Israel Medical Association Journal

Background: Israel has experienced three waves of coronavirus disease-2019 (COVID-19) infection since late February 2020, with lockdown and other measures employed to contain infection rates. In cooperation with the Israel Ministry of Health, serological testing was conducted by all four health maintenance organizations (HMO) in order to estimate national infection rates and the proportion of previously undetected disease.

Objectives: To estimate the proportion of the population that was seropositive, identify factors associated with seropositive outcome, and approximate the proportion of residents that were asymptomatic.

Methods: Seroconversion rates (IgG) were measured in a representative sample of over 17,000 members of Maccabi Healthcare Services. Direct standardization was used to estimate the seropositive rates for COVID-19 infection for members of the HMO. Rates were adjusted for sensitivity and specificity of the testing products used. In addition to blood sampling, respondents were asked to complete a digital survey regarding potential exposures and symptoms experienced.

Results: It was estimated that 1.9% of the adult HMO population was seropositive 4 months after the first infected person was identified in the country. Seroconversion was associated with travel abroad and exposure to infected individuals. Loss of smell and taste, fever, cough, and fatigue are associated with infection. Of those found to be seropositive for COVID-19, 160 (59%) had a prior negative polymerase chain reaction (PCR) or no PCR test at all.

Conclusions: Adult seropositive rates of infection were low relative to other countries. The findings suggest that early initiatives to limit infection entry and spread were effective

Background: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce.

Objectives: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia.

Methods: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level.

Results: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas.

Conclusions: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.

Background: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies.

Objectives: To describe the design and patient population of the first pediatric aerodigestive center in Israel.

Methods: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children’s Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020.

Results: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3–216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1–5 (5 = highest satisfaction) was 4.5.

Conclusions: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

Background: Acute extremity compartment syndrome is a surgical emergency for which timely diagnosis is essential.

Objectives: To assess whether the time from the initial insult to the fasciotomy of compartment syndrome of the upper extremity affects outcomes and to examine the differences between compartment syndrome secondary to fractures and that resulting from a non-fracture etiology with regard to the time from insult to fasciotomy and the long-term patient outcomes.

Methods: Patients presented with documented fasciotomy treatment following acute upper extremity compartment syndrome and a minimum of 6 months follow-up. Patient information included demographics, cause of compartment syndrome, method of diagnosis, and outcome on follow-up.

Results: Our study was comprised of 25 patients. Fasciotomies were performed for compartment syndrome caused by fracture in 11 patients (44%), and due to insults other than fractures in 14 patients (56%). The average time to fasciotomy in patients without a fracture was 10.21 hours and 16.55 hours with a fracture. Fasciotomy performed more than 24 hours from the initial insult was not found to significantly affect long-term sequelae compared to fasciotomy performed earlier than 24 hours from the initial insult. The non-fracture group had more long-term sequelae than the fracture group (13/15 patients and 5/11 patients, respectively).

Conclusions: Most injuries treated for fasciotomy of compartment syndrome were non-fracture related, with more complications found in patients with non-fracture related injuries. Time interval from insult to fasciotomy did not affect outcome and was longer in the fracture group, suggesting longer monitoring in this group and supporting fasciotomy even with late presentation.

Background: Cervical spinal surgery is considered safe and effective. One of the few specific complications of this procedure is C5 nerve root palsy. Expressed primarily by deltoid muscle and biceps brachii weakness, it is rare and has been related to nerve root traction or to ischemic spinal cord damage.

Objectives: To determine the clinical and epidemiological traits of C5 palsy. To determine whether C5 palsy occurs predominantly in one specific surgical approach compared to others.

Methods: A retrospective study of patients who underwent cervical spine surgery at our medical center during a consecutive 8-year period was conducted. The patient data were analyzed for demographics, diagnosis, and surgery type and approach, as well as for complications, with emphasis on the C5 nerve root palsy.

Results: The study group was comprised of 124 patients. Seven (5.6%) developed a C5 palsy following surgery. Interventions were either by anterior, by posterior or by a combined approach. Seven patients developed this complication. All of whom had myelopathy and were older males. A combined anteroposterior (5 patients) and posterior access (2 patients) were the only approaches that were associated with the C5 palsy. None of the patients who were operated via an anterior approach did develop this sequel.

Conclusions: The incidence of the C5 root palsy in our cohort reached 5.6%. Interventions performed through a combined anterior-posterior access in older myelopathic males, may carry the highest risk for this complication

Background: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.

Objectives: To describe changes in teaching during the first phase of the COVID-19 pandemic.

Methods: We described the steps implemented at the Technion–Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. 

Results: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. 

Conclusions: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching

Background: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL).

Objectives: To characterize medication burden during the last hospitalization in children dying from cancer

Methods: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters.

Results: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with “Do not resuscitate” (DNR) orders (P = 0.055).

Conclusions: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.

Background: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM.

Objectives: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation.

Methods: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months.

Results: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group.

Conclusions: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed.

Objectives: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores.

Methods: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month.

Results: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005).

Conclusions: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.