Israel Medical Association Journal

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

Background: Sheba Medical Center, Tel Hashomer, is a tertiary hospital located in the center of Israel. It is the largest hospital in Israel and was the first to face coronavirus disease-2019 (COVID-19) patients in the country at the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.

Objectives: To describe our experience with the COVID-19 pandemic, focusing on our triage method in the emergency department (ED). Our goal was to keep the main hospitalization buildings clean of infection by separating COVID-19 positive patients from COVID-19 negative patients.

Methods: We divided our ED into two separate sections: a regular non-COVID-19 ED and an advanced biological ED. We created clear protocols of triage for suspected and confirmed COVID-19 patients. We reviewed the data of patients admitted to our ED during the month of March and analyzed the results of our triage method in separating COVID-19 positive from negative patients.

Results: During the month of March 2020, 7957 patients were referred to our ED. Among them 2004 were referred to the biological ED and 5953 were referred to the regular ED. Of the 2004 patients referred to the biological ED, 1641 (81.8%) were sampled for SARS-CoV-2 polymerase chain reaction of whom 143 (8.7%) were positive. Only two COVID-19 positive patients unintentionally entered the main clean hospital, making our triage almost full proof.

Conclusions: Our triage method was successful in separating COVID-19 positive from negative patients and maintained the regular hospital clean of COVID-19 allowing treatment continuation of regular non-COVID-19 patients.

Background: The potential excess flow of patients into emergency departments and community clinics for testing and examination during a pandemic poses a major issue. These additional patients may lead to the risk of viral transmission to other patients and medical teams. To contain the spread of coronavirus disease-2019 (COVID-19), the Israeli Ministry of Health initiated a plan spearheaded by Magen David Adom (MDA), Israel’s national emergency medical services (EMS) organization.

Objectives: To describe outbreak containment actions initiated by MDA, including a COVID-19 tele-triage center and home testing by paramedics.

Methods: Retrospective analysis was conducted of de-identified data from the call management and command and control systems during the first period of the COVID-19 outbreak in Israel (23 February 2020–15 March 2020).

Results: During the study period, the total number of calls to the dispatch centers was 477,321 with a daily average of 21,696, compared to 6000–6500 during routine times. The total number of COVID-19 related calls was 334,230 (daily average 15,194). There were 28,454 calls (8.51% of all COVID-19 related calls, average 1293/day) transferred to the COVID-19 call center. Of the COVID-19 call center inquiries, 8390 resulted in the dispatch of a dedicated vehicle, including a paramedic wearing personal protective equipment, to collect samples for testing (daily average 381).

Conclusions: Maximizing EMS during a pandemic using phone triage, in addition to dispatching paramedics to perform home testing, may significantly distance infected patients from the public and health care system. These steps can further minimize the spread of disease.

Background: Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general.

Objectives: To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit.

Methods: A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored.

Results: The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease.

Conclusions: This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.

Background: Transanal minimally invasive surgery (TAMIS) is a single port access platform used for full thickness local excision of rectal lesions. It is an appealing alternative to a radical resection of rectum that often can cause a significant bowel dysfunction described as low anterior resection syndrome (LARS). LARS is evaluated using a validated score. Functional outcomes of patients undergoing TAMIS has not yet been evaluated using the LARS score.

Objectives: To evaluate long-term bowel function in patients who underwent TAMIS.

Methods: In this case series, all patients who underwent TAMIS in a single tertiary institute between 2011 and 2017 were retrospectively reviewed. We evaluated bowel function using the LARS score questionnaire through telephone interviews.

Results: The study consisted of 23 patients, average age of 67 ± 6.98 year; 72% were male. The median follow-up from the time of surgery was 5 years. Six patients (26.08%) had malignant type lesions. The average height of the lesion from the anal verge was 7.4 cm. The average size of the specimen was 4 cm. The total LARS score revealed that 17 patients (73.91%) had no definitive LAR syndrome following the surgery. Four patients (17.39%) fit the description of minor LARS and only two (8.69%) presented with major LARS.

Conclusions: TAMIS provides relatively good long-term functional outcomes in terms of bowel function. Further randomized studies with larger cohorts are still needed to better evaluate the outcomes.

Background: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs).

Objectives: To determine factors associated with attaining upper-range doses in patients with HFrEF.

Methods: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines.

Results: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65–78) and LVEF of 30% (IQR 25–35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05–1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m²/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34–5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13–0.90, P = 0.031).

Conclusions: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

Background: Recent data regarding polymicrobial bacteremia (PMB) are lacking.

Objectives: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting.

Methods: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls.

Results: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41–9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06–3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups.

Conclusions: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.

Background: Although indwelling catheters are increasingly used in modern medicine, they can be a source of microbial contamination and hard-to-treat biofilms, which jeopardize patient lives. At times 70% ethanol is used as a catheter-lock solution due to its bactericidal properties. However, high concentrations of ethanol can result in adverse effects and in malfunction of the catheters.

Objective: To determine whether low concentrations of ethanol can prevent and treat biofilms of Pseudomonas aeruginosa.

Methods: Ethanol was tested at a concentration range of 0.625–80% against laboratory and clinical isolates of P. aeruginosa for various time periods (2–48 hours). The following parameters were evaluated following ethanol exposure: prevention of biofilm formation, reduction of biofilm metabolic activity, and inhibition of biofilm regrowth.

Results: Exposing P. aeruginosa to twofold ethanol gradients demonstrated a significant biofilm inhibition at concentrations as low as 2.5%. Treating pre-formed biofilms of P. aeruginosa with 20% ethanol for 4 hours caused a sharp decay in the metabolic activity of both the laboratory and clinical P. aeruginosa isolates. In addition, treating mature biofilms with 20% ethanol prevented the regrowth of bacteria encased within it.

Conclusions: Low ethanol concentrations (2.5%) can prevent in vitro biofilm formation of P. aeruginosa. Treatment of previously formed biofilms can be achieved using 20% ethanol, thereby keeping the catheters intact and avoiding complications that can result from high ethanol concentrations.

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Background: Urinary tract infection (UTI) is a common bacterial infection in children.

Early treatment may prevent renal damage in pyelonephritis. The choice of empiric antibiotic treatment is based on knowledge of the local susceptibility of urinary bacteria to antibiotics. In Israel the recommended empiric oral antibiotic treatment are First or second generation cephalosporin, trimethoprim-sulfamethoxazole or amoxicillin-clavulanic acid.

Objectives: To describe resistance rates of urine bacteria isolated from children with UTI in the community settings. Identify risk factors for resistance.

Methods: A retrospective cross-sectional study of UTI in children aged 3 months to 18 years diagnosed with UTI and treated as outpatients in a large community clinic between 7/2015 and 7/2017 with a diagnosis of UTI.

Results: A total of 989 urinary samples were isolated, 232 were included in the study. Resistance rates to cephalexin, cefuroxime, ampicillin/clavulanate and Trimethoprim-Sulfamethoxazole were 9.9%, 9.1%, 20.7%, and 16.5%, respectively. Urinary tract abnormalities and recurrent UTI were associated with an increase in antibiotic resistance rates. Other factors such as age, fever, and previous antibiotic treatment were not associated with resistance differences.

Conclusions: Resistance rates to common oral antibiotics were low compared to previous studies performed in Israel in hospital settings. First generation cephalosporins are the preferred empiric antibiotics for febrile UTI for outpatient children. Amoxicillin/clavulanate is not favorable due to resistance of over 20% and the broad spectrum of this antibiotic. Care should be taken in children with renal abnormalities as there is a worrying degree of resistance rates to the oral first line antibiotic therapy.