Israel Medical Association Journal

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: Anorexia nervosa (AN) is a severe psychiatric disease that is refractory to treatment. To date, there is no effective pharmacological therapy and existing psychotherapy treatment is only partially effective. In neuropsychological terms, AN is characterized by cognitive inflexibility and an overly detailed processing style. Creating artwork and drawing requires integrative thinking that encompasses the big picture.

Objectives: To describe preliminary observations of drawing treatment modality based on precise scientific drawing.

Methods: The artwork method is based on the classic work by squares and on additional techniques from scientific drawing. The method was developed and implemented in a sheltered home for patients with eating disorders in Parma, Italy. Five patients, four women and one man, agreed to participate in a 10-session workshop as a part of multidisciplinary intervention. The ages of participants were 17–28 years and all had presented with AN for several years.

Results: Using the method of copying drawings on squares made it possible to identify features that were common to all the patients, such as focusing on the external form of the drawing rather than on the internal details, exerting strong pressure on the pencil without consideration of the need for future corrections, drawing distorted perceptions of curves, and the adding of significant volume.

Conclusions: Precise scientific drawing could be a useful instrument in the understanding and correction of a patient’s distorted world and self-perspective. More evidence could be provided by further studies with a larger sample and a control group.

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014–2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

Results: The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00–7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients).

Conclusions: Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion

Background: Potentially preventable readmissions of surgical oncology patients offer opportunities to improve quality of care. Identifying and subsequently addressing remediable causes of readmissions may improve patient-centered care.

Objectives: To identify factors associated with potentially preventable readmissions after index cancer operation.

Methods: The New York State hospital discharge database was used to identify patients undergoing common cancer operations via principal diagnosis and procedure codes between the years 2010 and 2014. The 30-day readmissions were identified and risk factors for potentially preventable readmissions were analyzed using competing risk analysis.

Results: A total of 53,740 cancer surgeries performed for the following tumor types were analyzed: colorectal (CRC) (42%), kidney (22%), liver (2%), lung (25%), ovary (4%), pancreas (4%), and uterine (1%). The 30-day readmission rate was 11.97%, 47% of which were identified as potentially preventable. The most common cause of potentially preventable readmissions was sepsis (48%). Pancreatic cancer had the highest overall readmission rate (22%) and CRC had the highest percentage of potentially preventable readmissions (51%, hazard ratio [HR] 1.42, 95% confidence interval [95%CI] 1.28–1.61). Risk factors associated with preventable readmissions included discharge disposition to a skilled nursing facility (HR 2.22, 95%CI 1.99–2.48) and the need for home healthcare (HR 1.61, 95%CI 1.48–1.75).

Conclusions: Almost half of the 30-day readmissions were potentially preventable and attributed to high rates of sepsis, surgical site infections, dehydration, and electrolyte disorders. These results can be further validated for identifying broad targets for improvement

Background: Extra peritoneal packing (EPP) is a quick and highly effective method to control pelvic hemorrhage.

Objectives: To determine whether EPP can be as safely and efficiently performed in the emergency department (ED) as in the operating room (OR).

Methods: Retrospective study of 29 patients who underwent EPP in the ED or OR in two trauma centers in Israel 2008–2018.

Results: Our study included 29 patients, 13 in the ED-EPP group and 16 in the OR-EPP group. The mean injury severity score (ISS) was 34.9 ± 11.8. Following EPP, hemodynamic stability was successfully achieved in 25 of 29 patients (86.2%). A raise in the mean arterial pressure (MAP) with a median of 25 mmHg (mean 30.0 ± 27.5, P < 0.001) was documented. All patients who did not achieve hemodynamic stability after EPP had multiple sources of bleeding or fatal head injury and eventually succumbed. Patients who underwent EPP in the ED showed higher change in MAP (P = 0.0458). The overall mortality rate was 27.5% (8/29) with no difference between the OR and ED-EPP. No differences were found between ED and OR-EPP in the amount of transfused blood products, surgical site infections, and length of stay in the hospital. However, patients who underwent ED-EPP were more prone to develop deep vein thrombosis (DVT): 50% (5/10) vs. 9% (1/11) in ED and OR-EPP groups respectively (P = 0.038).

Conclusions: EPP is equally effective when performed in the ED or OR with similar surgical site infection rates but higher incidence of DVT

Background: Radical cystectomy is a complicated surgery with significant risks. Complications of Clavien–Dindo grade 3–4 range from 25% to 40% while risk of mortality is 2%. Pelvic surgery or radiotherapy prior to radical cystectomy increases the challenges of this surgery.

Objectives: To assess whether radical cystectomy performed in patients with prior history of pelvic surgery or radiation was associated with increased frequency of Clavien–Dindo grade 3 or higher complications compared to patients without prior pelvic intervention.

Methods: We retrospectively evaluated all patients who underwent radical cystectomy at our center over a 7-year period. All patients with pelvic radiation or surgery prior to radical cystectomy comprised group 1, while group 2 included the remaining patients.

Results: In our study, 65 patients required radical cystectomy at our institution during the study period. Group 1 was comprised of 17 patients and group 2 included 48 patients. Four patients from group 2 received orthotopic neobladder, while an ileal conduit procedure was performed in the remaining patients. Estimated blood loss and the amount of blood transfusions given was the only variable found to be statistically different between the two groups. One patient from group 1 had four pelvic interventions prior to surgery, and her cystectomy was aborted.

Conclusions: Radical cystectomy may be safely performed in patients with a history of pelvic radiotherapy or surgery, with complication rates similar to those of non-irradiated or operated pelvises.

Background: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction.

Objectives: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS).

Methods: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4.

Results: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54–88). ULD scan radiation exposure was comparable on average to 3.6–4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04–-0.08 vs. 0.08–0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization.

Conclusions: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.

Background: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.

Objectives: To describe changes in teaching during the first phase of the COVID-19 pandemic.

Methods: We described the steps implemented at the Technion–Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. 

Results: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. 

Conclusions: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching

Background: Immune cell counts in blood in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be useful prognostic biomarkers of disease severity, mortality, and response to treatment.

Objectives: To analyze sub-populations of lymphocytes at hospital admission in survivors and deceased from severe pneumonia due to coronavirus disease-2019 (COVID-19).

Methods: We conducted a cross-sectional study of healthcare workers confirmed with SARS-CoV-2 in convalescents (control group) and healthy controls (HC) diagnosed with severe COVID-19. Serum samples were taken at hospital admission and after recovery. Serum samples ≥ 25 days after onset of symptoms were analyzed for lymphocyte subpopulations through flow cytometry. Descriptive statistics, Kruskall-Wallis test, receiver operating characteristic curve, calculation of sensitivity, specificity, predictive values, and Kaplan-Meier analysis were performed.

Results: We included 337 patients: 120 HC, 127 convalescents, and 90 severe COVID-19 disease patients (50 survivors, 40 deceased). For T cells, total lymphocytes ≥ 800/μL, CD3+ ≥ 400/μL, CD4+ ≥ 180/μL, CD8+ ≥ 150/μL, B cells CD19+ ≥ 80/μL, and NK ≥ 34/μL subsets were associated with survival in severe COVID-19 disease patients. All subtypes of lymphocytes had higher concentrations in survivors than deceased, but similar between HC and convalescents. Leukocytes ≥ 10.150/μL or neutrophils ≥ 10,000/μL were associated with increased mortality. The neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5 increased the probability of death in severe COVID-19 (odds ratio 11.68).

Conclusions: Total lymphocytes; NLR; and levels of CD3+, CD4+, CD8+, and NK cells are useful as biomarkers of survival or mortality in severe COVID-19 disease and commonly reach normal levels in convalescents.

Background: Patients diagnosed with coronavirus disease-19 (COVID-19) who deteriorate to respiratory failure and require mechanical ventilation may later need to be weaned from the ventilator and undergo a rehabilitation process. The rate of weaning COVID-19 patients from mechanical ventilation is unknown.

Objective: To present our experience with ventilator weaning of COVID-19 patients in a dedicated facility.

Methods: A retrospective cohort study was conducted of 18 patients hospitalized in a COVID-19 dedicated ventilator weaning unit.

Results: Eighteen patients were hospitalized in the dedicated unit between 6 April and 19 May 2020. Of these, 88% (16/18) were weaned and underwent decannulation, while two patients deteriorated and were re-admitted to the intensive care unit. The average number of days spent in our department was 12. There was no statistically significant correlation between patient characteristics and time to weaning from ventilation or with the time to decannulation.

Conclusions: Despite the high mortality of COVID-19 patients who require mechanical ventilation, most of the patients in our cohort were weaned in a relatively short period of time. Further large-scale studies are necessary to assess the cost effectiveness of dedicated COVID-19 departments for ventilator weaning.

Background: Guidelines recommend testing for multiple biomarkers in non-small cell lung cancer (NSCLC) tumors. Blood-based liquid biopsy analyzing cell-free DNA (cfDNA) could be used in addition to tumor biopsy genotyping, especially if tissue/time are limiting.

Objectives: To investigate the clinical utility of early cfDNA analysis (Guardant360^® CDx) in treatment-naïve NSCLC patients.

Methods: A prospective cohort of treatment-naïve patients with metastatic NSCLC who underwent tumor and cfDNA analysis between 12/2018 and 2/2019 were included.

Results: Ten patients were included: 6 males, median age 70.5 years (range 48–87), 8 prior smokers. Liquid biopsy was sent when cancer cells were detected in the biopsy specimen. Median time from diagnosis to receiving the report on the last biomarker from the tumor biopsy was 20 days (range 9–34); median time from blood draw to receiving the cfDNA findings was 9 days (range 7–12). The median difference between the cfDNA and the tumor analysis reports was 20 days (range 9–28). Actionable biomarkers were identified in four patients by both the biopsy analysis and the cfDNA analysis (2cases with EGFR mutations, one with ROS1 fusion, and one with EML4-ALK fusion for whom the biopsy analysis also identified an EGFR mutation not detected in the cfDNA analysis). Overall, eight patients received treatment (2 died before treatment initiation). Three patients received biomarker-based treatment (1 osimertinib, 1 alectinib, and 1 crizotinib).

Conclusions: These findings suggest that cfDNA analysis should be ordered by the pulmonologists early in the evaluation of patients with NSCLC, which might complement the tumor biopsy.

Background: While the routine performance of terminal ileum (TI) intubation during colonoscopy procedures is perceived to have a low yield, its utility during colonoscopies performed for specific indications have not been well studied.

Objectives: To assess the diagnostic yield of an indication-based ileoscopy in real-life practice.

Methods: The authors reviewed endoscopic reports of patients who underwent colonoscopies over an 8-year period (2011–2018) and had routine ileoscopy during these procedures. Demographic data, indications for colonoscopy, and endoscopic findings were documented. Diagnostic yield and odds ratio for TI findings were calculated.

Results: Over 30,000 colonoscopy reports performed during the study period were reviewed. Ilesocopy was performed in 1800 patients, 216 patients had findings in the TI (ileitis or ulcers). TI findings were more prevalent in younger ages (38.3 ± 17.6 vs. 43.6 ± 20, P < 0.05). The greatest yield of ileoscopy was evident when performed for the evaluation of chronic abdominal pain and diarrhea (14.4% vs. 9.3%, odds ratio [OR] 1.62, P < 0.05). Positive fecal occult blood test (FOBT) (OR 0.1, 95% confidence interval [95%CI] 0.02–0.5, P = 0.005) and constipation (OR 0.44, 95%CI 0.2–0.9, P = 0.04) were negatively associated with TI findings.

Conclusions: Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT