Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

Introduction: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).Objective: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.Design: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.Methods: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.Results: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score >= 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.Conclusions: the cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.Pfizer Inc.Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Med, Mexico City, DF, MexicoHosp Escuela Tegucigalpa, Tegucigalpa, HondurasUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilNatl Canc Inst, Div Infect Dis, Mexico City, DF, MexicoUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruHosp Vargas Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Texas Med Sch Houston, Mem Hermann Texas Med Ctr, Dept Med, Houston, TX USAUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilUniv Chile, Fac Med, Hosp Luis Calvo Mackenna, Dept Pediat, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Santiago, ChileHosp Clin Jose San Martin, Infect Dis Unit, Buenos Aires, DF, ArgentinaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilPfizer Inc.: INF-168Web of Scienc

Cinco años de experiencia en la utilización de la técnica del cono extendido

Fundamento: la utilización de mallas en la cirugía herniaria alcanzó su mayor popularidad a partir de los años 80. En el año 2007, en la Clínica Multiperfil de Luanda, Angola, se diseñó una nueva variante de colocación de la malla que cumple con todos los principios de la cirugía herniaria, basada en la oclusión del anillo herniario y el refuerzo de la pared del canal. En el año 2009 se introduce la técnica en el Hospital Enrique Cabrera en La Habana. Objetivo: mostrar los resultados de la aplicación de la técnica del cono extendido en el tratamiento de la hernia inguinal en el Hospital Docente Enrique Cabrera. Métodos: se realizó un estudio de serie de casos en 100 pacientes, en los cuales se operaron 110 hernias mediante una técnica protésica denominada cono extendido, durante los años 2009 al 2013 en el Hospital Enrique Cabrera de La Habana. Se utilizó la clasificación de Gilbert modificada por Rutkow y Robbin. Se analizó: edad, sexo, localización de la hernia, grado de la hernia según la clasificación de Gilbert, complicaciones e índice de recidivas. Resultados: hubo un predominó el sexo masculino. La localización más frecuente fue la región inguinal izquierda. Predominaron las hernias clasificadas como grado III según la clasificación de Gilbert. Hubo 15 complicaciones menores y hasta el momento no han ocurrido recidivas. Conclusiones: la técnica del cono extendido es una técnica segura y otra opción para el tratamiento de pacientes que presenten hernias inguinales del grado III, IV y VI de la clasificación de Gilbert modificada por Rutkow y Robbins

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM&ndash;ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM&ndash;ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.Acknowledgements: We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias´ (Grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (Grant Number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, cofunded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (Grant Numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by ESF (`Investing in your future´) (Grant Number CP16/00033)

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV

p38γ is essential for cell cycle progression and liver tumorigenesis

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Resultados de una encuesta sobre el soporte nutricional perioperatorio en la cirugía pancreática y biliar en España

Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (&lt; 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95 %: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95 %: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95 %: 7,6-13,3; rango, 2-33). Solo el 41,2 % de los grupos utilizaban soporte nutricional antes de la cirugía (< 50 % habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4 % habían intentado administrar una dieta oral precoz, pero el 88,2 % de los grupos usaron algún tipo de soporte nutricional y el 26,5 % usaron NP en el 100 % de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6 % utilizaron NP siempre y NE en el 19,3 % de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4 % de las unidades usan nutrición oral precoz y el 32,3 % emplean la NE tras este tipo de cirugía. El 22,6 % de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

PDGF-BB serum levels are decreased in adult onset Pompe patients

Adult onset Pompe disease is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzymatic replacement therapy with human recombinant alfa glucosidase. Motor functional tests and spirometry are commonly used to follow patients up. However, a serological biomarker that correlates with the progression of the disease could improve follow-up. We studied serum concentrations of TGFβ, PDGF-BB, PDGF-AA and CTGF growth factors in 37 adult onset Pompe patients and 45 controls. Moreover, all patients performed several muscle function tests, conventional spirometry, and quantitative muscle MRI using 3-point Dixon. We observed a statistically significant change in the serum concentration of each growth factor in patients compared to controls. However, only PDGF-BB levels were able to differentiate between asymptomatic and symptomatic patients, suggesting its potential role in the follow-up of asymptomatic patients. Moreover, our results point to a dysregulation of muscle regeneration as an additional pathomechanism of Pompe disease