Israel Medical Association Journal

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Heart rate disorders and in particular sinus arrhythmias are known to accompany viral infections. Sinus tachycardia is prevalent in the presence of increased body temperature and respiratory rate. However, bradycardia has also been described for centuries to complicate viral illnesses

Background: In response to the coronavirus disease-2019 (COVID-19) pandemic, routine clinical visits to the ophthalmic emergency department (OED) were deferred, while emergency cases continued to be seen.

Objectives: To assess the consequences of the COVID-19 pandemic for ophthalmic emergencies.

Methods: A retrospective chart analysis of patients who presented to the OED during the peak of the COVID-19 pandemic was conducted. The proportions of traumatic, non-traumatic-urgent, and non-traumatic-non-urgent presentations in 2020 were compared to those of the same time period in 2019. Duration of chief complains and best-corrected visual acuity were also assessed.

Results: There were 144 OED visits in 2020 compared to 327 OED visits during the same 3-week-period in 2019. Lower mean age of OED patients was present in 2020. Logarithmic expression (LogMAR) best corrected visual acuity (BVCA) was similar in both years. In 2020 there was a reduction in traumatic, non-traumatic-urgent, and non-traumatic-non-urgent cases compared to 2019 (15.4% reduction, P = 0.038; 57.6% reduction, P = 0.002; 74.6% reduction, P = 0.005, respectively). There was a higher proportion of same-day presentations at commencement of symptoms in 2020 compared with 2019 (52.8% vs. 38.8%, respectively P = 0.006).

Conclusions: During the COVID-19 pandemic, the number of OED visits at a tertiary hospital dropped by more than half. Although the drop in visits was mostly due to decrease in non-traumatic-non-urgent cases, there was also decrease in non-traumatic-urgent presentations with possible important visual consequences. Additional studies should elucidate what happened to these patients

Background: Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL.

Objectives: To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors.

Methods: We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP^1–7d) of life and subdivided into two timing groups: days 1–3 (CRP^1–3d) and days 4-7 (CRP^4–7d).

Results: The cPVL group had significantly higher mean CRP^4–7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP^1–3d levels were similar. CRP^1–7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO₂-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels.

Conclusions: Our finding of elevated CRP^4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO₂-12h and CRP^1–7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants

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: Adenovirus infections are prevalent in children. They usually cause a mild self-limited disease. However, this infection can be associated with considerable morbidity and mortality in specific populations, especially among immunocompromised children. Children with Down syndrome are susceptible to a higher frequency and increased severity of viral infections. Little is known about the severity and clinical course of adenovirus infections in children with Down syndrome.

Objectives: To characterize hospitalized children diagnosed with Down syndrome and presenting with adenovirus infection.

Methods: We performed a retrospective review of children admitted with adenovirus from January 2005 to August 2014 from a single tertiary pediatric medical center in Israel. Data were compared between patients with and without Down syndrome.

Results: Among the 486 hospitalized children with adenoviral infection, 11 (2.28%) were diagnosed with Down syndrome. We found that children with Down syndrome were more likely to experience a higher incidence of complications (18.2% vs. 2.4%, P = 0.008), a higher rate of admissions to the intensive care unit (36.4% vs. 2.4%, P < 0.001), and more prolonged hospitalizations (17 ± 15.9 days compared to 4.46 ± 3.16, P = 0.025).

Conclusions: Children with Down syndrome who were hospitalized with adenovirus infection represent a high-risk group and warrant close monitoring. If a vaccine for adenovirus becomes available, children with Down syndrome should be considered as candidates

Background: Pregnant women with Marfan syndrome (MS) have a high risk of aortic dissection around delivery and their optimal management requires a multi-disciplinary approach, including proper cardio-obstetric care and adequate pain management during labor, which may be difficult due to the high prevalence of dural ectasia (DE) in these patients.

Objectives: To evaluate the multidisciplinary management of MS patients during labor.

Methods: Nineteen pregnant women (31 pregnancies) with MS were followed by a multi-disciplinary team (cardiologist, obstetrician, anesthesiologist) prior to delivery.

Results:^. Two patients had kyphoscoliosis; none had previous spine surgery nor complaints compatible with DE. In eight pregnancies (7 patients), aortic root diameter (ARd) before pregnancy was 40 to 46 mm. In this high-risk group, one patient underwent elective termination, two underwent an urgent cesarean section (CS) under general anesthesia, and five had elective CS; two under general anesthesia (GA), and three under spinal anesthesia. In 23 pregnancies (12 patients), ARd was < 40 mm. In this non-high-risk group three pregnancies (1 patient) were electively terminated. Of the remaining 20 deliveries (11 patients), 14 were vaginal deliveries, 9 with epidural analgesia and 5 without. Six patients had a CS; four under GA and two2 under spinal anesthesia. There were no epidural placement failures and no failed responses. There were 2 cases of aortic dissection, unrelated to the anesthetic management.

Conclusions: The optimal anesthetic strategy during labor in MS patients should be decided by a multi-disciplinary team. Anesthetic complications due to DE were not encountered during neuraxial block

Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.

Background: The coronavirus disease-2019 (COVID-19) social-distancing strategy, including 7 weeks of strict lockdown, enabled an extraordinary test of stay-at-home regulations, which forced a sedentary lifestyle on all children and adolescents.

Objectives: To assess the lockdown effect on pediatric weight.

Methods: A retrospective-prospective cohort study at our hospital’s pediatric outpatient clinics following the COVID-19 lockdown. Patients aged 0–18 years visiting the clinic were weighed and previous weight and other clinical data were collected from the medical charts. Weight-percentile-for-age standardization was calculated according to the U.S. Centers for Disease Control and Prevention and the World Health Organization growth tables. Pre- and post-lockdown weight-percentiles-for-age were compared using paired t-test. Multivariate analysis was conducted using linear regression model.

Results: The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved.

Conclusions: A general weight gain among children was noted, especially in boys during the lockdown, with substantial effect under the age of 6 years. This collateral side-effect should be considered in further quarantine regulations