Israel Medical Association Journal

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: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting.

Objectives: To examine the change in corneal and conjunctival sensation post-pterygium surgery.

Methods: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively.

Results: Nine patients participated in the study. Mean follow-up time was 9 months (9 ± 3.3, 6–12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation).

Conclusions: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

Background: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE).

Objective: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs.

Methods: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit.

Results: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32–6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28–0.87, P = 0.016), depicting a medium-to-high disease activity among the former.

Conclusions: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

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.

To the reviewers of 2022, who gave of their time to constructively assess the articles sent to them

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Background: The prognosis of long-term clinical outcomes for each patient is of utmost importance.

Objectives: To evaluate the association between rates of family attendance during rounds and long-term outcomes.

Methods: We conducted a historic cohort study.

Results: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium.

Conclusions: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

We clarified the diagnostic and therapeutic challenges associated with pseudohypertension in very elderly patients. Pseudohypertension is diagnosed when cuff blood pressure measurements for both systolic and diastolic blood pressure are significantly higher than direct intra-arterial blood pressure recordings. Pseudohypertension is considered a manifestation of combined intimal and medial arterial calcifications. Non-invasive diagnosis is extremely difficult, but pseudohypertension should be considered in certain groups of very elderly hypertensive patients. Importantly, most of the very elderly patients diagnosed with pseudohypertension present with hypertension, especially isolated systolic hypertension, and this condition should be treated. Treatment must be undertaken cautiously (start low, go slow), with a recommended target blood pressure ≤ 150/80 mmHg. Orthostatism should be measured routinely, both by the patient and the attending physician.

Docetaxel (Taxotere®), obtained from the European yew Taxus baccata, is a widely used chemotherapeutic agent active against a variety of solid tumors including breast, lung, ovarian, gastric, head and neck, and prostate cancers. The drug is administered intravenously on a weekly or three-weekly schedule. Its main side effects include myelosuppression, fatigue, myalgias, arthralgias, fluid retention, peripheral neuropathy, paronychia, and lacrimation [1]. Myositis, however, has rarely been reported.

We describe a breast cancer patient who developed severe acute myositis while on treatment with docetaxel.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Worldwide, students of healthcare professions attend clinical rotations at medical facilities. Much research, and consequently scientific publications, is produced during their studies, bearing the fruits of student–faculty collaboration. To the best of our knowledge, no previous contract has been proposed detailing the fine print to pre-determine mutual responsibilities and privileges of students and faculty. Our objective was to present such a contract to the relevant students and faculty. We conducted a literature review to study existing proposals and solutions for this dilemma. Appropriate guidelines were also scanned. We included a proposal for a standard contract as the basis for student–faculty agreement for conducting research and publishing collaborative work. Questions regarding the relative contribution of students and subsequent authorship often arise. Vague rules and absent regulations in this realm can, at times, can be disadvantageous to students. We foresee a future role for our proposed agreement.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.