA2 female pathogenic sequence variant (PSV) carriers in Israel are offered semiannual cancer antigen 125 (CA125) serum level determination and transvaginal ultrasound until performing risk reducing salpingo-oophorectomy (RRSO), even with the lack of proven efficacy of these procedures in providing adequate early detection of ovarian cancer.

Objectives: To report the results of longitudinal CA125 measurements in BRCA1/BRCA2 carriers as a tool for ovarian cancer detection in a single medical center in Israel.

Methods: Asymptomatic BRCA1/BRCA2 PSV carriers attending the Meirav High Risk Clinic at Sheba Medical Center for more than 3 years were eligible. Data on specific PSV, risk reducing surgeries, and cancer diagnoses were obtained from participant records. We used chi-square and Wilcoxon-Rank tests for statistical analyses.

Results: Overall, 739 (399 BRCA1, 336 BRCA2, 4 BRCA1 + BRCA2) PSV carriers were included. Mean age at the start of follow-up was 38.96 ± 11.13 years, mean follow-up time was 7.93 ± 2.34 years, (5860.80 women/years). Most participants (490/739 [66.3%]) had stable CA125 levels (± 5 U/µl). Of participants, 61 had CA125 levels > 35 U/µl at least twice (n=42) or at least doubling of marker levels to a minimum of 20 U/µl (n=19), results that have led to further cancer defining investigations. Of these, 14 and 4 were diagnosed with breast and ovarian cancer, respectively.

Conclusions: Longitudinally stable CA125 levels were noted in most BRCA1/BRCA2 PSV carriers and elevated levels were a poor marker for ovarian cancer development.

Background: Acute cholecystitis (ACC) is one of the most common diagnoses encountered in surgical wards. A number of treatment modalities are available, and various guidelines have been developed to help decision making. Many factors influence treatment strategies, including patient age and frailty. Due to the increasing proportion of older patients, consideration into the best treatment modalities for this population are warranted.

Objectives: To determine outcomes of elderly patients with ACC according to different treatment strategies.

Methods: A retrospective analysis of consecutive patients aged ≥ 80 years who were admitted with a diagnosis of ACC between 2015 and 2019 to a single academic center. Patients were divided into three groups according to treatment: percutaneous cholecystostomy tube placement, cholecystectomy, intravenous antibiotic treatment only.

Results: Overall, 466 patients were included in the cohort. The majority (approximately 75%) were treated with antibiotics only, 17% underwent percutaneous cholecystostomy, and 8% underwent laparoscopic cholecystectomy. One-year mortality was 28.1%. The highest mortality rate was 41.6% in the cholecystostomy group (P = 0.002). In multivariable analysis age, functional status, C-reactive protein, and albumin levels were found to be independent risk factors for 1-year mortality (hazard ratio [HR] 1.08, 0.56, 0.98, 0.4, respectively). Cholecystostomy increased risk of one-year mortality compared to cholecystectomy and antibiotics alone (HR 0.61, 0.23, respectively).

Conclusions: The use of cholecystostomy for ACC in older adults is an independent risk factor for 1-year mortality. Its use in older adults should be reserved for carefully selected cases.

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

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.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.