Predictive factors of neurological complications and one-month mortality after liver transplantation.

BackgroundNeurological complications are common after orthotopic liver transplantation (OLT). We aimed to characterize the risk factors associated with neurological complications and mortality among patients who underwent OLT in the post-model for end-stage liver disease (MELD) era.MethodsIn a retrospective review, we evaluated 227 consecutive patients at the Keck Hospital of the University of Southern California before and after OLT to define the type and frequency of and risk factors for neurological complications and mortality.ResultsNeurological complications were common (n = 98), with encephalopathy being most frequent (56.8%), followed by tremor (26.5%), hallucinations (11.2%), and seizure (8.2%). Factors associated with neurological complications after OLT included preoperative dialysis, hepatorenal syndrome, renal insufficiency, intra-operative dialysis, preoperative encephalopathy, preoperative mechanical ventilation, and infection. Preoperative infection was an independent predictor of neurological complications (OR 2.83, 1.47-5.44). One-month mortality was 8.8% and was independently associated with urgent re-transplant, preoperative intubation, and intra-operative arrhythmia.ConclusionNeurological complications are common in patients undergoing OLT in the post-MELD era, with encephalopathy being most frequent. An improved understanding of the risk factors related to both neurological complications and one-month mortality post-transplantation can better guide perioperative care and help improve outcomes among OLT patients

Treating oxidative stress in heart failure:past, present and future

Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the development and progression of heart failure. Oxidative stress is defined as the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defence system. Under physiological conditions, small quantities of ROS are produced intracellularly, which function in cell signalling, and can be readily reduced by the antioxidant defence system. However, under pathophysiological conditions, the production of ROS exceeds the buffering capacity of the antioxidant defence system, resulting in cell damage and death. Over the last decades several studies have tried to target oxidative stress with the aim to improve outcome in patients with heart failure, with very limited success. The reasons as to why these studies failed to demonstrate any beneficial effects remain unclear. However, one plausible explanation might be that currently employed strategies, which target oxidative stress by exogenous inhibition of ROS production or supplementation of exogenous antioxidants, are not effective enough, while bolstering the endogenous antioxidant capacity might be a far more potent avenue for therapeutic intervention. In this review, we provide an overview of oxidative stress in the pathophysiology of heart failure and the strategies utilized to date to target this pathway. We provide novel insights into modulation of endogenous antioxidants, which may lead to novel therapeutic strategies to improve outcome in patients with heart failure

Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy

OBJECTIVE: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF). METHODS: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-terminal telopeptide, procollagen 1 N-terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate. RESULTS: Despite overall hip and spine BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was associated 1.0% (P = 0.02) and 0.8% (P = 0.01) less BMD decline. Women had lower baseline spine (P = 0.04; n = 59 women, 418 men) and hip BMD (P = 0.01) in adjusted models, with 1.7% more hip decline on ART than men (P = 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P = 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P = 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n = 44 women, 326 men). Women also had 0.6% (P = 0.004) more hip BMD decline than men associated with each 100 CD4 cells/μl increase on ART (P = 0.02; n = 49 women, 379 men). CONCLUSION: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss

Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality

Background: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. Methods: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling. Results: In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73-6.57; P < .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp. Conclusions: In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates

Transmisión de Klebsiella pneumoniae resistente a carbapenemes en hospitales de EE.UU.

Antecedentes. La Klebsiella pneumoniae resistente a los carbapenemes (CRKp) es el Enterobacterales resistente a los carbapenemes más prevalente en los Estados Unidos. Se evaluó la agrupación de CRKp en pacientes de hospitales estadounidenses. Métodos. De abril de 2016 a agosto de 2017, 350 pacientes con grupo clonal 258 CRKp se inscribieron en el Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, un estudio de cohortes prospectivo y multicéntrico. Se construyó un árbol de máxima verosimilitud utilizando RAxML. Los conglomerados estáticos compartían ≤21 polimorfismos de un solo nucleótido (SNP) y un ancestro común más reciente. Los conglomerados dinámicos incorporaron la distancia SNP, el tiempo de cultivo y las tasas de acumulación y transmisión SNP utilizando el programa R TransCluster. Resultados. La mayoría de los pacientes ingresaron desde su domicilio (n=150, 43%) o desde centros de cuidados de larga duración (n=115, 33%). La orina (n=149, 43%) fue el lugar de aislamiento más común. En total, se identificaron 55 conglomerados estáticos y 47 dinámicos en 210 de 350 (60%) y 194 de 350 (55%) pacientes, respectivamente. Aproximadamente la mitad de los clusters estáticos eran idénticos a los dinámicos. Los conglomerados estáticos consistían en 33 (60%) conglomerados intrasistema y 22 (40%) conglomerados intersistema. Los conglomerados dinámicos estaban formados por 32 (68%) conglomerados intrasistema y 15 (32%) conglomerados intersistema y presentaban menos diferencias de SNP que los conglomerados estáticos (8 frente a 9; P=.045; intervalo de confianza [IC] del 95%: -4 a 0). Los conglomerados dinámicos intersistema contenían más pacientes que los conglomerados dinámicos intrasistema (mediana [intervalo intercuartílico], 4 [2, 7] frente a 2 [2, 2]; P=,007; IC del 95%: -3 a 0). Conclusiones. Se identificó una amplia transmisión intrasistémica e intersistémica de CRKp en pacientes estadounidenses hospitalizados. El uso de diferentes métodos para evaluar la similitud genética sólo dio lugar a diferencias menores en la interpretación.Background. Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. Methods. From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. Results. Most patients were admitted from home (n=150, 43%) or long-term care facilities (n=115, 33%). Urine (n=149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P=.045; 95% confidence interval [CI]: −4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P=.007; 95% CI: −3 to 0). Conclusions. Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation

Residence in Skilled Nursing Facilities Is Associated with Tigecycline Nonsusceptibility in Carbapenem-Resistant Klebsiella pneumoniae

OBJECTIVE To determine the rates of and risk factors for tigecycline nonsusceptibility among carbapenem-resistant Klebsiella pneumoniae (CRKPs) isolated from hospitalized patients DESIGN Multicenter prospective observational study SETTING Acute care hospitals participating in the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRaCKle) PATIENTS A cohort of 287 patients who had CRKPs isolated from clinical cultures during hospitalization METHODS For the period from December 24, 2011 to October 1, 2013, the first hospitalization of each patient with a CRKP during which tigecycline susceptibility for the CRKP isolate was determined was included. Clinical data were entered into a centralized database, including data regarding pre-hospital origin. Breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used to interpret tigecycline susceptibility testing. RESULTS Of 287 patients included in the final cohort, 155 (54%) had tigecycline-susceptible CRKPs. Of all index isolates, 81 (28%) were tigecycline-intermediate and 51 (18%) were tigecycline resistant. In multivariate modeling, independent risk factors for tigecycline nonsusceptibility were (1) admission from a skilled nursing facility (OR, 2.51; 95% CI, 1.51–4.21; P =.0004), (2) positive culture within 2 days of admission (OR, 1.82; 95% CI, 1.06–3.15; P =.03), and (3) receipt of tigecycline within 14 days (OR, 4.38, 95% CI, 1.37–17.01, P =.02). CONCLUSIONS In hospitalized patients with CRKPs, tigecycline nonsusceptibility was more frequently observed in those admitted from skilled nursing facilities and occurred earlier during hospitalization. Skilled nursing facilities are an important target for interventions to decrease antibacterial resistance to antibiotics of last resort for treatment of CRKPs. Infect Control Hosp Epidemiol 2015;36(8):942–94

Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important healthcare-associated pathogen. We evaluated the impact of CRKP strain type and treatment on outcomes of patients with CRKP bacteriuria

Older HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction

The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated

Proteinuria, CrCl, and Immune Activation in Antiretroviral-Naïve HIV-Infected Subjects

Because both renal disease and immune activation predict progression to AIDS, we evaluated the relationships between dipstick proteinuria ≥1+ [7% of 1012 subjects], CrCl <90mL/min [18% of 1071 subjects], and percentages of peripheral activated CD8 cells (CD8+CD38+HLA-DR+) in antiretroviral-naïve, HIV-infected subjects enrolled into AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not CrCl, was associated with higher percentages of CD8+CD38+HLA-DR+ cells [55% vs. 50%; P=0.01], with even more pronounced differences in men and among Blacks and Hispanics. Proteinuria may be a surrogate measure of greater immune activation in HIV-infected patients initiating antiretroviral therapy