Israel Medical Association Journal

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.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen that causes coronavirus disease-2019 (COVID-19), is thought to be transmitted via droplets and aerosols, and was detected in saliva of infected individuals. These droplets from the upper airway may infect the inhalation sedation mask and tubing. The authors determined the adequate measures needed to prevent the transmission of COVID-19 by nitrous-oxide (N₂O) system during inhalation sedation in dentistry and provided evidence on mask and tubing sterilization. Additional measures to protect patients and healthcare workers from COVID-19 that may be transmitted by the inhalation sedation system are discussed. The authors recommend minimal use of a N₂O system during inhalation sedation in dentistry. In case of need, the practitioners should have more than one scavenger kit and nasal masks for each N₂O/O₂ mixer. Biologic barriers should be mounted between the scavenger's tubing and the central evacuation system. Strict cleansing and sterilization should be performed for all parts of the N₂O system. The use a disposable scavenger system and nasal mask should be considered as a viable option

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: Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent exacerbations and need to be hospitalized, resulting in an economic and social burden. Although data exist regarding reasons of frequent hospitalizations, there is no data available about the impact on the length of stay (LOS).

Objectives: To characterize the causes of prolonged hospitalizations in COPD patients.

Methods: A retrospective study was conducted of patients who were diagnosed and treated in the pulmonary department for severe COPD exacerbations. All patient demographic data and medical history were collected. Data regarding the disease severity were also collected (including Global Initiative for Obstructive Lung Disease [GOLD] criteria, pulmonologist follow-up, prior hospitalizations, and LOS).

Results: The study comprised 200 patients, average age 69.5 ± 10.8 years, 61% males. Of these patients, 89 (45%) were hospitalized for up to 4 days, 111 (55%) for 5 days or more, and 34 (17%) for more than 7 days. Single patients had longer LOS compared with married patients (48% vs. 34%, P = 0.044). Multivariate analysis showed that the number of prior hospital admissions in the last year was a predictor of LOS (P = 0.038, odds ratio [OR] = 0.807, 95% confidence interval [95%CI] = 0.659–0.988), as well as the use of non-invasive respiratory support by bilevel positive airway pressure (BiPAP) during the hospitalization (P = 0.024, OR = 4.662, 95%CI = 1.229–17.681).

Conclusions: Fewer previous hospitalizations due to COPD exacerbations and the need for non-invasive respiratory support by BiPAP were found as predictors of longer LOS.

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: Fetal ventriculomegaly is one of the more common fetal anomalies detected during prenatal screening.

Objectives: To assess the rate of genetic aberrations as the cause for ventriculomegaly in these fetuses.

Methods: A historic cohort study was conducted on 164 fetuses with sonographic diagnosis of ventriculomegaly. All cases were analyzed for karyotype and 41 cases were further analyzed by chromosomal microarray (CMA). The study group was subdivided by laterality, severity, and whether the ventriculomegaly was an isolated finding or not. Subgroups were compared and the study group was compared to a control group of 209 fetuses.

Results: Karyotype aberrations were more common among fetuses with ventriculomegaly (6.6%) compared to controls (0%, P < 0.001). CMA aberrations were more common in the non-isolated ventriculomegaly cases (24.1%) compared to controls (6.2%, P = 0.031). The rate of genetic aberrations was not associated with the degree of dilatation or laterality.

Conclusions: It is equivocal whether CMA testing should be conducted on every amniotic fluid sample taken from fetuses with isolated ventriculomegaly. However, if more anomalies are detected during an anatomical survey, CMA analysis should be conducted to decrease oversights of genetic diagnoses.

Background: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities.

Objectives: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19.

Methods: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March–April 2020 (during the COVID-19 outbreak) with March–April of the preceding year, 2019.

Results: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods.

Conclusions: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients

Background: The safe completion of cholecystectomy is dependent on proper identification and secure closure of the cystic duct. Effecting this closure poses a great challenge when inflammatory changes obscure the anatomy. Subtotal cholecystectomy allows for near complete removal of the gallbladder and complete evacuation of the stones while avoiding dissection in the hazardous area.

Objectives: To describe experience with laparoscopic subtotal cholecystectomy.

Methods: Subtotal cholecystectomy was performed when the critical view of safety could not be achieved. Surgical technique was similar in all cases and included opening the Hartmann’s pouch, removing stones obstructing the gallbladder outlet, and identifying the opening of the cystic duct, as well as circumferential transection of the gallbladder neck, closure of the gallbladder stump, and excision of the gallbladder fundus. Data retrieved from patient charts included demographics, pre-operative history, operative and postoperative course, and late complications. No bile duct injuries were observed in this series.

Results: A total of 53 patients underwent laparoscopic subtotal cholecystectomy (2010–2018). Ten patients were operated during the acute course of the disease and 43 electively. Acute cholecystitis was the leading cause for gallbladder removal. Cholecystostomy tube was placed in 18 patients during acute hospitalization. The gallbladder remnant was closed and a drain was placed in most patients. Of the 53 patients, 42 had an uneventful postoperative course.

Conclusions: Laparoscopic subtotal cholecystectomy is an effective surgical technique to avoid bile duct injury when the cystic duct cannot safely be identified. Subtotal cholecystectomy has acceptable morbidity and obviates the need for conversion in these difficult cases.

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.

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment