Rapid gastrointestinal loss of Clostridial Clusters IV and XIVa in the ICU associates with an expansion of gut pathogens

Commensal gastrointestinal bacteria resist the expansion of pathogens and are lost during critical illness, facilitating pathogen colonization and infection. We performed a prospective, ICU-based study to determine risk factors for loss of gut colonization resistance during the initial period of critical illness. Rectal swabs were taken from adult ICU patients within 4 hours of admission and 72 hours later, and analyzed using 16S rRNA gene sequencing and selective culture for vancomycin-resistant Enterococcus (VRE). Microbiome data was visualized using principal coordinate analyses (PCoA) and assessed using a linear discriminant analysis algorithm and logistic regression modeling. 93 ICU patients were analyzed. At 72 hours following ICU admission, there was a significant decrease in the proportion of Clostridial Clusters IV/XIVa, taxa that produce short chain fatty acids (SCFAs). At the same time, there was a significant expansion in Enterococcus. Decreases in Cluster IV/XIVa Clostridia were associated with loss of gut microbiome colonization resistance (reduced diversity and community stability over time). In multivariable analysis, both decreased Cluster IV/XIVa Clostridia and increased Enterococcus after 72 hours were associated with receipt of antibiotics. Cluster IV/XIVa Clostridia, although a small fraction of the overall gastrointestinal microbiome, drove distinct clustering on PCoA. During initial treatment for critical illness, there was a loss of Cluster IV/XIVa Clostridia within the distal gut microbiome which associated with an expansion of VRE and with a loss of gut microbiome colonization resistance. Receipt of broad-spectrum antibiotics was associated with these changes

Fecal-Based Colorectal Cancer Screening Among the Uninsured in Northern Manhattan

Background Colorectal cancer (CRC) screening reduces CRC mortality; however, for many reasons, uninsured individuals are less likely to utilize CRC screening tests. Purpose To compare CRC screening behaviors and outcomes with guaiac fecal occult blood testing (gFOBT) from 1998 to 2006 and fecal immunochemical testing (FIT) from 2006 to 2010 in a community-based program serving uninsured patients in northern Manhattan. Methods In 2013, we conducted a retrospective record review of individuals aged ≥50 years who received fecal-based CRC screening at the Northern Manhattan Cancer Screening Partnership between 1998 and 2010. Included were those with household income ≤250% of the federal poverty level, no medical insurance coverage, and who were not up to date with CRC screening. We assessed screening positivity rate, positive predictive value, differences in the use of diagnostic colonoscopy, colonoscopic findings, and adenoma detection rates for gFOBT versus FIT. Results In total, 7,710 patients completed CRC screenings (4,951 gFOBT and 2,759 FIT). The majority were female, Hispanic, foreign born, and young at age of first screening. Compared to gFOBT, FIT detected twice as many positive tests (3.2% vs 1.5%, p≤0.001) and had a higher adenoma detection rate (18.2 vs 11.8, p=0.002). Conclusions The improved positivity and adenoma detection rates with greater number of screening tests over time favor the use of FIT over gFOBT for colorectal screening among uninsured populations in northern Manhattan

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy