Uretroplastia de sustitución con doble injerto de mucosa oral como opción terapéutica para pacientes con estenosis de uretra bulbar asociada a UroLume®

ResumenEl UroLume® o endoprótesis uretral fue concebido como un dispositivo de fácil colocación para pacientes con estenosis uretral bulbar recurrente. Con el paso del tiempo se demostró que ocasionaba más complicaciones que beneficios por lo que se abandonó su uso. Sin embargo, se generó un grupo de pacientes con estenosis uretral compleja que necesitaban múltiples tratamientos quirúrgicos con resultados poco favorecedores. Con la divulgación a finales de la década de los 90 del uso de injertos de mucosa oral para el tratamiento de estenosis uretral se inició una nueva etapa en la búsqueda de un tratamiento definitivo para este tipo de pacientes. El objetivo del artículo es presentar una técnica quirúrgica no descrita en la literatura para el tratamiento de estenosis uretral bulbar asociada a UroLume®. Se describe el caso de un paciente masculino de 71 años de edad con estenosis uretral bulbar secundaria a resección transuretral de próstata al cual le fue colocado un UroLume® hace 8 años presentando reestenosis uretral, tratado con múltiples dilataciones uretrales. Mediante un abordaje perineal se retiró la endoprótesis en su totalidad, en base a las características locales de los tejidos se decidió colocar un doble injerto de mucosa oral dorsal inlay y ventral onlay con resultados exitosos a 6 meses de seguimiento.AbstractUroLume®, or urethral endoprosthesis, was conceived as an easy placement device for patients with recurrent bulbar urethral stricture. With the passage of time, it was shown to cause more complications than benefits and its use was discontinued. However, it created a group of patients with complex urethral stricture that required multiple surgical treatments with unsatisfactory results. The widespread use at the end of the 1990s of buccal mucosa grafts for the treatment of urethral stricture began a new stage in the search for a definitive treatment for this type of patient.The aim of our article was to present a surgical technique for the treatment of UroLume®-associated bulbar urethral stricture that has not been described in the literature.A 71-year-old man presented with bulbar urethral stricture secondary to transurethral resection of the prostate who, 8 years ago, had UroLume® placement. He presented with another urethral stricture and was treated with numerous urethral dilations. Through the perineal approach, the endoprosthesis was completely removed, and based on the local tissue characteristics, a dorsal inlay and ventral onlay double buccal mucosa graft was placed with successful results at the 6th month of follow-up

On the sensitivity of the HAWC observatory to gamma-ray bursts

We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very high-energy gamma-ray observatory currently under construction in Mexico at an altitude of 4100 m. It will observe atmospheric air showers via the water Cherenkov method. HAWC will consist of 300 large water tanks instrumented with 4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main DAQ system reads out coincident signals in the tanks and reconstructs the direction and energy of individual atmospheric showers. The scaler DAQ counts the hits in each photomultiplier tube (PMT) in the detector and searches for a statistical excess over the noise of all PMTs. We show that HAWC has a realistic opportunity to observe the high-energy power law components of GRBs that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The two DAQ systems have an energy threshold that is low enough to observe events similar to GRB 090510 and GRB 090902b with the characteristics observed by Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs which in turn could help to understanding about e-pair attenuation in GRB jets, extragalactic background light absorption, as well as establishing the highest energy to which GRBs accelerate particles

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

Impact of International Nosocomial Infection Control Consortium (INICC) strategy on central line-associated bloodstream infection rates in the intensive care units of 15 developing countries

BACKGROUND. The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. METHODS. Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. RESULTS. During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line-days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001 ), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P=.018 ), and that sought to remove unneeded catheters increased from 37% to 83% (P=.004); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). CONCLUSIONS. Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years. © 2010 by The Society for Healthcare Epidemiology of America. All rights reserved

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s)