Cell-based therapies hold promise for many chronic conditions; however, the continued need for immunosuppression along with challenges in replacing cells to improve durability or retrieving cells for safety are major obstacles. We subcutaneously implanted a device engineered to exploit the innate transcapillary hydrostatic and colloid osmotic pressure generating ultrafiltrate to mimic interstitium. Long-term stable accumulation of ultrafiltrate was achieved in both rodents and nonhuman primates (NHPs) that was chemically similar to serum and achieved capillary blood oxygen concentration. The majority of adult pig islet grafts transplanted in non-immunosuppressed NHPs resulted in xenograft survival >100 days. Stable cytokine levels, normal neutrophil to lymphocyte ratio, and a lack of immune cell infiltration demonstrated successful immunoprotection and averted typical systemic changes related to xenograft transplant, especially inflammation. This approach eliminates the need for immunosuppression and permits percutaneous access for loading, reloading, biopsy, and recovery to de-risk the use of “unlimited” xenogeneic cell sources to realize widespread clinical translation of cell-based therapies.

Introduction: The incidence of short‐term (90‐day) hospital readmission and morbidity following liver transplantation (LT) for metabolic dysfunction‐associated steatotic liver disease (MASLD) is poorly characterized, and no study to date has distinguished these short‐term outcomes between MASLD and non‐MASLD LT recipients. The primary objective of this study was to leverage the National Readmissions Database (NRD) to distinguish 90‐day readmission rates and morbidity among those undergoing LT for MASLD and non‐MASLD etiologies. Methods: Recipients undergoing LT were identified in the NRD between January 1, 2016, and December 31, 2022. Morbidity was defined as an aggregate of common surgical complications. Univariate and age‐sex adjusted quasi‐Poisson regressions were used to identify trends and differences in characteristics for patients stratified by indication for LT. Multivariable logistic regression models were used to identify factors associated with 90‐day readmissions and morbidity. Results: A weighted total of 58 148 LT procedures were identified, of which 11 235 (19.3%) had MASLD etiology. LT for MASLD increased over the study period, while LT for hepatitis C and liver cancer decreased. Relative to non‐MASLD LT recipients, MASLD LT recipients had increased comorbid risk profiles, including higher rates of class 3 obesity (body mass index [BMI] ≥ 40) and associated liver cancer. MASLD LT recipients had lower rates of 90‐day readmission, morbidity, and cardiovascular complications (all p < 0.05). Among patients with class 3 obesity and liver cancer, MASLD etiology was associated with improved or non‐inferior 90‐day outcomes relative to non‐MASLD LT recipients. Finally, among MASLD LT recipients, the presence of chronic kidney disease, prior bariatric surgery, dialysis, female sex, and chronic obstructive pulmonary disease were independent predictors of 90‐day morbidity and readmission. Conclusions: Despite an increased comorbid risk profile, MASLD LT recipients had superior 90‐day readmission rates and morbidity outcomes relative to non‐MASLD LT recipients. MASLD etiology appears to normalize 90‐day outcomes among patients with obesity and liver cancer.

Background: Bariatric surgery is an effective treatment for class III obesity, and higher hospital volume is associated with improved outcomes. We examined readmission, morbidity, and length of stay (LOS) by bariatric center volume in the Nationwide Readmissions Database (NRD). Methods: The NRD from 2016 to 2022 was used to identify VSG and RYGB procedures with each hospital stratified by very low (1–24), low (25–49), medium (50–124), and high (≥ 125) annual case volume. Univariate tests assessed differences for each volume stratum. 90-day readmission and morbidity were modeled using multivariable logistic regression; LOS was analyzed with a random intercepts model for unique hospitals. Results: Overall, 4.6%, 6.9%, 31.1%, and 57.6% of patients underwent surgery at very low, low, medium, and high volume centers. Patients at lower volume centers had lower socioeconomic status and higher risk profiles. Readmission and morbidity rates were 15.4%, 6.9%, 4.1%, and 3.2% and 26.0%, 13.2%, 11.9%, and 10.9%, respectively for each volume designation. Very low volume centers showed the highest risk, with low and medium volumes also significantly associated with increased readmission and morbidity. For LOS, low volume had the highest estimated increase of all predictors with medium volume centers also predicting increased LOS. Individual hospitals represented a significant source of variation for total LOS. Conclusions: Although patients who had surgery at lower volume centers had higher risk profiles, after adjustment there is evidence that lower volume centers are more often associated with increased adverse events. Healthcare teams, accreditation centers, and insurance providers should strive to design and follow patterns of care associated with lower risk.

Animals in the veterinary and experimental settings, including nonhuman primates (NHPs), often require repeated and prolonged vascular access for indications including blood sampling or administration of fluids, blood products, medication, or other therapies. A vascular access approach should be tailored to experimental or clinical use meeting the needs of the individual animal such that benefits outweigh risks. The optimal device and placement technique is based on the inherent advantages and disadvantages of specific anatomic sites and planned use. Totally implanted vascular access ports (VAPs) enable reliable central venous access for frequent sample collection and/or intravenous therapies. VAPs minimize discomfort with IV access to facilitate cooperation with handling and minimize stress-induced physiologic changes which can confound biologic data and drug responses. VAPs do not limit species-typical behavior and social group activities and are compatible with animal enrichment programs that include play and swim because there are no externalized components. VAPs are typically used long-term and demonstrate excellent durability with high patency and low complication rates over time, presenting a safe and dependable vascular access approach.

Anticoagulant and antiplatelet therapies are used to prevent life-threatening complications associated with thrombosis. While there are numerous clinical guidelines for antithrombotic medications, there is an incomplete understanding of whether these interventions yield similar effects in preclinical models, potentially impacting their predictive value for translational studies on the development of medical devices, therapies, and surgical techniques. Due to their close physiologic similarities to humans, we employed nonhuman primates (NHPs) using a reverse translational approach to analyze the response to clinical regimens of unfractionated heparin, low-molecular-weight heparin (LMWH) and aspirin to assess concordance with typical human responses and evaluate the predictive validity of this model. We evaluate activated clotting time (ACT) in nine rhesus and six cynomolgus macaques following the intraoperative administration of intravenous unfractionated heparin (100–300 U/kg) reflecting the clinical dose range. We observed a significant dose-dependent effect of heparin on ACT (low-dose average = 114.1 s; high-dose average = 148.3 s; p = 0.0011). LMWH and aspirin, common clinical antithrombotic prophylactics, were evaluated in three rhesus macaques. NHPs achieved therapeutic Anti-Xa levels (mean = 0.64 U/mL) and ARU (mean = 459) via VerifyNow, adhering to clinical guidance using 1.0 mg/kg enoxaparin and 81 mg aspirin. Clinical dosing strategies for unfractionated heparin, LMWH, and aspirin were safe and effective in NHPs, with no development of thrombosis or bleeding complications intraoperatively, postoperatively, or for prophylaxis. Our findings suggest that coagulation studies, performed as an integrative part of studies on biologics, bioengineered devices, or transplantation in NHPs, can be extrapolated to the clinical situation with high predictive validity.