Tel Aviv Sourasky Medical Center Research Articles

GI disorders: Key research at Digestive Disease Week

Digestive Disease Week (DDW) 2014, held May 3–6 in Chicago, focused on new developments in gastroenterology, liver disease, endoscopy, and gastrointestinal surgery. The annual meeting—cosponsored by the American Association for the Study of Liver Diseases (AASLD), American Gastroenterological Association (AGA), American Society for Gastrointestinal Endoscopy (ASGE), and Society for Surgery of the Alimentary Tract (SSAT)—is the largest meeting in the world for gastroenterology professionals. Following are a few key research studies presented during the meeting with a pharmacotherapy focus. Chronic hepatitis C Direct-acting antiviral agents (DAA) for hepatitis C that are associated with cure rates greater than 90% and minimal adverse effects received a signifi cant amount of attention throughout the week. With the FDA approval of simeprevir (Olysio—Janssen Therapeutics) and sofosbuvir (Sovaldi—Gilead Sciences) in late 2013 and additional oral DAA therapies anticipated for approval in 2014, research suggests that nearly all people with chronic hepatitis C can soon be treated successfully. AbbVie 3D. SAPPHIRE II (A Study to Evaluate Chronic Hepatitis C Infection in Treatment Experienced Adults) evaluated AbbVie’s interferon-free triple oral antiviral regimen “3D” containing the hepatitis C virus (HCV) protease inhibitor ABT-450, the NS5A inhibitor ombitasvir, and the nonnucleoside NS5B polymerase inhibitor dasabuvir. The twice-daily 3D combination plus ribavirin for 12 weeks in patients who did not respond to previous therapies

An algorithm for treating extracranial head and neck schwannomas

Surgical resection of extracranial head and neck schwannomas (ECHNS) may be associated with major morbidity, but some ECHNSs can be safely treated expectantly. The aim of this study is to present a large case series and an algorithm for therapeutic decision-making in the management of ECHNS. The clinical records of patients diagnosed and treated for ECHNS between 1999 and 2012 at The Tel Aviv Sourasky Medical Center were reviewed retrospectively. All relevant demographic and medical data were extracted, among them presenting symptoms, surgical approaches, nerve of origin, complications and follow-up. A total of 53 patients with ECHNS were included in this clinical study. There were 29 males and 24 females whose mean age was 49.2 years, and all were treated surgically. The schwannomas originated from the brachial plexus, sympathetic chain, vagus nerve, trigeminal nerve, lip, hypoglossal nerve and larynx. Intracapsular enucleation was performed in 32 (60 %) patients, and the remaining 21 (40 %) patients underwent complete excision of the tumor with the involved nerve segment. Thirty-two patients (60 %) had postoperative neurological deficits. This study provides an algorithm to serve as a guideline in the decision-making process for this patient population. Although there is abundant evidence regarding the efficacy of radiotherapy for acoustic schwannoma, the value of radiotherapy as a treatment alternative for patients with ECNHS, especially those unsuitable for surgery, has not been established and further studies are warranted.

Increased epidermal expression and absence of mutations inCARD14in a series of patients with sporadic pityriasis rubra pilaris

Increased epidermal expression and absence of mutations in<i>CARD14</i>in a series of patients with sporadic pityriasis rubra pilaris

Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation.

Is it important to maintain high-dose intensity chemotherapy in the treatment of adults with osteosarcoma?

Neoadjuvant chemotherapy for osteosarcoma is the standard of care, but there is still confusion regarding the best chemotherapy regimen and the optimal intensity. This retrospective study intends to evaluate whether there is a clear correlation between the chemotherapy dose intensity (DI) and the percentage of tumor necrosis, the risk of tumor recurrence after surgery and patient survival. The medical records of all adult patients with localized osteosarcoma that received treatment between the years of 1998 and 2009 at the Tel Aviv Sourasky Medical Center were analyzed. We used multiple logistic/linear regression models to test the effect of the neoadjuvant chemotherapy relative DI (RDI) on histological response, recurrence and time to recurrence. A Cox regression analysis was conducted for the effects of neoadjuvant chemotherapy RDI, histological response, tumor location, gender and age on patient survival. Thirty medical records were analyzed. Survival, histological response, recurrence and time to recurrence were not affected by the chemotherapy RDI. The 5-year overall survival of the patient's population was found to be 63% with a median survival of 9.4 years. Patients with a good histological response had a longer survival than those with a bad response (mean survival times 11.0 vs. 6.6 years, log-rank test, P = 0.046). High DI is not a prognostic factor in osteosarcoma and maintaining it should not be a prime priority. Histological response is a prognostic but possibly not a reliable predictive factor, and further research is needed in order to find other reliable factors.

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients

The aim of this study was to evaluate progression-free survival, overall survival (OS), response rate (RR), and clinical benefit in recurrent ovarian cancer patients treated with gemcitabine and carboplatin and to compare the outcome among platinum-resistant and platinum-sensitive patients. A retrospective study using the medical records of patients diagnosed and treated for recurrent epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma with gemcitabine and carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical Center. The treatment regimen was carboplatin (area under the curve=5) administered on day 1 and gemcitabine 850 mg/m administered on days 1 and 8 in a 21-day cycle. Seventy patients with a median age of 57 years (range: 38-86) were included in the study. Most patients (94.3%) were initially diagnosed with stage III-IV disease and 44.3% had platinum-sensitive disease. Median progression-free survival in platinum-sensitive patients was 6.3 months [95% confidence interval (CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in the platinum-resistant patients. Platinum-sensitive patients had a RR of 43.2% and platinum-resistant patients had a RR of 39.1%. The clinical benefit was 70.5% in platinum-sensitive patients and 65.2% in platinum-resistant patients. Overall treatment had a favorable safety profile. Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.

Predicting the need for hospital admission of TIA patients

BackgroundIt is unknown which patient will benefit most from hospital admission after transient ischemic attack (TIA). Our aim was to define predictors of a positive hospital outcome. MethodsWe used two cohorts of TIA patients: the University of Texas at Houston Stroke Center (UTH); and Tel-Aviv Sourasky Medical Center in Israel (TASMC) for external validation. We retrospectively reviewed medical records and imaging data.We defined positive yield (PY) of the hospital admission as identification of stroke etiologies that profoundly changes clinical management. ResultsThe UTH cohort included 178 patients. 24.7% had PY. In the multivariate analysis, the following were associated with PY: coronary disease (CAD); age; and acute infarct on DWI. We then derived a composite score termed the PY score to predict PY. One point is scored for: age>60, CAD, and acute infarct on DWI. The proportion of PY by PY score was as follows: 0–6%; 1–22%; 2–47%; 3–67% (p<0.001). In the validation cohort PY score was highly predictive of PY and performed in a very similar manner. ConclusionsOur data suggest, the PY score may enable physicians to make better admission decisions and result in better, safer and more economical care for TIA patients.

Determinants of adherence to screening by colonoscopy in individuals with a family history of colorectal cancer

ObjectiveAlthough first-degree relatives (FDRs) of colorectal cancer (CRC) patients, as a high-risk population, have the most to gain from colonoscopy screening, their adherence is suboptimal. Thus, an assessment of the determinants of adherence to screening is of potential importance. MethodsA cross-sectional study was conducted among 318 FDRs of 164 CRC patients treated at Tel-Aviv Sourasky Medical Center. Interviews were conducted with a questionnaire using I-Change Model. ResultsAdherence to interval colonoscopy was low with only 73 FDRs (23.0%). Greater adherence was associated with socio-demographic variables (older age, siblings, having spouse, higher level of education and income) and behavioral variables (healthier lifestyle, utilization of preventive health services).Family physicians and kin were identified as the most influential figures on uptake. Intention, affective barriers, positive attitudes, social support, cues to action, age, and health maintenance were the strongest determinants of participation in CRC screening. ConclusionAdherence to colonoscopy is determined by multiple variables. Medical staff can play a key role in increasing adherence to colonoscopy. Practice implicationsFuture interventions should focus on fostering positive attitudes, overcoming barriers, enhancing social support and providing a medical recommendation. Special efforts should be invested in young FDRs, those of low socio-economic status and those who underutilize preventive medicine.

Prolonged Febrile Seizures and their Management

Investigators at Tel-Aviv Sourasky Medical Center, and three other medical centers in Israel, obtained data, prospectively, on all children presenting in the emergency departments from January 2008 to March 2010 with prolonged febrile seizures.

Pancreaticoduodenectomy in Elderly Adults: Is It Justified in Terms of Mortality, Long‐Term Morbidity, and Quality of Life?

To evaluate long-term morbidity, mortality, and quality of life (QoL) after pancreaticoduodenectomy (PD) in elderly adults. Retrospective cohort study. Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. One hundred and sixty-eight individuals aged 70 and older who underwent PD between 1995 and 2010. A prospective pancreatic surgery database was analyzed for postoperative morbidity; mortality; intensive care unit (ICU), hospital, and rehabilitation facility stay; and readmissions after surgery. QoL was assessed using a validated questionnaire completed 3, 6, and 12 months after surgery. Seventy-two percent of the participants had an American Society of Anesthesiologists score of 3 or greater. There was no intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9% and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was 22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation facility. The first-year readmission rate was 31%. One- and 2-year overall survival rates were 58% and 36%, respectively. Global QoL scores 3 and 12 months after surgery were 68% and 73%, respectively. Scores were lower yet comparable with those of matched individuals undergoing laparoscopic cholecystectomy. Most elderly adults with pancreatic cancer survive longer than 1 year after PD; 36% survive longer than 2 years. These individuals are likely to have acceptable long-term morbidity and overall good QoL, corresponding with their age.

Do individuals with a family history of colorectal cancer adhere to medical recommendations for the prevention of colorectal cancer?

Individuals with a family history of colorectal cancer (CRC), have a two-to-five-fold increased lifetime risk to develop CRC. Thus, they are particularly likely to benefit from adherence to medical recommendations for CRC prevention. Despite this increased risk, previous studies have shown an underutilization of colonoscopy for screening and a paucity of data on lifestyle habits that could enhance colonoscopy rates in this population. The primary aims were (a) to assess CRC screening patterns and lifestyle choices among siblings and children of CRC patients, (b) to ascertain discrepancies between actual behavior and medical recommendations, and (c) to identify family members with multiple unhealthy lifestyle habits. The secondary aim was to test for possible associations between utilization rates for CRC screening and other preventive health services. A cross-sectional study was conducted among 318 first-degree relatives (FDRs) of 164 CRC patients treated at the Tel Aviv Sourasky Medical Center. Interviews were conducted with a structured questionnaire. There was significant underutilization of colonoscopy for screening with only 73 FDRs (23.0%) adhering to the recommended screening schedule. This rate was slightly improved (N = 58, 31.9%) among subjects aged 40 years and above, although it was still far below the optimum. A similar result (N = 70, 21.7%) was observed for other cancer screening tests and routine medical check-ups. A significant association (P < 0.0001) was found for healthful lifestyles, overall use of preventive health services, and adherence to CRC screening recommendations. CRC screening is significantly underutilized among FDRs of CRC patients. FDRs who do not comply with CRC screening guidelines, lead unhealthy lifestyles, and avoid other cancer screening tests are at increased risk and should be addressed specifically in future interventions.

Elective central compartment neck dissection in patients with papillary thyroid carcinoma recurrence

To investigate the role of elective central compartment neck dissection (CND) in patients with recurrent papillary thyroid carcinoma in the jugular chain lymph nodes. Retrospective medical record review and analysis of survival outcomes. The study was conducted at Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University. Fifty-one patients who had prior thyroidectomy underwent therapeutic lateral neck dissection (LND) without radiological evidence of central neck metastases. Therapeutic LND without elective CND was performed in 17 patients, and 34 patients had elective CND. The clinical variables were similar in both groups. The median follow-up was 44 months. Disease-free survival and overall survival were the main outcome measures. The recurrence rate in the central neck was 9% (n = 3/34) in patients undergoing CND and 12% (n = 2/17) in patients without CND. The overall recurrence rate was 18% (6/34) in patients with CND and 36% (6/17) in patients without CND (P = 0.16). The 5-year disease-free survival rate was 82% and 65% in patients with or without CND, respectively (P = 0.69). Long-term thyroglobulin levels and complication rates were similar in both groups. The lack of significant disease-free survival advantage demonstrates the need for a prospective evaluation of the common practice of this disease.

Early and Late Presentations of Graft Arterial Pseudoaneurysm Following Pancreatic Transplantation

Graft pseudoaneurysm (PSA) following pancreatic transplantation (PT) is a rarely reported complication that has significant morbidity and mortality. Few case reports and small series of this complication exist. Retrospective review of files of 106 patients who underwent PT at the Tel-Aviv Sourasky Medical center between 1995 and 2010. Accessible asymptomatic patients (n = 35) were referred for graft PSA screening using ultrasound-Doppler. Eight patients developed graft PSA (8 %). All had early posttransplant sepsis. PSA incidence among patients who had perioperative sepsis is 13 %. Three patients developed early postoperative PSA, presenting as massive abdominal bleeding requiring urgent laparotomy and graft resection. Five patients were diagnosed with late-onset graft PSA between 3 months and 11 years posttransplant: clinical presentations were massive gastrointestinal bleeding (n = 2), acute renal failure (n = 1), and asymptomatic finding on screening ultrasound-Doppler (n = 2, 6 % of screened patients). PSA following PT occurs in 8 % of patients. Perioperative infection is a risk factor. Early PSAs present as massive intra-abdominal bleeding. PSA may develop years posttransplant, may be asymptomatic, but late rupture is possible and presents as gastrointestinal bleeding. We recommend screening of patients at risk with ultrasound Doppler for early detection and treatment of asymptomatic PSAs.

A binational cohort study of intestinal colonization with extended-spectrum β-lactamase-producing Proteus mirabilis in patients admitted to rehabilitation centres

The aims of our study were to analyse the risk factors for colonization by Extended-spectrum β-lactamases (ESBL)-produclng Proteus mirabilis (ESBL-PM) in rehabilitation patients and to characterize the molecular features of these strains. The study was conducted in two rehabilitation centres located in Rome, Italy (Fondazione Santa Lucia IRCCS (FSL)), and Tel-Aviv, Israel (Tel-Aviv Sourasky Medical Center (TASMC)). Carriage of ESBL-PM was surveyed by rectal swabs. Strain typing was performed by pulsed-field gel electrophoresis (PFGE). Identification of ESBL genes was done by PCR and sequencing. Patients admitted to the same institutions without ESBL carriage were included as controls. The study group included 70 and 41 patients from FSL and TASMC, respectively. In FSL, the multivariate analysis identified severe acute brain injury (OR = 15, 95% CI = 3.2–69.5, p 0.001), decubitus ulcer (OR = 3.5, 95% CI = 1.2–9.8, p 0.018) and recent treatment with quinolones (OR = 5.7, 95% CI = 1.07–30.1, p 0.042) as independent risk factors. ESBL-PM carriers stayed longer in the hospital on average and were less likely to be discharged home. No significant risk factor was identified in TASMC. There were no similarities in PFGE types or ESBL genes between the ESBL-PM isolates from the two institutions. In both hospitals, a variety of PFGE types existed but a single ESBL type predominated, namely TEM-92 in FSL (n = 64/70; 91%) and CTX-M-2 in TASMC (n = 37/41; 90%). A new TEM ESBL variant, TEM-177 was identified in FSL. The clonal diversity and the predominance of a single ESBL type suggested that horizontal gene transfer played an important role in dissemination of resistance. The development of a population analysis tool that would allow tracing deeper genetic relationships is required.

Poor correlation between intracranial pressure and intraocular pressure by hand-held tonometry

PurposeThe aim of this study is to provide data on the controversial issue of whether handheld measurements of intraocular pressure (IOP) are capable of accurately predicting elevated intracranial pressure (ICP) in patients undergoing lumbar puncture (LP).MethodsAll patients over the age of 18 years who underwent an LP in the emergency or neurological departments at the Tel Aviv Medical Center for any reason between October 2007 and July 2010 were eligible to participate in this prospective observational pilot study. IOP was measured with the Tono-Pen XL while patients were in the supine position before undergoing LP. ICP was measured in the lateral recumbent position. ICP and bilateral IOP were measured, and the mean and maximum values of IOP were calculated. The association between ICP and each one of the four IOP measures was evaluated by the Pearson correlation coefficient.ResultsTwenty-four patients (mean age 37.8 ± 15.8 years, ten males and 14 females) were enrolled. The reasons for their requiring an LP were headache (19/24 patients), evaluation for hemiparesis (2/24), cognitive deterioration (1/24), and seizures (2/24). Nine had elevated mean opening pressure (>20 cm H2O), six had an elevated mean IOP (>20 mmHg), and four of these six also had an elevated opening pressure. There was no significant correlation between the ICP measurements and any of the IOP measurements.ConclusionHandheld ocular tonometry has poor sensitivity and specificity for the prediction of increased ICP and is not an effective tool for screening for ICP in the ED or in the neurology department.

Diet of patients after pouch surgery may affect pouch inflammation

To investigate the diet of pouch patients compared to healthy controls, and to correlate pouch patients' diet with disease behavior. Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center. Pouch behavior was determined based on clinical, endoscopic and histological criteria. Healthy age- and sex-matched volunteers were selected from the "MABAT" Israeli Nutrition and Public Health Governmental Study and served as the control group. All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid. Data on Dietary behavior, food avoidance, the use of nutritional supplements, physical activity, smoking habits, and body-mass index (BMI) were also obtained. Pouch patients who had familial adenomatous polyposis (n = 3), irritable pouch syndrome (n = 4), or patients whose pouch surgery took place less than one year previously (n = 5) were excluded from analysis. The pouch patients (n = 80) consumed significantly more from the bakery products food group (1.2 ± 1.4 servings/d vs 0.6 ± 1.1 servings/d, P < 0.05) and as twice as many servings from the oils and fats (4.8 ± 3.4 servings/d vs 2.4 ± 2 servings/d, P < 0.05), and the nuts and seeds food group (0.3 ± 0.6 servings/d vs 0.1 ± 0.4 servings/d, P < 0.05) compared to the controls (n = 80). The pouch patients consumed significantly more total fat (97.6 ± 40.5 g/d vs 84.4 ± 39 g/d, P < 0.05) and fat components [monounsaturated fatty acids (38.4 ± 16.4 g/d vs 30 ± 14 g/d, P < 0.001), and saturated fatty acids (30 ± 15.5 g/d vs 28 ± 14.1 g/d, P < 0.00)] than the controls. In contrast, the pouch patients consumed significantly fewer carbohydrates (305.5 ± 141.4 g/d vs 369 ± 215.2 g/d, P = 0.03), sugars (124 ± 76.2 g/d vs 157.5 ± 90.4 g/d, P = 0.01), theobromine (77.8 ± 100 mg/d vs 236.6 ± 244.5 mg/d, P < 0.00), retinol (474.4 ± 337.1 μg/d vs 832.4 ± 609.6 μg/d, P < 0.001) and dietary fibers (26.2 ± 15.4 g/d vs 30.7 ± 14 g/d, P = 0.05) than the controls. Comparisons of the food consumption of the patients without (n = 23) and with pouchitis (n = 45) showed that the former consumed twice as many fruit servings as the latter (3.6 ± 4.1 servings/d vs 1.8 ± 1.7 servings/d, respectively, P < 0.05). In addition, the pouchitis patients consumed significantly fewer liposoluble antioxidants, such as cryptoxanthin (399 ± 485 μg/d vs 890.1 ± 1296.8 μg/d, P < 0.05) and lycopene (6533.1 ± 6065.7 μg/d vs 10725.7 ± 10065.9 μg/d, P < 0.05), and less vitamin A (893.3 ± 516 μg/d vs 1237.5 ± 728 μg/d, P < 0.05) and vitamin C (153.3 ± 130 mg/d vs 285.3 ± 326.3 mg/d, P < 0.05) than the patients without pouchitis. The mean BMI of the pouchitis patients was significantly lower than the BMI of the patients with a normal pouch: 22.6 ± 3.2 vs 27 ± 4.9 (P < 0.001). Decreased consumption of antioxidants by patients with pouchitis may expose them to the effects of inflammatory and oxidative stress and contribute to the development of pouchitis.

Bevacizumab plus chemotherapy as salvage treatment in chemorefractory patients with metastatic colorectal cancer

PurposeThe combination of chemotherapy and bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, is consistently being used as first- and second-line treatment in patients with metastatic colorectal cancer (mCRC). There is little data of the activity of bevacizumab in chemorefractory mCRC patients. The aim of this retrospective single center study was to evaluate the activity of bevacizumab combined with chemotherapy in this study population.MethodsForty-six consecutive mCRC patients treated in the University Hospital Gasthuisberg (Leuven, Belgium) receiving bevacizumab in advanced lines following failure of conventional chemotherapy were included in this study. Treatment regimen consisted of bevacizumab 5 mg/kg in combination with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI).ResultsBevacizumab plus chemotherapy was used in third-line treatment in eight (17%) patients and in fourth-line treatment or more in 38 patients (83%). All patients previously failed irinotecan-based chemotherapy, 44 (96%) failed oxaliplatin-based regimens, and 40 (87%) failed treatment with cetuximab. Bevacizumab was given in combination with irinotecan-based chemotherapy in 36 patients, oxaliplatin-based chemotherapy in nine patients, and with single agent 5-fluorouracil in one patient. Objective response was demonstrated in ten patients (22%) and disease control in 38 (83%) with a median progression-free survival of 8.9 months and a median overall survival of 13.8 months. Only four patients experienced grade III and above bevacizumab-related toxicity.ConclusionTaking into account the retrospective nature of the study which can influence the selection of patients, bevacizumab given in advanced lines after failure of conventional chemotherapy and antiepidermal growth factor receptor agents can result in high disease control rates in patients with mCRC.

Editorial Comment to Impact of pre‐implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy

International Journal of UrologyVolume 19, Issue 12 p. 1090-1090 Editorial Comment Editorial Comment to Impact of pre-implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy Nicola J Mabjeesh M.D., Ph.D., Nicola J Mabjeesh M.D., Ph.D. Department of Urology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel [email protected]Search for more papers by this author Nicola J Mabjeesh M.D., Ph.D., Nicola J Mabjeesh M.D., Ph.D. Department of Urology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel [email protected]Search for more papers by this author First published: 26 November 2012 https://doi.org/10.1111/iju.12018Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume19, Issue12December 2012Pages 1090-1090 RelatedInformation

Detection of the plasmid-mediated KPC-2 carbapenem-hydrolysing enzyme in three unusual species of the Enterobacteriaceae family in Israel

Sir, Carbapenem-resistant Enterobacteriaceae (CRE) pose a major threat to public health worldwide. One of the most frequently encountered mechanisms is the Ambler class A Klebsiella pneumoniae carbapenemase (KPC)-type enzyme. Since the initial report of a KPC-producing K. pneumoniae in 2001, these organisms have spread worldwide, mainly due to the spread of a single successful clone, sequence type 258 (ST258). In addition, KPC enzymes have been detected in multiple genera and species of the Enterobacteriaceae family, including Salmonella spp., Klebsiella oxytoca, Enterobacter spp., Citrobacter freundii, Escherichia coli, Proteus mirabilis and Serratia marcescens. The blaKPC gene is typically located on the Tn4401 transposon, which may be carried on various plasmids. Transfer of mobile genetic elements may serve as a vector for inter-species transmission and thus poses a serious challenge for infection control measures. In this report, we describe three unusual Enterobacteriaceae species carrying the blaKPC-2 gene: Leclercia adecarboxylata, Kluyvera cryocrescens and Kluyvera ascorbata. The molecular and microbiological characteristics of these isolates are discussed. All strains in this research were isolated from rectal surveillance cultures of patients from three medical centres: Laniado Medical Center (LMC), Tel Aviv Sourasky Medical Center (TASMC) and Rambam Medical Center (RMC). Table 1 summarizes the molecular and microbiological characteristics of the isolates. Bacterial identification was performed with the VITEK-2 system using GN-ID and GN09 cards (bioMerieux, Marcy l’Etoile, France) and confirmed by 16S rDNA sequencing. We identified the isolates as K. cryocrescens (two isolates), K. ascorbata (one isolate) and L. adecarboxylata (one isolate). All isolates carried the blaKPC-2 gene. 5 Plasmid DNAs purified from the four isolates were transformed into E. coli DH10B. Transformants were selected on lysogeny broth (LB) agar supplemented with 100 mg/L ampicillin and confirmed by PCR. Susceptibility to ertapenem, imipenem and meropenem was tested by agar dilution and interpreted based on the 2012 CLSI criteria. All isolates were resistant to ertapenem, imipenem and meropenem. In the transformants, the MICs of ertapenem, imipenem and meropenem were 2–8, 4–8 and 2–4 mg/L, respectively. Determination of plasmid sizes was done as previously described, revealing various sizes of the blaKPC-2-harbouring plasmids. The plasmid incompatibility group (Inc) was identified as IncN. The blaKPC-2 gene was located on the Tn4401 transposon and was typed by sequencing as Tn4401c. The presence of the Tn4401c variant in these isolates is in contrast with isolates belonging to the Israeli epidemic clone, K. pneumoniae ST258, which harbours the Tn4401a variant on the pKpQIL plasmid, which belongs to the IncFII incompatibility group. It was shown previously that isolates harbouring Tn4401c had a 10-fold reduction in their blaKPC expression. This also correlated with lower MICs of carbapenems. The identical plasmid incompatibility group and Tn4401 type in all isolates suggests horizontal inter-species transmission of the Tn4401c element between different plasmids of the same type, as recently described by Mathers et al. Kluyvera spp. and L. adecarboxylata are present ubiquitously in the environment in water and soil and were also described as part of the normal gastrointestinal flora in humans. Human infections with these bacteria are rare. Several cases of L. adecarboxylata infections in humans have been reported, especially in immunocompromised patients. In such patients, L. adecarboxylata was reported to cause bacteraemia, sepsis, peritonitis, cellulitis, endocarditis and cholecystitis. Reported human infections caused by Kluyvera spp. include bacteraemia, soft tissue infections, intra-abdominal abscesses and urinary tract infections. Recently, Ribeiro et al. reported on the first isolate of a carbapenem-resistant Kluyvera georgiana possessing the blaKPC-2 gene. Although clinical infections were absent in all of these cases, the spread of blaKPC-carrying plasmids into unusual Enterobacteriaceae species is of concern from an infection control perspective. These bacteria, though commonly regarded as avirulent, could serve as a reservoir for the spread of resistance genes between different species, leading to dissemination of resistant bacteria between patients and in the environment.