Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury

Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI). Methods This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days. Results Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI ( P =0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI ( P =0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (ρ= -0.47; P =0.002), PaO 2 /FiO 2 ratio (ρ= -0.33; P =0.04) and age (ρ=0.35; P =0.015) only in patients without AKI. Conclusions A poor correlation between renal RI and MAP, age, or PaO 2 /FiO 2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain.

A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients

The Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) is a consensus-based classification system for diagnosing acute kidney insufficiency (AKI), based on serum creatinine (SCr) and urine output criteria (RIFLE SCr+UO) . The urine output criteria, however, are frequently discarded and many studies in the literature applied only the SCr criteria (RIFLE SCr ). We diagnosed AKI using both RIFLE methods and compared the effects on time to AKI diagnosis, AKI incidence and AKI severity. Methods This was a prospective observational cohort study during four months in adult critically ill patients admitted to the ICU for at least 48 hours. During the first week patients were scored daily for AKI according to RIFLE SCr+UO and RIFLE SCr. We assessed urine output hourly and fluid balance daily. The baseline SCr was estimated if a recent pre-ICU admission SCr was unknown. Based on the two RIFLE methods for each patient we determined time to AKI diagnosis (AKI-0) and maximum RIFLE grade. Results We studied 260 patients. A pre-ICU admission SCr was available in 101 (39%) patients. The two RIFLE methods resulted in statistically significantly different outcomes for incidence of AKI, diagnosis of AKI for individual patients, distribution of AKI-0 and distribution of the maximum RIFLE grade. Discarding the RIFLE urine criteria for AKI diagnosis significantly underestimated the presence and grade of AKI on admission and during the first ICU week ( P < 0,001) and significantly delayed the diagnosis of AKI ( P < 0.001). Based on RIFLE SCr 45 patients had no AKI on admission but subsequently developed AKI. In 24 of these patients (53%) AKI would have been diagnosed at least one day earlier if the RIFLE urine criteria had been applied. Mortality rate in the AKI population was 38% based on RIFLE SCr and 24% based on RIFLE SCr+UO ( P = 0.02). Conclusions The use of RIFLE without the urine criteria significantly underscores the incidence and grade of AKI, significantly delays the diagnosis of AKI and is associated with higher mortality.

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration International Standard Randomized Control Trial Registry ISRCTN64637517 .

Novel origins of copy number variation in the dog genome

Background Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. Results We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. Conclusions A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9 . These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.

In silico analysis of HLA associations with drug-induced liver injury: use of a HLA-genotyped DNA archive from healthy volunteers

Background Drug-induced liver injury (DILI) is one of the most common adverse reactions leading to product withdrawal post-marketing. Recently, genome-wide association studies have identified a number of human leukocyte antigen (HLA) alleles associated with DILI; however, the cellular and chemical mechanisms are not fully understood. Methods To study these mechanisms, we established an HLA-typed cell archive from 400 healthy volunteers. In addition, we utilized HLA genotype data from more than four million individuals from publicly accessible repositories such as the Allele Frequency Net Database, Major Histocompatibility Complex Database and Immune Epitope Database to study the HLA alleles associated with DILI. We utilized novel in silico strategies to examine HLA haplotype relationships among the alleles associated with DILI by using bioinformatics tools such as NetMHCpan, PyPop, GraphViz, PHYLIP and TreeView. Results We demonstrated that many of the alleles that have been associated with liver injury induced by structurally diverse drugs (flucloxacillin, co-amoxiclav, ximelagatran, lapatinib, lumiracoxib) reside on common HLA haplotypes, which were present in populations of diverse ethnicity. Conclusions Our bioinformatic analysis indicates that there may be a connection between the different HLA alleles associated with DILI caused by therapeutically and structurally different drugs, possibly through peptide binding of one of the HLA alleles that defines the causal haplotype. Further functional work, together with next-generation sequencing techniques, will be needed to define the causal alleles associated with DILI.

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model

Perceptions of Roles, Practice Patterns, and Professional Growth Opportunities

Broadening the scope of advanced practice providers (APPs) has been offered as a solution to increasing healthcare costs, workforce shortage, and increased demand. To understand present scope and barriers to broadening it, the authors describe the perceptions and practice patterns of APPs. This cross-sectional study used a computerized self-report survey of 32 targeted nurse practitioners and physician assistants employed in the cancer center of an urban teaching hospital; 31 were included in the quantitative analyses. Survey items covered education and training background, expertise, professional resources and support, duties, certification, and professional development. Respondents practiced in a variety of oncology specialty areas, but all had advanced degrees, most held specialty certifications, and 39% had attended a professional or educational meeting within the last year. They spent a majority of their time on essential patient-care activities, but clerical duties impeded these; however, 64% reported being satisfied with the time they spent with patients and communicating with collaborating physicians. A model of advanced oncology practice needs to be developed that will empower APPs to provide high-quality patient care at the fullest extent of their knowledge and competence.

Gastrointestinal Symptom Representation in Cancer Symptom Clusters: A Synthesis of the Literature

To review how gastrointestinal (GI)symptoms are represented within symptom clusters in patients with cancer receiving chemotherapy.

Physical Health, Mental Health, and Life Changes Among Family Caregivers of Patients With Lung Cancer

To describe physical health, mental health, and life changes among family caregivers of patients with lung cancer.