Israel Medical Association Journal

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: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality.

Objective: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI.

Methods: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission.

Results: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithm_ebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis.

Conclusions: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.

Background: Despite its wide use, evidence is inconclusive regarding the effect of percutaneous endoscopic gastrostomy (PEG) in patients with chronic diseases and dementia among hospitalized patients with malnutrition.

Objectives: To examine the effect of PEG insertion on prognosis after the procedure.

Methods: This retrospective analysis of medical records included all adult patients who underwent PEG insertion between 1 January 2009 and 31 December 2013 during their hospitalization. For each PEG patient, two controls similar in age, sex, referring department, and underlying condition were randomly selected from the entire dataset of patients admitted. The effect of PEG on mortality and repeated admissions was examined.

Results: The study comprised 154 patients, 49 referred for PEG insertion and 105 controls (mean age 74.8 ± 19.8 years; 72.7% females; 78.6% admitted to internal medicine units). Compared to controls, the PEG group had a higher 2-year mortality rate (59.2% vs. 17.1%, P < 0.001) but the 2-year readmission rate did not differ significantly (44.9% vs. 56.2% respectively, P = 0.191). Regression analysis showed PEG was  associated with increased risk of the composite endpoint of death or readmission (hazard ratio 1.514, 95% confidence interval 1.016–2.255, P = 0.041). No specific characteristic of admission was associated with increased likelihood of death or readmission. Among readmitted patients, reasons for admission and baseline laboratory data, including albumin and cholesterol, did not differ between the PEG patients and controls.

Conclusions: In-hospital PEG insertion was associated with increased mortality at 2 years but had no effect on readmissions.

Background: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE).

Objective: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs.

Methods: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit.

Results: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32–6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28–0.87, P = 0.016), depicting a medium-to-high disease activity among the former.

Conclusions: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Late, preterm premature rupture of the membranes (PPROM) presents a major obstetrical challenge balancing between iatrogenic prematurity and risk of prolonged rupture of membranes. In recent years, the pendulum has been shifting toward expectant management until gestation week 37 + 0. We examined the latest guidelines and major trials and summarized optimal management. We addressed the major dilemmas of women with PPROM during gestation weeks 34 + 0 to 36 + 6.

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

Background: Several approaches are used to access the hip joint; most common are the direct lateral and posterior. Little consensus exists on which to use when treating hip fractures.

Objectives: To compare short-term complications, postoperative ambulation, and patient-reported outcome measures (PROMS) of direct lateral vs. posterior approaches in hemiarthroplasty for acute hip fractures.

Methods: We conducted a retrospective clinical trial with 260 patients who underwent bipolar hemiarthroplasty in the direct lateral or posterior approach (166 and 94, respectively) between January 2017 and December 2018. The clinical data included short-term complications: prosthetic dislocation, periprosthetic fractures, and infection. Postoperative ambulation was collected 6 weeks postoperatively; PROMS were collected for 173 patients at 2 years follow-up.

Results: There were six dislocations overall, average time to dislocation was 22 days postoperative (range 4–34). Five dislocations were after the posterior approach (5.3%) and one after direct lateral (0.6%) (P = 0.01). At 6 weeks follow-up, inability to walk was found in 16.9% of the direct lateral group and 6.4% of the posterior approach group (P = 0.02). In the posterior approach group, 76% could walk more than 20 meters; only half of the direct lateral group could (P = 0.0002). At 2 years follow-up, PROMS did not show a statistically significant difference between the groups.

Conclusions: Posterior approach for hemiarthroplasty following femoral neck fractures allows superior ambulation to the direct lateral approach only for the short-term. However, no long-term clinical advantage was found. This short-term benefit does not justify the increased dislocation rate in the posterior approach.

Background: Implant-based breast reconstruction (IBR) is the most common method of reconstruction for breast cancer. Bacterial infection is a well-known risk with reported rates ranging from 1% to 43%. The most common pathogens of breast implant infection described in the literature are Staphylococcus aureus, Staphylococcus epidermidis, and coagulase-negative staphylococci. However, the prevalence of other pathogens and their antibiotic sensitivity profile differs profoundly in different parts of the world.

Objectives: To review the current literature and protocols with respect to our region and to determine a more accurate antibiotic protocol aimed at our specific local pathogens.

Methods: A retrospective review was conducted of all cases of clinically infected implant-based breast reconstruction in our institution from June 2013 to June 2019, as well as review of microbiologic data from around the world based on current literature.

Results: A total of 28 patients representing 28 clinically infected implant-based breast reconstruction were identified during the studied period. Thirteen patients (46.4%) had a positive bacterial culture growth, with P. aeruginosa being the most common microorganism identified (46.1%). Review of international microbiological data demonstrated significant variation at different places and time periods.

Conclusions: Microbiological data in cases of infected breast reconstructions should be collected and analyzed in every medical center and updated every few years due to the variations observed. These data will help to adjust the optimal empirical antibiotic regimens given to patients presenting with infections after breast reconstruction.

Background: Previous epidemiological studies on shoulder instability evaluated specific and relatively small subgroups of patients.

Objectives: To determine the incidence rate of primary shoulder dislocations.

Methods: Cohort analysis of electronic health records from 2004 to 2019 was conducted in a urban district of a major health maintenance organization (HMO) in Israel. Patients presented with primary shoulder dislocation that was treated with closed reduction in any medical facility within the district. Overall incidence density rates (IDR) of primary shoulder dislocations and stabilization surgeries were determined.

Results: Over a period of 16 years 13,158 patients underwent closed reduction of primary shoulder dislocation. Of those, 712 shoulder stabilization surgeries were performed (5%). The IDR of primary shoulder dislocations were 124 per 100,000 person-years. The IDR of primary shoulder stabilizations were 7 per 100,000 person-years. The peak in the number of dislocations was observed in those 20–29 years old and ≥ 60 years of. In patients under 59 years old, dislocations were more common in men. In those ≥ 60 years of age, dislocations were more common in women. Most shoulder stabilization surgeries were performed on young patients. The annual mean time from the first dislocation to stabilization surgery linearly declined to 6 months in 2019.

Conclusions: The IDR of primary shoulder dislocations calculated from the largest HMO in Israel were 124 per 100,000 person-years. Shoulder dislocations had bimodal age distribution. Overall, 5% of the patients (mainly young) with shoulder dislocations underwent shoulder stabilization surgery during the study period.

Background: Surgical resection is the only curative option for gastric carcinoma (GC). Minimally invasive techniques are gaining popularity.

Objectives: To present a single-surgeon's experience in transitioning from an open to a minimally invasive approach, focusing on surgical and oncological outcomes.

Methods: We conducted a retrospective analysis including distal gastrectomy patients 2012–2020 operated by a single surgeon. Two cohorts were compared: open (ODG) and laparoscopic distal gastrectomy (LDG).

Results: Overall, 173 patients were referred for gastrectomy during the study years. We excluded 80 patients because they presented with non-GC tumors, underwent proximal or total gastrectomy, or underwent palliative surgery. Neoadjuvant treatment was administered to 62 patients (33.3%). Billroth 1 was the preferred method of reconstruction (n=77, 82.8%), followed by Roux-en-Y (n=12, 13%). Fifty-one patients (54.8%) underwent LDG, 42 (45.2%) underwent ODG. The LDG group had significantly shorter lengths of stay (6 days, interquartile range [IQR] 1–3 5–8 vs. 5 days, IQR 1–3 4–6, P = 0.001, respectively), earlier return to oral feeding (1 day, IQR 1–3 1–3 vs. 2 days, IQR 1–3 1–3.2, P < 0.001), and earlier removal of drains (4 days, IQR 1–3 3–5.2 vs. 5 days, IQR 1–3 3.5–6.7, P < 0.001). Overall lymph node yield was 30 (IQR 1–3 24–39) and was similar among groups (P = 0.647).

Conclusions: Laparoscopic techniques for resection of distal GC are feasible and safe, leading to good perioperative outcomes and adequate lymph node yield.

Background: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease and stroke. Metformin is an old, relatively safe, first line therapy for T2DM; however, it has been associated with stroke.

Objectives: To study the effects of metformin use and vitamin B12 deficiency on stroke rate among patients with T2DM.

Methods: We conducted a prospective study of patients admitted with ischemic stroke within 12 months (starting March 2020). We studied the clinical impact of metformin on vitamin B12 deficiency and stroke evolution. Student's t-test and ANOVA were used to compare the groups of patients and to determine whether there was any direct or indirect effect of metformin use on vitamin B12 deficiency and stroke.

Results: In total, 80 patients were admitted with ischemic stroke. Clinical status and biochemical data were collected and compared with healthy volunteers. There were 39 diabetic patients, 16 took metformin for at least 1 year. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014).

Conclusions: T2DM is a significant risk factor to the development of ischemic stroke. We found an association between metformin use and vitamin B12 deficiency and an association between vitamin B12 deficiency and stroke risk in patients with T2DM. Diabetic patients who are taking metformin should monitor their vitamin B12 level.

Background: Polyp detection rate (PDR) is a convenient quality measure indicator. Many factors influence PDR, including the patient's background, age, referral (ambulatory or hospitalized), and bowel cleansing.

Objectives: To evaluate whether years of professional experience have any effect on PDR.

Methods: A multivariate analysis of a retrospective cohort was performed, where both patient- and examiner-related variables, including the experience of doctors and nurses, were evaluated. PDR, as the dependent variable was calculated separately for all (APDR), proximal (PPDR), and small (SPDR) polyps.

Results: Between 1998 and 2019, 20,996 patients underwent colonoscopy at a single center. After controlling for covariates, the experience of both doctors and nurses was not found to be associated with APDR (odds ratio [OR] 0.99, 95% confidence interval [95%CI] 0.98–1.00, P = 0.15 and OR 1.03, 95%CI 1.02–1.04, P < 0.0001, respectively). However, after 2.4 years of colonoscopy experience for doctors, and 9.5 years of experience for nurses, a significant increase in APDR was observed. Furthermore, results revealed no association for PPDR and SPDR, as well.

Conclusions: Years of colonoscopy experience for both doctors and assisting nurses were not associated with APDR, PPDR, and SPDR. In doctors with 2.4 years of experience and nurses with 9.5 years of experience, a significant increase in APDR was observed.

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Background: Bacterial meningitis (BM) remains a considerable cause of morbidity.

Objectives: To evaluate BM incidence rate trends in diverse age groups.

Methods: We conducted a retrospective cohort study based on the Israeli national registry. Inclusion criteria were acute admissions 2000 to 2019 with primary diagnosis of BM. Predefined age groups were neonates (≤ 30 days), infants (31 days to 1 year), younger children (1 ≤ 5 years), older children (5 ≤ 18 years), and adults (≥ 18 years). Average annual incidence rates per 100,000/year were calculated for the entire period and by decade. Incidence rates for neonates and infants were calculated per 100,000 live births (LB).

Results: There were 3039 BM cases over 2 decades, 60% were adults. The overall BM incidence rate was 2.0/100,000/year, neonates, 5.4/100,000/year LB, infants 17.6/100,000/year LB. First year of life incidence rate (neonates and infants combined) was 23.0/100,000/year, younger children 1.5/100,000/year, older children 0.9/100,000/year, and adults 1.8/100,000/year. All age groups presented a decrease in incidence rate (last decade vs. previous) except neonates, which increased by 34%. Younger and older children presented the most considerable decrease: 48% and 37% (last decade vs. previous).

Conclusions: Adults showed the highest number of BM cases. The incidence rate was highest during the first year of life (neonates and infants combined). All age groups, except neonates, showed a decreasing trend. Younger and older children presented the most considerable decrease, most likely attributable to vaccination. The observed increase in BM incidence rate in neonates may influence whether preventive strategy is considered.