Utility of scores to predict alcohol use after liver transplant (lt): take them with a grain of salt.

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

'Burn and Push' technique: A novel robotic liver parenchymal transection technique.

BACKGROUND: Liver parenchymal transection during robotic liver resection (RLR) remains a significant challenge due to the limited range of specialised instruments. This study introduces our 'Burn and Push' technique as a novel approach to address these challenges. METHODS: A retrospective analysis was conducted on 20 patients who underwent RLR using the 'Burn and Push' technique at Virginia Commonwealth University Health System from November 2021 to August 2023. The study evaluated peri- and post-operative outcomes. RESULTS: The median operation time was 241.5 min (range, 90-620 min), and the median blood loss was 100 mL (range, 10-600 mL). Major complications occurred in one case, with no instances of postoperative bleeding, bile leak, or liver failure. CONCLUSIONS: The 'Burn and Push' technique is a viable and efficient alternative for liver parenchymal transection in RLR. Further research with larger sample sizes and consideration of the learning curve is necessary to validate these findings.

Robotic management of primary cholecystoduodenal fistula: A case report and brief literature review.

BACKGROUND: Cholecystoduodenal fistula (CDF) arises from persistent biliary tree disorders, causing fusion between the gallbladder and duodenum. Initially, open resection was common until laparoscopic fistula closure gained popularity. However, complexities within the gallbladder fossa yielded inconsistent outcomes. Advanced imaging and robotic surgery now enhance precision and detection. METHOD: A 62-year-old woman with chronic cholangitis attributed to cholecystoduodenal fistula underwent successful robotic cholecystectomy and fistula closure. RESULTS: Postoperatively, the symptoms subsided with no complications during the robotic procedure. Existing studies report favourable outcomes for robotic cholecystectomy and fistula closure. CONCLUSIONS: Our case report showcases a rare instance of successful robotic cholecystectomy with CDF closure. This case, along with a review of previous cases, suggests the potential of robotic surgery as the preferred approach, especially for patients anticipated to face significant laparoscopic morbidity.

Inflammatory and hypoxic stress-induced islet exosomes released during isolation are associated with poor transplant outcomes in islet autotransplantation.

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exoS) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exoS: damage-associated molecular patterns (DAMPs), chaperones, and autoantigens. The involvement of endosomal-sorting complex required for transport proteinsincluding ras-associated binding proteins7A, ras-associated binding protein GGTA, vacuolar protein sorting associated protein 45, vacuolar protein sorting associated protein 26B, and the tetraspanins CD9 and CD63, in exoS biogenesis was confirmed through immunoblotting. Next, we isolated similar exoS from the islet infusion bags of TPIAT recipients (N = 20). The exosomes from infusion bags exhibited higher DAMP (heat shock protein family A [Hsp70] member 1B and histone H2B) levels, particularly in the insulin-dependent TPIAT group. Additionally, elevated DAMP protein levels in islet infusion bag exosomes correlated with increased insulin requirements (P = .010) and higher hemoglobin A1c levels 1-year posttransplant. A deeper exploration into exoS functionality revealed their potential to activate monocytes via the toll-like receptor 3/7: DAMP axis. This stimulation resulted in the induction of inflammatory phenotypes marked by increased levels of CD68, CD80, inducible nitric oxide synthase, and cyclooxygenase-2. This activation mechanism may impact the successful engraftment of transplanted islets.

Right versus left fully robotic live donor nephrectomy and open kidney transplantation: Does the laterality of the donor kidney really matter?

Objective: Robotic-assisted live donor nephrectomy (LDN) is being gradually adopted across transplant centers. The left donor kidney is preferred over right due to anatomical factors and ease of procurement. We aimed to study donor and recipient outcomes after robotic procurement and subsequent open implantation of right and left kidneys. Methods: All fully robotic LDNs and their corresponding open kidney transplants performed at our center between February 2016 and December 2021 were retrospectively analyzed. Results: Out of 196 robotic LDN (49 [right] vs. 147 [left]), 10 (5.1%) donors had intra-operative events (6.1% [right] vs. 4.8% [left], p=0.71). None of the LDN required conversion to open surgery. The operative times were comparable for the two groups. Nausea (13.3%) was the most common post-operative complication. There was no mortality in either LDN group. Herein, we report our outcomes on 156 recipients (39 right and 117 left allografts) excluding robotic implants, exports, and pediatric recipients. There were no significant differences between right and left kidney recipients with respect to 1-year post-transplant patient survival (100.0% vs. 98.1%, p=0.45) or graft survival (93.9% vs. 97.1%, p=0.11), or delayed graft function (7.7% vs. 5.1%, p=0.55). Conclusion: Non-hand-assisted robotic live donor nephrectomies can be safely performed with excellent outcomes. Right LDN was not associated with higher incidence of complications compared to left LDN. Open implantation of robotically procured right renal allografts was not associated with higher risk of recipient complications.

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report.

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

Robotic hepatectomy and cholecystectomy in the management of intraductal papillary mucinous neoplasm of the biliary tract: A case report and literature review.

BACKGROUND: In the Western Hemisphere, Intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B) is a rare lesion with uncertain aetiology. This report outlines a scarcely documented instance of IPMN-B treated using robotic hepatectomy and cholecystectomy supplemented with intraoperative imagery aimed at informing future robotic procedures. METHODS: A healthy person with acute cholangitis symptoms underwent diagnostic imaging followed by successful robotic hepatectomy and cholecystectomy. Pathological examination confirmed IPMN-B. RESULTS: The patient was consulted regarding the proposed procedure of robotic left hepatectomy, cholecystectomy, and potential hepaticojejunostomy, to which she provided consent. Subsequent surgical intervention resulted in clear margins for malignancy, and the patient recovered without complications. CONCLUSIONS: This case emphasises the importance of early diagnosis and intervention in managing IPMN. The use of a robotic approach, specifically through robotic left hepatectomy combined with cholecystectomy, offers minimally invasive surgery that provides exceptional visualisation and precise control.

Exosomes in transplantation: Role in allograft rejection, diagnostic biomarker, and therapeutic potential.

Exosomes are 50-200 nm-sized extracellular vesicles that are secreted by cells to transfer signals and communicate with other cells. Recent research has revealed that allograft-specific exosomes containing proteins, lipids, and genetic materials are released into circulation post-transplantation which are powerful indicators of graft failure in solid-organ and tissue transplantations. The macromolecular content of exosomes released by the allograft and the immune cells serve as potential biomarkers for assessing the function and the acceptance/rejection status of the transplanted grafts. Identifying these biomarkers could aid in the development of therapeutic strategies to improve graft longevity. Exosomes can be used to deliver therapeutic agonists/antagonists to grafts and prevent rejection. Inducing long-term graft tolerance has been demonstrated in many studies using exosomes from immunomodulatory cells such as immature DCs, T regulatory cells, and MSCs. The use of graft-specific exosomes for targeted drug therapy has the potential to reduce the unwanted side effects of immunosuppressive drugs. Overall, in this review, we have explored the critical role of exosomes in the recognition and cross-presentation of donor organ-specific antigens during allograft rejection. Additionally, we have discussed the potential of exosomes as a biomarker for monitoring graft function and damage, as well as their potential therapeutic applications in mitigating allograft rejection.

Single incision simultaneous liver kidney transplantation: Feasibility and outcomes.

BACKGROUND: Traditionally, simultaneous liver kidney transplantation (SLK) has been performed using a subcostal incision for the liver allograft and a lower abdominal incision for kidney transplantation (dual incision, DI). At our institution, we performed SLK using a single subcostal incision (SI). The aim of this study was to report the outcomes of single versus dual incisions for SLK. METHODS: A retrospective cohort study of consecutive SLK procedures performed at our center from January 2015 to April 2021 was performed. The demographic characteristics, complications, intraoperative findings, and complications after SI and DI were statistically compared. RESULTS: A total 37 SLK were performed (19 DI and 18 SI). The age and indications for transplantation were comparable between the two groups. Patient in SI group had significantly higher MELD score (27.0 ± 1.5 vs. 31.7 ± 1.5, p = .038). The cold ischemic time of kidney transplantation (599 ± 26 min vs. 447 ± 27 min, p < .001) and the total surgical time (508 ± 21 min vs. 423 ± 22 min, p = .008) were significantly shorter in the SI group. The incidence of complications and post-transplant kidney function was comparable between the groups. A slightly higher incidence of surgical site complications was noted in the DI group without any statistically significance (p = .178). CONCLUSIONS: Single-subcostal incision SLK is technically feasible and has comparable outcomes to dual-incision SLK. SI was associated with shorter cold ischemic time for kidney transplant, as well as shorter overall operative time.

Assessment of Culture/Preservation Conditions of Human Islets for Transplantation.

Islet culture before clinical transplantation has been adopted by various centers, but its effect on the survival and function of islets relative to the culture conditions and media needs further assessment. Human islets were cultured or preserved under four different conditions and three media options. Parameters such as recovery, viability, function, islet damage, and gene expressions for markers of hypoxia, and inflammation were assessed after 48-h culture or preservation. Preservation of islets was performed at 4°C in Connaught's Medical Research Lab (CMRL) and University of Wisconsin (UW) media. Islets were cultured at 22°C, 37°C, and 37°C-22°C in CMRL and PRODO culture media. Islets preserved in UW solution had visually good morphology and exhibited higher recovery with less islet damage compared with the rest of the groups, whereas islets preserved in CMRL at 4°C resulted in poor morphology, recovery, viability, and function compared with the rest of the treatment conditions. Culture at 22°C and 37°C demonstrated an increase in the expression of inflammatory and hypoxia-related genes. In conclusion, islets preserved at 4°C in UW solution showed the best overall outcomes after 48 h compared with islets cultured at 22°C, 37°C, or 37°C-22°C in PRODO. Advancement in islet culture media is warranted to reduce inflammatory gene activation and improve recovery of islets for transplantation.

Purification and Isolation of Hepatic Stellate Cells.

Quiescent human hepatic stellate cells (HSCs) serve as important reservoirs of fat-soluble vitamins in the body, namely vitamin A. In an activated form, HSCs are the drivers of fibrosis following chronic liver injury. In non-alcoholic steatohepatitis (NASH) specifically, activated HSCs are drivers of induction and progression of fibrogenesis. Isolation and purification of HSCs from donor liver samples provides an avenue to study HSCs and their fibrotic capabilities. Manual and chemical digestion of donor liver via dissection and Pronase, collagenase, and DNAse treatment creates a suspension of non-parenchymal liver cells. Quiescent HSCs can be further isolated from this suspension by density-gradient centrifugation in a 6%, 8%, 12%, and 15% arabinogalactan medium. After collection of HSCs from the low-density layers of the gradient, they can be grown on uncoated plastic. Rodent HSCs can also be isolated via density-gradient centrifugation. To isolate activated HSCs, liver tissue explants or established immortalized HSC lines can be utilized. Here, we described protocols for isolation of human and rodent HSCs.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Chyle Leak After Robotic Living Donor Nephrectomy: Literature Review And Management.

Chyle leak after living donor nephrectomy is a rare complication and is associated with a significant postoperative burden. To the best of our knowledge, only 1 case of chyle leak after robotic living donor nephrectomy has been reported in the literature. In this study, we present our experience with 2 cases of chyle leak: 1 after and 1 during robotic donor nephrectomy. We discuss previously published studies and man - agement options of chyle leak in kidney donors.

Dissection of External Iliac Artery During Pediatric En bloc Kidney Transplant: Successful Rescue and Reimplant.

En bloc kidney transplant is a surgical treatment option that increases available donor organs and has excellent graft survival for patients with end-stage renal disease. Herein, we report a case of dissection of the external iliac artery that occurred during en bloc kidney transplant in an adult recipient. The en bloc kidneys were removed, flushed, and then reimplanted after restoring the blood flow to the lower limb. To our knowledge, this is the first case of dissection of the external iliac artery managed successfully during en bloc kidney transplant.

Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis.

BACKGROUND: Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients. METHODS: Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages. RESULTS: Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months. DISCUSSION: Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

BACKGROUND: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology. METHODS: In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection. RESULTS: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology: 27 (13%) versus MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI: 0.74-0.86) versus histology (AUC = 0.75; 95% CI: 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies. CONCLUSIONS: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D-/R- transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R- compared with D-/R- (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c ), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.