Israel Medical Association Journal

Testimonies, articles, or books on Nazi medical atrocities written by physicians, whether Holocaust survivors or not and whether written during the Holocaust or just after 1945, are very important teaching materials. The professional views of physicians give special insight. In this review we highlighted a few biographical and eyewitness accounts by Jewish physicians about their medical activities and the inhuman medical activities of the Nazis. The activities of Jewish doctors in the ghettos and camps, including research projects on hunger or infectious diseases, are truly suitable case studies. We presented representative case studies that can be effectively introduced in medical school curricula.

Background: Meibomian gland dysfunction (MGD) causes significant patient morbidity as well as economic burden.

Objectives: To evaluate a novel eyelid warming and a neuro-stimulating device that delivers heat via low-level infrared radiation to the eyelids of patients with MGD.

Methods: In this prospective interventional study, patients with MGD were recruited at a single medical center. The main outcome measures included changes in tear break-up time (TBUT), Schirmer’s test, and Ocular Surface Disease Index (OSDI), overall satisfaction, and corneal signs of dry eye. Patients were instructed to use the device twice daily for 5 minutes on each eye for a total of 14 days. Follow-up assessments were performed after the 2-week treatment.

Results: A total of 10 patients were included; mean age was 67 ± 16 years; six males (60%). Changes in pre- vs. post-treatment TBUT (5.0–6.11), OSDI (28.1–23.9), and Schirmer score (8.67–7.11) were not statistically significant. Over a course of 243 treatments, 131 (54%) demonstrated improvement in symptoms, 40% found no change, and 6% experienced worsening of symptoms. General satisfaction was observed overall in 80% of the patients. No adverse events were observed.

Conclusions: In this first study of a novel eyelid warming device, overall subjective satisfaction was reported in 80% of patients. Potential advantages of this user-friendly device include its ability to improve MGD and tear film stability, as well as symptomatic relief, while allowing the user to continue with normal daily functioning while undergoing treatment.

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: Injuries to the anterior cruciate ligament (ACL) are common and complete tears often fail to heal. ACL reconstruction is considered the surgical gold standard of care for ACL injuries in young active patients.

Objectives: To determine the corresponding morphological and histological features of the torn ACL in different time periods after injury.

Methods: The study included 28 remnant specimens of torn ACLs from patients who had ACL reconstruction surgery of the knee. The remnant pathology was evaluated by its morphology during arthroscopy and by histopathologic measurements.

Results: At surgery there were three progressive and distinct morphological tear patterns. The first pattern was noticed within the first 3 months from injury and showed no scar tissue. The second pattern appeared later and was characterized by the appearance of scar tissue with adhesion to the femoral wall. The third pattern was characterized by adhesion of the ACL remnant to the posterior cruciate ligament. The histological changes of the first morphological pattern showed abundance of blood vessels and lymphocytes at the torn femoral end with few irregular collagen fibers. The second and third tear patterns showed decrement in the number of blood vessels and lymphocytes with longitudinally oriented collagen fibers.

Conclusions: The morphological features of the ACL remnant in the first 3 months after injury showed no scar tissue and its histological features had the characteristics of a reparative phase. This phase was followed by a prolonged remodeling phase that ended with attachment of the remnant to the posterior cruciate ligament.

Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed.

Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential.

Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases.

Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10).

Conclusion: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.

Background: The epidemiology of human brucellosis (HB) continues to evolve.

Objectives: To describe the current epidemiology of HB in Israel in general and in the population at risk.

Methods: We calculated the incidence of HB in Israel for the period 2009–2015, overall and for the Arab population. Data are based on mandatory reporting of HB in Israel, defined clinically with either laboratory confirmation or epidemiological linkage to a laboratory-confirmed case. We mapped the geographic distribution of HB throughout the study period according to localities. We specified localities with high incidence (≥ 10 per 100,000 population) and mapped the distribution of dense localities with time.

Results: The incidence of HB in the general population in Israel increased sharply from 1.9 per 100,000 in 2009 to a peak of 7.3 per 100,000 in 2014. Each year, 95–100% of cases occurred among Arabs, thus the incidence in the Arab population increased from 10 per 100,000 in 2009 to 33.5 per 100,000 in 2014. Throughout this period 133 different localities reported at least one case of HB, and of these 20 were high-incidence localities during one year at least. During the period 2009–2013 the number of affected localities ranged from 35 to 44 per year and the disease was local, while in 2014 there were 82 localities distributed across the country.

Conclusions: We demonstrate the importance of analyzing incidence in the population at risk for a disease. HB is an urgent public health issue in the Arab population in Israel, mandating an immediate and long-term eradication and control program.

Background: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate.

Objectives: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC.

Methods: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher’s exact tests.

Results: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001).

Conclusions: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Invasive cervical cancer is caused by human papillomavirus (HPV).

Objectives: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.

Methods: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006–2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).

Results: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.

Conclusions: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.