Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance

Phosphorylation of the muscle-specific formin splice variant FHOD3 by CK2 regulates its stability, myofibril targeting, and myofibril integrity

Colonization of Extended-Spectrum- β -Lactamase-and NDM-1-Producing Enterobacteriaceae among Pregnant Women in the Community in a Low-Income Country: a Potential Reservoir for Transmission of Multiresistant Enterobacteriaceae to Neonates

International audienceThe spread of extended-spectrum-␤-lactamase-producing Enterobacteriaceae (ESBL-PE) in low-income countries, where the burden of neonatal sepsis is high, may have a serious impact on neonatal mortality rates. Given the potential for mother-to-child transmission of multiresistant bacteria, this study investigated the ESBL-PE rectal colonization among pregnant women at delivery in the community in Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to 22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo-␤-lactamase-1 (NDM-1) producer. S evere bacterial infections are responsible for a large number of neonatal deaths in low-income countries (LICs) (1, 2), with Enterobacteriaceae most frequently isolated in neonatal sepsis (3, 4). The production of plasmid-borne extended-spectrum ␤-lacta-mases (ESBL) is the main mechanism of resistance against expanded spectrum cephalosporins (ESC) among Enterobacteria-ceae, with the CTX-M-15 variant being the most common enzyme (5). In LICs, where neonatal sepsis caused by ESBL-producing Enterobacteriaceae (ESBL-PE) may be associated with higher fatality rates (6), colonized mothers could represent a source of transmission to neonates. The objectives of this study were to estimate the prevalence of ESBL-PE rectal colonization among pregnant women in Madagascar in an urban area, Antananarivo, and a semirural area, Moramanga, and to identify associated risk factors. This study was conducted in the context of an international pediatric cohort, the BIRDY (bacterial infections and antibiotic resistance disease among young children in low-income countries) program, approved by the Ethics Committees of Ministry of Health, Madagascar, and Institut Pasteur, France. All pregnant women living in the study areas were identified by medical or community workers and enrolled after giving written informed consent. A stool sample was taken at delivery for ESBL-PE screening. Among the women enrolled, 356 gave birth between June 2013 and March 2014 and were included in the present study. A risk factor analysis was conducted on a subset of 231 women who delivered during a 6-month period (. Sociodemographic characteristics, previous health care exposure, and antibiotic consumption (collected with prescription documents, remaining tablets, or visual aid) were recorded. Fresh stools were plated onto Drigalski agar supplemented with 3 mg/liter of ceftriaxone at the clinical laboratory of Institut Pasteur of Madagascar. Plates were incubated for 24 to 48 h at 37°C. Every oxidase and Gram-negative colony type wa

Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian, fallopian, and peritoneal cancer in day-to-day practice: a Retrospective French Multicentric Study

Objectives: To evaluate the outcome of maximal cytoreductive surgery in patients with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding overall survival (OS) and disease-free survival (DFS). Materials and Methods: Five hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery between January 2003 and December 2007 in 7 gynecologic oncology centers in France. Patients undergoing primary and interval debulking surgery were included, whichever the number of chemotherapy cycles. The extent of disease, type of surgical procedure, and amount of residual disease were recorded. A multivariate analysis of the outcome was performed, taking into account the stage, grade, and timing of surgery. Results: Median DFS was 17.9 months, but median OS was not reached at the time of analysis. Complete cytoreductive surgery, without evident residual tumor at the end of the procedure, was obtained in 71% of all patients (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty-three percent of patients needed 'ultra radical surgery' to achieve this goal. The most significant predictive factor for DFS and OS was complete cytoreductive surgery compared to any amount, even minimal (1Y10mm), of residual disease. In the group of patients with complete cytoreductive surgery, the patients undergoing surgery before chemotherapy showed better DFS than those having first chemotherapy. Conclusion: The findings confirm that complete cytoreduction is the criterion standard of surgery in the management of advanced ovarian, peritoneal, and fallopian tube cancer, whatever the timing of surgery. With experienced teams, surgery was completed, without evident residual tumor in 71% of the cases. © 2012 by IGCS and ESGO

Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial

AbstractAimTo investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma.MethodsMulticentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented.ResultsIn the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached.ConclusionThe primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated