Israel Medical Association Journal

Background: Extra peritoneal packing (EPP) is a quick and highly effective method to control pelvic hemorrhage.

Objectives: To determine whether EPP can be as safely and efficiently performed in the emergency department (ED) as in the operating room (OR).

Methods: Retrospective study of 29 patients who underwent EPP in the ED or OR in two trauma centers in Israel 2008–2018.

Results: Our study included 29 patients, 13 in the ED-EPP group and 16 in the OR-EPP group. The mean injury severity score (ISS) was 34.9 ± 11.8. Following EPP, hemodynamic stability was successfully achieved in 25 of 29 patients (86.2%). A raise in the mean arterial pressure (MAP) with a median of 25 mmHg (mean 30.0 ± 27.5, P < 0.001) was documented. All patients who did not achieve hemodynamic stability after EPP had multiple sources of bleeding or fatal head injury and eventually succumbed. Patients who underwent EPP in the ED showed higher change in MAP (P = 0.0458). The overall mortality rate was 27.5% (8/29) with no difference between the OR and ED-EPP. No differences were found between ED and OR-EPP in the amount of transfused blood products, surgical site infections, and length of stay in the hospital. However, patients who underwent ED-EPP were more prone to develop deep vein thrombosis (DVT): 50% (5/10) vs. 9% (1/11) in ED and OR-EPP groups respectively (P = 0.038).

Conclusions: EPP is equally effective when performed in the ED or OR with similar surgical site infection rates but higher incidence of DVT

Background: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease with the presence of autoantibodies, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA). The presence of RF or ACPA predicts RA severity. Data on the influence of ACPA titer on RA course are limited.

Objectives: To determine the correlation between ACPA titers at the time of RA diagnosis to RA features and severity during 3 years of follow-up.

Methods: We performed a retrospective study of RA patients treated at our institution during the years 2006–2015 with known ACPA titers at RA diagnosis who completed at least 3 years of follow-up. Patients (N=133) were divided according to ACPA titer: seronegative (< 15 U/ml, n=55), weakly positive (15–49 U/ml, n=18), moderately positive (50–300 U/ml, n=29), and strongly positive (> 300 U/ml, n=31). Patient data, including disease activity score (DAS28), bone erosion on hand and/or foot X-rays, treatments with corticosteroids and disease-modifying-anti-rheumatic drugs (DMARDs), and hospitalizations, were recorded. Chi-square and Mann-Whitney method were used for statistical analysis. P < 0.05 was considered as statistically significant.

Results: Male gender, smoking, and RF positivity correlated with ACPA positivity and higher ACPA titers. There was no correlation between ACPA titer and the variables defined as representing RA severity: higher DAS28, bone erosions, hospitalizations, need for corticosteroids, and conventional and biological DMARDs.

Conclusions: Titer of ACPA was not identified as a predictive factor for RA severity

Background: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography

Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease.

Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged.

Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls.

Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups.

Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies

Background: Iron deficiency anemia is a widespread problem. Although oral and intravenous therapy are available, iron malabsorption is a distinct possibility.

Objectives: To evaluate the applicability of the oral iron absorption test (OIAT) as a simple and effective means of determining the degree of oral iron absorption.

Methods: The study comprised 81 patients diagnosed with iron deficiency anemia who were referred to a hematology outpatient clinic. Participants were given two ferrous sulphate tablets. Iron levels in the blood were evaluated at intervals from 30 to 180 minutes after iron administration.

Results: We divided patients into three distinct groups. The first group consisted of patients with little iron absorption with a maximum iron increment (Cmax) in the blood of 0–49 ug/dl. The second group had a moderate maximum absorption of 50–100 ug/dl, while a third group had considerable absorption of with maximum iron increase of over 100 ug/dl.

Conclusions: The oral iron absorption test, although not clearly standardized, is easy to conduct in any outpatient clinic. This test can readily and clearly determine absorption or nonabsorption of iron. This test can have major implications on the need of oral or intravenous iron therapy and can also determine the need for further gastrointestinal evaluation of the small intestine, where iron absorption takes place and the success of therapy on subsequent iron absorption

An arginine-rich apolipoprotein was discovered 50 years ago and became known as apolipoprotein E (ApoE) 10 years later. ApoE is associated with triglyceride-rich lipoproteins and mediates the clearance of these lipoproteins from the plasma. The ApoE-deficient hypercholesterolemic mice are an excellent platform for experimental atherosclerosis because they are similar to human pathology with regard to an atherogenic diet. ApoE is mainly produced in the liver and central nervous system cells. Three alleles determine six ApoE phenotypes with different metabolic effects and plasma cholesterol levels. Type III dysbetalipoproteinemia is associated with wide-spread atherogenesis with a defective ApoE2 resulting in delayed clearance of triglyceride-rich lipoproteins. ApoE4 substantially increases the risk including age of onset, progression, and prognosis of Alzheimer’s disease. Therefore, much effort has been directed to the elucidation of the pathogenic role of ApoE related to amyloid β (Aβ) acquisition in the brain. The ApoE trail passing from an enigmatic protein to a major player in cardiovascular and neurodegenerative disorders is reviewed

Background: Radical cystectomy is a complicated surgery with significant risks. Complications of Clavien–Dindo grade 3–4 range from 25% to 40% while risk of mortality is 2%. Pelvic surgery or radiotherapy prior to radical cystectomy increases the challenges of this surgery.

Objectives: To assess whether radical cystectomy performed in patients with prior history of pelvic surgery or radiation was associated with increased frequency of Clavien–Dindo grade 3 or higher complications compared to patients without prior pelvic intervention.

Methods: We retrospectively evaluated all patients who underwent radical cystectomy at our center over a 7-year period. All patients with pelvic radiation or surgery prior to radical cystectomy comprised group 1, while group 2 included the remaining patients.

Results: In our study, 65 patients required radical cystectomy at our institution during the study period. Group 1 was comprised of 17 patients and group 2 included 48 patients. Four patients from group 2 received orthotopic neobladder, while an ileal conduit procedure was performed in the remaining patients. Estimated blood loss and the amount of blood transfusions given was the only variable found to be statistically different between the two groups. One patient from group 1 had four pelvic interventions prior to surgery, and her cystectomy was aborted.

Conclusions: Radical cystectomy may be safely performed in patients with a history of pelvic radiotherapy or surgery, with complication rates similar to those of non-irradiated or operated pelvises.

Background: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction.

Objectives: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS).

Methods: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4.

Results: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54–88). ULD scan radiation exposure was comparable on average to 3.6–4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04–-0.08 vs. 0.08–0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization.

Conclusions: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.

Background: Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time.

Objectives: To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies.

Methods: The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013–2014 to the years 2015–2019.

Results: We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients’ relatives were satisfied with EOL care.

Conclusions: Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.

Background: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies.

Objectives: To describe the design and patient population of the first pediatric aerodigestive center in Israel.

Methods: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children’s Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020.

Results: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3–216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1–5 (5 = highest satisfaction) was 4.5.

Conclusions: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

Background: Oral anticoagulants (OAC) reduce the risk for stroke and death from all causes in patients with non-valvular atrial fibrillation (NVAF)

Objective: To explore adherence rates of OAC among patients with NVAF in long-term use in a real-world setting and to examine patient characteristics associated with good adherence.

Methods: We conducted a population-based cohort study with members of Clalit Health Services, Israel. All patients aged ≥ 30 years with a diagnosis of NVAF before 2016 who were treated with OAC were included. We included patients who filled at least one prescription per year in the three consecutive years 2016–2018. We analyzed all prescriptions that were filled for the medications from 1 January 2017 to 31 December 2017. We considered purchasing of at least nine monthly prescriptions during 2017 as good medication adherence.

Results: We identified 26,029 patients with NVAF who were treated with OAC; 10,284 (39.5%) were treated with apixaban, 6321 (24.3%) with warfarin, 6290 (24.1%) with rivaroxaban, and 3134 (12.0%) with dabigatran. Rates of good medication adherence were 88.9% for rivaroxaban, 84.9% for apixaban, 83.6% for dabigatran, and 55.8% for warfarin (P < 0.0001). Advanced age was associated with higher adherence rates (P < 0.001). Socioeconomic status was not associated with medication adherence. Good adherence with OAC was associated with lower low density lipoprotein (LDL) cholesterol and glucose levels.

Conclusions: Adherence rates to OAC in chronic use among patients with chronic NAVF are high. Investing in OAC adherence may have a wider health impact than expected.

Background: Adherence to treatment by adolescents and adults with cystic fibrosis (CF) is often poor.

Objectives: To assess the impact of a focused clinical intervention on adherence in individual patients, including help in problem-solving key barriers to adherence. To implement a patient-centered problem-solving intervention using CF My Way tools. To identify and overcome a selected barrier to adherence.

Methods: Medication possession ratios (MPRs), number of airway clearance sessions, forced expiratory volume (FEV₁), body mass index (BMI), and health-related quality of life (HRQoL) were measured before and after the intervention.

Results: Sixteen patients with CF, aged 23.4 ± 6.7 years, participated. MPR increased for colistimethate sodium and tobramycin inhalations from a median of 21 (range 0–100) to 56 (range 0–100), P = 0.04 and 20 (range 0–100) to 33.3 (range 25–100), P = 0.03, respectively. BMI standard deviation score rose from -0.37 to -0.21, P = 0.05. No significant improvements were found in FEV₁, airway clearance, or HRQoL scores.

Conclusions: The CF My Way problem-solving intervention increased adherence to medical treatments by removing barriers directly related to the needs and goals of young adults with CF