Interpenetrating Networks of Collagen and Hyaluronic Acid That Serve as In Vitro Tissue Models for Assessing Macromolecular Transport.

High-fidelity preclinical in vitro tissue models can reduce the failure rate of drugs entering clinical trials. Collagen and hyaluronic acid (HA) are major components of the extracellular matrix of many native tissues and affect therapeutic macromolecule diffusion and recovery through tissues. Although collagen and HA are commonly used in tissue engineering, the physical and mechanical properties of these materials are variable and depend highly on processing conditions. In this study, HA was chemically modified and crosslinked via hydrazone bonds to form interpenetrating networks of crosslinked HA (HAX) with collagen (Col). These networks enabled a wide range of mechanical properties, including stiffness and swellability, and microstructures, such as pore morphology and size, that can better recapitulate diverse tissues. We utilized these interpenetrating ColHAX hydrogels as in vitro tissue models to examine macromolecular transport and recovery for early-stage drug screening. Hydrogel formulations with varying collagen and HAX concentrations imparted different gel properties based on the ratio of collagen to HAX. These gels were stable and swelled up to 170% of their original mass, and the storage moduli of the ColHAX gels increased over an order of magnitude by increasing collagen and HA concentration. Interestingly, when HAX concentration was constant and collagen concentration increased, both the pore size and spatial colocalization of collagen and HA increased. HA in the system dominated the ζ-potentials of the gels. The hydrogel and macromolecule properties impacted the mass transport and recovery of lysozyme, ß-lactoglobulin, and bovine serum albumin (BSA) from the ColHAX gels─large molecules were largely impacted by mesh size, whereas small molecules were influenced primarily by electrostatic forces. Overall, the tunable properties demonstrated by the ColHAX hydrogels can be used to mimic different tissues for early-stage assays to understand drug transport and its relationship to matrix properties.

What is the ideal timing of cholecystectomy after percutaneous cholecystostomy for acute cholecystitis?

BACKGROUND: Acute cholecystitis (AC) is one of the most prevalent diseases in clinical practice. Poor surgical candidates may benefit from early percutaneous cholecystostomy (PC) drainage followed by interval cholecystectomy (IC), which is the definitive treatment. The optimal timing between the PC drainage and the IC has not been identified. This study aimed to investigate how the duration between PC and IC affects perioperative outcomes and identify the optimal IC timing to minimize complications. METHODS: This retrospective cohort study included all adult patients diagnosed with AC who underwent PC followed by IC at a single institution center between 2014 and 2022. Patients with a history of hepatobiliary surgery, stones in the common bile duct, cirrhosis, active malignancy, or prolonged immunosuppression were excluded. The analysis did not include cases with major concurrent procedures during cholecystectomy, previously aborted cholecystectomies, or failure of the PC drain to control the inflammation. Linear and logistic regression models were used to analyze the impact of the interval between PC and IC on intra- and perioperative outcomes. RESULTS: One hundred thirty-two patients (62.1% male) with a mean age of 64.4 ± 15 (mean ± SD) years were diagnosed with AC (25% mild, 47.7% moderate, 27.3% severe). All patients underwent PC followed by IC after a median of 64 [48-91] days. Longer ICU stay was associated with longer time intervals between PC and IC (Coef 105.98, p < 0.001). No significant variations were detected in the intraoperative and perioperative outcomes between patients undergoing IC within versus after 8 weeks from PC placement. However, a higher percentage of patients with delayed IC (after 8 weeks) were discharged home (96.4% vs. 83.7%; p = 0.019). CONCLUSIONS: Patients may benefit from undergoing IC after the 8-week cutoff after PC. However, very long periods between PC and IC procedures may increase the risk of longer ICU stay.

Early postoperative weight loss predicts nadir weight and weight regain after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

BACKGROUND: Weight regain (WR) post bariatric surgery affects almost 20% of patients. It has been theorized that a complex interplay between physiologic adaptations and epigenetic mechanisms promotes WR in obesity, however, reliable predictors have not been identified. Our study examines the relationship between early postoperative weight loss (WL), nadir weight (NW), and WR following laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG). METHODS: A retrospective review of prospectively collected data was conducted for LRYGB or LSG patients from 2012 to 2016. Demographics, preoperative BMI, procedure type, and postoperative weight at 6, 12, 24, 36, and 48 months were recorded. WR was defined as > 20% increase from NW. Univariate and multivariate linear and logistic regression models were used to determine the association between early postoperative WL with NW and WR at 4 years. RESULTS: Thousand twenty-six adults were included (76.8% female, mean age 44.9 ± 11.9 years, preoperative BMI 46.1 ± 8); 74.6% had LRYGB and 25.3% had LSG. Multivariable linear regression models showed that greater WL was associated with lower NW at 6 months (Coef - 2.16; 95% CI - 2.51, - 1.81), 1 year (Coef - 2.33; 95% CI - 2.58, - 2.08), 2 years (Coef - 2.04; 95% CI - 2.25, - 1.83), 3 years (Coef - 1.95; 95% CI - 2.14, - 1.76), and 4 years (Coef - 1.89; 95% CI - 2.10, - 1.68), p ≤ 0.001. WR was independently associated with increased WL between 6 months and 1 year (Coef 1.59; 95% CI 1.05,2.14; p ≤ 0.001) and at 1 year (Coef 1.24; 95% CI 0.84,1.63;p ≤ 0.001) postoperatively. The multivariable logistic regression model showed significantly increased risk of WR at 4 years for patients with greater WL at 6 months (OR 1.20, 95% CI 1.08,1.33; p = 0.001) and 1 year (OR 1.14; 95% CI 1.06,1.23; p ≤ 0.001). CONCLUSION: Our findings demonstrate that higher WL at 6 and 12 months post bariatric surgery may be risk factors for WR at 4 years. Surgeons may need to follow patients with high early weight loss more closely and provide additional treatment options to maximize their long-term success.

Cholecystectomy After Percutaneous Cholecystostomy for Acute Cholecystitis: Experience and Outcomes in an Academic Practice.

Percutaneous cholecystostomy (PC) tube insertion has been shown to be an effective treatment of acute cholecystitis (AC) as a temporary step to subsequent laparoscopic cholecystectomy (LC). However, the optimal time gap between PC implantation and LC has not been identified. Adult patients who underwent PC followed by LC for the treatment of AC between 2016 and 2020 were retrospectively reviewed and analyzed. One hundred twelve patients, consisting of 59.8% males, were included and received LC after a median of 65 [48 - 96.5] days following the PC placement. No deaths or reoperations occurred within 30 days, but 16 (14.3%) patients were readmitted, and 16 (14.3%) required subsequent reintervention. Although a longer interval between PC and LC had no effect on perioperative outcomes, it was associated with considerably longer intensive care unit (ICU) stay. According to these findings, patients may benefit from early LC following PC for the treatment of AC.