Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Observational Study
Impact of coexisting pneumonia in the patients admitted with Clostridium difficile infection: a retrospective study from a national inpatient database.
Clostridium difficile is a gram-positive anaerobic spore forming bacillus that can cause infection in a setting of antibiotic use. Pneumonia is a major cause of morbidity and mortality in an inpatient setting and is frequently associated with significant antibiotic administration. This study aims to compare the outcomes of C. difficile infection (CDI) with and without pneumonia to determine the impact of pneumonia in hospitalized patients with CDI. ⋯ In-hospital mortality was noted to be higher in patients with pneumonia than those without (6.5% vs 1.2%, adjusted OR (aOR) 3.85; 95% CI 2.90 to 5.11, p<0.001). The following outcomes were more prevalent in patients with pneumonia compared with those without pneumonia: sepsis (9.8% vs 1.8%, aOR 4.69, 95% CI 3.73 to 5.87, p<0.001), septic shock (4.0% vs 0.5%, aOR 6.32, 95% CI 4.43 to 9.03, p<0.001), NSTEMI (1.9% vs 0.5%, aOR 2.95, 95% CI 1.85 to 4.71, p<0.001), and acute renal failure (31.5% vs 23.1%, aOR 1.23, 95% CI 1.07 to 1.40, p=0.003). In conclusion, patients with pneumonia were associated with significantly higher rates of system-based complications and higher in-hospital mortality rates.
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Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. ⋯ Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.
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Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually, academic health centers also created institutionally focused trial monitoring mechanisms. The basic general principles that define traditional DSMBs extend to the institutional level. ⋯ Academic health centers should recognize the importance and existence of institution level safety and data monitoring and provide support as much as possible. Investigators should have sufficient resources available to assemble DSMBs. The Clinical and Translational Science Awards Collaborative DSMB Workgroup provides an online manual to assist investigators.
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The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. ⋯ We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5-1 g/day proteinuria (relative to SBP 110-119 mm Hg, the adjusted HR for SBP 120-129 mm Hg, 130-139 mm Hg, and 140-149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p<0.05). In grade A2 microalbuminuria or proteinuria near 0.5 g/day, a non-significant but possible connection was seen between tighter BP and decreased CKD (aforementioned HRs all <2; all p>0.05), while in grade A1 albuminuria or proteinuria <0.2 g/day no significant association was apparent (HRs all <1.5; all p>0.1). We conclude that in non-diabetic CKD, stricter BP targets <130 mm Hg may help limit CKD progression as proteinuria rises.
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MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as candidate biomarkers. Single-nucleotide polymorphisms (SNPs) in miRNA genes can be related to the risk of different autoimmune diseases. ⋯ C and T alleles in the variants rs2910164 and rs1044165, respectively, are associated with increased risk of MS. Such association was obtained in codominant, dominant, and overdominant models for both variants (OR ~3 and OR ~1.5, respectively). Furthermore, this study determined that the C and T alleles of rs2910164 and rs1044165 are risk factors for MS in the Iranian population.