Israel Medical Association Journal

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Background: Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent exacerbations and need to be hospitalized, resulting in an economic and social burden. Although data exist regarding reasons of frequent hospitalizations, there is no data available about the impact on the length of stay (LOS).

Objectives: To characterize the causes of prolonged hospitalizations in COPD patients.

Methods: A retrospective study was conducted of patients who were diagnosed and treated in the pulmonary department for severe COPD exacerbations. All patient demographic data and medical history were collected. Data regarding the disease severity were also collected (including Global Initiative for Obstructive Lung Disease [GOLD] criteria, pulmonologist follow-up, prior hospitalizations, and LOS).

Results: The study comprised 200 patients, average age 69.5 ± 10.8 years, 61% males. Of these patients, 89 (45%) were hospitalized for up to 4 days, 111 (55%) for 5 days or more, and 34 (17%) for more than 7 days. Single patients had longer LOS compared with married patients (48% vs. 34%, P = 0.044). Multivariate analysis showed that the number of prior hospital admissions in the last year was a predictor of LOS (P = 0.038, odds ratio [OR] = 0.807, 95% confidence interval [95%CI] = 0.659–0.988), as well as the use of non-invasive respiratory support by bilevel positive airway pressure (BiPAP) during the hospitalization (P = 0.024, OR = 4.662, 95%CI = 1.229–17.681).

Conclusions: Fewer previous hospitalizations due to COPD exacerbations and the need for non-invasive respiratory support by BiPAP were found as predictors of longer LOS.

Background: Recent data regarding polymicrobial bacteremia (PMB) are lacking.

Objectives: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting.

Methods: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls.

Results: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41–9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06–3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups.

Conclusions: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.

Background: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria.

Objectives: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center.

Methods: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted.

Results: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21–9.43), pulmonary disease (OR 3.99, 95%CI 1.49–10.73), current or past smoking (OR 2.93, 95%CI 1.21–7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16–8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27–10.33) and pulmonary disease (OR 4.37, 95%CI 1.58–12.10) were associated with a greater risk.

Conclusions: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.

Background: With the widespread use of antifungal agents, the frequency of non-albicans Candida (NAC) blood-stream infections (BSI) is increasing.

Objectives: To describe the epidemiology, clinical manifestations, and risk factors for NAC BSI, focusing on prior antifungal and immunosuppressive therapy.

Methods: The authors conducted an observational, retrospective cohort study among adult patients with candidemia at the Rambam Health Care Campus, a tertiary medical center in Israel, between 2009 and 2015. Comparisons between patients with Candidemia albicans and NAC candidemia were performed. Regression analysis, with NAC BSI as the dependent variable and significant risk factors for NAC as independent variables, was performed.

Results: A total of 308 episodes of candidemia were included. C. albicans was isolated in 30.8% of patients (95/308), while NAC spp. were isolated in the rest. Significant independent risk factors for NAC included immunosuppression therapy (odds ratio [OR] 0.38, 95% confidence interval [95%CI] 0.19–0.76) and previous azole use (OR 0.2, 95%CI 0.06–0.710). The interaction between prior azole and immunosuppression therapy in the model was not significant, and after its inclusion in the model only immunosuppression remained significantly associated with NAC. In the subgroup of patients who did not receive prior azoles, immunosuppression therapy, neutropenia, and bone marrow transplantation were significantly associated with NAC.

Conclusions: Independent of previous azole treatment, immunosuppressive therapy was a significant risk factor for NAC in our cohort.

Background: Respiratory syncytial virus (RSV)-related bronchiolitis is a common cause of morbidity in young infants. The recommendations for its passive prevention by palivizumab are currently under intensive debate.

Objectives: To elucidate the optimal prevention strategy by studying the morbidity of RSV disease under the current recommendations for palivizumab prophylaxis in Israel.

Methods: We collected demographic and clinical data of all children hospitalized with microbiologically confirmed RSV bronchiolitis during 2015–2016 at Schneider Children's Medical Center. The seasonality of RSV disease was also studied for the period 2010–2017 in sentinel clinics scattered throughout Israel.

Results: Of the 426 hospitalized children, 106 (25%) had underlying diseases but were not eligible for palivizumab prophylaxis according to the current criteria in Israel. Their course was severe, with a mean hospital stay of 6.7 days and a 12% admission rate to the pediatric intensive care unit (PICU). Palivizumab-eligible children who did not receive the prophylaxis before hospitalization had the most severe course, with 22% admitted to the PICU. More children were diagnosed with RSV disease in October than in March among both hospitalized and ambulatory children; 44% of the palivizumab-eligible hospitalized children were admitted in the last 2 weeks of October, before 1 November which is the recommended date for starting palivizumab administration in Israel.

Conclusions: According to the results of the present study we suggest advancing RSV prophylaxis in Israel from 1 November to mid-October. The precise palivizumab-eligible categories should be reconsidered.

Background: Skin colonization of microorganisms in blood cultures (BCs) are generally considered clinically non-significant and can be the source of a true infection, particularly in immunosuppressed patients.

Objectives: To study the epidemiology and risk factors for bacteremia caused by contaminants.

Methods: This retrospective, descriptive study is based on adult BCs collected (2004–2013) and categorized as positive (True bacteremia [TrueB] or contamination) or negative. Clinical, demographic, and laboratory characteristics of BCs positive for the six most common potential contaminant pathogens (PCPs) that can cause TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp., Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196 contaminations (1:2 ratio).

Results: From 74,014 BCs, PCPs were found in 3735 samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The overall rate of BC contamination decreased during the study period from 6.7% to 3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants. Clostridium spp. and Streptococcus viridans were more often TrueB. In a multivariate model, predictors of TrueB included high creatinine levels, Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS was strongly predictive of contamination.

Conclusions: Ten years of data on BCs, focusing on six PCPs, demonstrates a significant, yet insufficient reduction in the rate of contamination. High creatinine level, isolation of Streptococcus viridans, and multiple positive BCs were predictors of TrueB, while growth of CoNS was strongly predictive of contamination. This model could assist in diagnostic and therapeutic decision making.

Background: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean).

Objectives: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications.

Methods: We analyzed all gastrectomies for gastric cancer performed 2009–2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification.

Results: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05).

Conclusions: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Background: Coronary artery disease (CAD) has known risk factors. Individual risks related to specific ethnicities are complex and depend on genetic predisposition and lifestyle.

Objectives: To compare the nature and prevalence of risk factors in Arab and non-Arab ethnic patients with symptomatic obstructive CAD referred for coronary angiography.

Methods: CAD, defined as coronary angiography with a ≥ 50% narrowing in ≥ 1 vessel, was diagnosed in 1029 patients admitted to a medical center between April 2014 and October 2015. Patients were divided into two groups according to ethnic origin: Arab vs. non-Arab. Demographics, clinical presentation, and coronary risk profiles were compared.

Results: The diagnosis of CAD was made during ST-elevation myocardial infarction (STEMI) in 198 patients (19%) who arrived at the clinic, 620 (60%) with unstable angina/non-STEMI, and 211 (21%) with stable angina. Patients with symptomatic CAD and Arab ethnicity were 47% more prevalent than non-Arab patients presenting with CAD. The Arab patients were appoximately 5 years younger, 50% more likely to be active smokers, 25% more likely to be obese, and more likely to have a family history of CAD. Other coronary risk factors were similar between the two groups.

Conclusions: Smoking and obesity, which are potentially modifiable CAD risk factors, stood out as major risk factors, in addition to genetic disposition, among Arab and non-Arab patients with symptomatic CAD. Screening and educational interventions for smoking cessation, obesity control, and compliance to treatment of co-morbidities should be attempted in order to decrease CAD in the Arab population.

Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.

Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.

Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.

Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).

Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.

Background: Recurrent tuberculosis (TB) is one of the indices used to assess the effectiveness of the Israeli National TB Programs (NTP).

Objectives: To estimate the incidence of recurrent TB in Israel and to identify the associated risk factors.

Methods: We conducted a retrospective cohort study of all TB patients who were Israeli citizens and diagnosed between 1999 and 2011 with a treatment outcome recorded as “success." We compared those who had recurrent TB with those who did not. In addition, a nested case-control study included all those who had recurrent TB with a random sample from this cohort matched by age, gender, and year of TB diagnosis.

Results: Of 3515 TB patients diagnosed between 1999 and 2011, 37 (1.05%) had recurrent TB during the follow-up period, with an incidence rate of 1.55 cases per 1000 person-years (PY). Male gender [hazard ratio (HR) 3.2, 95% confidence interval (95%CI) 1.4–7.4], human immunodeficiency virus (HIV) infection (HR 3.9, 95%CI 1.5–10.4), positive sputum culture [odds ratios (OR) 2.7, 95%CI 1.1–6.9], and low adherence to anti-TB treatment (OR 3.2, 95%CI 1.0–10.3) were found to be risk factors for recurrent TB.

Conclusions: Male gender, HIV infection, positive sputum culture, and low adherence to anti-TB drugs during the initial TB episode were risk factors for developing recurrent TB.