Faculty Bibliography

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

Type 1 Diabetes (T1D), an autoimmune disease, is rising in incidence around the world with a decreasing average age of onset and changed environmental triggers may account for this rise. Our recent studies of exposing non-obese diabetic (NOD) mice to 3 pulses of antibiotic (tylosin) treatment (3PAT) during D10-40 of life provided evidence that early-life antibiotic exposure alters the gut microbiota, significantly affecting immune system development and promoting T1D development (1). We now have developed a model to test the hypothesis that a single PAT (tylosin) exposure earlier in life (D5-10) (1PAT) is sufficient to perturb gut microbiome development and increases T1D development. NOD mice were bred and litters exposed to either 1PAT or 3PAT (non-acidified water alone as control). T1D development was monitored by measuring blood glucose and pancreatic islet histology. The gut microbiota was evaluated by high-throughput 16S rRNA Illumina sequencing followed by QIIME and LEfSe analyses. PAT-exposed or control NOD mice were sequentially sacrificed and the host ileal immune-response gene expression profiles were analyzed by NanoString and potentially involved pathways were further evaluated by RT-qPCR. Both 1PAT and 3PAT significantly and similarly accelerated T1D development in male NOD mice. Sequence analysis revealed that 1PAT dramatically decreased gut bacterial diversity over the long-term. Several specific taxa were identified that were irreversibly decreased in early life by 1PAT, which could potentially be protective against T1D onset. ELISA analysis indicated that fecal IgA was decreased by 1PAT for at least 6 weeks. NanoString and follow-up RT-qPCR revealed that 1PAT significantly repressed expression of multiple components in pathways involved in innate and adaptive immunity. In summary, our results provide evidence that early life gut microbiome perturbation by single pulse antibiotic treatment at levels that are therapeutically given to human children affects both adaptive and innate immunity and accelerates T1D onset, possibly through effects on particular taxa

BACKGROUND: The Center for Medicare and Medicaid Services (CMS) is transitioning Medicare from a fee-for-service program into a value-based pay-for-performance program. In order to accomplish this goal, CMS initiated 3 programs that attempt to define quality and seek to reward high-performing hospitals and penalize poor-performing hospitals. These programs include (1) penalties for hospital-acquired conditions (HACs), (2) penalties for excess readmissions for certain conditions, and (3) performance on value-based purchasing (VBP). The objective of this study was to determine whether high-volume total joint hospitals perform better in these programs than their lower-volume counterparts. METHODS: We analyzed data from the New York Statewide Planning and Research Cooperative System database on total New York State hospital discharges from 2013 to 2015 for total knee and total hip arthroplasty. This was compared to data from Hospital Compare on HAC's, excess readmissions, and VBP. From these databases, we identified 123 hospitals in New York, which participated in all 3 Medicare pay-for-performance programs and performed total joint replacements. RESULTS: Over the 3-year period spanning 2013-2015, hospitals in New York State performed an average of 1136.59 total joint replacement surgeries and achieved a mean readmission penalty of 0.005909. The correlation coefficient between surgery volume and combined performance score was 0.277. Of these correlations, surgery volume and VBP performance, and surgery volume and combined performance showed statistical significance (P < .01). CONCLUSION: Our study demonstrates that there is a positive association between joint replacement volumes and overall hospital quality, as well as joint replacement volumes and VBP performance, specifically. These findings are consistent with previously reported associations between patient outcomes and procedure volumes. However, a relationship between joint replacement volume and HAC scores or readmission penalties could not be demonstrated.