Kirby, Michelle

Abstract Background Short bowel syndrome (SBS) is a chronic condition requiring parenteral nutrition (PN) support and multidisciplinary management. However, disparities in access to care and standardized treatment pathways, in addition to economic burden, remain considerable for patients. Understanding healthcare resource utilization (HCRU) and treatment patterns, especially in relation to patient‐reported outcomes (PROs), is critical for improving care. Methods A cross‐sectional, multiphase study was conducted in 2023. This analysis focuses on phase 3, using a deidentified database that integrated claims and PROs from 68 patients in phase 2. Twenty‐three patients were included in the analytic cohort after applying additional criteria. Descriptive statistics summarized patient demographics, HCRU, and treatment patterns for the overall cohort and stratified by median SBS–quality of life (QoL) score. Results The median age at SBS diagnosis was 35 years, and 91% of patients were female. Patients saw a median of 35 different healthcare providers and underwent approximately five procedures before diagnosis. In the 6 months after diagnosis, 39% had been hospitalized, and 26% had emergency room (ER) visits. Healthcare costs increased after diagnosis, with long‐term PN use accounting for 34% of total costs. Patients with worse QoL had a higher number of ER visits than patients with better QoL. Patients who self‐reported being treated by SBS specialists had lower healthcare costs than patients who did not receive specialized care. Conclusion SBS is associated with high HCRU and costs, particularly for patients with poor QoL. Multidisciplinary care, especially from SBS specialists, may help reduce healthcare costs and improve patient outcomes.

Abstract Background Patients with short bowel syndrome–associated intestinal failure (SBS‐IF) require complex, personalized, and multidisciplinary care; however, there are disparities in access. This study measured the impact of unmet needs and treatment burden among patients and their caregivers. Methods This cross‐sectional, mixed‐method study included US adults self‐reporting SBS‐IF and receiving home parenteral nutrition for ≥6 months and their caregivers. One‐hour interviews informed the development of a 30‐min survey administered to participants from an online health community. Results Among 68 patients, the mean age was 42 years, 79% were female, and 88% were White. Most of the 16 caregivers were female (69%), and younger than 45 years (69%). Of 32 patients (47%) receiving care from an SBS specialist, only 19 (59%) were referred after diagnosis; in 58% of these, referral occurred >6 months after diagnosis. Depression was reported in 44 patients (65%), with 54% not receiving professional mental health care. Financial concerns were common, with 44 patients (65%) unable to work and 40 patients (59%) reporting annual household income of <$50,000. Of 32 patients reporting difficulty paying medical bills, 22 (32%) could not fill prescriptions and 19 (28%) canceled/delayed healthcare provider visits. Social determinant of health challenges were reported by 44 patients (65%). Caregivers' responsibilities impacted their ability to work (50%) and future outlook (63%). Conclusion Patients with SBS‐IF face difficulties accessing specialized healthcare, and are at risk of adverse healthcare outcomes, financial hardships, and poor quality of life. Mental health and work/financial issues were common among both patients and caregivers.

AbstractBackground & AimsC‐Jun N‐terminal kinase (JNK) activation is pivotal in the development of nonalcoholic steatohepatitis (NASH). Mixed lineage kinase 3 (MLK) 3 is one of the mitogen activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in the liver. Despite this concept, the role of MLK3 in modulating liver injury during nutrient excess has not been explored. Our aim was to determine if MLK3 deficient mice were protected against high fat high carbohydrate (HFHC) diet‐induced NASH.MethodsWe employed eight‐week‐old Mlk3−/− male C57BL/6J mice, and wild type (WT) mice C57BL/6J as controls. Mice were fed a HFHC or a chow diet adlib for 16 weeks.ResultsHepatic JNK activating phosphorylation was readily absent in the Mlk3−/− mice fed the HFHC diet, but not in WT mice. This inhibition of JNK activation was hepatoprotective. Despite a comparable increase in weight gain, hepatic steatosis by histological examination and hepatic triglyceride quantification was reduced in HFHC diet‐fed Mlk3−/− mice compared with WT mice. In addition, compared with the WT mice, HFHC diet‐fed Mlk3−/− mice had significantly attenuated liver injury as manifested by reduced ALT levels, hepatocyte apoptosis, markers of hepatic inflammation and indices of hepatic fibrogenesis.ConclusionOur results suggest that loss of MLK3 in mice is protective against HFHC diet‐induced NASH, in a weight‐independent fashion, through attenuation of JNK activation. MLK3 is a potential therapeutic target for the treatment of human NASH.

AbstractBariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease.