Israel Medical Association Journal

Background: Cannabis consumption is suspected of causing arrhythmias and potentially sudden death.

Objectives: To investigate prevalence and temporal relationships between cannabis use and onset of symptomatic arrhythmias among cancer patients using Belong.life, a digital patient powered network application.

Methods: Real-world data (RWD) were obtained through Belong.Life, a mobile application for cancer patients who use cannabis routinely. Patients replied anonymously and voluntarily to a survey describing their demographics, medical history, and cannabis use.

Results: In total, 354 cancer patients (77% female, 71% 50–69 years of age) replied: 33% were smokers and 49% had no co-morbidities. Fifteen had history of arrhythmias and two had a pacemaker; 64% started cannabis before or during chemotherapy and 18% had no chemotherapy. Cannabis indication was symptom relief in most patients. The mode of administration included oil, smoking, or edibles; only 35% were prescribed by a doctor. Cannabis type was delta 9-tetrahydrocannabinol > 15% in 43% and cannabidiol in 31%. After starting cannabis, 24 patients (7%) experienced palpitations; 13 received anti-arrhythmic drugs and 6 received anticoagulation. Eleven needed further medical investigation. Three were hospitalized. One had an ablation after starting cannabis and one stopped cannabis due to palpitations. Seven patients (2%) reported brady-arrhythmias after starting cannabis, but none needed pacemaker implantation.

Conclusions: RWD showed that in cancer patients using cannabis, the rate of reported symptomatic tachy- and brady-arrhythmias was significant (9%) but rarely led to invasive treatments. Although direct causality cannot be proven, temporal relationship between drug use and onset of symptoms suggests a strong association.

Background: The two cerebral hemispheres influence the immune response differently. While the left hemisphere enhances cellular immunity, the right hemisphere inhibits it.

Objectives: To determine whether immune and inflammatory markers correlated with stroke severity and hospitalization duration as a function of stroke side.

Methods: The study included 137 patients with unilateral ischemic stroke. The medical records were reviewed for demographic and clinical laboratory data, including C-reactive protein (CRP), white blood cell (WBC) count, its differential stroke side and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), and length of hospital stay (LOS). We examined differences between right side (RS) and left side (LS) stroke on immune and inflammatory markers and compared correlations between these markers and NIHSS and LOS as a function of stroke side.

Results: RS stroke patients had higher CRP and monocytes than LS stroke patients. In RS stroke patients, CRP, total WBC, and lymphocyte levels positively correlated with both NIHSS and LOS, whereas levels of neutrophils were positively correlated with NIHSS alone. No correlations were found for LS stroke patients.

Conclusions: Immune-inflammatory markers correlated with stroke severity and LOS only in patients with RS stroke. Neuroimmunological processes influence short-term clinical outcomes after stroke, especially considering the differential effects of the hemispheres on immunity. Prospective studies that evaluate long-term clinical outcomes are needed. Testing the effects of anti-inflammatory treatments on prognosis of RS stroke patients should be considered.

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: Thiamine is an essential co-factor for aerobic intracellular respiration, nerve conduction, and muscle contraction. Thiamine deficiency is common in the intensive care unit (ICU). Delirium is a frequent unwanted symptom among critical ill patients. Although the exact cause of ICU-associated delirium is unknown, abnormal nutrition and thiamine deficiency may contribute to the etiology.

Objectives: To compare the prevalence of delirium among ICU patients who received thiamine with those who did not and to compare morbidity and mortality.

Methods: A retrospective study was conducted among ICU patients admitted 2014–2018. Routine thiamine administration began in 2016. Collected data included patient demographics, medical history, indication for ICU admission, hospital admission times, ventilation days, inotropic therapy, hemodialysis, tracheostomy, 28-day mortality, and need for anti-psychotic therapy. Group A received thiamine, group B did not. All data were statistically analyzed according to type.

Results: The study included 930 patients: 465 patients in group A and 465 in group B. At admission and throughout the hospitalization severity of disease parameters was worse in group A compared to group B, including acute physiology and chronic health evaluation (APACHE) score, admission lactate level, ventilation days, inotropic support, renal replacement therapy, tracheostomy, and ICU hospitalization. Group A had fewer delirium events without difference of maximal delirium score. No difference in mortality rate was observed.

Conclusions: Thiamine administration was associated with lower delirium prevalence despite longer ICU admission times and higher disease severity parameters at admission and during ICU stay.

Background: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality.

Objective: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI.

Methods: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission.

Results: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithm_ebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis.

Conclusions: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.

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: Several approaches are used to access the hip joint; most common are the direct lateral and posterior. Little consensus exists on which to use when treating hip fractures.

Objectives: To compare short-term complications, postoperative ambulation, and patient-reported outcome measures (PROMS) of direct lateral vs. posterior approaches in hemiarthroplasty for acute hip fractures.

Methods: We conducted a retrospective clinical trial with 260 patients who underwent bipolar hemiarthroplasty in the direct lateral or posterior approach (166 and 94, respectively) between January 2017 and December 2018. The clinical data included short-term complications: prosthetic dislocation, periprosthetic fractures, and infection. Postoperative ambulation was collected 6 weeks postoperatively; PROMS were collected for 173 patients at 2 years follow-up.

Results: There were six dislocations overall, average time to dislocation was 22 days postoperative (range 4–34). Five dislocations were after the posterior approach (5.3%) and one after direct lateral (0.6%) (P = 0.01). At 6 weeks follow-up, inability to walk was found in 16.9% of the direct lateral group and 6.4% of the posterior approach group (P = 0.02). In the posterior approach group, 76% could walk more than 20 meters; only half of the direct lateral group could (P = 0.0002). At 2 years follow-up, PROMS did not show a statistically significant difference between the groups.

Conclusions: Posterior approach for hemiarthroplasty following femoral neck fractures allows superior ambulation to the direct lateral approach only for the short-term. However, no long-term clinical advantage was found. This short-term benefit does not justify the increased dislocation rate in the posterior approach.

Background: Chronic suppurative otitis media is a long-standing middle ear infection with a perforated tympanic membrane. Tympanoplasty is the mainstay of treatment. Most surgeons prefer to operate on dry ears; however, this may be difficult to achieve.

Objectives: To investigate the effect of otorrhea and positive cultures on the outcome of tympanoplasty.

Methods: This retrospective analysis reviewed patients with chronic suppurative otitis media who underwent tympanoplasty 2008–2015. Patients were divided into three groups: active discharge and bacterial growth, active discharge without bacterial growth, and no ear discharge. Surgical outcomes were compared among the groups.

Results: Among 101 patients included, 43 ears (42.6%) had discharge preoperatively, 58 (57.4%) were dry. Overall closure rate was 81.2% (82/101). Preoperative active discharge closure rate was 88.3% (38/43) and without discharge 75.9% (44/58). There were 38 positive cultures preoperatively and five negative cultures. Cultures were not obtained in 58 cases. Success rates were 89.5%, 80%, and 75.9%, respectively. No significant difference was found between patients who had positive or negative cultures before the procedure (P > 0.48) or among the three groups (P = 0.25). The most common bacteria were Pseudomonas aeruginosa (n=17), followed by Staphylococcus species (n=10). None was significantly associated with operative failure (P = 0.557). The postoperative air threshold difference was not affected by culture results (P = 0.3).

Conclusions: Tympanoplasty success rates and postoperative air threshold differences were not affected by the presence of preoperative otorrhea or positive ear cultures. Surgery can be performed even when the ear is not dry.

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.

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.

Background: Chest trauma is among the most common types of trauma, corresponding to 10% of trauma patients admitted to hospitals. In the military setting, thoracic trauma was reported as a significant cause of death. With well-timed treatment, chest trauma is regarded as survivable. Emergency thoracotomy (ET) is considered when the patient with trauma to the chest needs immediate resuscitation. Survival rate is reported as low as 1% in some reports and 20% in others. The survival rate depends on injury mechanism, protocols for intervention, and other decompressive procedures.

Objectives: To determine parameters that may impact survival of ET.

Methods: We conducted a retrospective cohort study to compare prehospital and in-hospital data regarding ET in the emergency department (ED) versus the operating room (OR).

Results: Between 2009 and 2017, 6532 casualties presented to the ED; 1125 with trauma to the chest. Fifty-four of those with chest trauma underwent ET in the hospital (4.8%), 22 (41%) in the ED, and 32 (59%) in the OR. The overall mortality of the ET subgroup was 48%. With regard to thoracotomies, 19/22 of patients (86%) who underwent ET in the ED died compared to 2/28 in the OR (13%).

Conclusions: Utilizing ET after chest trauma with appropriate clinical indications, well-trained personnel, and prompt transportation poses a significant challenge, but may be associated with better survival than that reported previously with military casualties. Adoption of indications and timed allocation to the OR may improve outcomes with chest trauma casualties.

Background: Diabetes mellitus (DM) is one of the risk factors for progression from latent to active tuberculosis. However, the effect of DM on subsequent tuberculosis treatment is still inconclusive.

Objectives: To compare tuberculosis treatment outcomes and the rate of drug resistance of tuberculosis patients with or without DM.

Methods: This case-control study was conducted between 2005 and 2015 at the only tuberculosis ward in Israel. All 80 tuberculosis patients who had DM and were hospitalized during the study period were included in this study, as were a randomized sample of 213 tuberculosis patients without DM. Demographic, clinical, and laboratory data were collected from patient files in the hospital and clinics after discharge.

Results: Tuberculosis patients with DM were more often older and more likely to be Israeli citizens with a lower socioeconomic status than patients without DM. No statistically significant differences were found in clinical presentation, radiological findings, and sputum smear tests between the two groups. Culture converting times were prolonged in patients with DM compared to normoglycemic patients. Multidrug drug resistance tuberculosis was more common among normoglycemic tuberculosis patients than tuberculosis patients with DM (9.2% vs. 1.6%, P = 0.12). Treatment success rates were 76.2% and 83.1% for tuberculosis patients with or without DM, respectively (P = 0.18). DM was not statistically significant in the multivariate analysis predicting treatment success, which controlled for age, citizenship, compliance, addictions, and chronic diseases.

Conclusions: The presence of DM does not necessarily affect tuberculosis treatment outcomes as long as treatment compliance is optimal.

Background: Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable.

Objectives: To assess possible predictors of primary and secondary failure of vascular access.

Methods: This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up.

Results: A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure.

Conclusions: Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.

Background: Lower extremity amputation related to diabetes is a serious outcome, which can have devastating effects on the patient and family. The epidemiology of amputations has recently been used as a possible measure of the adequacy of medical prevention and treatment of diabetes and diabetic foot complications.

Objectives: To report on patients undergoing amputations at one medical center in Israel, their co-morbidities, and the outcomes.

Methods: A retrospective chart study was conducted of amputees operated between 1 September 2017 and 30 September 2018.

Results: The study population comprised 72 patients who had major amputations for diabetes and/or ischemia, mean age 72 ± 10 years, 74% males, 93% with type 2 diabetes. Mean age corrected Charlson Comorbidity Index was 8.2 ± 2.1 with 90% (65 patients) presenting with a score of 6 or higher. Before the recent deterioration, fewer than 20% of the patients exited their home routinely and 24% had an official diagnosis of dementia. There were 31 below knee amputations (BKA) and 41 above knee amputations (AKA). The 30-day, 3-month, 1-year, and 2-year mortality rates were 15.3%, 27.8%, 43.1%, and 54.2% respectively. Median survival period was 20 months. Survival after AKA was 13.4 ± 20, which was significantly less than after BKA (25.4 ± 2.7, P = 0.097).

Conclusions: Factors other than the quality of management of patients with diabetes and complications may contribute to amputation rates; thus, making speculations from international comparisons of raw amputation rates problematic. This population was less healthy than reported in most studies.