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: The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.

Objectives: To assess perinatal complications in offspring of women with GDM and PGDM.

Methods: The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.

Results: In the study period 2015–2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P < 0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.

Conclusions: Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks

Background: Channeling medical resources for coronavirus disease-2019 (COVID-19) management can potentially endanger routine healthcare practices. As a preventive measure, a department of obstetrics and gynecology in Israel constructed a separate, designated complex for its COVID-19-exposed patients.

Objectives: To evaluate the effect of the COVID-19 pandemic infection control measures on obstetric care in the obstetrical emergency department and delivery unit.

Methods: The authors collected data retrospectively from February 2020 to March 2020 and compared it to data of a parallel period in 2019.

Results: From 1 February 2020 to 28 March 2020, 3897 women were referred to the emergency department (ED), compared to 4067 the previous year. Mean duration of treatment until decision and referral indications did not differ between 2020 and 2019 (207 vs. 220 minutes, P = 0.26; urgent referrals 58.8% vs. 59.2%, P = 0.83). A per-week comparison showed a significant reduction in ED referrals only in the last week of the period (337 [2020] vs. 515 [2019], P < 0.001). The proportion of women admitted to the delivery unit in active labor was significantly higher in the last three weeks (39.1% vs. 28.2%, P = 0.005). During February and March 2020, 1666 women delivered, compared to 1654 during February and March 2019. The proportion of types and modes of delivery did not differ. In a per-week comparison, the number of deliveries did not differ (mean 208 vs. 206, P = 0.88).

Conclusions: With timely preparation and proper management, negative impact of COVID-19 can be reduced in obstetrical emergency departments.

Background: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic.

Objectives: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19).

Methods: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel.

Results: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02.

Conclusions: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.

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: 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.

In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients

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: Opposition to neonatal Hepatitis B vaccination is a growing trend in Israel.

Objectives: To assess the sociodemographic factors and attitudes associated with non-vaccination of term singleton newborns.

Methods: This prospective, pair-matched, controlled trial was conducted in a tertiary university-affiliated hospital. Data on maternal sociodemographic parameters, delivery, and infant care practices were gathered. Knowledge and references of Hepatitis B virus (HBV) vaccination, vaccination schedule, and health government policies were assessed. A follow-up telephone survey was completed at the age of 7 weeks postpartum regarding vaccine catch-up rate.

Results: Mothers in the study group were mostly Jewish white middle class married multiparous women with some higher education. Hepatitis B serology was not tested in most. Higher rates of rooming-in and exclusive breastfeeding were observed. Knowledge about HBV was stated, multiple sources of information were significantly associated with newborn non-vaccination. Many objected to the timing of the vaccine and its necessity. Multiple medical encounters are viewed as missed opportunities.

Conclusions: Multiple sources of vaccine information are associated with non-vaccination. Medical encounters prior and post-delivery should be used for vaccination education and may improve vaccination coverage.

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.