Israel Medical Association Journal

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: 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: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography

An arginine-rich apolipoprotein was discovered 50 years ago and became known as apolipoprotein E (ApoE) 10 years later. ApoE is associated with triglyceride-rich lipoproteins and mediates the clearance of these lipoproteins from the plasma. The ApoE-deficient hypercholesterolemic mice are an excellent platform for experimental atherosclerosis because they are similar to human pathology with regard to an atherogenic diet. ApoE is mainly produced in the liver and central nervous system cells. Three alleles determine six ApoE phenotypes with different metabolic effects and plasma cholesterol levels. Type III dysbetalipoproteinemia is associated with wide-spread atherogenesis with a defective ApoE2 resulting in delayed clearance of triglyceride-rich lipoproteins. ApoE4 substantially increases the risk including age of onset, progression, and prognosis of Alzheimer’s disease. Therefore, much effort has been directed to the elucidation of the pathogenic role of ApoE related to amyloid β (Aβ) acquisition in the brain. The ApoE trail passing from an enigmatic protein to a major player in cardiovascular and neurodegenerative disorders is reviewed

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: Hip fractures in elderly patients are a major cause of morbidity and mortality. Variability in length of hospital stay (LOS) was evident in this population. The coronavirus disease-2019 (COVID-19) pandemic led to prompt discharge of effected patients in order to reduce contagion risk. LOS and discharge destination in COVID-19 negative patients has not been studied.

Objectives: To evaluate the LOS and discharge destination during the COVID-19 outbreak and compare it with a similar cohort in preceding years.

Methods: A retrospective study was conducted comparing a total of 182 consecutive fragility hip fracture patients operated on during the first COVID-19 outbreak to patients operated on in 2 preceding years. Data regarding demographic, co-morbidities, surgical management, hospitalization, as well as surgical and medical complications were retrieved from electronic charts.

Results: During the pandemic 67 fragility hip fracture patients were admitted (COVID group); 55 and 60 patients were admitted during the same time periods in 2017 and 2018, respectively (control groups). All groups were of similar age and gender. Patients in the COVID group had significantly shorter LOS (7.2 ± 3.3 vs. 8.9 ± 4.9 days, P = 0.008) and waiting time for a rehabilitation facility (7.2 ± 3.1 vs. 9.3 ± 4.9 days, P = 0.003), but greater prevalence of delirium (17.9% vs. 7% of patients, P = 0.028). In hospital mortality did not differ among groups.

Conclusions: LOS and time to rehabilitation were significantly shorter in the COVID group. Delirium was more common in this group, possibly due to negative effects of social distancing.

Background: Surgery for hip fractures within 48 hours of admission is considered standard. During the lockdown period due to the coronavirus disease-2019 (COVID-19) epidemic, our medical staff was reduced.

Objectives: To compare the demographics, treatment pathways, and outcomes of patients with hip fractures during the COVID-19 epidemic and lockdown with the standard at routine times.

Methods: A retrospective study was conducted of all patients who were treated surgically for hip fracture in a tertiary center during the COVID-19 lockdown period between 01 March and 01 June 2020 and the equivalent period in 2019. Demographic characteristics, time to surgery, surgery type, hospitalization time, discharge destination, postoperative complications, and 30- and 90-day mortality rates were collected for all patients.

Results: During the COVID-19 period, 105 patients were operated due to hip fractures compared to 136 in the equivalent period with no statistical difference in demographics. The rate of surgeries within 48 hours of admission was significantly higher in the COVID-19 period (92% vs. 76%, respectively; P = 0.0006). Mean hospitalization time was significantly shorter (10 vs. 12 days, P = 0.037) with diversion of patient discharge destinations from institutional to home rehabilitation (P < 0.001). There was a significant correlation between the COVID-19 period and lower 90-day mortality rates (P = 0.034). No statistically significant differences in postoperative complications or 30-day mortality rates were noted.

Conclusions: During the COVID-19 epidemic, despite the limited staff and the lack of therapeutic sequence, there was no impairment in the quality of treatment and a decrease in 90-day mortality was noted.

Background: Flexible flatfoot (FF) is a common foot deformity that can often consist of foot pain. Surgical treatment is designed to lengthen the lateral column.

Objectives: To resolve whether radiographic standing feet measurements of normo-plantigrade feet and FF, symptomatic or not, differ and to determine whether the lateral column is shorter.

Methods: The study comprised 72 patients (127 feet) consecutive patients, 18 years of age and older, who were divided into three groups: normal feet (56), asymptomatic FF (29), and symptomatic FF (42). All patients had a standing anterior posterior (AP) and lateral radiographs. AP images were used for the measurement of the talocalcaneal angle, talar-1st metatarsal angle, and talonavicular coverage. Lateral X-rays were used to estimate the talocalcaneal angle, talar-1st metatarsal angle, calcaneal pitch, naviculocuboid overlap, and column ratio.

Results: All three of the AP radiograph measurements differed among groups, and higher values were measured in the symptomatic FF group. Post hoc analysis found that the talonavicular coverage and the talocalcaneal angles also differed between symptomatic and asymptomatic FF patients. While some lateral measurements differed within groups, only the lateral talar-1st metatarsal angle distinguished between asymptomatic and symptomatic patients. The lateral column length was not found to be shorter among FF patients, weather symptomatic or not.

Conclusions: Only the talonavicular coverage, the AP talocalcaneal, and the lateral talar-1st metatarsal angles were found to differ between asymptomatic and symptomatic FF patients. The lateral column was not found to be shorter

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: 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: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue.

Objectives: To report three unique cases of GPA presenting with tumor-like lesions in various organs.

Methods: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass.

Results: The patients were treated successfully with rituximab.

Conclusions: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener’s granulomatosis