In utero delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia.

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy in utero as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-ß pathway are critically involved in lung branching morphogenesis. Here, we characterize the expression of miR200b and the TGF-ß pathway at different gestational times using a rat model of CDH. Fetal rats with CDH are deficient in miR200b at gestational day 18. We demonstrate that novel polymeric nanoparticles loaded with miR200b, delivered in utero via vitelline vein injection to fetal rats with CDH results in changes in the TGF-ß pathway as measured by qRT-PCR; these epigenetic changes improve lung size and lung morphology, and lead to favorable pulmonary vascular remodeling on histology. This is the first demonstration of in utero epigenetic therapy to improve lung growth and development in a pre-clinical model. With refinement, this technique could be applied to fetal cases of CDH or other forms of impaired lung development in a minimally invasive fashion.

Risk Factors for the Failure of Non-operative Management Among Patients Admitted for Colonic Diverticulitis.

BACKGROUND: Diverticulitis is one of the most diagnosed gastrointestinal diseases in the country, and its incidence has risen over time, especially among younger populations, with increasing attempts at non-operative management. We elected to look at acute diverticular disease from the lens of a failure analysis, where we could estimate the hazard of requiring operative intervention based upon several clinical factors. MATERIALS AND METHODS: The National Inpatient Sample (NIS) was queried between 2010 and 2015 for unplanned admissions among adults with a primary diagnosis of diverticulitis. We used a proportional hazards regression to estimate the hazard of failed non-operative management from multiple clinical covariates, measured as the number of inpatient days from admission until colonic resection. We also evaluated patients who received percutaneous drainage, to investigate whether this was associated with decreasing the failure rate of non-operative management. RESULTS: A total of 830,993 discharges over the study period, of whom 83,628 (10.1%) underwent operative resection during the hospitalization, and 35,796 (4.3%) patients underwent percutaneous drainage. Half of all operations occurred by hospital day 1. Among patients treated with percutaneous drainage, 11% went on to require operative intervention. The presence of a peritoneal abscess (HR 3.20, P < .01) and sepsis (HR 4.16, P < .01) were the strongest predictors of failing non-operative management. Among the subset of patients with percutaneous drains, the mean time from admission to drain placement was 2.3 days. CONCLUSION: Overall 10.1% of unplanned admissions for diverticulitis result in inpatient operative resection, most of which occurred on the day of admission. Percutaneous drainage was associated with an 11% operative rate.

Institutional Variation in Gastrostomy Tube Placement After Duodenal Atresia Repair in Children With Trisomy 21.

OBJECTIVES: To compare institutional practice patterns for gastrostomy tube placement in neonates with duodenal atresia (DA) and trisomy 21. METHODS: A retrospective review of the Pediatric Health Information System (PHIS) from 2015 to 2018 identified infants <10 days old with ICD-10 diagnostic codes for DA and trisomy 21, in addition to procedure codes for an intestinal bypass or duodenoduodenostomy. This cohort was then queried for gastrostomy tube procedure codes and diagnostic codes for associated co-morbidities. RESULTS: Two hundred and nine infants were identified with DA, trisomy 21, and an intestinal bypass. Fifty-seven (27%) underwent gastrostomy placement. Baseline characteristics of those with and without gastrostomy tubes were similar. Patients from 16 hospitals that placed no gastrostomy tubes (No-G-tube-Hospitals) were compared to children from 30 hospitals that placed at least one gastrostomy tube (G-tube-Hospitals). Open atresia repairs occurred more frequently at G-tube-Hospitals, but patients were otherwise similar. There was no difference in readmission at 12 months for gastrostomy placement between children from No-G-tube-Hospitals and those from G-tube-Hospitals that did not undergo gastrostomy during their index admission. CONCLUSIONS: One-third of institutions in this study did not place gastrostomy tubes during index admissions for neonates with trisomy 21 and DA, yet this did not negatively impact the length of stay or incidence of subsequent gastrostomy placement as a result. Future research is needed to determine factors that predispose patients to failure without gastrostomy, as well as best practices for post-operative management in these patients to reduce unnecessary tube placement.

Methadone Access for Opioid Use Disorder During the COVID-19 Pandemic Within the United States and Canada.

Importance: Methadone access may be uniquely vulnerable to disruption during COVID-19, and even short delays in access are associated with decreased medication initiation and increased illicit opioid use and overdose death. Relative to Canada, US methadone provision is more restricted and limited to specialized opioid treatment programs. Objective: To compare timely access to methadone initiation in the US and Canada during COVID-19. Design, Setting, and Participants: This cross-sectional study was conducted from May to June 2020. Participating clinics provided methadone for opioid use disorder in 14 US states and territories and 3 Canadian provinces with the highest opioid overdose death rates. Statistical analysis was performed from July 2020 to January 2021. Exposures: Nation and type of health insurance (US Medicaid and US self-pay vs Canadian provincial). Main Outcomes and Measures: Proportion of clinics accepting new patients and days to first appointment. Results: Among 268 of 298 US clinics contacted as a patient with Medicaid (90%), 271 of 301 US clinics contacted as a self-pay patient (90%), and 237 of 288 Canadian clinics contacted as a patient with provincial insurance (82%), new patients were accepted for methadone at 231 clinics (86%) during US Medicaid contacts, 230 clinics (85%) during US self-pay contacts, and at 210 clinics (89%) during Canadian contacts. Among clinics not accepting new patients, at least 44% of 27 clinics reported that the COVID-19 pandemic was the reason. The mean wait for first appointment was greater among US Medicaid contacts (3.5 days [95% CI, 2.9-4.2 days]) and US self-pay contacts (4.1 days [95% CI, 3.4-4.8 days]) than Canadian contacts (1.9 days [95% CI, 1.7-2.1 days]) (P < .001). Open-access model (walk-in hours for new patients without an appointment) utilization was reported by 57 Medicaid (30%), 57 self-pay (30%), and 115 Canadian (59%) contacts offering an appointment. Conclusions and Relevance: In this cross-sectional study of 2 nations, more than 1 in 10 methadone clinics were not accepting new patients. Canadian clinics offered more timely methadone access than US opioid treatment programs. These results suggest that the methadone access shortage was exacerbated by COVID-19 and that changes to the US opioid treatment program model are needed to improve the timeliness of access. Increased open-access model adoption may increase timely access.

The effect of sociodemographic factors on outcomes and time to discharge after bariatric operations.

INTRODUCTION: Bariatric surgery is an effective treatment for obesity resulting in both sustained weight loss and reduction in obesity-related comorbidities. It is uncertain how sociodemographic factors affect postoperative outcomes. METHODS: The National Inpatient Sample was queried for patients undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2005 to 2014. Factors associated with selection of SG over RYGB, increased postoperative length of stay (LOS) greater than 3 days, and inpatient mortality were compared by race, insurance status, and other clinical and hospital factors. RESULTS: The database captured 781,413 patients, of which 525,986 had a RYGB and 255,428 had SG. There was an increase in the incidence of SG over RYGB over time. Among the self-pay/uninsured, the increased incidence began several years earlier than other groups. Black patients had greater odds of increased postoperative LOS (OR 1.40) and in-hospital mortality (OR 2.11). CONCLUSION: Sociodemographic factors are associated with differences in temporal trends in the adoption of SG versus RYGB for surgical weight loss.