To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Background Little is known about the role of the microbiome in primary sclerosing cholangitis. Aim Our goal was to explore the mucosa-associated microbiota in PSC patients across different locations in the gut, and to compare it with IBD-only patients and healthy controls. Methods Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies. Results Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only, and 9 healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit (OTU) level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order. Conclusion The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of PSC patients was characterized by enrichment of Blautia and Barnesiellaceae and by major shifts in OTUs within Clostridiales order.

BackgroundHeart failure (HF) is a condition that affects approximately 6.2 million people in the United States and has a 5-year mortality rate of approximately 42%. With the prevalence expected to exceed 8 million cases by 2030, projections estimate that total annual HF costs will increase to nearly US $70 billion. Recently, the advent of remote monitoring technology has significantly broadened the scope of the physician’s reach in chronic disease management.ObjectiveThe goal of our program, named the Heart Health Program, was to examine the feasibility of using digital health monitoring in real-world home settings, ascertain patient adoption, and evaluate impact on 30-day readmission rate.MethodsA digital medicine software platform developed at Mount Sinai Health System, called RxUniverse, was used to prescribe a digital care pathway including the HealthPROMISE digital therapeutic and iHealth mobile apps to patients’ personal smartphones. Vital sign data, including blood pressure (BP) and weight, were collected through an ambulatory remote monitoring system that comprised a mobile app and complementary consumer-grade Bluetooth-connected smart devices (BP cuff and digital scale) that send data to the provider care teams. Care teams were alerted via a Web-based dashboard of abnormal patient BP and weight change readings, and further action was taken at the clinicians’ discretion. We used statistical analyses to determine risk factors associated with 30-day all-cause readmission.ResultsOverall, the Heart Health Program included 58 patients admitted to the Mount Sinai Hospital for HF. The 30-day hospital readmission rate was 10% (6/58), compared with the national readmission rates of approximately 25% and the Mount Sinai Hospital’s average of approximately 23%. Single marital status (P=.06) and history of percutaneous coronary intervention (P=.08) were associated with readmission. Readmitted patients were also less likely to have been previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (P=.02). Notably, readmitted patients utilized the BP and weight monitors less than nonreadmitted patients, and patients aged younger than 70 years used the monitors more frequently on average than those aged over 70 years, though these trends did not reach statistical significance. The percentage of the 58 patients using the monitors at least once dropped from 83% (42/58) in the first week after discharge to 46% (23/58) in the fourth week.ConclusionsGiven the increasing burden of HF, there is a need for an effective and sustainable remote monitoring system for HF patients following hospital discharge. We identified clinical and social factors as well as remote monitoring usage trends that identify targetable patient populations that could benefit most from integration of daily remote monitoring. In addition, we demonstrated that interventions driven by real-time vital sign data may greatly aid in reducing hospital readmissions and costs while improving patient outcomes.

Summary 34To identify factors that regulate the absolute microbiota and the impact of varied microbiota density on health, we assayed 35 gut microbiota density across mammals, disease, and therapeutic interventions. Physiologic features of the host (carrying 36 capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in 37 mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, 38 ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower 39 density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between 40 microbiota and disease through the conceptual framework of microbiota density, host carrying capacity, and microbiota fitness 41 could provide biomarkers to identify candidates for microbiota therapeutics and monitor their response.

Background Evidence-based patient education and consistent, timely communication is key to ensuring good outcomes among joint replacement patients. Mount Sinai Hospital (MSH) participates in the mandatory CMS bundle for comprehensive joint replacement (CJR). MSH’s bundled payment strategy focuses on the development of a standardized model of care, built around evidence-based best practices to achieve the triple aims of strengthening population health while controlling cost and improving the quality of care. MSH launched a comprehensive digital navigation program (DNP) to guide joint replacement patients and their caregivers through pre-surgical preparation and recovery. Objective The objective was to improve the quality of care for joint replacement patients through creation of a digital navigation program specifically tailored to Medicare patients (age 65+) across the continuum of care. Methods Mount Sinai App Lab, in collaboration with the Department of Orthopedics, developed three digital therapeutic modules that were delivered through the RxUniverse Digital Medicine platform (Rx.Health, NY). These automated messages, programmed to send at specific times, included exercise instructions, medication reminders, and suggestions for how to prepare the home for optimal recovery. Messages specifically targeted key patient outcomes: length of stay, readmissions, ambulation on postoperative day 0, and discharge disposition. Staff “prescribed” each module to patients to ensure that engagement aligned with their process of care. Results Clinicians, patients, and their caregivers were receptive to the DNP. Patients showed a high rate of engagement, clicking links to educational content 873 times, and patients called their case manager or surgeon’s office to clarify their next steps when prompted. After 9 months, clinical outcomes for the digital navigation program were compared to other Medicare patients who had not received it. DNP patients had significantly shorter length of stay than their peers (2.81 vs 4.31 days). They also had a lower readmission rate (1.9% vs 2.9%) as well as a higher rate of discharge to home (87.8% vs 64.3%) and were more likely to ambulate on the day of surgery (47.9% vs 33.3%). Twenty patients responded to an end-of-program survey about their experience; 18 patients (90%) agreed that the program was helpful with the process of their total joint replacement surgery, 2 patients neither agreed nor disagreed (10%), and 0 patients disagreed. When asked about their satisfaction with the message volume, 19 patients answered “yes, this was the perfect number,” (95%) and 1 patient answered “no, I want fewer messages” (5%). Patient qualitative feedback was very positive. Patients reported, “Texts reassured me and helped me along with my progress and recovery,” and “Good support. Thank you.” A third said, “The texting program serves as a great reminder as what to do and when.” Conclusions The CJR DNP provided a direct, automated channel to educate and support patients at each stage of care. It demonstrated that digital navigation technology can be used even among non-digital native populations. It resulted in a significantly reduced length of stay and hospital readmissions among participating patients. Next steps include scaling the program across the health system and adding Spanish-language support. Similar programs are now being implemented for other surgical and disease use cases.