Israel Medical Association Journal

Background: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable.

Objectives: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005.

Methods: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007.

Results: The INCR’s completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005.

Conclusions: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

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: Injuries to the anterior cruciate ligament (ACL) are common and complete tears often fail to heal. ACL reconstruction is considered the surgical gold standard of care for ACL injuries in young active patients.

Objectives: To determine the corresponding morphological and histological features of the torn ACL in different time periods after injury.

Methods: The study included 28 remnant specimens of torn ACLs from patients who had ACL reconstruction surgery of the knee. The remnant pathology was evaluated by its morphology during arthroscopy and by histopathologic measurements.

Results: At surgery there were three progressive and distinct morphological tear patterns. The first pattern was noticed within the first 3 months from injury and showed no scar tissue. The second pattern appeared later and was characterized by the appearance of scar tissue with adhesion to the femoral wall. The third pattern was characterized by adhesion of the ACL remnant to the posterior cruciate ligament. The histological changes of the first morphological pattern showed abundance of blood vessels and lymphocytes at the torn femoral end with few irregular collagen fibers. The second and third tear patterns showed decrement in the number of blood vessels and lymphocytes with longitudinally oriented collagen fibers.

Conclusions: The morphological features of the ACL remnant in the first 3 months after injury showed no scar tissue and its histological features had the characteristics of a reparative phase. This phase was followed by a prolonged remodeling phase that ended with attachment of the remnant to the posterior cruciate ligament.

Background: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines.

Objectives: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel.

Methods: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result.

Results: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment.

Conclusions: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Background: Primary spontaneous pneumothorax (PSP) tends to occur in young adults without underlying lung diseases and is usually followed by limited symptoms, while secondary spontaneous pneumothorax (SSP) is a complication of a pre-existing lung disease. Surprisingly, for such common conditions, there is a considerable inconsistency regarding management guidelines.

Objectives: To evaluate the risk factors for spontaneous pneumothoraxes and to summarize outcomes and complications based on our clinical experience.

Methods: This retrospective study group was comprised of 250 consecutive patients older than 18 years of age who were diagnosed with spontaneous pneumothorax and hospitalized at the Meir Medical Center (2004–2017). Data on demographic characteristics, indicating symptoms, chest X-rays, and chest computed tomography (CT) results were collected. Our experience and outcomes were then compared to a large multicenter study.

Results: Most of the patients were male (85%) and past or current smokers; 69% presented with PSP, while the rest were SSP. No occupational relation was noted. About 55% of the cases presented with a moderate or large pneumothorax (over 1/3 hemithorax). Most patients (56%) required chest tube drainage and 20% undergone surgery. Nearly 10% presented with a recurrent pneumothorax with the mean time to recurrence being 11 ± 20 days. Although the length of hospital stay of patients that underwent surgery was the longest (P < 0.001) for both PSP and SSP, the recurrence rate was actually reduced, suggesting some benefit for the surgical treatment option.

Conclusions: Our experience showed that the traditional approach to the PSP treatment should be further considered, as previously suggested.

Background: Our 1600-bed teaching hospital opened the first physician-led specialist pleural service in Israel in November 2016. Thoracentesis is one of the frequently performed procedures in clinic.

Objectives: To review the incidence of thoracentesis-related symptoms, complications, and risk factors in a specialist pleural clinic.

Methods: Prospective analysis was conducted of 658 ultrasound-assisted thoracenteses between November 2016 and November 2019. Data were collected on patient demographics, clinical characteristics, procedural aspects, symptoms, complications, and additional interventions required.

Results: Of the procedures, 24% were accompanied by a reported symptom of any intensity or duration. Cough and chest discomfort were noted in 56.4% and 52% of these cases, respectively. Large-volume drainage was associated with symptoms (P = 0.002). Ultrasound-estimated effusion volume before drainage predicted pain (P = 0.001) and pneumothorax (P = 0.021). Of 8 cases of pneumothorax, 6 were due to non-expandable lung. Two patients were hospitalized (0.3%), and one required a chest drain.

Conclusions: Symptoms are a common feature of thoracentesis even when performed by experienced operators in ideal settings. Complications, however, are rare when the procedure is performed with bedside ultrasound and attention is paid to patient-reported symptoms and volume drained. Specialist pleural clinics provide a good model for a standardized approach to safe performance of this common procedure.

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: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease.

Objectives: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE.

Methods: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results.

Results: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function.

Conclusions: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Background: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates.

Objectives: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance.

Methods: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen.

Results: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin.

Conclusion: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.

Background: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality.

Objectives: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit.

Methods: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia.

Results: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures.

Conclusions: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia

Background: Acetaminophen is the most common drug involved in pediatric poisonings, both intentionally and accidentally, and is the leading cause of acute liver failure among all age groups.

Objectives: To define the characteristics of patients admitted to a pediatric emergency department (ED) where serum acetaminophen concentrations were measured, and to determine which variables are associated with significant risk of acetaminophen toxicity.

Methods: Acetaminophen serum concentrations were measured, in a retrospective case series, of patients younger than 18 years who had been admitted to the ED at Shamir Medical Center between 1 January 2008 and 31 December 2015.

Results: During the study period 180,174 children were admitted to the ED. Acetaminophen serum concentrations were measured in 209 (0.12%) patients. Mean age was 12.4 ± 5.9 years. Elevated liver enzymes were found in 12 patients, 5 of whom had documented acute liver injury. All five were older than 11years.Two cases of acute liver injury were attributable to acetaminophen ingestion. In both cases the cause was intentional overdose. Univariate analysis showed a significant (P < 0.05) correlation between detectable acetaminophen blood level and a positive history of drug or acetaminophen ingestion, and suicide attempt. Not all children with non-severe acetaminophen poisoning had been diagnosed during the study period. A positive history of acetaminophen ingestion was associated with a 28-fold higher risk for detectable acetaminophen blood level.

Conclusions: In the absence of a positive history of acetaminophen ingestion and in young children with accidental intoxication, the risk of hepatotoxicity is relatively low.

Background: Social distancing, implemented to decrease the spread of coronavirus disease-2019 (COVID-19), forced major changes in medical practices, including an abrupt transition from face-to-face to remote patient care. Pre-clinical medical studies were concomitantly switched to electronic distance learning.

Objectives: To explore potential implications of COVID-19 on future pre-clinical medical studies.

Methods: We examined responses of pre-clinical medical students to the remote electronic learning in terms of quality of and satisfaction with teaching and technical support, attendance to classes, and the desire to continue electronic learning in the post-epidemic era. A survey of responses from first-year students at the Adelson School of Medicine was conducted. To optimize the reliability of the survey, a single research assistant conducted telephone interviews with each student, using a structured questionnaire concerning aspects of participation and satisfaction with teaching and with technical components of the remote electronic learning.

Results: With 100% response rate, the students reported high satisfaction with the electronic learning regarding its quality, online interactions, instructions given, technical assistance, and availability of recording for future studies. Most of the students (68.6%) noted a preference to continue < 90% of the learning online in the post-outbreak era. A high level of overall satisfaction and a low rate of technical problems during electronic learning were significantly correlated with the desire to continue online learning (P < 0.01).

Conclusions: The high satisfaction and the positive experience with the electronic distance learning imposed by the COVID-19 epidemic implied a successful transition and might induce future changes in pre-clinical medical studies.