Assaf Harofeh Research Articles

Sex-dependent outcomes of recanalization-treated acute ischemic stroke patients at Shamir (Assaf Harofeh) medical center, Israel, 2011–2020

Background/objectivesSex-based differences in incidence, etiologies, severity and recanalization treatment outcomes of patients with acute ischemic stroke (AIS) have been studied extensively. We set out to determine if there were sex-based differences in outcomes among AIS patients who received recanalization treatments at Shamir (Assaf Harofeh) Medical Center (SMC), Israel, between 2011 and 2020. MethodsThis was a single-center, retrospective chart review. The primary analysis compared outcomes for men and women, overall and stratifying by disease severity. We compared also demographics, risk factors and workflow data. ResultsEight hundred and eleven patients received recanalization treatment between 2011 and 2020: 472 (58.1%) men and 339 (41.8%) women. Mean age, NIHSS score and proportion with an NIHSS score ≥ 6 were higher for women. Cerebrovascular risk factors were more prevalent in women, particularly atrial fibrillation, except that current smoking was more prevalent in men. Six hundred and twenty patients (78.1%) were treated with TPA alone, 89 (11.2%) with TPA and endovascular treatment (EVT), and 85 (10.7%) with EVT alone. Fifty percent of patients were discharged home, 41% to a rehabilitation hospital or nursing home, and 9% did not survive. Twenty-four patients (3%) sustained symptomatic bleeds. Outcomes were worse in patients with NIHSS score ≥ 6. Outcomes did not differ by sex. ConclusionsWhile treated women presented with more severe AIS and more risk factors, we did not find significant sex-related differences in outcomes. Meticulous adherence to risk factor modification remains the best strategy to reduce stroke incidence, morbidity, and mortality in women and in men.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013–2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and “Dana Dwek” Children’s Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4–6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes—allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Sleeve Gastrectomy Is the Most Common Cause of Gastroesophageal Reflux Disease in Comparison with Other Bariatric Operations

Introduction: Gastroesophageal reflux disease (GERD) is one of the complications of bariatric operations that might affect the quality of life. We aim to perform a retrospective cohort study to determine the incidence of symptomatic GERD following different types of bariatric surgery and which operations are considered a contraindication of GERD. Besides, we are attempting to identify the risk factors of GERD after bariatric surgery. Methods: Medical records of 729 patients who had undergone bariatric operations between January 2010 and June 2019 at the Shamir (Assaf Harofeh) Medical Center were reviewed. Results: There was a significant difference between the type of bariatric procedure and the incidence of GERD symptoms after the operation. The incidence of symptomatic GERD in patients who underwent sleeve gastrectomy (SG) was 39.9% (p = 0.0131). This was significantly higher compared to 16.4% following Roux-en-Y gastric bypass, 23.4% following laparoscopic adjustable gastric band, and 11% following one anastomosis gastric bypass. 113 patients out of 718 had a positive swallow test, and of these patients, 71 developed GERD symptoms postoperatively without correlation to the degree of reflux at the swallow test but with statistically significant correlation to the type of operation especially for SG (p value < 0.001), and to our knowledge, this was never reported in the literature. Conclusion: SG is a good bariatric procedure option but should be considered carefully in asymptomatic patients with reflux at contrast swallow study and symptomatic GERD patients preoperatively because of high levels of symptomatic GERD postoperatively. Asymptomatic reflux at contrast swallow study preoperatively could be considered a risk factor for GERD after the operation. More studies are needed to be performed on this subject with the addition of postoperative contrast swallow test and pH monitoring preoperatively and postoperatively.

Is Familial Nonmedullary Thyroid Cancer A More Aggressive Type of Thyroid Cancer?

Familial non-medullary thyroid cancer (FNMTC) is a distinct entity, increasingly diagnosed. By lacking an accurate genetic diagnostic test, its diagnosis is currently clinically based, with an ongoing debate over whether it has a more aggressive clinical behavior than sporadic non-medullary thyroid cancer (SNMTC). We seek to compare in this study, the clinicopathological variables, and the outcome of FNMTC versus SNMTC patients. We retrospectively searched a database of 465 patients that underwent thyroidectomy at Assaf Harofeh Medical Center (91.4% between 1990 and 2019) for demographics, risk factors, medical history, diagnostic workup, primary treatment, follow-up, and disease outcome data. We compared 47 FNMTC versus 321 SNMTC patients, and FNMTC patients with ≥2 (n = 34) versus ≥3 (n = 13) first-relative affected members. There were no significant differences in demographics, histopathology, TNM stage, treatment, and disease outcome between the FNMTC and SNMTC groups. The T2 and T4 tumor stage in the ≥3-member group were 25% and 8.3% compared to 0% and 0% in the two-member group (P = .02 and P = ns, respectively). Also, LN involvement was significantly higher in the ≥3-member group (61.6% vs. 24.2%, respectively; P = .036). FNMTC is not a more aggressive disease than SNMTC, but this may not apply for the ≥3-affected-relatives group. A large multicenter study including only families with three or more affected relatives is needed. Until then, a family history of NMTC should not be overlooked. 3/5 Laryngoscope, 131:E677-E681, 2021.

The Clinical and Molecular Epidemiology of Noncarbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae: A Case-Case-Control Matched Analysis.

BackgroundRisk factors and outcomes associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisitions are derived primarily from cohorts consisting of carbapenemase-producing (CP) strains. Worldwide epidemiology of non-CP-CRE is evolving, but controlled epidemiological analyses are lacking.MethodsA matched case-case-control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, on November 2014–December 2016. Noncarbapenemase-producing CRE (as defined by the US Clinical and Laboratory Standards Institute Standards) carriers were matched to patients with non-CRE Enterobacterales and to uninfected controls (1:1:1 ratio). Matched and nonmatched multivariable regression models were constructed to analyze predictors for acquisition and the independent impact of carriage on multiple outcomes, respectively. Representative isolates were whole genome sequenced and analyzed for resistome and phylogeny.ResultsNoncarbapenemase-producing CRE carriers (n = 109) were matched to the 2 comparative groups (overall n = 327). Recent exposure to antibiotics (but not specifically to carbapenems), prior intensive care unit admission, and chronic skin ulcers were all independent predictors for non-CP-CRE acquisition. Acquisitions were almost exclusively associated with asymptomatic carriage (n = 104), and despite strong associations per univariable analyses, none were independently associated with worse outcomes. Genomic analyses of 13 representative isolates revealed polyclonality, confirmed the absence of carbapenemases, but confirmed the coexistence of multiple other genes contributing to carbapenem-resistance phenotype (multiple beta-lactamases and efflux pumps).ConclusionsNoncarbapenemase-producing CRE acquisitions are primarily associated with asymptomatic carriage, specifically among prone populations with extensive recent exposures to antibiotics. The prevalent mode of acquisition is “emergence of resistance” (not “patient-to-patient transmission”), and therefore the role of stewardship interventions in reducing the spread of these therapeutically challenging pathogens should be further explored.

496. Carbapenem-resistant Enterobacter: A Case-Case–Control Investigation

Background. BackgroundThe World Health Organization has declared carbapenem-resistant Enterobacteriaceae (CRE) as a worldwide public health threat. Analyzing the epidemiology of CRE was derived from cohorts consisting primarily of Klebsiella pneumoniae isolates. The second most frequent CRE is Enterobacter (CREn), but its molecular and clinical epidemiology differ from that of K. pneumoniae, and it has not been analyzed while implementing updated methodological tools and design.MethodsA matched case-case–control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, for calendar years 2007–2017. Each CREn case was matched to a carbapenem-susceptible Enterobacter (CSEn) case and to an uninfected control (1:1:1 ratio). Logistic and Cox regression-matched analyses were conducted in order to study predictors and outcomes of CREn colonization and/or infection, respectively.ResultsThe study included 216 cases (72 in each group). Numerous predictors were significantly associated with CREn as per bivariable analyses, but the only independent significant predictors were: (1) recent (3 months) exposure to fluoroquinolones (aOR=2.94, P = 0.04), (2) intensive care unit stay in current hospitalization prior to culture (aOR=3.56, P = 0.003), and (3) a rapidly fatal McCabe score (aOR=0.471, P = 0.01). Patients with CREn suffered from significant delays in instituting appropriate antimicrobials (P = 0.03), and for those who survived the hospitalization, were more frequently discharged to a long-term care facility after being admitted to the index hospitalization from home (aOR=3.3, P = 0.02).ConclusionThis case-case–control-matched investigation of CREn epidemiology, revealed a unique modifiable predictor, i.e., recent fluoroquinolone exposure, which could represent a target for stewardship intervention. The case-case–control-matched design allowed for the control of numerous confounders previously reported to be associated with CREn but may represent a risk factor for Enterobacter infection in general. As with other CRE, CREn carriers suffer from significant delays in initiation of appropriate antimicrobials and from worse outcomes.Disclosures All authors: No reported disclosures.

Newborn gender as a predictor of neonatal outcome in mixed gender twins born with very low birth weight

BackgroundMost studies have revealed that the incidence of morbidity and mortality of preterm male infants is greater than that of preterm female infants. Recently, conflicting outcomes have been reported regarding mixed-gender twins. The aim of this study was to estimate the association between gender and outcome in newborn twins of different gender.MethodsWe conducted a retrospective review of mixed-gender twins weighing < 1500 g that were born at Shamir Medical Center (Assaf Harofeh) between the years 1995 and 2016 (158 newborns). The incidence of morbidity and mortality until discharge from the hospital were evaluated while looking at gender differences.ResultsNo significant differences were found in neonatal mortality or morbidity between females and males from different-gender twins. Even after considering confounding variables (gestational age, birth weight & birth order) in linear and logistic regression models, no significant differences were found between the genders.ConclusionsOur study suggests that there are no significant differences in neonatal mortality or morbidity among different-gender twins. Our results support the need for further studies.

The Role of an Interventional Program for Improving Pharmacovigilance at a Pediatric Facility.

Background: The reporting rate of adverse drug reactions (ADRs) by healthcare professionals is low. ADR interventional programs may improve the reporting rate by the medical team. Our literature search revealed that only a few interventional studies among the pediatric population have been published. Objective: We aimed to create an interventional program in order to improve the reporting rate of ADRs during the interventional period compared to the control period, detect which drugs frequently lead to ADRs and determine the most serious ADRs. Design: A 3-month prospective intervention study compared with one year prior to the intervention (control period). ADR data was also collected for the year following the study period. Healthcare professionals were encouraged to report ADRs and an ADR reporting system was created for them. Setting: Pediatric Division at Shamir Medical Center (Assaf Harofeh), a tertiary care medical center. Results: The study population included 3,753 admitted patients with 1,323 prescriptions during the study period. During the period before the intervention was started, the ADR reporting rate was null. During the study period, 46 reports were collected: 46% from the general pediatric department, 26% from the pediatric neurology department, and 22% and 6% from the pediatric and neonatal intensive care units, respectively. Antiepileptic medications, IVIG, steroids and antibiotics were frequently reported to induce ADRs. Serious ADRs were also reported in 5 cases. One year of follow up after the intervention revealed a significant decline in the reporting rate. Conclusion: It is important to periodically encourage healthcare professionals to report any ADRs in order to increase knowledge about medication safety and prevent fatal harm.

Surgical Site Infection Risk Factor Analysis in Postbariatric Patients Undergoing Body Contouring Surgery: A Nested Case-Control Study.

Surgical site infections (SSIs) following body-contouring plastic surgery pose a significant burden on patients and caregivers, possibly leading to undesired surgical outcomes. Surgical site infection incidence following body-contouring plastic surgery ranges from 2% to 7%, but is estimated much higher among postbariatric massive weight loss (MWL) patients. The aim of this study was to evaluate SSI rate, risk and protective factors among postbariatric MWL patients following body-contouring plastic surgery. This was a nested case-control study of MWL patients who underwent body-contouring plastic surgery at the Department of Plastic Surgery at Assaf Harofeh Medical Center, between 2007 and 2014. Data were obtained from medical records. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Logistic regression was conducted to assess independent risk factors for SSIs. From a cohort of 172 patients, 86 were included in the study. Surgical site infection rate was 20% (n = 17). Significant SSI risk factors included lifetime maximal weight and lifetime maximal body mass index (P = 0.039 and P = 0.002, respectively), body mass index loss prior to surgery (P = 0.032), estimated blood loss during surgery (P = 0.002), and gynecomastia repair procedure (P = 0.038). Independent SSI-associated factors included thigh lift procedure (odds ratio, 4.66; 95% confidence interval, 1.13-19.28) and preoperative antimicrobial prophylaxis (odds ratio, 0.04; 95% confidence interval, 0.03-0.61). Although not required by current guidelines for body-contouring plastic surgery, preoperative antimicrobial prophylaxis in our study demonstrated a significant protective effect against SSIs. Further research may reveal its true contribution to SSI prevention in body-contouring plastic surgery.

Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes – is recommended weight gain too liberal?

This is a retrospective cohort study of women with GDM treated with glucose-lowering agents that were followed and gave birth between 2005 and 2015 in the Assaf Harofeh medical center, Israel. Classification and regression tree method identified four groups according to adverse outcomes, consisted of 74 women with pre-gestational BMI below 25, 98 women with BMI 25–31, 90 women 31–39 and 18 women above 39. Respectively, median GWG was 12 kg (8–16), 11 kg (8–15), 7.5 kg (3.75–11) and 5 kg (–1.5 to 11.5) (p < .001). The risk for composite adverse outcomes was higher in the groups of BMI 25–31 (73.5%) and 31–39 (83.3%) in comparison to BMI <25 (51.4%) and 39 < (55.6%), p < .001. In women with pre-gestational BMI of <25, GWG of more than the median resulted in odds ratio of 2.75 (1.07–7.08, p = .036) for adverse pregnancy outcomes compared with participants who gained less than the median. Maternal obesity is related to adverse pregnancy outcomes. Women with GDM with normal pre-gestational BMI who gained weight according to IOM recommendations still experienced adverse outcomes.

1150. Cleaning High Touch Surfaces of Patients’ Rooms: Make It Easier, and It Simply Gets Cleaner

BackgroundThe healthcare environment has been established as a reservoir for human pathogens and specifically multidrug-resistant organisms (MDRO). High touch surfaces and fomites in a patient’s room mediate transmission between infected and uninfected patients and personnel. Efforts to reduce hospital-associated infections due to MDROs often focus on room cleaning; however, adherence to and thoroughness of cleaning pose significant challenges.MethodsA crossover trial was implemented in January 2016 (for 15 months) at Assaf Harofeh Medical Center (Israel) in four identical medical units. Single-use wipes (Clinell®; universal wipes and sporicidal wipes for rooms of patients with C. difficile), were compared with common practices which consisted of reusable cloths and bleach (1,000–5,000 ppm). Six-month cleaning and intervention periods were used on units in alternating sequences, separated by washout periods. Cleaning was monitored twice a week (bedrail, bedside table, clinical binder, call button, and lamp switch), by a fluorescent marker system (Clinell®). Comparisons used GEE with clustering for room. Staff were surveyed on intervention feasibility, acceptability, and satisfaction.ResultsComplete cleaning in all five test locations was found in 23% of 400 total assessments and was more common in the intervention group (34% vs. 12%; OR = 3.7; P < 0.001). Cleaning adherence was highest for the bed rail (71%) and lowest for the call button (38%). The use of wipes had the largest effect on adherence for the light switch (59% vs. 26%; OR = 4.2; P < 0.001). Intervention timing was not associated with overall adherence (P = 0.10). 94% of staff reported overall satisfaction of “very good” or “excellent,” and 90% of staff reported that use of the wipes shortened the cleaning process.ConclusionThe use of cleaning wipes resulted in greater adherence to room cleaning and the method was reported to be acceptable to staff. Future aims of this large study (over 10,000 patients were enrolled and data collection not yet completed) are to determine the impact of this intervention on rates of hospital-acquired infections, MDRO acquisitions, and mortality.Disclosures E. T. Martin, Clinell: Grant Investigator, Research grant. D. Marchaim, Clinell: Grant Investigator, Grant recipient.

1204. The MDR Upon Admission Score for Shortening Time to Initiation of Appropriate Antimicrobial Therapy in the Era of Widespread Resistance to Antimicrobials

BackgroundMulti-drug-resistant organisms (MDRO) pose a growing burden, including in non-hospital settings. Delay in initiation of appropriate antimicrobial therapy (DAAT) upon admission to an acute care hospital is common and is associated with worse outcomes. The aim of this study was to develop a prediction score for MDRO infection upon admission, in order to improve patients’ outcomes and avoid misuse of broad-spectrum antimicrobials.MethodsA retrospective case–control analysis was conducted at Assaf Harofeh Medical Center, Israel, comparing adult patients with MDRO infections diagnosed in the first 48 hours of hospitalization to patients presenting with non-MDRO sepsis (i.e., patients with microbiologically confirmed non-MDRO infection, or patients with non-microbiologically confirmed sepsis). MDROs were determined by clinical laboratory testing. Patients were identified over four consecutive months (August–December 2016). A multivariable logistic regression of predictors for MDRO infection upon admission was used to develop the prediction score.ResultsNinety-five of 818 total patients (11.6%) had MDRO infection. The final score included 10 parameters: (1) home therapy (IV therapy, wound care, or specialized nursing care, 16 points), (2) routine (at least weekly) outpatient clinic visits in the past 3 months (15 points), (3) history (2 years) of past MDRO colonization (14 points), (4) any antibiotics in the preceding 3 months (12 points), (5) invasive procedure in the past 6 months (11 points), (6) elderly (≥65 years old, 10 points), (7) hemiplegia or paraplegia (8 points), (8) resident of long-term care facility (7 points), (9) severe sepsis (i.e., severe sepsis, septic shock, or multi-organ failure, 6 points), and (10) acute kidney injury (5 points). A cutoff of ≥24 points had a sensitivity of 90%, a specificity of 73% and an ROC AUC = 0.88 (figure).ConclusionThis study presents the development of a new prediction score for MDRO infection upon admission, based on parameters that could easily be extracted at bedside for patients admitted with sepsis. A future prospective interventional study is needed in order to validate the score, captured at bedside electronically, in terms of improving patients’ outcomes. Disclosures All authors: No reported disclosures.

Towards a Definition for Health Care-Associated Infection.

BackgroundHealth care–associated infection (HcAI) is a term frequently used to describe community-onset infections likely to be caused by multidrug-resistant organisms (MDROs). The most frequently used definition was developed at Duke University Medical Center in 2002 (Duke-2002). Although some professional societies have based management recommendations on Duke-2002 (or modifications thereof), neither Duke-2002 nor other variations have had their performance measured.MethodsA case–control study was conducted at Assaf Harofeh Medical Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable model was used to develop a prediction score for HcAI, measured by the presence of MDRO infection on admission. The performances of this new score and previously developed definitions at predicting MDRO infection on admission were measured.ResultsOf the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled patients with nosocomial infections (n = 189) in terms of epidemiological characteristics, illness acuity, and outcomes more than patients with non-MDRO-BSI on admission (n = 215). The performances of both the newly developed score and the Duke-2002 definition to predict MDRO infection on admission were suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68, respectively).ConclusionsAlthough the term HcAI is frequently used, its definition does not perform well at predicting MDRO infection present on admission to the hospital. A validated score that calculates the risk of MDRO infection on admission is still needed to guide daily practice and improve patient outcomes.

Chronic use of psychotropic medications in breastfeeding women: Is it safe?

BackgroundCurrent knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant.Materials and methodsIn this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11–33) months versus 36 (20–48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics.ResultsAt follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008).ConclusionsChronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.

Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non-Susceptible to Carbapenems but Susceptible to "Old" Cephalosporins and/or to Penicillins.

It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic (“cases”) to those who received an appropriate non-beta-lactam antibiotic (“controls”). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-β-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype.

The yield of targeted genotyping for the recurring mutations in BRCA1/2 in Israel

Hereditary breast cancer is predominantly associated with germline mutations in the BRCA1 or BRCA2 genes. A few recurring mutations in these genes were reported in ethnically diverse Jewish populations. Since 2013, most oncogenetic laboratories in Israel adopted a two-step approach for BRCA1/2 genotyping, where the first step is genotyping for 14 seemingly recurring mutations-first-pass genotyping. The aim of this study was to assess the yield of this targeted BRCA sequencing. Clinical and genotyping data of all individuals who underwent oncogenetic counseling and first-pass BRCA genotyping at the Oncogenetic Service Sheba and Assaf Harofeh Medical Centers from 1 February 2013 to 30 June 2017 were reviewed. All study participants were unrelated to each other. Overall, 5152 oncogenetic tests were reviewed in the present study, of which 4452 had no a priori known familial mutation. The majority of participants (68.6%) were genotyped because of personal history of cancer; 20.6% were tested because of family history of cancer, and details for the remaining 10.7% were missing. Overall, 256/4452 (5.8%) carriers were detected, 141 BRCA1 and 115 BRCA2 mutation carriers. In 54% of cancer-free carriers, no clinically suspicious family history of cancer was ascertained. The currently used scheme of first-pass genotyping in Israel seems to have a high yield of mutation detection even in the absence of a significant family history of cancer. The challenge is to optimize the currently used targeted panel of common mutations and adjust it to the accumulating new data in the Israeli population.

Serum Procalcitonin as a Marker for Infection in Patients with Acute Myocardial Infarction

BackgroundSignificant proportion of patients with acute myocardial infarction (AMI) also present with systemic inflammatory response syndrome (SIRS). Thus it is difficult to determine in certain situations, whether empiric antibiotic treatment is warranted. Serum procalcitonin (PCT) is known to be elevated in bacterial infections, but its performances in predicting bacterial infection among patients with AMI, who might benefit from appropriate empiric management, is unknown.MethodsA prospective observational study was conducted at Assaf Harofeh Medical Center, Israel. Serum PCT was collected within 48 hours from patients presenting with AMI. Demographic, clinical, and laboratory data, were collected prospectively. Two experienced Infectious Diseases (ID) specialists who were blinded to the PCT results, independently determined the gold standard for infection in every patient. By utilizing sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve (AUC), the performance of PCT, fever, white-blood cells (WBC) count and C-reactive protein (CRP) for infection diagnosis was calculated.ResultsThe analysis included 230 AMI patients (age 63.0 ± 13.0 years), of which 36 (15.6%) were determined to be infected. The best cutoff for PCT as a differentiating marker between infected and non-infected patients was achieved at 0.09ng/dl (sensitivity 94.4%, specificity 85.1%, AUC ROC 0.94). This test outperformed CRP, WBC, and fever, for infection diagnosis (figure).ConclusionPCT should be utilized for ruling out infection in AMI patients by utilizing serum PCT>0.09ng/dl (i.e., ≥0.1ng/dl) as a cutoff.Disclosures All authors: No reported disclosures.

Comparative Effectiveness of Vancomycin vs. Metronidazole in Mild Clostridium difficile Infections, and Potential Impact on Subsequent Vancomycin-Resistant Enterococcus (VRE) Isolation

BackgroundThe epidemiology and clinical characteristics of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI, with superior cure rates observed in comparative trials. However, controlled comparative efficacy data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent Vancomycin-Resistant Enterococcus (VRE) isolation rates remains unknown at the individual patient level.MethodsA Retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, Israel, from 2010 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs..metronidazole was evaluated in the subset of patients with mild CDI. The outcomes of patients, who received vancomycin or metronidazole (but not both), were compared by Cox regression. A prediction score was used to control for possible confounders associated with being treated with vancomycin. The independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation was analyzed using Cox regression.ResultsA total of 413 patients with CDI were included in the study. The majority were elderly (median age 75 years, range 19–120), and had extensive comorbidities (mean Charlson’s combined condition score 6.7 ± 3.4) and significant acute illness indices (35% with severe to fulminant Horn index). Among 126 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a “vancomycin case”. Ten patients had new post-CDI VRE isolation. In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=6.7, P = 0.04).ConclusionOur study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.Disclosures All authors: No reported disclosures.

Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy.

To assess the risk of adverse pregnancy outcomes in subsequent pregnancies among women treated with methotrexate for ectopic pregnancy. In a retrospective single-center study, data were assessed for women treated with methotrexate for ectopic pregnancy at Asaf Harofe Medical Center, Zerifin, Israel, between May 2004 and May 2014. Overall, 226 women were treated with methotrexate for ectopic pregnancy and subsequently conceived. The median time from treatment to conception was 10months (range 1-120months), and 127 women conceived within 12months of treatment. Except for early missed abortion-which affected 23 (10.2%) pregnancies-adverse pregnancy outcomes such as fetal malformations were rare. The frequency of early abortion was lowest for women who conceived within 6months of treatment with methotrexate (3/93, 3.2%), increased between 6 and 23months (15/83, 18.1%), and remained high thereafter (7/50, 14.0%; P=0.006). The frequency of fetal malformation in a subsequent pregnancy was low among women treated with methotrexate for ectopic pregnancy. The frequency of early missed abortion was lowest during the first 6months after treatment with methotrexate.

Superior and Lateral Rectus Myopexy for Acquired Adult Distance Esotropia: A “One Size Fits All” Surgery

ABSTRACTAim: To evaluate the results of bilateral lateral rectus to superior rectus myopexy for the treatment of acquired adult distance esotropia.Methods: The charts of all adult patients who were operated for esotropia by the first author at the Department of Ophthalmology, Assaf Harofeh Medical Center, Tel Aviv University, Zrifin, Israel, between the years 2010-2015 were analyzed. Patients with the following inclusion criteria were included: acquired esotropia (not present during childhood); deviation greater for distance than near by at least 4 prism diopters (PD); slight abduction deficit in one or both eyes and/or displacement of the lateral rectus downwards as evident by CT/MRI with or without superior rectus nasal shift and no neurologic abnormalities such as cranial nerve palsies or other.Results: Eighteen patients were identified (age 31–80 years, mean 49.6 years, 77.7% females). Pre-operative esodeviation averaged 24.3 PD (range 14–35 PD) for distance and 15.7 PD (range 8-25 PD) for near. Thirteen patients (72%) had diplopia. All patients were myopic (average -5.54 diopters, range -2.00 to -13.00). All patients underwent bilateral superior rectus–lateral rectus myopexy. Seven patients needed additional single medial rectus recession of between 2–6 mm, and two had additional inferior rectus recession. After a follow-up period of 3–52 months (average 16 months), 16/18 patients (88%) had a deviation less than 5 PD. No overcorrections were noted.Conclusion: Lateral to superior rectus myopexy is a safe and effective treatment for patients with distance esotropia in which displacement of these muscles is identified. Additional single medial rectus and/or inferior rectus recession may be needed in some patients.