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.

In this review we described the values of commonly available HScore laboratory markers in patients with coronavirus-19 (COVID-19)-pneumonia associated cytokine storm syndrome (CPN-CSS) and compared results with those of other forms cytokine storm syndrome (O-CSS) to determine a pattern for CPN-CSS. Twelve CPN-CSS studies and six O-CSS studies were included. CPN-CSS typically obtained a single HScore value (e.g., aspartate transaminase > 30 U/L) while failing all other HScore criteria. A typical pattern for CPN-CSS was revealed when compared to O-CSS: lymphopenia vs. pancytopenia and increased vs. decreased fibrinogen. Findings, other than HScore commonly found in CPN-CSS studies, showed elevated lactate dehydrogenase, D-dimer, and C-reactive protein. Although CPN-CSS studies describe severely ill patients, the HScore markers are typically less toxic that O-CSS

Background: Emergency department (ED) overcrowding is associated with worse patient outcomes.

Objectives: To determine whether physician assistants (PAs), fairly recently integrated into the Israeli healthcare system, improve patient outcomes and ED timings.

Methods: We compared patients seen by physicians with patients seen by PAs and then by physicians between January and December 2018 using propensity matching. Patients were matched for age, gender, triage level, and decision to hospitalize. Primary endpoints included patient mortality, re-admittance. and leaving on own accord rates. Secondary endpoints were ED timing landmarks.

Results: Patients first seen by PAs were less likely to leave on their own accord (MD1 1.5%, PA 1.0%, P = 0.015), had lower rates of readmission within 48 hours (MD1 2.1%, PA 1.5%, P= 0.028), and were quicker to be seen, to have medications prescribed, and to undergo imaging without differences in timings until decisions were made or total length of stay. Patients seen by a physician with the assistance of a PA were attended to quicker (MD2 47.79 minutes, range 27.70–78.82 vs. MD + PA 30.59 minutes, range 15.77–54.85; P < 0.001) without statistically significant differences in primary outcomes. Mortality rates were similar for all comparisons.

Conclusions: Patients first seen by PAs had lower rates of re-admittance or leaving on their own accord and enjoyed shorter waiting times. Pending proper integration into healthcare teams, PAs can further improve outcomes in EDs and patient satisfaction.

Background: Belimumab was the first biological drug approved for the treatment of systemic lupus erythematosus (SLE) patients. Phase II/III randomized controlled trials and real-life studies identified patients with musculoskeletal involvement as best responders.

Objective: To evaluate the effectiveness of belimumab in SLE-related joint involvement.

Methods: The cohort comprised SLE patients receiving belimumab for musculoskeletal indications. Belimumab was intravenously administrated according to protocols; all the patients were evaluated at baseline (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. We assessed joint activity by disease activity score 28, simple disease activity index (SDAI), clinical disease activity index (CDAI), and swollen tender ratio. Each patient underwent musculoskeletal ultrasound of 34 joints to assess synovial effusion synovial hypertrophy, and power Doppler; by using a semi-quantitative scale (0–3) we obtained the total inflammatory score (0–216).

Results: We evaluated 20 patients (males/females 1/19, median age 45 years [interquartile range (IQR) 12], median disease duration 144 months [IQR 144]). CDAI and SDAI significantly decreased at T1 (P = 0.02 and P = 0.01 respectively) and this improvement was maintained at the following time-points (CDAI: T2 P = 0.008, T3 P = 0.004; SDAI: T2 P = 0.006, T3 P = 0.01). A significant reduction of median ultrasound score was identified at T1 (T0 20.5 [IQR 13.5] vs. T1 7.5 [IQR 4.7], P < 0.001), and maintained at T2 (7.0 [IQR 5], P < 0.0001), and T3 (7.0 [IQR 9.0], P < 0.0001).

Conclusions: Belimumab induces a sustained improvement of ultrasound-detected inflammatory status at the articular level.

Background: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring.

Objectives: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB.

Methods: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB.

Results: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB.

Conclusions: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

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: Stress hyperglycemia (SH) is a common finding in patients in pediatric emergency departments (PED) and has been related to increased morbidity and mortality.

Objectives: To assess the incidence of SH among children visiting the PED. To identify which diseases predispose patients to SH and whether they indicate a worse outcome.

Methods: Data were collected retrospectively from the medical records of all children aged 0–18 years who visited the PED during the years 2010–2014 and who had a glucose level of ≥ 150 mg/dl. Data collected included age, gender, weight, blood glucose level, presence or absence of a pre-existing or a new diagnosis of diabetes mellitus, and previous treatment with medications affecting blood glucose levels or with intravenous fluids containing dextrose. Data were collected regarding hospitalization, duration of hospitalization, discharge diagnosis, and survival status.

Results: The study population included 1245 children with SH, which comprised 2.6% of all patients whose blood glucose level was measured in the PED during the study period. The mean age of children with SH was 49 months; 709 (56.9%) were male. The mean blood glucose level was 184 mg/dl. The rate of hospitalization was 57.8%. The mean duration of hospital stay was 5.6 days and mortality rate was 0.96%. The majority were diagnosed with a respiratory illness.

Conclusions: SH is a common phenomenon among children evaluated in the PED and is associated with a high incidence of hospitalization. It may serve as an additional clinical indicator of disease severity.

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.

Fibromyalgia is a common pain syndrome treated by physicians of many disciplines and presents with many co-morbidities. We reviewed the complexities in assessing disabilities in fibromyalgia patients and the complex interrelationships between patients, their working places, and  the medical community regarding preserving productivity. Flexibility is essential to keep the patients functional and productive. Job loss is costly to both society and patients and joint measures are needed to prevent unemployment.