Israel Medical Association Journal

Background: Apparent treatment-resistant hypertension (aTRH) is a high-risk phenotype associated with increased cardiovascular and renal morbidity. Renal denervation (RDN) has emerged as a promising intervention for patients with refractory blood pressure (BP) despite maximal medical therapy.

Objectives: To present the first Israeli prospective cohort evaluating RDN outcomes in aTRH patients.

Methods: The Tel Aviv Renal Denervation registry is a single-center, prospective cohort of 19 patients with aTRH who underwent RDN between 2021 and 2024. Baseline data included demographics, co-morbidities, medication burden, ambulatory BP monitoring (ABPM), and renal function. Outcomes were assessed at 3 and 12 months post-procedure, with repeated measures analyses used to evaluate longitudinal trends.

Results: The cohort (median age 62 years, 42% female) exhibited a high burden of co-morbidities including ischemic heart disease (37%), diabetes (26%), and chronic kidney disease (21%). Baseline ABPM showed a median 24-hour systolic BP of 152 mmHg. Following RDN, mean systolic BP decreased to 143 mmHg at 3 months and 138 mmHg at 12 months (P = 0.097), with a significant reduction in nighttime systolic BP (P = 0.033). Pill burden decreased from a median of 7 to 4 pills daily (P = 0.037). The number of antihypertensive drug classes declined from 6 to 4 (P = 0.052). Renal function remained stable throughout follow-up.

Conclusions: In this Israeli RDN cohort, patients with aTRH experienced clinically meaningful reductions in BP and medication burden, with preserved renal function and minimal complications. These findings support further expansion of national RDN registries to better guide patient selection and optimize long-term outcomes.

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.

Cerebral arterial air embolism (CAAE) is a rare, but often fatal, complication of interventional bronchoscopy. Despite its rarity, a high index of suspicion can facilitate early diagnosis and prompt treatment. Standard of care treatment for CAAE is hyperbaric oxygen therapy, despite limited definitive data supporting its efficacy, given the conceptual potential for reversibility of neurological impairment. We describe five cases from our institution, and review the clinical presentation, pathophysiology, diagnosis, and management of suspected CAAE. Based on published case reports involving transbronchial lung biopsies (TBLB), standard of care treatment for CAAE secondary to TBLB is hyperbaric oxygen therapy, although its efficacy in this context has not been unambiguously validated in clinical practice.

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: Cesarean section (CS) comprised almost one-third of all births. One of the complications after CS is intra-abdominal and pelvic adhesions formation.

Objectives: To investigate whether a previous CS poses an additional perioperative or postoperative risk for complications when performing a total laparoscopic hysterectomy (TLH).

Methods: We conducted a retrospective cohort study of women who had undergone a TLH between 2014 and 2020. Perioperative and postoperative complications were assessed according to the Clavien-Dindo classification system. Descriptive statistics were used to analyze the results.

Results: In total, 190 women underwent TLH during the study period, 50 (26.5%) had a previous CS (study group) and 140 (73.5%) had no history of CS. The complication rates using the Clavien-Dindo classification system were similar in both groups; however, the major complications rate was not significantly higher in the study group (CS 6% vs. no CS 1.4%, P = 0.08). Urethral injury was the most common major complication (2, 4% vs. 1, 0.7%). The duration of surgery (125 min vs. 112 min, P = 0.02), estimated blood loss (174 ml vs. 115 ml, P = 0.02), and additional postoperative endoscopic interventions (4% vs. 0%, P = 0.01) and were significantly greater in patients with a previous CS.

Conclusions: Although the need for postoperative endoscopic interventions, surgery duration, and estimated blood loss were significantly higher in patients with a previous CS, TLH remains a safe and recommended procedure for these patients. Major complications are rare and do not occur more frequently following a previous CS.

Background: The Iron Swords war created stressful circumstances that could negatively impact glycemic control in individuals with type 1 diabetes (T1D).

Objectives: To evaluate changes in continuous glucose monitoring (CGM) metrics in pediatric T1D patients during the war.

Methods: This retrospective study included T1D patients monitored by CGM. Metrics from three selected 2-week periods were compared (before the war, after the war outbreak, and 4 months later). Study variables included time-in-range (70–180 mg/dl; 3.9–10 mmol/L), time-in-tight-range (70–140 mg/dl; 3.9–7.8 mmol/L), time-in-marked-hypoglycemia (< 54 mg/dl; < 3 mmol/liter), and time-in-severe-hyperglycemia (> 250 mg/dl; >13.3 mmol/liter). Patients were treated with either a multiple daily insulin (MDI) regimen or insulin pump, with or without an open-source automated insulin delivery (OS-AID) system.

Results: Data of 99 patients were analyzed (mean age 12.2 ± 4.0 years, mean diabetes duration 4.6 ± 3.9 years, 52.5% males). No significant changes in CGM metrics were observed across the entire cohort at any time point. Patients with higher socioeconomic position (SEP; cluster > 7) had better CGM metrics, with an increase in time-in-tight-range in the lower SEP group and in time-in-severe-hyperglycemia in the higher SEP group (P = 0.003). OS-AID users (n=20) had superior pre-war CGM metrics and maintained stable glycemia during the war, MDI users showed increased time-in-severe-hyperglycemia post-outbreak (P = 0.05).

Conclusions: Throughout the war, children and adolescents with T1D treated with insulin pumps maintained relatively stable glycemic control. Susceptibility to change following the onset of war was influenced by SEP and mode of insulin therapy.

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: The coronavirus disease 2019 (COVID-19) pandemic posed significant challenges to healthcare systems worldwide, including a surge in the use of extracorporeal membrane oxygenation (ECMO).

Objectives: To compare outcomes and costs of COVID-19 and non-COVID-19 adult patients treated with ECMO in the intensive care unit (ICU) at Tel Aviv Sourasky Medical Center.

Methods: We conducted a retrospective study. Clinical outcomes, ECMO duration, ICU and hospital length of stay (LOS), and healthcare costs were examined and compared between the two groups.

Results: A total of 119 patients were treated with ECMO between 2016 and 2023; 56 (47.1%) diagnosed with COVID-19. The study found no significant difference in mortality rates between COVID-19 and non-COVID-19 patients. However, COVID-19 patients experienced significantly longer ECMO durations and ICU LOS. Hospitalization and ECMO operation costs were notably higher for COVID-19 patients, but overall admission costs were lower compared to non-COVID-19 patients, with cost of surgical interventions, consultations and imaging contributing to the price gap.

Conclusions: Despite longer durations of ECMO and LOS, the economic burden of ECMO in COVID-19 patients was significantly lower than non-COVID-19 patients. Strict patient selection should be utilized, a fortiori during times of surge-capacity.

Background: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. 

Objectives: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children.

Methods: We assessed 54 children aged 2–17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification.

Results: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36).

Conclusions: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Background: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment.

Objectives: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis.

Methods: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012–2022 at a single tertiary medical center.

Results: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP.

Conclusions: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization. 

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by restricted airflow, changes of lung tissues, and breathing difficulties [1]. Most patients are treated at home to maintain a stable lifestyle and quality of life [2].

An important feature of COPD is exacerbation, which is an acute worsening of symptoms that can result in decreased pulmonary functions, increased risk of death, and poorer quality of life. The frequency and severity of each exacerbation results in further worsening of pulmonary function [3]. Depression in COPD patients may cause objective impairment in function and decreased adherence to therapeutic interventions [4].

Acute stress disorder is characterized by acute reaction in the first month following exposure to a traumatic event such as threatened death, serious injury, or sexual assault. Symptoms include intrusion, dissociation, negative mood avoidance, and arousal [5]. Stress on a more continuous basis can significantly debilitate a person's emotional and physical wellbeing, lead to depression and weakened immune system, and influence patients with already stressful and progressive conditions such as COPD.

We present a patient previously diagnosed with COPD who experienced an acute terror attack, which was a major and stressful event that caused severe exacerbation of the disease.

Background: With age, colorectal cancer (CRC) prevalence rises. The elderly (> 75 years), and the very elderly (> 85 years) are especially vulnerable. The advantages of screening must be assessed in the context of diminished life span and co-morbidities.

Objective: To compare CRC findings in colonoscopies that were performed following a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) in both elderly and very elderly age groups with those of younger patients.

Methods: We identified colonoscopies conducted between 1998 and 2019 following a positive stool test for occult blood in asymptomatic individuals. A finding of malignancy was compared between the two patient age groups. Furthermore, a sub-analysis was performed for positive malignancy findings in FOBT/FIT among patients > 85 years compared to younger than < 75 years.

Results: We compared the colonoscopy findings in 10,472 patients: 40–75 years old (n=10,146) vs. 76–110 years old (n=326). There was no significant difference in prevalence of CRC detection rate between the groups following positive FOBT/FIT (2.1% vs. 2.7%, P = 0.47). Similar results for non-significant differences were obtained in the sub-analysis compared to malignancy detection rates in the very elderly 0% (n=0) vs. 2.1% for < 75 years old (n=18), P = 0.59.

Conclusions: Although the prevalence of CRC increases with age, no significant increase in the detection rate of CRC by FOBT was found in either the elderly or very elderly age groups. Screening colonoscopies in elderly patients should be performed only after careful consideration of potential benefits, risks, and patient preferences.

Background: Ventricular assist devices (VADs) play a critical and increasing role in treating end-stage heart failure in pediatric patients. A growing number of patients are supported by VADs as a bridge to heart transplantation. Experience with VADs in the pediatric population is limited, and experience in Israel has not been published.

Objectives: To describe this life-saving technology and our experience with VAD implantation in children with heart failure, including characteristics and outcomes.

Methods: We conducted a retrospective chart review of all patients who underwent VAD implantation at Schneider Children's Medical Center from 2018 to 2023.

Results: We analyzed results of 15 children who underwent VAD implantation. The youngest was 2.5 years old and weighed 11 kg at implantation. In eight patients, HeartMate 3, a continuous-flow device, was implanted. Seven patients received Berlin Heart, a pulsatile-flow device. Three children required biventricular support; 11 underwent heart transplants after a median duration of 169 days. Two patients died due to complications while awaiting a transplant; two were still on VAD support at the time of submission of this article. Successful VAD support was achieved in 86.6% of patients. In the last 5 years,79%  of our heart transplant patients received VAD support prior to transplant.

Conclusions: Circulatory assist devices are an excellent bridge to transplantation for pediatric patients reaching end-stage heart failure. VADs should be carefully selected, and implantation techniques tailored to patient's weight and diagnosis at a centralized pediatric cardiac transplantation center. Israeli healthcare providers should be cognizant of this therapeutic alternative.

Higher potency bisphosphonates, typically intravenous formulations, are given at lower doses for postmenopausal women. The treatment has improved compliance compared to daily oral therapy. Since bisphosphonates are exclusively excreted via the kidneys, intravenous formulation has been associated with deterioration of renal function, specifically in the setting of preexisting renal disease or concomitant use of nephrotoxic agents [1].

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.