Israel Medical Association Journal

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied.

Objectives: To investigate the demographic and clinical profile of HS in the Israeli Arab population.

Methods: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups.

Results: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, p < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, p < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, p = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, p = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs.

Conclusions: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

Sulfonylureas have been used to treat patients with diabetes for the last 80 years. The main side effect of this drug class is hypoglycemia, which might be severe and protracted. With the emergence of new medications with improved safety and better efficacy in preventing diabetes complications and cardiovascular morbidity and mortality, the use of these agents is waning.

Sulfonylureas are historically classified into two generations. The generation first includes drugs such as tolbutamide and chlorpropamide, which are no longer used. The second generation includes glibenclamide and glimepiride, which have different pharmacokinetic properties and active metabolites.

In this case report, we present a patient with diabetes and end-stage renal disease (ESRD) who developed prolonged hypoglycemia following the unauthorized use of a food supplement containing the first-generation sulfonylurea - tolbutamide.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severe consequences in terms of mortality and morbidity. Knowledge of factors that impact COVID-19 may be useful in the search for treatments.

Objectives: To determine the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on morbidly and mortality associated with COVID-19.

Methods: All patients admitted to Hadassah Hebrew University Medical Center between 01 March 2020 and 03 May 2021 with a diagnosis of COVID-19 were included. We retrospectively retrieved demographic, clinical, and laboratory data from the hospital’s electronic medical records. The main outcomes were mortality, intensive care unit (ICU) admission, and severity of COVID-19.

Results: The presence of G6PD deficiency emerged as an independent protective predictor for ICU admission (odds ratio [OR] 0.258, 95% confidence interval [95%CI] 0.077–0.619, P = 0.003) and the development of critical illness (OR 0.121, 95%CI 0.005–0.545, P = 0.006). Moreover, patients with G6PD deficiency had a trend toward lower mortality rates that did not reach statistical significance (OR 0.541, 95%CI 0.225–1.088, P = 0.10).

Conclusions: Patients with G6PD deficiency were less likely to have a severe disease, had lower rates of ICU admission, and trended toward lower mortality rates.

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: 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: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10–15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach.

Objectives: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection.

Methods: A prospective observational study was conducted in 2014–2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%).

Results: During the study period 15,433 newborns were born. The predicted rate of infection was 10–15% (symptomatic) of 0.7% of newborns, namely 0.07–0.105% or 10–15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066–0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range.

Conclusions: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended

Background: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality.

Objectives: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit.

Methods: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia.

Results: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures.

Conclusions: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia

Background: Controlled ovarian hyperstimulation (COH) followed by oocyte retrieval is a leading option for fertility preservation before chemotherapy, yet this procedure causes excessive serum levels of estradiol (E2), which are often detrimental for cancer patients. Aromatase inhibitors are often used in breast cancer patients during COH to prevent elevated levels of E2.

Objectives: To describe our experience with COH for oocyte cryopreservation in non-breast cancer patients using aromatase inhibitors.

Methods: Of the five patients treated, two had an aggressive abdominal desmoid tumor, one had endometrial carcinoma, one had uterine sarcoma, and one patient had a brain oligodendroglioma. In all cases the treating oncologist suggested an association between estrogen and possible tumor progression. All patients were treated with a standard in vitro fertilization antagonist protocol combined with aromatase inhibitors, similar to the protocol used for breast cancer patients.

Results: The average duration of treatment was 10.5 days, mean peak E2 was 2348 pmol/L, mean number of oocytes aspirated was 17.3, and a mean of 14.6 embryos/oocytes were cryopreserved.

Conclusions: COH with aromatase inhibitors is apparently effective in non-breast cancer patients and spares exposure to high E2 levels.

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

Background: Secondary thrombocytosis is associated with a variety of clinical conditions, one of which is lower respiratory tract infection. However, reports on thrombocytosis induced by viral infections are scarce.

Objectives: To assess the rate of thrombocytosis (platelet count > 500 x 10⁹/L) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection.

Methods: Clinical data on 469 infants aged ≤ 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between RSV[1]-positive and RSV-negative infants.

Results: The rate of thrombocytosis was significantly higher in RSV-positive than RSV-negative infants (41.3% vs. 29.2%, P = 0.031). The odds ratio of an infant with bronchiolitis and thrombocytosis to have a positive RSV infection compared to an infant with bronchiolitis and a normal platelet count was 1.7 (P = 0.023, 95% confidence interval 1.07–2.72). There was no significant difference in mean platelet count between the two groups.

Conclusions: RSV-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.

Background: Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial.

Objectives: To assess the approach of leading pediatric specialists throughout Israel.

Methods: A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI[1], according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel.

Results: Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72–75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists.

Conclusions: The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to up-to-date evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.

Background: Women frequently suffer perineal trauma while giving birth. Interventions to increase the possibility for an intact perineum are needed.

Objectives: To evaluate the effectiveness of antenatal perineal massage in increasing the likelihood of delivering with an intact perineum.

Methods: This single blinded prospective controlled trial included 234 nulliparous women with a singleton fetus. Women allocated to the study group were instructed to practice a 10 minute perineal massage daily from the 34th week of gestation until delivery. Primary outcome measures included the episiotomy rate; first, second, third and fourth-degree perineal tear rates; and intact perineum. Secondary outcomes were related to specific tear locations and the amount of suture material required for repair.

Results: Episiotomy rates, overall spontaneous tears and intact perineum rates were similar in the study and control groups. Women in the massage group had slightly lower rates of first-degree tears (73.3% νs. 78.9%, P = 0.39) and slightly higher rates of second-degree tears (26.7% νs. 19.3%, P = 0.39), although both of these outcomes did not reach statistical significance. The rates of anterior perineal tears were significantly higher in the massage group (9.5% vs. 3%, P = 0.05), whereas internal lateral tears rates were slightly lower but without statistical significance (11.5% νs.13.1%, P = 0.44).

Conclusions: The practice of antenatal perineal massage showed neither a protective nor a detrimental significant effect on the occurrence of perineal trauma.