Israel Medical Association Journal

Background: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities.

Objectives: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19.

Methods: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March–April 2020 (during the COVID-19 outbreak) with March–April of the preceding year, 2019.

Results: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods.

Conclusions: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients

Background: The safe completion of cholecystectomy is dependent on proper identification and secure closure of the cystic duct. Effecting this closure poses a great challenge when inflammatory changes obscure the anatomy. Subtotal cholecystectomy allows for near complete removal of the gallbladder and complete evacuation of the stones while avoiding dissection in the hazardous area.

Objectives: To describe experience with laparoscopic subtotal cholecystectomy.

Methods: Subtotal cholecystectomy was performed when the critical view of safety could not be achieved. Surgical technique was similar in all cases and included opening the Hartmann’s pouch, removing stones obstructing the gallbladder outlet, and identifying the opening of the cystic duct, as well as circumferential transection of the gallbladder neck, closure of the gallbladder stump, and excision of the gallbladder fundus. Data retrieved from patient charts included demographics, pre-operative history, operative and postoperative course, and late complications. No bile duct injuries were observed in this series.

Results: A total of 53 patients underwent laparoscopic subtotal cholecystectomy (2010–2018). Ten patients were operated during the acute course of the disease and 43 electively. Acute cholecystitis was the leading cause for gallbladder removal. Cholecystostomy tube was placed in 18 patients during acute hospitalization. The gallbladder remnant was closed and a drain was placed in most patients. Of the 53 patients, 42 had an uneventful postoperative course.

Conclusions: Laparoscopic subtotal cholecystectomy is an effective surgical technique to avoid bile duct injury when the cystic duct cannot safely be identified. Subtotal cholecystectomy has acceptable morbidity and obviates the need for conversion in these difficult cases.

Background: In 2006, the International Society for Heart and Lung Transplantation amended the guidelines for the upper age limit of heart transplantation (HTx) from 55 years to 70 years and older for carefully selected patients. However, the relation of age to outcomes following of HTx has not been well studied.

Objectives: To investigate the impact of recipient age on the occurrence of rejections, vasculopathy, and mortality after HTx.

Methods: Study population comprised all consecutive 291 patients who underwent HTx between 1991–2016 and were followed at our center. Patients were categorized by age tertiles: < 46 years (mean 31.4 ± 11.7, range 16–45, n=90), 46–57 years (mean 51.4 ± 3.2, range 46–56, n=92), and ≥ 57 years (mean 61.6 ± 3.4, range 57–73, n=109).

Results: Patients aged ≥ 57 years were more often males and had more pre-HTx co-morbidities including hypertension, diabetes, dyslipidemia, and history of smoking (P < 0.05) compared to the younger age groups. Kaplan-Meier analysis by age tertiles showed the rates of major rejections and vasculopathy at 15 years were similar among the three age groups. Mortality rates at 15 years were directly related to the age groups (39%, 52%, 62% log-rank, P = 0.01). However, the association between age and mortality was no longer statistically significant after multivariate analysis (hazard ratio 1.01, 95% confidence interval 1.00–1.03).

Conclusions: In a contemporary cohort of patients undergoing HTx, recipient age does not significantly impact the risk of major rejections, vasculopathy, and long-term mortality.

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: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment

Background: Dependence on technology and electronic media devices (EMDs) is a significant phenomenon of modern life with many people experiencing adverse symptoms during abstention. Orthodox Jews abstain from using all forms of EMDs for 25 consecutive hours every week on the Sabbath but do not appear to experience significant adverse reactions during this abstention.

Objectives: To better examine whether Sabbath observant Jews experience fewer and less severe adverse symptoms while abstaining from EMDs on the Sabbath compared to weekdays.

Methods: Ten Sabbath observant Jews abstained from using all forms of EMDs for 25 hours on a Sabbath and again on a weekday. At the end of each 25-hour period participants completed a 12-item Likert-type scale self-assessment of 1–5, once as a report of their condition at 10:00 and again after 25 hours of abstaining. The authors compared the mean results of Sabbath and weekday using Wilcoxon signed ranks test. P ≤ 0.05 was considered significant.

Results: Overall, discomfort on Sabbath was less than on weekdays. A statistically significant decrease on the Sabbath was found at both the 10:00 reporting time and after 25 hours in anxiety, restlessness, thoughts and plans of using devices, and overall difficulty to abstain. Significance was found for feelings of not knowing what to do with time (10:00) and moodiness and irritability, being drawn to devices, and cravings achieved significance (after 25 hours).

Conclusions: Sabbath observant Jews reported statistically significant less adverse reactions while abstaining from EMDs on the Sabbath compared to on a weekday.

Background: Channeling medical resources for coronavirus disease-2019 (COVID-19) management can potentially endanger routine healthcare practices. As a preventive measure, a department of obstetrics and gynecology in Israel constructed a separate, designated complex for its COVID-19-exposed patients.

Objectives: To evaluate the effect of the COVID-19 pandemic infection control measures on obstetric care in the obstetrical emergency department and delivery unit.

Methods: The authors collected data retrospectively from February 2020 to March 2020 and compared it to data of a parallel period in 2019.

Results: From 1 February 2020 to 28 March 2020, 3897 women were referred to the emergency department (ED), compared to 4067 the previous year. Mean duration of treatment until decision and referral indications did not differ between 2020 and 2019 (207 vs. 220 minutes, P = 0.26; urgent referrals 58.8% vs. 59.2%, P = 0.83). A per-week comparison showed a significant reduction in ED referrals only in the last week of the period (337 [2020] vs. 515 [2019], P < 0.001). The proportion of women admitted to the delivery unit in active labor was significantly higher in the last three weeks (39.1% vs. 28.2%, P = 0.005). During February and March 2020, 1666 women delivered, compared to 1654 during February and March 2019. The proportion of types and modes of delivery did not differ. In a per-week comparison, the number of deliveries did not differ (mean 208 vs. 206, P = 0.88).

Conclusions: With timely preparation and proper management, negative impact of COVID-19 can be reduced in obstetrical emergency departments.

Background: Social distancing, implemented to decrease the spread of coronavirus disease-2019 (COVID-19), forced major changes in medical practices, including an abrupt transition from face-to-face to remote patient care. Pre-clinical medical studies were concomitantly switched to electronic distance learning.

Objectives: To explore potential implications of COVID-19 on future pre-clinical medical studies.

Methods: We examined responses of pre-clinical medical students to the remote electronic learning in terms of quality of and satisfaction with teaching and technical support, attendance to classes, and the desire to continue electronic learning in the post-epidemic era. A survey of responses from first-year students at the Adelson School of Medicine was conducted. To optimize the reliability of the survey, a single research assistant conducted telephone interviews with each student, using a structured questionnaire concerning aspects of participation and satisfaction with teaching and with technical components of the remote electronic learning.

Results: With 100% response rate, the students reported high satisfaction with the electronic learning regarding its quality, online interactions, instructions given, technical assistance, and availability of recording for future studies. Most of the students (68.6%) noted a preference to continue < 90% of the learning online in the post-outbreak era. A high level of overall satisfaction and a low rate of technical problems during electronic learning were significantly correlated with the desire to continue online learning (P < 0.01).

Conclusions: The high satisfaction and the positive experience with the electronic distance learning imposed by the COVID-19 epidemic implied a successful transition and might induce future changes in pre-clinical medical studies.

Background: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic.

Objectives: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19).

Methods: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel.

Results: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02.

Conclusions: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.

Background: The 2019 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continued into 2020, and the coronavirus disease-2019 (COVID-19) associated death toll increased.

Objectives: To analyze COVID-19 death rates in European countries or regions to determine whether there was a significant association between bacillus Calmette-Guérin (BCG) vaccination policy and lower rates of COVID-19 related deaths.

Methods: Certain Northern European countries or regions had low death rates regardless of BCG policy. The authors assumed the consumption of foods containing salmiak (NH₄Cl) was a common and peculiar cause of the reduced COVID-19 related death rates in these countries, because NH₄Cl is a known lysosomotropic agent, which has been indicated to inhibit or prevent SARS-CoV infection. To check the possible effectiveness of salmiak consumption against COVID-19 related death, the authors used a linear regression model with the death rate as the dependent variable and BCG-policy and salmiak consumption score as independent variables.

Results: Using least squares regression and a robust standard error algorithm, the authors found a significant effect exerted by the independent variables (P < 0.0005 for BCG and P = 0.001 for salmiak). Salmiak score alone was significant (P = 0.016) when using least squares regression with robust error algorithm. 

Conclusions: The results seem to confirm an association between BCG-positive vaccination policy and salmiak consumption, and lower death rates from COVID-19. Implementing BCG vaccination policy and fortification of foods with salmiak (NH₄Cl) may have a significant impact on the control of SARS-CoV epidemic.

In this review we described the values of commonly available HScore laboratory markers in patients with coronavirus-19 (COVID-19)-pneumonia associated cytokine storm syndrome (CPN-CSS) and compared results with those of other forms cytokine storm syndrome (O-CSS) to determine a pattern for CPN-CSS. Twelve CPN-CSS studies and six O-CSS studies were included. CPN-CSS typically obtained a single HScore value (e.g., aspartate transaminase > 30 U/L) while failing all other HScore criteria. A typical pattern for CPN-CSS was revealed when compared to O-CSS: lymphopenia vs. pancytopenia and increased vs. decreased fibrinogen. Findings, other than HScore commonly found in CPN-CSS studies, showed elevated lactate dehydrogenase, D-dimer, and C-reactive protein. Although CPN-CSS studies describe severely ill patients, the HScore markers are typically less toxic that O-CSS