Israel Medical Association Journal

Background: Massive, non-compressible bleeding is a leading cause of preventable trauma mortality. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a minimally invasive procedure in which a balloon catheter is maneuvered into the aorta to temporarily occlude large vessels and enable stabilization of the exsanguinating patient.

Objectives: To present experiences in assimilating REBOA at a single level 1 trauma center in Israel, to evaluate the technical aspects of the procedure, and to describe patient characteristics and outcomes.

Methods: This retrospective cohort study comprised civilians admitted with hemorrhagic shock to our trauma department who were treated with REBOA between November 2017 and July 2021. Descriptive statistics of the patients, characteristics of the injuries and patient outcomes are presented.

Results: The study included 22 patients (median age 30.1 years, 21 male). The mean systolic blood pressure (SBP) before REBOA inflation was 59.6 ± 11.4 mmHg, and the mean SBP measured after the procedure was 115.2 ± 26.3 mmHg. In 20 patients (91%), the SBP was normalized (> 90 mmHg) shortly after inflation of the balloon, and they survived the treatment in the trauma department; 15 (75%) survived the first 30 days. 

Conclusions: REBOA is an effective method for the initial resuscitation and hemorrhage control of patients with massive, non-compressible bleeding and is relatively easy to assimilate in a hospital. The achievement of immediate normalization of SBP enables medical personnel to correct physiological parameters and obtain accurate imaging before proceeding to the operating theater. 

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: 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: 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: 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: The prognosis of long-term clinical outcomes for each patient is of utmost importance.

Objectives: To evaluate the association between rates of family attendance during rounds and long-term outcomes.

Methods: We conducted a historic cohort study.

Results: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium.

Conclusions: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

Stress urinary incontinence (SUI), defined as involuntary leakage of urine associated with increased intra-abdominal pressure during an effort such as sneezing or coughing, is a highly prevalent condition that affects women of all ages and impacts a women's quality of life (QoL). The prevalence of SUI reaches 14% in younger women and up to 35% in older women. Vaginal deliveries, gravidity, advanced age, menopause status, obesity, diabetes, and ethnicity are known risk factors for SUI [1].

The prevalence of pelvic organ prolapse (POP) varies greatly and is reported to be between 3% and 50% differing greatly when based on POP symptoms or vaginal examination [1]. Age is a well-established risk factor in the reported prevalence of POP [2]. With advancing age, the prevalence escalates dramatically, from 6% at age of 30 years to over 50% at the age of 80 years [3]. The increase in life expectancy observed in recent years will most probably be accompanied by a respective increase in the absolute numbers of women presenting with POP [4]. POP is a major health burden and is expected to continue being so in the upcoming future; hence, the importance of a safe and efficient treatment.

Serum sickness is an immune-complex-mediated hypersensitivity reaction that classically presents with fever, rash, polyarthritis, or poly arthralgias. Damage is caused by formation or deposition of antigen-antibody complexes in vessels or tissues. Deposition of immune complexes causes complement activation and/or recruitment of neutrophils by interaction of immune complexes with Fc immunoglobulin G receptors. The condition was first recognized as an entity in the early 1900s in patients who had received heterologous antisera, which was historically used to treat infectious diseases. The symptoms typically occur one to two weeks after exposure to an offending agent and resolve within several weeks of discontinuation [1].

Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients.

Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment.

Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization.

Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change.

Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.

Objectives: To evaluate the association of FMS with osteoporosis.

Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.

Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).

Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.

Background: Statins have anti-inflammatory effects that are independent of their lipid-lowering activity.

Objectives: To examine whether prior statins therapy affects the clinical course of the first episode of acute idiopathic pericarditis (AIP) as the 1-year recurrence and length of hospitalization (LOH).

Methods: This retrospective study included 148 subjects with first episode AIP admitted between the years 2015 and 2019. Data were collected from two hospitals in Northern Israel. We divided the patients in into two groups: 117 those without statins use and 31 those with prior statins use. We compared age, sex, co-morbidities, drugs, laboratory data, 1-year recurrence, and LOH.

Results: The mean age of participants was 43.1 ± 19.4 years. Comparisons between subjects without statins and with prior statins use were made according to age (37.5 ± 16.7 years vs. 64.4 ± 12.7 years, P < 0.01), C-reactive protein (50 ± 40 vs. 48 ± 35 mg/dl, P = 0.9), LOH (5.4 ± 2.85 vs. 8.03 ± 4.92 days, P < 0.01), 1-year recurrence of pericarditis (23 vs. 6 cases, P = 0.95), respectively. Multivariate logistic regression analysis revealed that 1-year recurrence (odds ratio [OR] 0.8, 95% confidence interval [95%CI 0 0.6–1.1, P = 0.41), was not associated with prior statin use, while LOH (OR 2.56, 95%CI 2.08–2.75, P = 0.01) was prolonged with prior statins use in patients with first episode of AID.

Conclusions: Prior statins use in patients with the first episode of AIP did not reduce the 1-year recurrence of pericarditis and prolong the LOH.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Background: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking.

Objectives: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents.

Methods: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses.

Results: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability.

Conclusions: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.