Israel Medical Association Journal

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Background: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce.

Objectives: To compare the outcomes of patients with both the Omicron variant and influenza during 2021–2022.

Methods: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality.

Results: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25–0.81).

Conclusions: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis and usually constitutes a diagnostic challenge. There are many causes for recurrent and chronic pancreatitis, with the main etiology being alcohol and choledocholithiasis [1]. However, the association between pancreatic divisum (PD), a common congenital anomaly of the pancreas that is rarely symptomatic, and complications of pancreatitis is still not firmly established [2]. Furthermore, the optimal management of PPF is still uncertain due to its rarity [3]. We describe a rare case of a 45-year-old woman with recurrent pancreatitis that presented with a PPF on the background of PD, successfully managed with conservative treatment. The purpose of this report is to highlight the rare association between PPF and PD together with the excellent response to conservative therapy.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Background: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED).

Objectives: To assess the association between CIEDs and severity of COVID-19 infection.

Methods: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed.

Results: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED.

Conclusions: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although,CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.

Background: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children.

Objectives: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain.

Methods: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2–18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts.

Results: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS.

Conclusions: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

Background: Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation and delayed growth in children. Several prenatal and environmental factors might be associated with the disease.

Objectives: To determine the prevalence and risk factors of permanent CH and transient congenital hypothyroidism (TCH) in Israel.

Methods: We conducted a retrospective analysis of the Israeli national newborn screening program database from 2011 to 2015. Chi-square and logistic regression were used to assess the association of the demographic and gestational factors with the CH and TCH.

Results: Of the 889,033 live births screened between 2011 and 2015, 860 were diagnosed with CH (9.76 per 10,000 live births) and 298 with TCH (3.35 per 10,000 live births). In multivariate analyses, CH was positively associated with female sex, gestational ages < 38 or > 39 weeks, birth weight < 3000 grams, and winter birth. A decreased risk of TCH was detected in Arabs and neonates from high socioeconomic areas. An increased risk was independently associated with gestational ages < 38 weeks, low birth weight, and winter birth.

Conclusions: Several demographic, gestational, and geographical factors are associated with the development of CH and TCH. Future studies are needed to further investigate the pathogenesis in Israel.

Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.

Background: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial.

Objectives: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients.

Methods: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy

Results: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2–5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33).

Conclusions: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.

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: 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

Background: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates.

Objectives: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance.

Methods: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen.

Results: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin.

Conclusion: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.