Israel Medical Association Journal

Background: There is limited clinical information on coronavirus disease-19 (COVID-19) patients in Israel.

Objectives: To describe the characteristics, outcomes, and potential associations of hospitalized COVID-19 patients in Israel.

Methods: We conducted a single-center, retrospective study of 58 consecutive laboratory-confirmed COVID-19 patients admitted to Laniado Hospital, Israel, between 14 March 2020 and 14 May 2020. Demographic, clinical, and laboratory data on admission were collected and analyzed, and the association to subsequent respiratory failure was assessed.

Results: Mean age of patients was 70.7 ± 16.9 years (53% males, 47% females.); 74% had at least one co-morbidity. Most patients were of Jewish Ashkenazi descent. During hospitalization 15 patients (mean age 78.18 ± 10.35 years); 80% male, 73% Sephardi descent developed respiratory failure rates of 60% occurring on average 10.6 days following intubation. Laboratory tests at admission displayed a significant increase in C-reactive protein (CRP) and creatine kinase (CK) and a decrease in absolute lymphocyte count (ALC) in patients who eventually developed respiratory failure (163.97 mg/L, 340.87 IU/L, 0.886 K/μl vs. 50.01 mg/L and 123.56 IU/L, 1.28 K/μl, respectively). Multivariate logistic analysis revealed an integrated parameter of CRP, CK, and ALC highly correlated with respiratory failure. Receiver operating characteristic curve revealed the area under the curve of CRP, CK, and ALC and the integrated parameter to be 0.910, 0.784, and 0.754, respectively. CRP was the strongest predictor to correlate with respiratory failure.

Conclusions: CRP, CK, and ALC levels on admission could possibly be used to detect high-risk patients prone to develop respiratory failure.

Background: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards.

Objectives: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards.

Methods: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital.

Results: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations.

Conclusions: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

Objectives: To review the experience with MBC of a single center in Israel over a period of 22 years.

Methods: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993–2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

Results: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A–2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2–178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

Conclusions: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.

Background: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.

Objectives: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).

Methods: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.

Results: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06–6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01–1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01–1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22–4.11).

Conclusions: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Background: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is associated with decreased perioperative morbidity and mortality.

Objectives: To report the outcomes of EVAR among patients older than 80 years of age.

Methods: In this retrospective study, we reviewed patients older than 80 years of age who underwent elective EVAR at our institution between 2007 and 2017. The demographics, perioperative morbidity and mortality, and long-term results are reported.

Results: During the study period, 444 patients underwent elective EVAR for AAAs. Among them 128 patients (29%) were > 80 years of age. Mean age was 84 ± 3.4 (range 80–96) years, and 110 patients (86%) were male. The EVAR was technically successful in 127 patients (99%) and there were intraoperative mortalities. Within 30 days of the surgery, nine patients (7%) died. Major and minor adverse events occurred in 26 (20%) and 59 (46%) patients, respectively. Factors associated with increased risk of perioperative morbidity and mortality included chronic kidney disease, peripheral artery disease, and the existence of three or more co-morbidities.

Conclusions: EVAR in the elderly can be performed with a high rate of success; however, it is associated with a substantial rate of morbidity and mortality, particularly when patients present with multiple co-morbidities. When performing EVAR in this population group, the risk of rupture must be considered opposed to the life expectancy of these patients and the risk of perioperative morbidity and mortality.

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood.

Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents.

Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations.

Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809–0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941–0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728–0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035–1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001).

Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Background: Israel's population is diverse, with people of different religions, many of whom seek spiritual guidance during ethical dilemmas. It is paramount for healthcare providers to be familiar with different religious approaches.

Objectives: To describe the attitudes of the three major monotheistic religions when encountering four complex neonatal situations.

Methods: A questionnaire related to four simulated cases was presented to each participant: a non-viable extremely premature infant (case 1), a severely asphyxiated term infant with extensive brain damage (case 2), a small preterm infant with severe brain hemorrhage and likely extensive brain damage (case 3), and a term infant with trisomy 21 syndrome and a severe cardiac malformation (case 4).

Results: Major differences among the three religious opinions were found in the definition of viability and in the approach towards quality of life.

Conclusions: Neonatologists must be sensitive to culture and religion when dealing with major ethical issues in the neonatal intensive care unit.

Background: Falls while turning are associated with increased risk of hip fracture in older adults. Reliable and clinically valid methods for turn ability assessments are needed.

Objectives: To explore the inter-observer reliability and known group validity of the TURN 180 test.

Methods: We divided 78 independent older adults (mean age 76.6 ± 6.5 years) into three groups: non-fallers, infrequent fallers (1–2 falls per year), and recurrent fallers (> 2 falls per year). Participants underwent performance-based tests: Timed Up and Go (TUG), Performance Oriented Mobility Assessment (POMA), and Berg Balance Scale (BBS). TUG was videotaped for later analysis of the TURN 180 test by two blinded observers.

Results: A significant difference was found in the TURN 180 test parameters among the groups (P < 0.04). TURN 180 was highly correlated with TUG (r = 0.81–0.89, P < 0.001) and BBS (r = -0.704–0.754, P < 0.0001) and moderately with POMA (r = -0.641–0.698, P < 0.0001). The number of steps was found to be the strongest parameter to determine fallers among older adults (specificity 96.3%, sensitivity 40%). Inter-rater reliability (intraclass correlation coefficient 0.91–0.96, P < 0.0001) was found to be excellent for the number of steps, time taken to accomplish a turn, and total test score categories.

Conclusions: The TURN 180 test is highly reliable and can identify the older adults who fall. Our results show that the TURN 180 test can serve as a good performance-based examination for research or clinical setting.

Background: Unilateral renal agenesis is a rare finding. There are no large-scale studies reporting this finding in early pregnancy.

Objectives: To evaluate the incidence of unilateral renal agenesis (URA) and of associated anomalies diagnosed by early prenatal trans-vaginal sonography.

Methods: We performed a retrospective chart review of all 59,382 trans-vaginal scans performed at 14–16 weeks gestation by a single operator at different clinics during the period 1994–2013.

Results: The incidence of URA was 1:1212 (49/59382 cases). Associated anomalies were diagnosed in 22 cases (45%). Renal anomalies were diagnosed in 22.4%. Extra-renal anomalies (with exclusion of a single umbilical artery or nuchal edema as isolated findings) were diagnosed in 24.5%. Ambiguous genitalia were diagnosed in 8.2%.

Conclusions: URA is a rare finding in early trans-vaginal sonography. Associated anomalies are very common and should be sought.

Background: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients.

Objectives: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF).

Methods: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group.

Results: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls.

Conclusions: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986–1987 (DC), and Tel Aviv Medical Center, Israel 1999–2009 (TA).

Results: The study comprised 227 patients (139 TA, 88 DC). TA patients were older (75.4 ± 9.8 vs. 63.8 ± 14.3 years, P < 0.001) and had more cardiovascular diseases (56.8% vs. 14.8%, P < 0.001), fewer cytopenias (1.67 ± 0.82 vs. 2.0 ± 0.93, P = 0.003), and lower mean corpuscular volume (94.3 ± 9.9 fl vs. 100.5 ± 15.3 fl, P < 0.001). Hemoglobin, leukocyte, neutrophil, and platelet counts were similar. More TA patients had dysplasias. Bone marrow cellularity and cytogenetics were similar, but more TA patients had blasts < 5% (73.4% vs. 50.6%, P = 0.003). More TA patients had early French-American-British (FAB) disease (66.9% vs. 40.9%, P < 0.001) and lower risk disease per International Prognostic Scoring System (81% vs. 50%, P < 0.001). The 5 year survival (5YS) of TA patients was not significantly greater (62% vs. 55%). 5YS by FAB was also slightly greater for TA patients (77% vs. 65% for early FAB; 43% vs. 37% for advanced FAB, P > 0.05).

Conclusions: Although patients diagnosed with MDS at a later period were older and had more cardiovascular co-morbidities, they had fewer cytopenias, tended to have earlier disease, and had minimally greater, but not significant, 5YS.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.