Israel Medical Association Journal

Background: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL).

Objectives: To characterize medication burden during the last hospitalization in children dying from cancer

Methods: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters.

Results: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with “Do not resuscitate” (DNR) orders (P = 0.055).

Conclusions: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.

Background: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM.

Objectives: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation.

Methods: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months.

Results: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group.

Conclusions: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed.

Objectives: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores.

Methods: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month.

Results: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005).

Conclusions: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.

Background: Primary spontaneous pneumothorax (PSP) tends to occur in young adults without underlying lung diseases and is usually followed by limited symptoms, while secondary spontaneous pneumothorax (SSP) is a complication of a pre-existing lung disease. Surprisingly, for such common conditions, there is a considerable inconsistency regarding management guidelines.

Objectives: To evaluate the risk factors for spontaneous pneumothoraxes and to summarize outcomes and complications based on our clinical experience.

Methods: This retrospective study group was comprised of 250 consecutive patients older than 18 years of age who were diagnosed with spontaneous pneumothorax and hospitalized at the Meir Medical Center (2004–2017). Data on demographic characteristics, indicating symptoms, chest X-rays, and chest computed tomography (CT) results were collected. Our experience and outcomes were then compared to a large multicenter study.

Results: Most of the patients were male (85%) and past or current smokers; 69% presented with PSP, while the rest were SSP. No occupational relation was noted. About 55% of the cases presented with a moderate or large pneumothorax (over 1/3 hemithorax). Most patients (56%) required chest tube drainage and 20% undergone surgery. Nearly 10% presented with a recurrent pneumothorax with the mean time to recurrence being 11 ± 20 days. Although the length of hospital stay of patients that underwent surgery was the longest (P < 0.001) for both PSP and SSP, the recurrence rate was actually reduced, suggesting some benefit for the surgical treatment option.

Conclusions: Our experience showed that the traditional approach to the PSP treatment should be further considered, as previously suggested.

Background: Lung percutaneous needle biopsy (PNB) is routinely used to diagnose lung cancer. The most prevalent complications of PNB are pneumothorax and bleeding. Differences in characteristics of medical procedures between rural and urban hospitals are well known.

Objectives: To compare characteristics of patients and lesions between two hospitals and to evaluate whether lung PNB complications differ in rural vs. urban settings.

Methods: The authors examined case records of 561 patients who underwent lung biopsy at two different medical centers in Israel: Tel Aviv Sourasky Medical Center (urban) and Barzilai Medical Center (rural). To evaluate the complication rates, the authors analyzed findings from chest X-ray performed 2 hours after biopsy and computed tomography (CT) images at the site of biopsy.

Results: The study comprised 180 patients who underwent lung biopsy at Barzilai and 454 at Sourasky. The rate of pneumothorax did not differ between centers (12% at Barzilai and 19% at Sourasky, P = 0.08). Distance from pleura was positively correlated to pneumothorax occurrence in both centers; however, neither lesion size nor lesion locus was found to be a risk factor for pneumothorax. Mild bleeding at the biopsy site occurred equally at Barzilai and Sourasky (32% vs. 36%, P = 0.3, respectively). Furthermore, immediate CT post-biopsy at Barzilai showed 95% negative predictive value, showing that a CT scan performed immediately after lung biopsy cannot replace the routine follow-up chest X-ray in predicting iatrogenic pneumothorax.

Conclusions: CT-guided percutaneous lung biopsies are comparable between rural and urban hospitals regarding procedure characteristics and complication rates.

Background: Transbronchial cryobiopsy (TBC) has recently emerged for the assessment of diffuse parenchymal lung disease (DPLD) as a less invasive procedure than surgical lung biopsy. The diagnostic usefulness and safety of TBC is still controversial.

Objectives: To evaluate the safety and diagnostic yield of TBC in a peripheral community medical center.

Methods: We retrospectively reviewed the charts of all patients with DPLD who underwent TBC from January 2015 to January 2020.

Results: The study comprised 97 patients. Three samples were taken from each patient with an average diameter of 0.59 cm. The histologic diagnostic yield was 54% (52 of 97 procedures). The most frequent histopathologic diagnoses were usual interstitial pneumonia in 13 patients (13%). Bleeding was observed in 19 cases (19%) and only one patient (1%) had severe bleeding. Pneumothorax developed in seven patients (7%) and one patient (1%) suffered from Interstitial lung disease exacerbation.

Conclusions: TBC was found to be safe; however, the diagnostic yield was rather low compared to other studies, which emphasizes the need for interstitial lung disease centers with expert in this field.

Background: Guidelines recommend testing for multiple biomarkers in non-small cell lung cancer (NSCLC) tumors. Blood-based liquid biopsy analyzing cell-free DNA (cfDNA) could be used in addition to tumor biopsy genotyping, especially if tissue/time are limiting.

Objectives: To investigate the clinical utility of early cfDNA analysis (Guardant360^® CDx) in treatment-naïve NSCLC patients.

Methods: A prospective cohort of treatment-naïve patients with metastatic NSCLC who underwent tumor and cfDNA analysis between 12/2018 and 2/2019 were included.

Results: Ten patients were included: 6 males, median age 70.5 years (range 48–87), 8 prior smokers. Liquid biopsy was sent when cancer cells were detected in the biopsy specimen. Median time from diagnosis to receiving the report on the last biomarker from the tumor biopsy was 20 days (range 9–34); median time from blood draw to receiving the cfDNA findings was 9 days (range 7–12). The median difference between the cfDNA and the tumor analysis reports was 20 days (range 9–28). Actionable biomarkers were identified in four patients by both the biopsy analysis and the cfDNA analysis (2cases with EGFR mutations, one with ROS1 fusion, and one with EML4-ALK fusion for whom the biopsy analysis also identified an EGFR mutation not detected in the cfDNA analysis). Overall, eight patients received treatment (2 died before treatment initiation). Three patients received biomarker-based treatment (1 osimertinib, 1 alectinib, and 1 crizotinib).

Conclusions: These findings suggest that cfDNA analysis should be ordered by the pulmonologists early in the evaluation of patients with NSCLC, which might complement the tumor biopsy.

Background: Lung cancer is the most common cause of cancer-related death.

Objectives: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period.

Methods: Primary lung cancers, all types and all stages, diagnosed during 1990–2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence.

Results: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005–2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients.

Conclusions: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

Background: As part of the effort to control the coronavirus disease-19 (COVID-19) outbreak, strict emergency measures, including prolonged national curfews, have been imposed. Even in countries where healthcare systems still functioned, patients avoided visiting emergency departments (EDs) because of fears of exposure to COVID-19.

Objective: To describe the effects of the COVID-19 outbreak on admissions of surgical patients from the ED and characteristics of urgent operations performed.

Methods: A prospective registry study comparing all patients admitted for acute surgical and trauma care between 15 March and 14 April 2020 (COVID-19) with patients admitted in the parallel time a year previously (control) was conducted.

Results: The combined cohort included 606 patients. There were 25% fewer admissions during the COVID-19 period (P < 0.0001). The COVID-19 cohort had a longer time interval from onset of symptoms (P < 0.001) and presented in a worse clinical condition as expressed by accelerated heart rate (P = 0.023), leukocyte count disturbances (P = 0.005), higher creatinine, and CRP levels (P < 0.001) compared with the control cohort. More COVID-19 patients required urgent surgery (P = 0.03) and length of ED stay was longer (P = 0.003).

Conclusions: During the COVID-19 epidemic, fewer patients presented to the ED requiring acute surgical care. Those who did, often did so in a delayed fashion and in worse clinical condition. More patients required urgent surgical interventions compared to the control period. Governments and healthcare systems should emphasize to the public not to delay seeking medical attention, even in times of crises