Israel Medical Association Journal

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.

Background: Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general.

Objectives: To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit.

Methods: A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored.

Results: The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease.

Conclusions: This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.

Background: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years.

Objectives: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD.

Methods: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups.

Results: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m² vs. 25 ± 2.5 kg/m², P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009).

Conclusions: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.

Background: The effect of weight reduction following bariatric surgery is already well known.

Objectives: To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss.

Methods: The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters.

Results: Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m². All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study.

Conclusions: In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient’s metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Background: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM.

Objectives: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach.

Methods: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA).

Results: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts.

Conclusions: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

Background: There are several ways to remove silicone oil (SO) from the vitreous cavity.

Objective: To describe a simple, safe and inexpensive method of 2-port SO removal.

Method: Medical charts of 33 patients who underwent SO removal combined with cataract extraction were retrospectively reviewed, from a cohort of 119 patients who had silicone oil removal. The primary outcome was the rate of re-detachment, secondary outcomes included visual acuity (VA) and intraoperative and postoperative complications.

Results: Mean follow-up time was 27.6 months (0.25–147 ± 33.1), and mean tamponade duration prior to SO removal was 16.77 months (4–51.5 ± 14.6). The re-detachment rate was 3% (one patient). Postoperatively, seven patients (20%) had epiretinal membrane (ERM), eight patients had posterior capsule opacification (24%), and proliferative vitreoretinopathy (PVR) was diagnosed in two patients (6%). Compared to the mean VA (logarithm of the minimum angle of resolution [LogMAR]) at the preoperative examination, the mean VA (LogMAR) improved significantly at the last visit when including all ranges of VA (n=32, LogMAR 1.52 vs. 1.05 P = 0.0002 [Student's t-test] and P = 0.001 [Wilcoxon test]).

Conclusions: The technique described is fast and simple, keeping the posterior capsule intact in pseudophakic patients, which is advantageous in the event of future re-detachment necessitating SO reinjection. Rates of re-detachment and postoperative ERM and PVR were low. Furthermore, our method does not require the use of a surgical microscope with posterior segment viewing systems, or opening a full disposable vitrectomy set, thus drastically reducing the procedure's cost.

Despite advances in therapeutic modalities, especially with biologic treatments, the number of hospitalizations due to complications for Crohn's disease did not decrease. We examined the prevalence and possible predictive factors of hospitalizations in Crohn's disease. A systematic literature search was conducted until 31 October 2018. Relevant studies were screened according to established protocol. Retrospective cohort studies describing hospitalizations of Crohn's disease patients were included. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the number of patients hospitalized. Twelve studies published before 31 March 2018 fulfilled the inclusion criteria and were comprised of 23 data-sets and included 4421 patients from six countries. A funnel plot demonstrates a moderate publication bias. We reported the event rates for the number of patients hospitalized, in a follow-up survey of 20,987 patient-years, and for the patients who underwent surgery in a follow-up of 5061 patient-years, with ORs of 0.233 with 95%CI 0.227–0.239, and 0.124 with 95%CI 0.114–0.135 (P < 0.001), respectively. Thus, when collecting the data from 12 cohort studies we found that hospitalization takes place in 23.3% of the patients, and operation in 12.4% along their disease duration. Patients with Crohn's disease may be hospitalized due to exacerbation of their inflammatory disease, because of non-inflammatory disease (such as fistula or stricture), or due to medical complications. The goal of therapy should be to keep the Crohn's disease patients in their natural environment and out of the hospital and to prevent surgery as much as possible.

Background: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited.

Objectives: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC.

Methods: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist.

Results: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7–7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1–12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1–5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9–26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2–not reached).

Conclusions: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC. 

Background: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined.

Objectives: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring.

Methods: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group.

Results: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02).

Conclusions: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.