Israel Medical Association Journal

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in repeated surges of patients, sometimes challenging triage protocols and appropriate control of patient flow. Available models, such as the National Early Warning Score (NEWS), have shown significant limitations. Still, they are used by some centers to triage COVID-19 patients due to the lack of better tools.

Objectives: To establish a practical and automated triage tool based on readily available clinical data to rapidly determine a distinction between patients who are prone to respiratory failure.

Methods: The electronic medical records of COVID-19 patients admitted to the Sheba Medical Center March–April 2020 were analyzed. Population data extraction and exploration were conducted using a MDClone (Israel) big data platform. Patients were divided into three groups: non-intubated, intubated within 24 hours, and intubated after 24 hours. The NEWS and our model where applied to all three groups and a best fit prediction model for the prediction of respiratory failure was established.

Results: The cohort included 385 patients, 42 of whom were eventually intubated, 15 within 24 hours or less. The NEWS score was significantly lower for the non-intubated patients compared to the two other groups. Our improved model, which included NEWS elements combined with other clinical data elements, showed significantly better performance. The model's receiver operating characteristic curve had area under curve (AUC) of 0.92 with of sensitivity 0.81, specificity 0.89, and negative predictive value (NPV) 98.4% compared to AUC of 0.63 with NEWS. As patients deteriorate and require further support with supplemental O₂, the need for re-triage emerges. Our model was able to identify those patients on supplementary O₂ prone to respiratory failure with an AUC of 0.86 sensitivity 0.95, and specificity 0.7 NPV 98.9%, whereas NEWS had an AUC of 0.76. For both groups positive predictive value was approximately 35%.

Conclusions: Our model, based on readily available and simple clinical parameters, showed an excellent ability to predict negative outcome among patients with COVID-19 and therefore might be used as an initial screening tool for patient triage in emergency departments and other COVID-19 specific areas of the hospital.

Several novel strategies have emerged in the last decade as potential therapies for patients with chemorefractory lymphoproliferative diseases and acute leukemia. While these treatments include exciting drugs that dramatically change the landscape of treatment, the organ-toxicity profile associated with these therapies may be significant. This article focuses on cardiac disorders associated with chimeric antigen receptor T-cell (CAR-T) therapy, as well as with novel regimens for acute leukemia

Background: Pilonidal disease in the natal cleft is treated traditionally by a wide and deep excision of the affected area. There is growing awareness, however, to the advantages of minimally invasive surgeries.

Objectives: To compare the efficacy of wide excision operations and minimal trephine surgery in patients with primary pilonidal disease.

Methods: In this retrospective study we examined surgical and inpatient records of 2039 patients who underwent surgery for primary pilonidal disease in five private hospitals between 2009 and 2012. Most procedures were of lay-open, primary midline closure, and minimal surgery types. Pilonidal recurrence rates were evaluated in a subset of 1260 patients operated by 53 surgeons each performing one type of surgery, regardless of patient characteristics or disease severity.

Results: With a mean follow-up of 7.2 years, 81.5%, 85%, and 88% of patients were disease-free after minimally invasive surgery, wide excision with primary closure, and lay-open surgery, respectively, with no statistically significant difference in recurrence rates. Minimal surgeries were usually performed under local anesthesia and involved lower pain levels, less need for analgesics, and shorter hospital stays than wide excision operations, which were normally performed under general anesthesia. The use of drainage, antibiotics, or methylene blue had no effect on recurrence of pilonidal disease.

Conclusions: Minimally invasive surgeries have the advantage of reducing the extent of surgical injury and preserving patient’s quality of life. They should be the treatment of choice for primary pilonidal disease

Background: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies.

Objectives: To describe the design and patient population of the first pediatric aerodigestive center in Israel.

Methods: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children’s Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020.

Results: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3–216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1–5 (5 = highest satisfaction) was 4.5.

Conclusions: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

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: Patients with critical limb ischemia (CLI) involving the below-the-knee (BTK) arteries are at increased risk of limb loss. Despite improvement in endovascular modalities, it is still unclear whether an aggressive approach results in improved limb salvage.

Objectives: To assess whether an aggressive approach to BTK arterial disease results in improved limb salvage.

Methods: A comparative study of two groups was conducted. Group 1 included patients treated between 2012 and 2014, primarily with transfemoral angioplasty of the tibial arteries. Group 2 included patients treated between 2015–2019 with a wide array of endovascular modalities (stents, multiple tibial artery and pedal angioplasty, retrograde access). Primary endpoint was freedom from amputation at 4 years.

Results: A total of 529 BTK interventions were performed. Mean age was 71 ± 10.6 years, 382 (79%) were male. Patients in group 1 were less likely to be taking clopidogrel (66% vs. 83%, P < 0.01) and statins (72 % vs. 87%, P < 0.01). Several therapeutic modalities were used more often in group 2 than in group 1, including pedal angioplasty (24 vs. 43 %, P = 0.01), tibial and pedal retrograde access (0 vs. 10%, P = 0.01), and tibial stenting (3% vs. 25%, P = 0.01). Revascularization of two or more tibial arteries was performed at a higher rate in group 2 (54% vs. 50%, P = 0.45). Estimated freedom from amputation at 40 months follow-up was higher in group 2 (53% vs. 63%, P = 0.05).

Conclusions: An aggressive, multimodality approach in treating BTK arteries results in improved limb salvage.

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Background: The single-breath diffusing capacity of the lungs (DLCO_SB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VA_SB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCO_SB) is the DLCO_SB divided by VA_SB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCO_SB appears insignificant in the assessment of pulmonary function in CF.

Objectives: To challenge the precision of normal KCO_SB in CF.

Methods: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCO_BP, and body plethysmography (_BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(_BP) to establish alveolar volume (VA_BP) and to determine KCO_BP. We also included individual data of arterial pCO₂ blood-gas level.  

Results: KCO_SB values were normal or higher in most patients, regardless of patient FEV1 value (R² = 0.2204; P < 0.02). In contrast, the measurements of KCO_BP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO₂ levels (R² = 0.1383; P = 0.0133, P > 0.05, respectively).

Conclusions: The 10- second perfusion time of the inert gas during DLCO_SB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCO_SB with the deterioration of FEV1 and elevation of pCO₂ levels.

The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy

Background: There is limited clinical information on coronavirus disease-19 (COVID-19) patients in Israel.

Objectives: To describe the characteristics, outcomes, and potential associations of hospitalized COVID-19 patients in Israel.

Methods: We conducted a single-center, retrospective study of 58 consecutive laboratory-confirmed COVID-19 patients admitted to Laniado Hospital, Israel, between 14 March 2020 and 14 May 2020. Demographic, clinical, and laboratory data on admission were collected and analyzed, and the association to subsequent respiratory failure was assessed.

Results: Mean age of patients was 70.7 ± 16.9 years (53% males, 47% females.); 74% had at least one co-morbidity. Most patients were of Jewish Ashkenazi descent. During hospitalization 15 patients (mean age 78.18 ± 10.35 years); 80% male, 73% Sephardi descent developed respiratory failure rates of 60% occurring on average 10.6 days following intubation. Laboratory tests at admission displayed a significant increase in C-reactive protein (CRP) and creatine kinase (CK) and a decrease in absolute lymphocyte count (ALC) in patients who eventually developed respiratory failure (163.97 mg/L, 340.87 IU/L, 0.886 K/μl vs. 50.01 mg/L and 123.56 IU/L, 1.28 K/μl, respectively). Multivariate logistic analysis revealed an integrated parameter of CRP, CK, and ALC highly correlated with respiratory failure. Receiver operating characteristic curve revealed the area under the curve of CRP, CK, and ALC and the integrated parameter to be 0.910, 0.784, and 0.754, respectively. CRP was the strongest predictor to correlate with respiratory failure.

Conclusions: CRP, CK, and ALC levels on admission could possibly be used to detect high-risk patients prone to develop respiratory failure.

Background: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards.

Objectives: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards.

Methods: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital.

Results: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations.

Conclusions: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.