Israel Medical Association Journal

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.

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.

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

Twenty-five years ago, we, the undersigned together with the chairman of the Israel Medical Association at the time, Prof. Yoram Blachar, and the Secretary General of the Israel Medical Association, Adv. Leah Wapner, joined forces to found an Israeli medical journal in English. The purpose of this journal was to present to the world Israeli clinical medicine and medical research. That journal is none other than the Israel Medical Association Journal (IMAJ), and in 2023 its 300th issue was published. In 2024 we keep going, taking pride in the fact that every one of those past 300 issues has been published and dispatched on time, without delay, regardless of any circumstances.

Background: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear.

Objectives: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates.

Methods: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34–36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012–December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea.

Results: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41–4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23–3.78, P = 0.007).

Conclusions: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

Background: Websites serve as a source of medical information for a large part of the public, some claim to be a substitute for a physician’s consultation. Many patients meet a physician after conducting internet research. Medical staff are concerned that internet sources of information are unreliable and may lead to erroneous decisions by patients.

Objectives: To examine the reliability of web-based sources of information (through the Google™ search engine) regarding five common orthopedic complaints and injuries.

Method: We performed a search of five common orthopedic complaints and injuries using the Google search engine. The reliability of web-based information was measured by the DISCERN tool, which is a valid and verified tool for examining the reliability of medical information sources to the public. The reliability of 47 websites was examined by two orthopedic surgeons and two senior residents.

Results: The overall average score given to the sites was 2.8, on a scale of 1 to 5. We found that the higher the site appeared in the search results, the higher the quality of its information. Commercial sites scored higher than general internet information sources.

Conclusions: The internet network is a very broad source of information. For those who lack scientific education and training it is not easy to distinguish between reliable and unreliable or biased sources. The trend of searching for medical information and self-healing is increasing. We must strengthen the network with reliable sources by creating official scientific position papers by medical teams and promoting them online.

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

Background: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI).

Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI.

Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI.

Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34–17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23–12.81, P = 0.06).

Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

Background: Bicalutamide monotherapy (BMT) is an option for androgen deprivation therapy (ADT) in patients with low- and intermediate-risk prostate cancer (LIR-PC). Painful gynecomastia (PG) is a common side effect of BMT. Few therapeutic options are available for preventing BMT-induced PG.

Objectives: To assess the efficacy and side effects of single fraction (SF) prophylactic breast irradiation (PBI) to prevent painful gynecomastia (PG) in patients LIR-PC treated with BMT.

Methods: We reviewed the results of bilateral PBI in a prospective cohort of LIR-PC patients who received 150 mg bicalutamide daily as a first-line treatment for at least 12 months. A single fraction of 8 Gy was administered to both breasts by a stationary field of 10 × 10 cm, using 10–15 MeV electron beam. PBI was commenced on the same day as BMT, but prior to the first dose of bicalutamide. A radiotherapy treatment plan was designed to cover breast tissue by the 90% isodose line. Subsequent monthly physical examinations were scheduled for all patients during the first year of BMT to evaluate any PG symptoms.

Results: Seventy-six patients received BMT and PBI, 80% (61/76) showed no signs of PG; 20% (15/76) experienced mild gynecomastia. The main adverse effect of PBI was grade 1 radiation dermatitis.

Conclusions: PBI using a SF of 8 Gy is an effective, safe, and low-cost strategy for the prevention of BMT-induced PG in LIR-PC patients.

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Background: Contact dermatitis is an inflammatory skin disorder characterized by an erythematous pruritic rash. The disorder can be either irritant or allergic. Allergic contact dermatitis is diagnosed by patch testing along with patient history.

Objectives: To review the results of patch tests conducted thought 2 years and to present real-life data characterizing clinical features and comparing prevalent local allergens to the ones common worldwide.

Methods: The retrospective cohort included 517 participants (384 females and 133 males) who underwent patch testing during a 2-year period. For each patient, clinical and demographic data were collected, and statistical analysis was conducted.

Results: We found that 261 patients had a positive test for at least one allergen. More females tested positive than males (52.9% vs. 43.6%). Test indications other than dermatitis were associated with a negative result. Hands, head, and neck were the most prevalent body parts affected. Patients with a background of atopic dermatitis had a higher rate of contact sensitization (69 vs. 43). Patients with a specific suspected offending allergen had significantly higher contact sensitizations. The most common allergen was nickel.

Conclusions: Patch testing should be conducted in patients with relevant dermatological findings accompanied by taking a thorough medical history. Clinicians should be updated on emerging allergens and exposure trends.

Background: Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable.

Objectives: To assess possible predictors of primary and secondary failure of vascular access.

Methods: This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up.

Results: A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure.

Conclusions: Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.