Israel Medical Association Journal

Background: In an effort to alter eye color during World War II, devout Nazi researcher Karin Magnussen had adrenaline eye drops administered to inmates at the concentration camp Auschwitz-Birkenau. A Sinti family, with a high prevalence of heterochromia iridis, was forced to participate in this study. Members of this family, as well as other victims, were later killed and had their eyes enucleated and sent to Magnussen for examination. Magnussen articulated the findings of these events in a manuscript that has never been published. The author is the first ophthalmologist to review this manuscript. The generation who experienced the atrocities of World War II will soon be gone and awareness of what happened during this tragic chapter of world history is fading.

Objectives: To describe these events to raise awareness among future generations.

Methods: A literature review and archival search was conducted.

Results: Magnussen’s research was based on an animal study published in 1937. For Magnussen’s study, adrenaline drops were administered to inmates, including a 12-year-old girl from the Sinti family. As there was a reported case of deaf-mutism within the family, Waardenburg syndrome seems to be the most plausible explanation for this family’s heritable heterochromia.

Conclusions: The effort to change eye color was doomed to fail from the beginning because there was a probable diagnosis of Waardenburg syndrome. Extinction of humans for ophthalmological research is an insane act beyond imagination. For the sake of these victims, and for the generations who still feel their pain, it is imperative to tell their stories.

Background: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce.

Objectives: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy.

Methods: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987–2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed.

Results: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15–190 days). Mean follow-up was 23.3 months (range 7.7–115 months).

Conclusions: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: The number of investigative esophagogastroduodenoscopies (EGD) in children has increased over several decades, despite their unclear diagnostic yields.

Objectives: To evaluate the indications for performing EGD, their diagnostic yields, and consequences on pediatric patient management.

Methods: A retrospective chart review was performed of consecutive pediatric patients aged 0–18 years, who underwent EGD between January and August 2014.

Results: During the study period, 547 EGD were performed on 478 children. The most frequent indications were suspected celiac disease, chronic non-specific abdominal pain, persistent Helicobacter pylori infection, and gastrointestinal hemorrhage. The yield of the diagnostic EGD was 59.2%, and the most common new diagnoses were celiac disease (28%), Helicobacter pylori-positive gastritis (16.5%), and Crohn’s disease (5.4%). Of the patients with documented follow-up, 74.1% reported improved symptoms. Procedures performed for chronic unexplained abdominal pain had significantly lower yields (26.2%) and only 39.3% improved at follow-up.

Conclusions: Our findings suggest a general high diagnostic yield for EGD in pediatric patients, stemming mainly from patients in whom a specific condition was suspected a priori. However, the role of the procedure in the diagnosis and management of non-specific gastrointestinal complaints was minor suggesting that EGD may be superfluous for some of these patients.

Background: The introduction of pneumococcal conjugate vaccine-13 (PCV-13) has reduced the burden of invasive pneumococcal disease.

Objective: To characterize true positive blood cultures of children who presented to our hospital following implementation of the PCV-13 vaccine.

Methods: A retrospective study was conducted on positive blood cultures of children presenting with fever from 2010–2017. Subjects were divided into two age groups: a younger group 3–36 months and an older group 3–18 years. Patients were classified as either having or not having a focus of infection at the time of their bacteremia. Pneumococcal isolates were typed at Israel's Streptococcal Reference Laboratory.

Results: The samples included 94 true positive blood cultures. Focal infection with concomitant bacteremia was more common than bacteremia without a focus both overall: 67/94 (71%) vs. 27/94 (28.7%), P <0.001 as well as in the two groups: 32/48 (66%) vs. 16/48 (33%), P = 0.02 in the younger group and 35/46 (76%) vs. 11/46 (24%), P = 0.001 in the older group. Streptococcus pneumoniae was the most common pathogen overall, 27/94 (29%), and in the younger group, 21/48 (44%), but rare in the older group, 6/46 (13%). In the latter, Brucella species predominated, 12/46 (26%), along with Staphylococcus aureus 12/46 (26%).

Conclusions: Our findings are consistent with other studies reporting decreased pneumococcal bacteremia, bacteremia primarily accompanying focal infection, and changing etiological agents among PCV-13-vaccinated children. Brucella species was prominent in older children with osteoarticular infections. Ongoing surveillance is warranted to better understand the implications of PCV-13.

Background: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting.

Objective: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer’s guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds

Methods: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement.

Results: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer’s guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds.

Conclusions: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Background: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is associated with decreased perioperative morbidity and mortality.

Objectives: To report the outcomes of EVAR among patients older than 80 years of age.

Methods: In this retrospective study, we reviewed patients older than 80 years of age who underwent elective EVAR at our institution between 2007 and 2017. The demographics, perioperative morbidity and mortality, and long-term results are reported.

Results: During the study period, 444 patients underwent elective EVAR for AAAs. Among them 128 patients (29%) were > 80 years of age. Mean age was 84 ± 3.4 (range 80–96) years, and 110 patients (86%) were male. The EVAR was technically successful in 127 patients (99%) and there were intraoperative mortalities. Within 30 days of the surgery, nine patients (7%) died. Major and minor adverse events occurred in 26 (20%) and 59 (46%) patients, respectively. Factors associated with increased risk of perioperative morbidity and mortality included chronic kidney disease, peripheral artery disease, and the existence of three or more co-morbidities.

Conclusions: EVAR in the elderly can be performed with a high rate of success; however, it is associated with a substantial rate of morbidity and mortality, particularly when patients present with multiple co-morbidities. When performing EVAR in this population group, the risk of rupture must be considered opposed to the life expectancy of these patients and the risk of perioperative morbidity and mortality.

Background: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency.

Objectives: To identify a unique heterogeneity pattern that is associated with true MMR loss.

Methods: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing.

Results: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases.

Conclusions: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.

Background: Falls are a common complication in persons with stroke (PwS). Reliable assessment of balance responses to unexpected loss of balance has the potential to identify risk for falls. 

Objectives: To examine inter-observer reliability of balance responses to unannounced surface perturbations in PwS and to explore the concurrent validity of a balance recovery assessment protocol.

Methods: Two observers evaluated balance recovery strategies and fall threshold (a fall into a harness system) in 15 PwS and 15 healthy adults who were exposed to forward, backward, right, and left unannounced surface translations in six increasing intensities while standing. 

Results: Observer agreement was 100% for the fall threshold. Kappa coefficients for step strategies were 0.960–0.988 in PwS and 0.886–0.938 in healthy adults, 0.905–0.988 for arm reactions in PwS and 0.754–0.926 in healthy adults. Significant correlations were found between fall threshold and Berg Balance Scale (r = 0.691), 6-minute walk test (r = 0.599), and fall efficacy scale-international (r= -0.581). 

Conclusions: A trained examiner can reliably classify reactive balance responses to surface perturbations. The high frequency of falls observed in PwS highlights the importance of assessing reactive balance responses to different directions and intensities of surface translations.

Background: Asthma is a common respiratory disease, which is linked to air pollution. However, little is known about the effect of specific air pollution sources on asthma occurrence.

Objective: To assess individual asthma risk in three urban areas in Israel characterized by different primary sources of air pollution: predominantly traffic-related air pollution (Tel Aviv) or predominantly industrial air pollution (Haifa bay area and Hadera). 

Methods: The medical records of 13,875, 16- 19-year-old males, who lived in the affected urban areas prior to their army recruitment and who underwent standard pre-military health examinations during 2012–2014, were examined. Nonparametric tests were applied to compare asthma prevalence, and binary logistic regressions were used to assess the asthma risk attributed to the residential locations of the subjects, controlling for confounders, such as socio-demographic status, body mass index, cognitive abilities, and education.

Results: The asthma rate among young males residing in Tel Aviv was 8.76%, compared to 6.96% in the Haifa bay area and 6.09% in Hadera. However, no statistically significant differences in asthma risk among the three urban areas was found in controlled logistic regressions (P > 0.20). This finding indicates that exposure to both industrial- and traffic-related air pollution is associated with asthma prevalence.

Conclusions: Both industrial- and traffic-related air pollution have a negative effect on asthma risk in young males. Studies evaluating the association between asthma risk and specific air pollutants (e.g., sulfur dioxide, particulate matter, and nitrogen dioxide) are needed to ascertain the effects of individual air pollutants on asthma occurrence. 

 

Background: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth.

Objectives: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism.

Methods: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms.

Results: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects.

Conclusions: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

Background: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria.

Objectives: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center.

Methods: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted.

Results: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21–9.43), pulmonary disease (OR 3.99, 95%CI 1.49–10.73), current or past smoking (OR 2.93, 95%CI 1.21–7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16–8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27–10.33) and pulmonary disease (OR 4.37, 95%CI 1.58–12.10) were associated with a greater risk.

Conclusions: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.