Israel Medical Association Journal

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: 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: Cyclophosphamide treatment has been associated with ovarian function impairment. Co-treatment with gonadotropin-releasing hormone-analogue (GnRH-a) seems to be able to prevent this complication. However, even though data are available on neoplastic patients, limited data have been published on systemic lupus erythematosus (SLE) women cohorts

Objectives: To evaluate GnRH-a efficacy on ovarian function preservation in SLE women receiving cyclophosphamide treatment

Methods: The authors performed a retrospective study including SLE women requiring cyclophosphamide treatment and compared those treated with and without GnRH-a (case and controls, respectively). All patients were evaluated before cyclophosphamide treatment and every 3 months in the following years. Ovarian function was evaluated using hormonal profiles

Results: The study comprised 33 SLE cyclophosphamide-treated women: 18 co-treated with triptorelin and 15 controls. The mean follow-up was 8.1 ± 5.1 years (range 4–11). Premature ovarian failure (POF) prevalence was significantly lower in SLE women treated by cyclophosphamide plus triptorelin compared to controls (11.1% vs. 33.3%, P = 0.0002). The occurrence of POF was significantly associated with higher age at the time of cyclophosphamide treatment (P = 0.008). Only patients in the GnRH-a treated group had successful pregnancies

Conclusions: The study provides information about the efficacy of co-treatment with GnRH-a in SLE women receiving cyclophosphamide, as demonstrated by the lower POF incidence compared to untreated subjects, based on long-term follow-up. These results reinforce the use of GnRH-a for fertility preservation in premenopausal SLE patients treated by cyclophosphamide

Background: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community.

Objectives: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention.

Methods: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients.

Results: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week.

Conclusions: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.

Background: Heart transplantation (HT) success rate is limited by a high incidence of cancer post-HT. Data on kidney cancer following solid organ transplantation, especially HT, are limited, and only a few cases have been reported.

Objectives: To report a unique case series of detected kidney cancer following HT.

Methods: Between 1997 and 2018, 265 patients who underwent HT were enrolled and prospectively followed in the HT registry of the Sheba Medical Center.

Results: The series included 5 patients, 4 men and a woman (age range 35–50 years at HT). The patients were diagnosed with kidney tumors 6–11 years after HT (age range at diagnosis 40–72 years). Two of the men were identical twin brothers. At HT four patients received induction therapy with anti-thymocyte globulin and all received an initial immunosuppressive regimen based on cyclosporine. All male HT recipients had a history of heavy smoking. Two male patients developed allograft vasculopathy, but all had preserved heart function. The 72-year-old woman developed a kidney tumor of the native kidney 5 years after re-HT and kidney transplantation. Two patients had features of multifocal papillary renal cell carcinoma (RCC) and eventually underwent bilateral nephrectomy, while another patient underwent left partial nephrectomy with preserved renal function.

Conclusions: To the best of our knowledge, this is the first case series study describing kidney tumors following HT. With the improving outcomes and life expectancy of HT patients, a better understanding of the factors that determine cancer risk is of the utmost importance and may have a major impact on the non-cardiac surveillance.

Background: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting.

Objective: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer’s guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds

Methods: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement.

Results: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer’s guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds.

Conclusions: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Background: Older age is an independent predictor of worse outcome from traumatic brain injury (TBI). No clear guidelines exist for the management of TBI in elderly patients.

Objectives: To describe the outcomes of elderly patients presenting with TBI and intracranial bleeding (ICB), comparing a very elderly population (≥ 80 years of age) to a younger one (70–79).

Methods: Retrospective analysis of the outcomes of elderly patients presenting with TBI with ICB admitted to a level I trauma center.

Results: The authors analyzed 100 consecutive patients aged 70–79 and 100 patients aged 80 and older. In-hospital mortality rates were 9% and 21% for groups 70–79 and ≥ 80 years old, respectively (P = 0.017). Patients 70–79 years old showed a 12-month survival rate of 73% and a median survival of 47 months. In patients ≥ 80 years old, 12-month survival was 63% and median survival was 27 months (P = NS). In patients presenting with a Glasgow Coma Scale score of ≥ 8, the in-hospital mortality rates were 41% (n=5/12) and 100% (n=8/8). Among patients ≥ 80 years old undergoing emergent surgical decompression, in-hospital mortality was 66% (n=12/18). Survivors presented with a severe drop in their functional score. Survival was dismal in patients ≥ 80 years old who were treated conservatively despite recommended operative guidelines.

Conclusions: There is a lack of reliable means to evaluate the outcome in patients with poor functional status at baseline. The negative prognostic impact of severe TBI is profound, regardless of treatment choices.