First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

A Multidisciplinary Technique for Concurrent Panniculectomy-Living Donor Renal Transplantation.

BACKGROUND: Recently, it has been shown that panniculectomy concurrent to living donor renal transplantation is a safe option for management of renal transplant recipients with a large focal pannus. This combined management requires precise coordination of teams. We describe the technique, timing, and sequence for combined renal transplantation and panniculectomy. METHODS: We conducted a retrospective chart review of adult patients (≥18 years old) who underwent simultaneous living donor renal transplantation-panniculectomy from 2015 to 2019. A multi-team approach that included urology, transplant, and plastic surgery was used to perform the combined operations. Typically, the plastic surgery team initiates the operation by performing the panniculectomy. This is followed by kidney transplantation and graft anastomosis. The plastic surgery team then completes the operation with closure of the wound. RESULTS: Twenty patients were identified. Most were male (12:8) with a mean age of 55 years and an average body mass index of 35 kg/m. The mean total operative duration was 394 minutes. On average, 17% of operating time was devoted to panniculectomy. At 90 days follow-up, there was 100% graft survival and all patients had primary graft function. There was a 25% wound complications rate and a 15% reoperation rate. CONCLUSION: By performing panniculectomy first in the sequence, concurrent panniculectomy provides wide exposure and a large operative field for transplantation. Wound closure by plastic surgeons may mitigate the high complication rate commonly seen in obese patients with end-stage renal disease. Future studies are needed to evaluate the cost-benefit of the combined living donor renal transplantation-panniculectomy.

Teamwork Makes the Dream Work: Maximizing Surgical Intervention at the Time of Living Donor Renal Transplantation.

BACKGROUND: Patients with obesity and end-stage renal disease represent a surgical population with multiple comorbidities and high risk for postoperative complications. One method for reducing the incidence of postoperative adverse events in this patient population is to limit the number of operations through combining operations into 1 operative encounter. METHODS: We conducted a retrospective review of adult patients at a single institution who underwent renal transplant, panniculectomy, and at least 1 additional abdominal or pelvic surgery concurrently. For those patients, we collected demographics, intraoperative variables, and postoperative data and analyzed surgical outcomes and postoperative complications. RESULTS: Thirteen patients met inclusion criteria. Most of the patients were female (85%) with ages ranging 33 to 70 years old and mean body mass index of 36.5 (SD 4.7). Three quarters of patients (77%) underwent 3 procedures and the remaining underwent 4 or 5 procedures with a median hospital length of stay of 5 days (range, 3-10 days). There was a single mortality. Overall, 8 patients (61.5%) experienced complications in the first 90 postoperative days. The wound complication rate was 46.2%, the overall readmission rate within 90 days was 38.5%, and the reoperation rate was 30.8%. All patients experienced immediate graft function, and the 12 patients that survived to postoperative day 90 maintained survival at 1 year. CONCLUSION: This study demonstrates that the combination of more than 2 surgical procedures with living donor renal transplant is a possible treatment option in high-risk obese patients in need of multiple operations.

Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program.

BACKGROUND: Perioperative cardiac xenograft dysfunction (PCXD) was described by McGregor and colleagues as a major barrier to the translation of heterotopic cardiac xenotransplantation into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24 to 48 hours of transplantation. We describe our experience with PCXD at a single program. METHODS: Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 monoclonal antibodies (mAb), thymoglobulin, cobra venom factor, and anti-CD40 mAb, and maintenance with anti-CD40 mAb, mycophenolate mofetil, and tapering doses of steroids. Telemetry was used to assess graft function. Extracorporeal membrane oxygenation was used to support 1 recipient. A full human clinical transplantation team was involved in these experiments and the procedure was performed by skilled transplantation surgeons. RESULTS: A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful, and all hearts were weaned from cardiopulmonary bypass without issue. Support with inotropes and vasopressors was generally required after separation from cardiopulmonary bypass. The cardiac xenografts performed well immediately, but within the first several hours they required increasing support and ultimately resulted in arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection. CONCLUSIONS: Despite excellent surgical technique, uneventful weaning from cardiopulmonary bypass, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24 to 48 hours without evidence of rejection. Modification of preservation techniques and minimizing donor organ ischemic time may be able to ameliorate PCXD.

Panniculectomy at the time of living donor renal transplantation: An 8-year experience.

Panniculectomy can be performed as a prophylactic procedure preceding transplantation to enable obese patients to meet criteria for renal transplantation. No literature exists on combined renal transplant and panniculectomy surgery (LRT-PAN). We describe our 8-year experience performing LRT-PAN. A retrospective chart review of all patients who had undergone LRT-PAN from 2010 to 2018 was conducted. Data were collected on patient demographics, allograft survival and function, and postoperative course. Fifty-eight patients underwent LRT-PAN. All grafts survived, with acceptable function at 1 year. Median length of stay was 4 days with a mean operative duration of 363 minutes. The wound complication rate was 24%. Ninety-day readmission rate was 52%, with medical causes as the most common reason for readmission (45%), followed by wound (32%) and graft-related complications (23%). Body mass index, diabetes status, and previous immunosuppression did not influence wound complication rate or readmission (P = .7720, P = .0818, and P = .4830, respectively). Combining living donor renal transplant and panniculectomy using a multidisciplinary team may improve access to transplantation, particularly for the obese and postobese population. This combined approach yielded shorter-than-expected hospital stays and similar wound complication rates, and thus should be considered for patients in whom transplantation might otherwise be withheld on the basis of obesity.

An Initial Investigation of Unmanned Aircraft Systems (UAS) and Real-Time Organ Status Measurement for Transporting Human Organs.

Organ transportation has yet to be substantially innovated. If organs could be moved by drone, instead of ill-timed commercial aircraft or expensive charter flights, lifesaving organs could be transplanted more quickly. A modified, six-rotor UAS was used to model situations relevant to organ transportation. To monitor the organ, we developed novel technologies that provided the real-time organ status using a wireless biosensor combined with an organ global positioning system. Fourteen drone organ missions were performed. Temperatures remained stable and low (2.5 °C). Pressure changes (0.37-0.86 kPa) correlated with increased altitude. Drone travel was associated with less vibration (<0.5 G) than was observed with fixed-wing flight (>2.0 G). Peak velocity was 67.6 km/h (42 m/h). Biopsies of the kidney taken prior to and after organ shipment revealed no damage resulting from drone travel. The longest flight was 3.0 miles, modeling an organ flight between two inner city hospitals. Organ transportation may be an ideal use-case for drones. With the development of faster, larger drones, long-distance drone organ shipment may result in substantially reduced cold ischemia times, subsequently improved organ quality, and thousands of lives saved.

Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients.

BACKGROUND: Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. METHODS: In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. RESULTS: Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. CONCLUSIONS: Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

Collaborative practice agreement in solid organ transplantation.

Background Given the complexity of solid organ transplant recipients, a multidisciplinary approach is required. To promote medication safety and enable providers to focus on the medical and surgical needs of these patients, our department of pharmacy created a collaborative practice agreement between physicians and pharmacists. Through this agreement, credentialed pharmacists are empowered to provide inpatient services including initiation and adjustment of medications through independent review of laboratory results after multidisciplinary rounds. Objective To evaluate the effect of our collaborative practice agreement on clinical care and institutional finances. Setting An inpatient setting at a large academic medical center. Methods Three transplant pharmacists entered all clinical interventions made on abdominal transplant recipients between September and October 2013 into Quantifi®, a software application that categorizes and assigns a cost savings value based on impact and type of intervention. Main outcome measure The main outcome measures in this study were number and categorization of interventions, as well as estimated cost savings to the institution. Results There were 1060 interventions recorded, an average of 20 interventions per pharmacist per day. The most common interventions were pharmacokinetic evaluations (36%) and dose adjustments (19%). Over the time period, these interventions translated into an estimated savings of $107,634.00, or an annual cost savings of $373,131.20 per pharmacist, or a cost-benefit ratio of 2.65 to the institution. Conclusions Based on our study, implementation of a collaborative practice agreement enables credentialed pharmacists to make clinically and financially meaningful interventions in a complex patient population.

Successful pancreas transplantation alone is associated with excellent self-identified health score and glucose control: A retrospective study from a high-volume center in the United States.

BACKGROUND: The benefits of pancreas transplantation are often difficult to measure. Here, we sought to determine the difference in quality of life for diabetic patients with and without a functional pancreas transplant alone (PTA). METHODS: Pancreas transplant alone cases from 1993 to 2015 were considered. An IRB-approved survey inclusive of 15 questions spanning four domains was employed. Chi-square, Fisher's exact, and the T test were used where appropriate. RESULTS: A total of 137 PTAs were performed during the study period. Of those reached (n = 32), 94% responded to the survey. Self-reported health scores were better (2.1 vs 3.0) for those with functioning pancreata (n = 18) vs those with a non-functional pancreas (n = 14), respectively (P = .036). Those with a functional pancreas had a HgbA1c of 5.3, vs 7.7 for a non-functional pancreas (P = .016). Significant hypoglycemia was reported in two of 18 with a functional transplant vs nine of 14 patients with a failed transplant (P = .003). Daily frustration with blood sugar affecting quality of life was significantly higher for patients with non-functional pancreas grafts (P < .001). CONCLUSIONS: Pancreas transplantation alone is associated with better glucose control than insulin. In addition, recipients of functional PTAs have improved quality of life and better overall health scores than those with failed grafts.

Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

BACKGROUND DATA: Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. METHODS: MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. RESULTS: Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. CONCLUSIONS: MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.

Sequential kidney-liver transplantation from the same living donor for lecithin cholesterol acyl transferase deficiency.

BACKGROUND: Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease (ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency. METHODS: A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). One year following the kidney transplant, auxiliary partial orthotopic liver transplant (APOLT) of a left lateral segment from the same donor was performed. RESULTS: At 5 years follow-up, there have been no major complications, readmissions, or rejection episodes. Serum lipid abnormalities recurred within the first year, but liver and kidney allograft function remains intact. CONCLUSION: Few cases of sequential transplantation from the same LD have been performed in adults. This is the first APOLT and multi-organ transplant performed for LCAT deficiency. Sequential organ transplant from the same LD for ESRD secondary to a metabolic disorder of the liver is feasible in adults and should be further investigated.

Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of ß-Cell Replacement.

The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.

Automated continuous vital signs predict use of uncrossed matched blood and massive transfusion following trauma.

BACKGROUND: Recognizing the use of uncross-matched packed red blood cells (UnXRBCs) or predicting the need for massive transfusion (MT) in injured patients with hemorrhagic shock can be challenging.A validated predictive model could accelerate decision making regarding transfusion. METHODS: Three transfusion outcomes were evaluated in adult trauma patients admitted to a Level I trauma center during a 4-year period (2009-2012): use of UnXRBC, use of greater than 4 U of packed red blood cells within 4 hours (MT1), and use of equal to or greater than 10 U of packed red blood cells within 24 hours (MT2). Vital sign (VS) features including heart rate, systolic blood pressure, and shock index (heart rate / systolic blood pressure) were calculated for 5, 10, and 15 minutes after admission. Five models were then constructed. Model 1 used preadmission VS, Model 2 used admission VS, and Models 3, 4, and 5 used continuous VS features after admission over 5, 10, and 15 minutes, respectively, to predict the use of UnXRBC, MT1, and MT2. Models were evaluated for their predictive performance via area under the receiver operating characteristic (ROC) curve, positive predictive value, and negative predictive value. RESULTS: Ten thousand six hundred thirty-six patients with more than 5 million continuous VS data points during the first 15 minutes after admission were analyzed. Model using preadmission and admission VS had similar ability to predict UnXRBC, MT1, or MT2. Compared with these two models, predictive ability was significantly improved as duration of VS monitoring increased. Continuous VS for 5 minutes had ROCs of 0.83 (confidence interval [CI], 0.83-0.84), 0.85 (CI, 0.84-0.86), and 0.86 (CI, 0.85-0.88) to predict UnXRBC, MT1, and MT2, respectively. Similarly, continuous VS for 10 minutes had a ROCs of 0.86 (CI, 0.85--0.86), 0.87 (CI, 0.86-0.88), and 0.88 (CI, 0.87-0.90) to predict UnXRBC, MT1, and MT2, respectively. Continuous VS for 15 minutes achieved the highest ROCs of 0.87 (CI, 0.87-0.88), 0.89 (CI, 0.88-0.90), and 0.91 (CI, 0.91-0.92) to predict UnXRBC, MT1, and MT2, respectively. CONCLUSION: Models using continuous VS collected after admission improve prediction for the use of UnXRBC or MT in patients with hemorrhagic shock. Decision models derived from automated continuous VS in comparison with single prehospital and admission VS identify the use of emergency blood use and can direct earlier blood product administration, potentially saving lives. LEVEL OF EVIDENCE: Therapeutic study, level III.

Critical Care Resuscitation Unit: An Innovative Solution to Expedite Transfer of Patients with Time-Sensitive Critical Illness.

BACKGROUND: Time-sensitive, critical surgical illnesses require care at specialized centers. Trauma systems facilitate patient transport to designated trauma centers, but formal systems for nontraumatic critical illness do not exist. We created the critical care resuscitation unit to expedite transfers of adult critically ill patients with time-sensitive conditions to a quaternary academic medical center, hypothesizing that this would decrease time to transfer, increase transfer volume, and improve outcomes. STUDY DESIGN: Critical care transfers to the University of Maryland Medical Center during the first year of the critical care resuscitation unit (July 2013 to June 2014) were compared with a previous year (July 2011 to June 2012). Times from transfer request to arrival and operating room and hospital mortality were compared. RESULTS: There was a 64.5% increase in transfers with a 93.6% increase in critically ill surgical patients. For patients requiring operation, median time to arrival and operating room (118 vs 223 minutes and 1,113 vs 3,424 minutes, respectively; p < 0.001 for both) and median hospital length of stay (13 vs 17 days; p < 0.001) were reduced significantly. There was a nonsignificant trend toward lower mortality (14.6% vs 16.5%; p = 0.27). CONCLUSIONS: The critical care resuscitation unit dramatically increased the volume of critically ill surgical patients. It decreased transfer times, increased volume, and, for those who required urgent operation, decreased time from initial referral to operating room. This benefit seems to be most marked in patients needing urgent operation. This might be a paradigm shift expediting the transfer of patients with time-sensitive critical illness to an appropriately resourced specialty center.

Vascularized Composite Allotransplantation: Medical Complications.

The objective of this review is to summarize the collective knowledge regarding the risks and complications in vascularized composite tissue allotransplantation (VCA), focusing on upper extremity and facial transplantation. The field of VCA has entered its second decade with an increasing experience in both the impressive good outcomes, as well as defining challenges, risks, and experienced poor results. The limited and selective publishing of negative outcomes in this relatively new field makes it difficult to conclusively evaluate outcomes of graft and patient survival and morbidities. Therefore, published data, conference proceedings, and communications were summarized in an attempt to provide a current outline of complications. These data on the medical complications of VCA should allow for precautions to avoid poor outcomes, data to better provide informed consent to potential recipients, and result in improvements in graft and patient outcomes as VCA finds a place as a therapeutic option for selected patients.

Live Donor Renal Transplant With Simultaneous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease Is Feasible and Satisfactory at Long-term Follow-up.

BACKGROUND: Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant. METHODS: Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys. RESULTS: Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously. CONCLUSIONS: Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.

Mechanistic similarities between trauma, atherosclerosis, and other inflammatory processes.

Most human diseases, including trauma, atherosclerosis, and malignancy, can be characterized by either an overexuberant inflammatory response or an inadequate immunologic response. As our understanding of the mechanisms underlying these inflammatory aberrations improves, so should our approach to the patient. The development of novel technologies capable of exploiting inflammatory mediators will undoubtedly play a role in future patient-directed therapies. Trauma surgeons are uniquely positioned to usher in a new era of patient diagnostics and patient-directed therapies based on an understanding of the immune system's response to stimuli. These improvements are likely to affect not only trauma care but all aspects of medicine.