Israel Medical Association Journal

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy).

Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery.

Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan–Meier method.

Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50–62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52–87%), LC was 84% (95%CI 65–93), and DFS 35% (95%CI 14–59). Grade 4–5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01).

Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Background: Medication reconciliation (MR) at hospital admission, transfer, and discharge has been designated as a required hospital practice to reduce adverse drug events.

Objectives: To perform MR among elderly patients admitted to the hospital and to determine factors that influence differences between the various lists of prescribed drugs as well as their actual consumption.

Methods: We studied patients aged 65 years and older who had been admitted to the hospital and were taking at least one prescription drug.

Results: The medication evaluation and recording was performed within 24 hours of admission (94%). The mean number of medications was 7.8 per patients, 86% consumed 5 or more medications. Mismatching between medication prescribed by a primary care physician (PCP) and by real medication use (RMU) was found in 82% of patients. In PCP the most common mismatched medications were cardiovascular drugs (39%) followed by those affecting the alimentary tract, metabolism (24%), and the nervous (12%) system. In RMU, the most commonly mismatched medications were those affecting the alimentary tract and metabolism (36%). Among all causes of mismatched medications, discrepancies in one drug were found in 67%, in two drugs in 21%, and in three drugs in 13%. The mismatching was more common in females (85%) than in males (46%, P = 0.042).

Conclusions: This study provided evidence in a small sample of patients on differences of drug prescription and their use on admission and on discharge from hospital. MR processes have a high potential to identify clinically important discrepancies for all patients.

Background: Little is known about the incidence of urinary tract infections (UTI) in the dispersed Bedouin population. UTIs are routinely treated empirically according to local resistance patterns, which is important when evaluating the risk factors and antibiotic resistance patterns in the Bedouin population.

Objectives: To analyze risk factors, pathogens, and antibiotic resistance patterns of UTIs in the Bedouin population compared to the general population in southern Israel. To compare data from this study to that from a previous study conducted at our center.

Methods: We prospectively followed all patients hospitalized with community acquired UTIs during a 4 month period at Soroka Medical Center. We also compared results from this study to those from a study conducted in 2000.

Results: The study comprised 223 patients: 44 Bedouin (19.7%), 179 (80.3) non-Bedouin; 158 female (70.9%), 65 male (29.1). The Bedouin were younger (51.7 vs. 71.1 years of age, P < 0.001) and had a lower Charlson Comorbidity Index (2.25 vs. 4.87, P < 0.001). Enterobacteriaceae were the most common pathogens identified, and Escherichia coli (E. coli) was the most common with 156 (70%) strains identified, followed by Klebsiella spp. with 29 (13%), Proteus spp. with 18 (8%), pseudomonas with 9 (4%), and other bacteria including enterococci with 11 (5%). The prevalence of E. coli increased significantly from 56% in 2000 to 70% in this study. We also noted an increase in community acquired extended spectrum beta lactamase (ESBL) pathogens from 4.5% in 2000 to 25.5% in the present study. No statistically significant difference was observed between the Bedouin and general populations in the causal pathogens, resistance to antibiotics, length of therapy, and readmission rate within 60 days. 

Conclusions: The Bedouin population hospitalized for UTIs is younger and presents with fewer co-morbidities. Isolated pathogens were similar to those found in the general population as was the presence of drug resistant infections. Overall, a substantial percentage of pathogens were resistant to standard first-line antibiotics, driving the need to change from empiric therapy to aminoglycoside therapy. 

 

Background: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. 

Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. 

Methods: In March 2013 the authors launched a seven-component intervention program: 

1. Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory


2. Education program for the emergency department staff


3. Dissemination of information regarding the urgency of the PPCI decision


4. Activation of the catheterization team by a single phone call


5. Reimbursement for transportation costs to on-call staff who use their own cars


6. Improvement in the quality of medical records


7. Investigation of failed cases and feedback 

Results: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. 

Conclusions: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival. 

 

Background: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population.

Objectives: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population.

Methods: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. 

Results: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. 

Conclusions: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. However, a subgroup of patients experiences extraglandular manifestations which worsens disease prognosis. To date evidence based guidelines for the management of pSS are lacking, hence the therapeutic approach is mainly based on expert opinion and data from other connective tissue diseases. In recent years, several studies have explored the efficacy and safety of biologic agents in pSS and after the failure of tumor necrosis factor inhibitors, the attention has been focused on compounds directly targeting B or T lymphocytes. The aim of this review article is to provide an overview of available data about B and T cell targeting in pSS and of future directions based on ongoing trials. 

Background: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. 

Objective: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). 

Methods: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. 

Results: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. 

Conclusions: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i. 

 

Background: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. 

Objectives: To analyze the interplay between TD and PF in a cohort of SSc women. 

Methods: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. 

Results: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). 

Conclusions: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

 

Background: Pulmonary arterial hypertension (PAH) is a significant consequence of congenital heart disease (CHD). Its presence and severity is associated with increased morbidity and mortality. 

Objectives: To evaluate the clinical and demographic characteristics of adults with congenital heart diseases (ADCHD) and PAH at a single center. 

Methods: A prospective registry of all patients with PAH was conducted between 2009 and 2015. 

Results: Thirty-two patients were identified. The mean age at the last visit was 44 years (range 19–77 years). The prevalence of PAH among all ADCHD patients was 6% (95% confidence interval 4.3%–8.4%). A much higher prevalence (53%) was found in patients with Down syndrome. Most patients with PAH had moderate or severe disease. Fifteen patients (47%) were treated with pulmonary vasodilators and 6 (19%) with combination therapy. The average World Health Organization functional class was 2.6. Morbidity included cerebral vascular accident or transient ischemic attack in 22% (mostly in patients with right-to-left shunt) and arrhythmia in 37% of the patients. During a median follow-up of 3.5 years, 5 patients (15.6%) died. Of 13 women with no mental retardation, 11 were or had been married and all had children (between 1 and 13, mean 3.3). 

Conclusions: Patients with congenital heart disease and PAH have significant morbidity and mortality. PAH is more prevalent in patients with Down syndrome. While pulmonary pressure during the reproductive years was not always known, 27% of women with PAH at the time of the study were multiparous.

 

Background: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. 

Objectives: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis.

Methods: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis.

Results: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. 

Conclusions: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation. 

 

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells.