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Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min (p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence.

The Public Health Service Increased Risk designation identified organ donors at increased risk of transmitting hepatitis B, hepatitis C, and human immunodeficiency virus. Despite clear data demonstrating a low absolute risk of disease transmission from these donors, patients are hesitant to consent to receiving organs from these donors. We hypothesize that patients who consent to receiving offers from these donors have decreased time to transplant and decreased waitlist mortality. We performed a single-center retrospective review of all-comers waitlisted for liver transplant from 2013 to 2019. The three competing risk events (transplant, death, and removal from transplant list) were analyzed. 1603 patients were included, of which 1244 (77.6%) consented to offers from increased risk donors. Compared to those who did not consent, those who did had 2.3 times the rate of transplant (SHR 2.29, 95% CI 1.88-2.79, p

BackgroundPreventing post-operative ileus (POI) is important given its associated morbidity and increased cost of care. The authors' prior work showed that POI in patients with newly created ileostomies is associated with a post-operative day (POD) 2 net fluid balance of > + 800 mL. The purpose of this study was to conduct an initial assessment of the efficacy of a pilot intervention.MethodsThis is a single-institution, pre-post-intervention, proof-of-concept study conducted on the Colorectal Surgery service at the University of California, San Francisco. The study included 58 procedures with ileostomy formation by board-certified colorectal surgeons between August 13, 2020 and June 1, 2021. The intervention included three adjustments to the standard Enhanced Recovery After Surgery protocol: addition of diuresis, delay in advancement to solid food, and earlier stoma intubation. Demographics, intraoperative factors, post-operative fluid balance, and outcomes (POI, post-procedure length of stay [LOS], hospitalization cost, and re-admissions) were compared between patients pre- and post-intervention.ResultsEight (13.8%) of the 58 procedures in the intervention period were associated with POI vs. a baseline POI rate of 32.6% (p = 0.004). Compared to patients without intervention, those with intervention had 67% less odds of POI (OR 0.33, 95% CI 0.15-0.73, p = 0.01). This difference remained significant when adjusted for age, gender, body mass index, procedure duration, and operative approach (adjusted OR 0.32, 95% CI 0.14-0.72, p = 0.01). Average POD2 stoma output was 0.3 L greater (1.1 L vs. 0.8L; p < 0.001) and net fluid balance was 1.8 L lower (+ 0.3 L vs. + 2.1 L; p < 0.00001) for these 58 cases. Average post-procedure LOS was 1.9 days lower (5.3 vs. 7.2 days, p < 0.001) and direct cost was $5561 lower ($21,652 vs. $27,213, p = 0.004), with no difference in 30-day readmissions (p = 0.43).ConclusionsThis pilot intervention shows promise for reduction in POI in patients with newly created ileostomies. Additional assessment is needed to confirm these initial findings.

Donation-after-circulatory-death (DCD), donation-after-brain-death (DBD), and living-donation (LD) are the three possible options for liver transplantation (LT), each with unique benefits and complication rates. We aimed to compare DCD-, DBD-, and LD-LT-specific graft survival and biliary complications (BC). We collected data on 138 DCD-, 3,027 DBD- and 318 LD-LTs adult recipients from a single center and analyzed patient/graft survival. BC (leak and anastomotic/non-anastomotic stricture (AS/NAS)) were analyzed in a subset of 414 patients. One-/five-year graft survival were 88.6%/70.0% for DCD-LT, 92.6%/79.9% for DBD-LT, and, 91.7%/82.9% for LD-LT. DCD-LTs had a 1.7-/1.3-fold adjusted risk of losing their graft compared to DBD-LT and LD-LT, respectively (p < 0.010/0.403). Bile leaks were present in 10.1% (DCD-LTs), 7.2% (DBD-LTs), and 36.2% (LD-LTs) (ORs, DBD/LD vs. DCD: 0.7/4.2, p = 0.402/

Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery.MethodsResearch tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal.ResultsThirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34).ConclusionsThe use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.

Postoperative ileus (POI) is associated with increased patient discomfort, length of stay (LOS), and healthcare cost. There is a paucity of literature examining POI in patients who have an ileostomy formed at the time of surgery. We aimed to identify risk factors for and outcomes associated with POI following ileostomy formation. We included 261 consecutive non-emergent cases that included formation of an ileostomy by a board-certified colorectal surgeon at our institution from July 1, 2015, to June 30, 2020. Demographic, clinical, and intraoperative factors associated with increased odds of POI were evaluated. Post-procedure LOS, hospitalization cost, and re-admissions between patients with and without POI were compared. Out of 261 cases, 85 (32.6%) were associated with POI. Patients with POI had significantly higher body mass index (BMI) than those without POI (26.6 kg/m2 vs. 24.8kg/m2; p = 0.01). Intraoperatively, patients with POI had significantly longer procedure duration than those without POI (313 min vs. 279 min; p = 0.02). Patients with POI had a significantly higher net fluid balance at postoperative day (POD) 2 than those without POI (+ 2.65 L vs. + 1.80 L; p = 0.004), with POD2 fluid balance greater than + 807 mL (determined as the maximum Youden index for sensitivity over 80%) associated with a higher rate of POI (p = 0.006). This difference remained significant when adjusted for age, gender, BMI, pre-operative opioid use, procedure duration, and operative approach (p = 0.01). Patients with POI had significantly longer LOS (11.40 days vs. 5.12 days; p < 0.001) and direct cost of hospitalization ($38K vs. $22K; p < 0.001). Minimizing fluid overload, particularly in the first 48 h after surgery, may be a strategy to reduce POI in patients undergoing ileostomy formation, and thus decrease postoperative LOS and hospitalization cost. Fluid restriction, diuresis, and changes in diet advancement or early stoma intubation should be considered measures that may improve outcomes and should be studied more intensively.

ObjectiveWe aimed to compare general surgery emergency (GSE) volume, demographics and disease severity before and during COVID-19.BackgroundPresentations to the emergency department (ED) for GSEs fell during the early COVID-19 pandemic. Barriers to accessing care may be heightened, especially for vulnerable populations, and patients delaying care raises public health concerns.MethodsWe included adult patients with ED presentations for potential GSEs at a single quaternary-care hospital from January 2018 to August 2020. To compare GSE volumes in total and by subgroup, an interrupted time-series analysis was performed using the March shelter-in-place order as the start of the COVID-19 period. Bivariate analysis was used to compare demographics and disease severity.Results3255 patients (28/week) presented with potential GSEs before COVID-19, while 546 (23/week) presented during COVID-19. When shelter-in-place started, presentations fell by 8.7/week (31%) from the previous week (p

Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally. Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems. Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not. Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.

BackgroundSarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants.MethodsWe estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients.ResultsOf the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5-9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P

Background Aim Design Methods Results Conclusion Implications for Practice Reporting Method Patient or Public Contribution National health and social care standards are complex, quality improvement interventions. Standards typically describe a process and/or outcome of safe, quality, person‐centred care according to best evidence. Currently, there are 11 national standards that apply to diverse services in Ireland including residential centres, acute hospitals and rehabilitation and community inpatient healthcare services. A better understanding of contextual factors influencing implementation will inform decision‐making when selecting implementation strategies to enhance the implementation of standards.To explore experiences of implementing national health and social care standards and secondly, to identify enablers and barriers to implementation with stakeholders from across multiple levels of the health system.A qualitative descriptive study.We conducted six focus groups and eight individual interviews from October to November 2021 with stakeholders at system level (n = 14), organizational level (n = 14) and individual level (n = 10). Focus groups and interviews were audio‐recorded, transcribed verbatim and analysed using reflexive thematic analysis.Six themes were generated; (1) Top‐down, bottom‐up, a team approach: everybody together, we are all involved, we are all responsible, (2) Support tools: accessible tools and bite‐size material pertaining to standards will support us to implement standards, (3) Empower with knowledge: increase awareness and understanding of standards, make them relatable in practice so we can make sense of them, (4) A system‐wide malaise: we do not have the bandwidth to implement standards, (5) Follow the leader: we need a lead person at every level to inspire implementation, (6) A bi‐directional influence: we know inspections drive quality improvements but we still feel trepidation around inspection outcomes.Key enablers identified related to teamwork, support tools, leadership and inspections. Key barriers related to workforce issues, a lack of awareness of standards and fear of inspection outcomes. Our findings can be incorporated into strategies to support implementation of standards, ultimately for the benefit of service‐users.The enablers and barriers described in this study reflect the importance of organizational factors in the implementation of standards. Interdisciplinary teams can infer from these findings, which enablers and barriers apply to their own context. These findings can inform decision‐making when selecting strategies that can be effective in supporting the implementation of standards.We have adhered to the Standards for Reporting Qualitative Research (SRQR) guidelines.No patient or public contribution. [ABSTRACT FROM AUTHOR]

ObjectiveEarly puberty in girls is linked to some adverse outcomes in adolescence and mid-life. We address two research questions: (1) Are socioeconomic circumstances and ethnicity associated with early onset puberty? (2) Are adiposity and/or psychosocial stress associated with observed associations?DesignLongitudinal data on 5839 girls from the UK Millennium Cohort Study were used to estimate associations between ethnicity, family income, adiposity and psychosocial stress with a marker of puberty.Main outcome measureReported menstruation at age 11 years.ResultsAll quoted ORs are statistically significant. Girls in the poorest income quintile were twice as likely (OR=2.1), and the second poorest quintile nearly twice as likely (OR=1.9) to have begun menstruation compared with girls in the richest income quintile. Estimates were roughly halved on adjustment for Body Mass Index and markers of psychosocial stress (poorest, OR=1.5; second poorest, OR=1.5). Indian girls were over 3 times as likely compared with whites to have started menstruation (OR=3.5) and statistical adjustments did not attenuate estimates. The raised odds of menstruation for Pakistani (OR=1.9), Bangladeshi (OR=3.3) and black African (OR=3.0) girls were attenuated to varying extents, from about a third to a half, on adjustment for income and adiposity.ConclusionsIn contemporary UK, excess adiposity and psychosocial stress were associated with social inequalities in early puberty, while material disadvantage and adiposity were linked to ethnic inequalities in early puberty among girls.

Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a 'thermal image' of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibres of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibres that innervate the pit organ. TRPA1 orthologues from pit-bearing snakes (vipers, pythons and boas) are the most heat-sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of transient receptor potential (TRP) channels as thermosensors in the vertebrate nervous system.