Antifungal Use in Perforated Peptic Ulcer Disease: A Western Australian Perspective.

Background Perforated peptic ulcer disease has a high mortality rate, and there is consensus regarding the use of antifungals in the management of immunocompromised patients; however, there is variability in the utilization of antifungals in the non-immunocompromised cohort. This study aims to describe the current practice related to the use of antifungals in perforated peptic ulcer disease in Western Australia and to determine the peri-operative morbidity and mortality in the immunocompromised and non-immunocompromised cohort receiving antifungals. Methods Medical records of patients who underwent surgical repair of perforated peptic ulcer in all Western Australian tertiary hospitals between January 1, 2010, and December 31, 2017, were reviewed retrospectively. Data regarding pre-operative patient factors such as age, gender, and comorbidities, post-operative outcomes such as intra-abdominal sepsis/bleeding, peri-operative antifungal prescription, and abundance of fungal growth on intra-operative samples were collected. Results The study included 359 patients. The antifungal prescription was variable. An American Society of Anesthesiologists (ASA) score of 3 or more, presence of pre-operative shock and acidosis, and level of abundance of fungal growth on intra-operative samples were associated with antifungal prescription. Amongst the non-immunocompromised cohort, receiving antifungals was associated with higher morbidity. Conclusion The use of antifungals for patients with perforated peptic ulcer disease was variable. An ASA score of 3 or greater and pre-operative shock and acidosis are pre-operative factors predisposing patients to receiving antifungals. There was no difference in morbidity or mortality amongst immunocompromised patients regardless of antifungal prescription or non-prescription. However, in the non-immunocompromised cohort, those who received antifungals had a higher morbidity compared to those who did not.

Implementation of a geriatric in-reach service improves acute surgical unit outcomes; a retrospective before-and-after study.

BACKGROUND: Australia's ageing population is challenging for surgical units and there is a paucity of evidence for geriatric co-management in acute general surgery. We aimed to assess if initiating a Geriatric Medicine in-reach service improved outcomes for older adults in our Acute Surgical Unit (ASU). METHODS: The Older Adult Surgical Inpatient Service (OASIS) was integrated into ASU in 2021. We retrospectively reviewed all patients over age 65 admitted to ASU over a 12-month period before and after service integration with a length of stay (LOS) greater than 24 h. There was no subsequent truncation or selection. Primary outcomes were 30-day mortality, LOS, and 28-day readmissions. Secondary outcomes were discharge disposition, in-hospital mortality, and hospital-acquired complications (HACs). RESULTS: 1339 consecutive patients were included in each group, with no differences in baseline characteristics. There was a significant decrease in 28-day readmissions from 20.2% to 16.0% (P < 0.05), greatest in patients undergoing non-EL operative procedures (21.9% pre-OASIS vs. 12.6% post-OASIS; P < 0.05). Trends towards reduced 30-day mortality (7.17% vs. 5.90%; P = 0.211), in-hospital mortality (3.88% vs. 2.91%; P = 0.201), permanent care placement (7.77% vs. 7.09%; P = 0.843) and HACs (8.14% vs. 7.62%; P = 0.667) were seen, although statistical significance was not demonstrated. LOS remained unchanged at 4 days (P = 0.653). CONCLUSION: The addition of a geriatric in-reach service to a tertiary ASU led to a significant reduction in 28-day readmissions. Downtrends were seen in mortality, permanent care placement, and HAC rates, while LOS remained unchanged.

Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway.

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity.

NAD+ precursors and bile acid sequestration treat preclinical refractory environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a diffuse small bowel disorder associated with poor growth, inadequate responses to oral vaccines, and nutrient malabsorption in millions of children worldwide. We identify loss of the small intestinal Paneth and goblet cells that are critical for innate immunity, reduced villous height, increased bile acids, and dysregulated nicotinamide adenine dinucleotide (NAD+) synthesis signaling as potential mechanisms underlying EED and which also correlated with diminished length-for-age z score. Isocaloric low-protein diet (LPD) consumption in mice recapitulated EED histopathology and transcriptomic changes in a microbiota-independent manner, as well as increases in serum and fecal bile acids. Children with refractory EED harbor single-nucleotide polymorphisms in key enzymes involved in NAD+ synthesis. In mice, deletion of Nampt, the gene encoding the rate-limiting enzyme in the NAD+ salvage pathway, from intestinal epithelium also reduced Paneth cell function, a deficiency that was further aggravated by LPD. Separate supplementation with NAD+ precursors or bile acid sequestrant partially restored LPD-associated Paneth cell defects and, when combined, fully restored all histopathology defects in LPD-fed mice. Therapeutic regimens that increase protein and NAD+ contents while reducing excessive bile acids may benefit children with refractory EED.