Israel Medical Association Journal

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.

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

In 2013, the idea of the hyperferritinemic syndrome was introduced to suggest the possible inflammatory properties of ferritin in contributing to the pathogenesis of four diseases, namely Still’s disease, macrophage activation syndrome (MAS), septic shock, and catastrophic antiphospholipid syndrome [1]. Based on this concept, ex vivo and in vitro studies were performed reporting the inflammatory properties of the heavy subunit of ferritin (FeH) in inducing the commitment of macrophages toward an inflammatory phenotype, production of pro-inflammatory cytokines, and the direct stimulation of NLRP3 and NF-kB pathway [2,4]. In addition, recent in vivo studies have established the pathogenic role of hyperferritinemia [4-6], mainly triggering a Still’s disease-like phenotype in a wild type murine model by the aberrant activation of immune cells and production of inflammatory mediators [5]. Moreover, the hyperferritinemic syndrome arena has seen many recent developments due to the rapid accrual of knowledge in coronavirus disease 2019 (COVID-19) [6,7]. Specifically, the appearance of hyperferritinemia is increasingly recognized to be associated with a more severe patient phenotype at higher risk of poor prognosis due to the appearance of the cytokine storm syndrome [8], which is a hyper-inflammatory state due to overwhelming massive release of inflammatory mediators and rapidly evolving to multiorgan failure [9].

War is a chaotic situation for most of the public sectors in the countries involved. These sectors also include the medical systems, especially medical education, of which medical communication is often neglected or forgotten due to objective and subjective causes on either side of the involved countries. By planning lessons on various aspects of medicine for countries at war and close mentoring and utilization of modern communications technologies, these difficulties can be minimized without jeopardizing the quality of medical studies nor medical communication. In this perspective article, we describe the objective and subjective measures taken by our team to achieve these goals during the Iron Swords war in our region.

Background: Fetal weight estimation at term is a challenging clinical task.

Objectives: To evaluate the association between peripheral white blood cell (WBC) count of the laboring women and neonatal birth weight (BW) for term uncomplicated pregnancies.

Methods: We conducted a single-center, retrospective cohort study (2006–2021) of women admitted in the first stage of labor or planned cesarean delivery. Complete blood counts were collected at admission. BW groups were categorized by weight (grams): < 2500 (group A), 2500–3499 (group B), 3500–4000 (group C), and > 4000 (group D). Two study periods were used to evaluate the association between WBC count and neonatal BW.

Results: There were a total of 98,632 deliveries. The dataset analyses showed a lower WBC count that was significantly and linearly associated with a higher BW; P for trend < 0.001 for women in labor. The most significant association was noted for the > 4000-gram newborns; adjusted odds ratio 0.97, 95% confidence interval 0.96–0.98; P < 0.001; adjusted for hemoglobin level, gestational age, and fetal sex. The 2018–2021 dataset analyses revealed WBC as an independent predictor of macrosomia with a significant incremental predictive value (P < 0.0001). The negative predictive value of the WBC count for macrosomia was significantly high, 93.85% for a threshold of WBC < 10.25 × 10³/µl.

Conclusions: WBC count should be considered to support the in-labor fetal weight estimation, especially valuable for the macrosomic fetus.

Background: Hemodialysis requires reliable, recurrent access to the circulatory system. Central venous tunneled dialysis catheters (TDC) are frequently used for patients receiving hemodialysis as a bridge to permanent vascular access or as a final option. TDC are prone to complications such as infection and dysfunction.

Objective: To assess the prevalence and predictors of TDC dysfunction in a cohort of chronic hemodialysis patients.

Methods: This single-center, retrospective study was based on data from an electronic database of chronic hemodialysis patients during 5 years of follow-up.

Results: A total of 625 TDC were inserted in 361 patients, of which 234 (37.4%) were replaced due to dysfunction. The main insertion site was the right internal jugular vein. Diabetes mellitus was an important predictor of TDC dysfunction and was significantly correlated with TDC extraction. Chronic anticoagulation and antiplatelet treatment did not affect the rate of TDC dysfunction or replacement.

Conclusions: TDC use for chronic dialysis patients is increasing and dysfunction is a major problem. In our study, we highlighted the high prevalence of TDC dysfunction and the need for further research to improve hemodialysis access as well as TDC patency and function.

Background: Exclusive breastfeeding is recommended through six months as it supports infant growth and development. Yet, many mothers do not exclusively breastfeed in early postpartum.

Objectives: To examine factors associated with exclusive breastfeeding at hospital discharge among culturally diverse women.

Methods: This cross-sectional study used data of women who gave birth at a major medical center in Israel in 2015–2017. Descriptive statistics and regression analysis were conducted to examine maternal characteristics and associated breastfeeding outcomes by hospital discharge.

Results: Among 10,978 women, 17.8% (n=1958) exclusively breastfed, 57.9% (n=6357) partially breastfed, and 24.3% (n=2663) did not breastfeed. Among Israeli-born and former Soviet Union-born Jewish women, breastfeeding intention (odds ratio [OR] 19.59, 95% confidence interval [95%CI] 10.27–37.35 and OR 15.92, 95%CI 5.79–43.80, respectively) and early breastfeeding (OR 2.415, 95%CI 1.91–3.05 and OR 2.04, 95%CI 1.57–2.64, respectively) were associated with exclusive breastfeeding. The only significant factor associated with exclusive breastfeeding among refugees and Israeli-born Muslim women was early breastfeeding (OR 1.61, 95%CI 1.20–2.16). For Ethiopian-born Jewish women, not married (OR 0.330, 95%CI 0.114–0.955) and cesarean delivery (OR 0.481, 95%CI 0.232–0.998) were negatively associated with exclusive breastfeeding.

Conclusions: Despite having access to the same hospital-based breastfeeding support, there were differences among ethno-culturally diverse women in Israel. In this study, we identified maternal characteristics associated with early breastfeeding among women of diverse ethno-cultural backgrounds. Study findings highlight the importance of ethno-cultural considerations in breastfeeding practices and inform health professionals of factors associated with exclusive breastfeeding in early postpartum.

Fibromyalgia is a pain-related condition common in women and is present in about 5% of the population [1]. Its treatment involves physical exercise, psychotherapy (mainly behavioral–cognitive therapy), and antidepressant/anticonvulsant use as class IA evidence treatments [1]. Although in several cases this treatment fails or loses effectiveness over time, necessitating novel therapeutical agents.

Naltrexone is an opioid antagonist drug used for opioid addiction therapy. It also has anti-inflammatory and analgesic properties when used in low dosages [2]. Our group recently wrote a systematic review of low-dose naltrexone (LDN) for treating rheumatic diseases, including fibromyalgia [3]. In all seven published articles on LDN for fibromyalgia, a benefit was observed in pain reduction and improvements in fibromyalgia questionnaires [3]. To the best of our knowledge, no study using LDN as the first option of treatment has been conducted. Therefore, in this study we aimed to evaluate the effects of LDN as the first line of therapy in patients with fibromyalgia.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.

Objectives: To study different triggers for DKA and their effect on outcomes.

Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.

Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35–14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).

Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated condition characterized by fibro-inflammatory lesions with lymphoplasmacytic infiltration. Diagnosis traditionally relies on histopathological findings, including the presence of IgG4+ plasma cells. However, due to challenges in biopsy accessibility, additional measures are needed to facilitate diagnosis.

Objectives: To identify additional parameters for characterizing IgG4-RD patients.

Methods: We compared several circulating factors between a cohort of patients with IgG4-RD disease seen at our hospital between 2017 and 2023 and healthy controls.

Results: Among 16 suspected patients, 13 were confirmed to have IgG4-RD, and 3 were classified as highly likely. Comparison with controls revealed differences in white blood cell count (WBC) (Folf change (FC) 1.46, P < 0.05), plasmablasts (FC 3.76, P< 0.05), plasmablasts CD38 (FC 1.43, P < 0.05), and CD27 (FC 0.66, P = 0.054), thus highlighting potential markers for IgG4-RD diagnosis. Treatments with steroids/rituximab tend to reduce plasmablast (FC 0.6) and IgG4 (FC 0.28) levels and to increase Gal-3 levels.

Conclusions: Levels of plasmablasts are a significant diagnostic feature in IgG4-RD. Healthy individuals have a lower level of plasmablasts. Elevated Gal-3 in serum of patients with IgG4-RD suggests a role in plasmablast activation. CD38/CD27 expression by plasmablasts emerges as a potential marker. Further research on a larger cohort is needed to confirm these findings.

Background: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost.

Objectives: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019.

Methods: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference.

Results: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019.

Conclusions: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied.

Objectives: To investigate the demographic and clinical profile of HS in the Israeli Arab population.

Methods: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups.

Results: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, p < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, p < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, p = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, p = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs.

Conclusions: The findings suggest a different phenotype of HS in Arabs, warranting further study.

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.

Echinococcus infections of the liver and lungs are well-known, but cardiac echinococcus is rare, requiring further understanding. A 19-year-old male presented with chest pain, shortness of breath and palpitations. Changes in an electrocardiogram, increased troponin, and a computed tomography (CT) scan revealed a cardiac cyst at the left ventricle’s posterior lateral wall. Medical management included albendazole and praziquantel for 2 weeks followed by surgical cyst removal.

Clinical presentation of cardiac involvement of echinococcus granulosis is variable, requiring high clinical suspicion. Cardiac CT scan and echocardiography provided sufficient information for the diagnosis. The treatment included surgical removal of the cyst and albendazole administration.

Hydatid cyst is a rare zoonotic disease caused by the parasite Echinococcus granulosus [1]. The incidence in endemic areas is about 1–200 cases per 100,000 in population [2].

The liver (60–70% of cases) and lungs (20–30%) are the most common locations of hydatid cysts, with rare cardiac involvement of only 0.05% to 2% of all cases [3], with the left ventricle most frequently involved (60%) [2,4].