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Surgical site infections (SSI) are a significant cause of morbidity in liver transplant recipients, and the current data in the pediatric population are limited. The goal of this study was to identify the incidence, classification, risk factors, and outcomes of SSIs among children undergoing liver transplantation (LT).A single-center, retrospective descriptive analysis was performed of patients age ≤18 years undergoing LT between September 2007 and April 2017. SSI identified within the first 30 days were analyzed. Primary endpoints included incidence, classification, risk factors, and outcomes associated with SSIs.We included 86 patients, eight patients (9.3%) developed SSIs. Among segmental grafts (SG) recipients, 7/61 (11.4%) developed SSI. Among whole grafts recipients, 1/25 (4%) developed SSI. SSIs were associated with the presence of biliary complications (35% vs. 3%, p.01; odds ratios 24, 95% CI: 3.41-487.37, p.01). There were no differences in long term graft or patient survival associated with SSI. Patients who developed SSI were more likely to undergo reoperation (50% vs. 16.7%, p = .045) and had an increased total number of hospital days in the first 60 days post-transplant (30.5 vs. 12.5 days, p = .001).SSIs after pediatric LT was less frequent than what has been previously reported in literature. SSIs were associated with the presence of biliary complications without an increase in mortality. SG had an increased rate of biliary complications without an association to SSIs but, considering its positive impact on organ shortage barriers, should not be a deterrent to the utilization of SGs.

Objectives The goal of this study was to describe outcomes of patients with bridge to heart transplantation (BTT) after changes were made to the donor heart allocation system. Background Left ventricular assist devices (LVADs) have been used as a BTT. On October 18, 2018, the donor heart allocation system in the United States was updated. Methods This study identified adults in the United Network for Organ Sharing database with durable, continuous-flow LVAD at listing or implanted while listed between April 2017 and April 2020. Baseline recipient and donor characteristics, waitlist survival, and post-transplantation outcomes were compared pre- and post-allocation system change. Results A total of 1,794 patients met inclusion criteria: 983 in the pre-change period and 814 afterward. The number of patients listed with LVAD decreased nationally over time from 102 in April 2017 to 12 in April 2020 (p Conclusions The number of patients with BTT on the transplant list decreased steadily and dramatically after the allocation system change. Although time to transplant decreased, there was an increase in post-transplant mortality. These data suggest that the risks and benefits of LVAD implantation as a BTT have changed under the new allocation system and that the appropriate indication for this treatment strategy warrants a re-evaluation.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Patient experience has become a priority for healthcare institutions as it affects clinical quality of care, financial reimbursement, provider, and patient satisfaction. We report our experience of improving patient experience measured by Press Ganey surveys in a busy multidisciplinary clinic over 65 months. We optimized patient flow in the clinic by technology-facilitated communication among the clinic staff and by a modest space redesign. We noted a significant improvement in “clinic visit” scores from baseline of 82.1 to 84.6 at year 1, 86.1 at year 2, 88.7 at year 3, and 88.9 at year 4 ( P

The Coronavirus Disease 2019 (COVID‐19) pandemic has had an impact on all facets of our health care system, including life‐saving procedures like organ transplantation. Concerns for potential exposure to the causative severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) have profoundly altered the process of organ donation and recovery that is vital to the execution of organ transplantation. Issues regarding adequate donor evaluation and consent, organ recovery, organ procurement organization (OPO) and donor hospital resources as well as the transplant center’s acceptance of organ offers for their candidates have all required new practice paradigms. Consequently, the ability to treat patients with organ failure, in particular patients with end stage liver disease where no temporizing treatments exist, and to obtain expected excellent outcomes for new liver transplant recipients has been challenged during this time. We summarize some of the negative effects of the current pandemic on organ recovery and liver transplantation as well as offer considerations and strategies for their mitigation that could have a lasting impact on the field even after COVID‐19 has waned.

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

The OPTN's simultaneous liver-kidney (SLK) allocation policy, implemented August 10, 2017, established medical eligibility criteria for adult SLK candidates and created Safety Net kidney allocation priority for liver-alone recipients with new/continued renal impairment. OPTN SLK and kidney after liver (KAL) data were analyzed (registrations as of December 31, 2019, transplants pre-policy [March 20, 2015-August 9, 2017] vs. post-policy [August 10, 2017-December 31, 2019]). Ninety-four percent of SLK registrations met eligibility criteria (99% CKD: 50% dialysis, 50% eGFR). SLK transplant volume decreased from a record 740 (2017) to 676 (2018, -9%), with a subsequent increase to 728 (2019, 1.6% below 2017 volume). For KAL listings within 1 year of liver transplant, waitlist mortality rates declined post-policy versus pre-policy (27 [95% CI = 20.6-34.7] vs. 16 [11.7-20.5]) while transplant rates increased fourfold (46 [32.2-60.0] vs. 197 [171.6-224.7]). There were 234 KAL transplants post-policy (94% Safety Net priority eligible), and no significant difference in 1-year patient/graft survival vs. kidney-alone (patient: 95.9% KAL, 97.0% kidney-alone [p = .39]; graft: 94.2% KAL, 94.6% kidney-alone [p = .81]). From pre- to post-policy, the proportion of all deceased donor kidney and liver transplants that were SLK decreased (kidney: 5.1% to 4.3%; liver: 9.7% to 8.7%). SLK policy implementation interrupted the longstanding rise in SLK transplants, while Safety Net priority directed kidneys to liver recipients in need with thus far minimal impact to posttransplant outcomes.

Organ shortage is a barrier to liver transplantation (LT). Split LT (SLT) increases organ utilization, saving 2 recipients. A simulation of Organ Procurement and Transplantation Network/United Network for Organ Sharing data (2007-2017) was performed to identify whole-organ LT grafts (WLT) that met the criteria for being splittable to 2 recipients. Waitlist consequences presented. Deceased donor (DD) livers transplanted as whole organs were evaluated for suitability to split. Of these DD organs, we identified the adolescent and adult recipients of WLT who were suitable for SLT. Pediatric candidates suitable to share the SLT were ascertained from DD match-run lists, and 1342 splittable DD organs were identified; 438 WLT recipients met the criteria for accepting a SLT. Review of the 438 DD match-run lists identified 420 children next on the list suitable for SLT. Three hundred thirty-three children (79%) underwent LT, but had longer wait-times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P < 0.001). Thirty-three of 420 children died on waitlist after a mean 206 days (standard deviation 317). Sharing organs suitable for splitting increases the number of LT, saving more lives. With careful patient selection, SLT will not be a disadvantage to the adult recipients. With a children-first allocation scheme, SLT will naturally increase the number of allografts because adult organs are too large for small children.

Gastrointestinal illnesses pose a significant worldwide disease burden and are associated with an array of medicinal and surgical therapies. Standard pharmaceutical options have adverse effects, prompting the rise of nutraceutical or food-derivative therapies. Here, we present an overview of the current nutraceutical therapies in gastrointestinal disease. We then introduce the calcium-sensing receptor (CaSR) as a novel therapeutic target. A G-protein-coupled receptor found in apical and basal intestinal cells, the CaSR modulates intestinal fluid secretion and mucosal integrity. Applying nutraceuticals that upregulate the CaSR may alleviate symptoms seen across a spectrum of illnesses. At last, we discuss how nanoparticle technology can be implemented to effectively deliver nutraceuticals to diseased regions of the intestine, thereby minimizing systemic side effects.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

PURPOSE OF REVIEW The regulatory framework set by the Organ Procurement and Transplantation Network (OPTN) and Center for Medicare and Medicaid Services (CMS) for practice of liver transplantation in US is periodically updated and risk adjusted. Therefore, it is prudent for transplant centers to know the rules of engagement as it pertains to their practice. RECENT FINDINGS OPTN besides providing the regulatory oversight for safe and continued practice of transplant centers, provides necessary tools like: advanced statistical models and technological platforms to aid, and guide transplant centers including the necessary safeguards for high-quality transplant care.CMS regulations although had different thresholds to flag underperformance, often covered common grounds similar to the OPTN, therefore considered duplicative and unnecessary. But with much deliberation and consideration CMS undertook a major overhaul to the final rule for re-approval applications, a giant leap in the positive direction for transplant innovation and growth. SUMMARY The duplicative regulatory framework of OPTN and CMS has although achieved the goal of improving 1-year patient outcomes, it has proven costly in terms of slowing innovation, increasing organ discard and stunting growth of transplant volume. But the new updates in effect and also in the pipeline are a long-awaited opportunity for waiting transplant patients.

Objective: Historically, bile in the biliary tract has been considered sterile. Most of the series are based on patients with biliary tract diseases or the bile has been obtained with procedures susceptible to contamination.Methods: We evaluated the bile in a heterogeneous cohort of liver donors and recipient patients, with samples obtained in a sterile way, directly from the gallbladder and the common bile duct.Results: We assessed the bile microbiota in six liver donors and in six liver recipients after whole or split liver procedures in adult or pediatric recipients. Bile samples were studied using PCR sequencing of the 16S ribosomal RNA gene amplification (rDNA).Conclusions: We demonstrated that the bile is sterile, thereby ruling this out as a source of contamination following transplant.

Background Approximately 30% of patients on the liver transplant waitlist experience at least one inactive status change which makes them temporarily ineligible to receive a deceased donor transplant. We hypothesized that inactive status would be associated with higher mortality which may differ on a transplant centers’ or donor service areas’ (DSA) Median MELD at Transplant (MMaT). Methods Multi-state models were constructed (OPTN database;06/18/2013-06/08/2018) using DSA-level and transplant center-level data where MMaT were numerically ranked and categorized into tertiles. Hazards ratios were calculated between DSA and transplant center tertiles, stratified by MELD score, to determine differences in inactive to active transition probabilities. Results 7,625 (30.2% of sample registrants;25,216 total) experienced at least one inactive status change in the DSA-level cohort and 7,623 experienced at least one inactive status change in the transplant-center level cohort (30.2% of sample registrants;25,211 total). Inactive patients with MELD≤34 had a higher probability of becoming re-activated if they were waitlisted in a low or medium MMaT transplant center or DSA. Transplant rates were higher and lower re-activation probability was associated with higher mortality for the MELD 26–34 group in the high MMaT tertile. There were no significant differences in re-activation, transplant probability, or waitlist mortality for inactivated patients with MELD≥35 regardless of a DSA’s or center’s MMaT. Conclusion This study shows that an inactive status change is independently associated with waitlist mortality. This association differs by a centers’ and a DSAs’ MMaT. Prioritization through care coordination to resolve issues of inactivity is fundamental to improving access.

Background Patients with restrictive or hypertrophic cardiomyopathy (RCM/HCM) and congenital heart disease (CHD) do not derive clinical benefit from inotropes and mechanical circulatory support. Concerns were expressed that the new heart allocation system implemented in October 2018 would disadvantage these patients. This paper aimed to examine the impact of the new adult heart allocation system on transplantation and outcomes among patients with RCM/HCM/CHD. Methods We identified adult patients with RCM/HCM/CHD in the United Network for Organ Sharing (UNOS) database who were listed for or received a cardiac transplant from April 2017-June 2020. The cohort was separated into those listed before and after allocation system changes. Demographics and recipient characteristics, donor characteristics, waitlist survival, and post-transplantation outcomes were analyzed. Results The number of patients listed for RCM/HCM/CHD increased after the allocation system change from 429 to 517. Prior to the change, the majority RCM/HCM/CHD patients were Status 1A at time of transplantation; afterwards, most were Status 2. Wait times decreased significantly for all: RCM (41 days vs 27 days; P Conclusions The new allocation system has had a positive impact on time to transplantation of patients with RCM, HCM, and CHD without negatively influencing survival.

Background and aims Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers. Approach and results This article discusses what is known about COVID-19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID-19 pandemic on their patients' care. Conclusions The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID-19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.

AimsTo establish and define a new, not previously reported hepatocellular carcinoma (HCC) variant, termed fibronodular HCC (FN-HCC).MethodsWe retrospectively reviewed 290 HCC cases and identified 29 FN-HCC and 24 scirrhous HCC (SCHCC). Clinical, pathological and radiological features of FN-HCC were reviewed and compared with 30 conventional HCCs (CV-HCC) and SC-HCC.ResultsFN-HCCs were more likely to arise in non-advanced fibrotic livers with lower advanced Barcelona Clinic Liver Cancer (BCLC) stage, had lower rates of progression and longer time to progression and were more likely to be surgically resected compared with CV-HCCs and SC-HCCs. Imaging analysis of FN-HCCs demonstrated higher rates of non-peripheral washout and a new distinct pattern of enhancement which is characterised by the presence of multiple rounded nodules within a lesion embedded in fibrotic-appearing parenchyma.ConclusionsFN-HCC may represent a specific variant of HCC with distinct pathological, radiological and clinical features with potential ramifications for outcome.

Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs. In a recent study of 8 transplant-declined human kidneys on NMP, we discovered microvascular obstructions that impaired microvascular blood flow. However, the nature and physiologic impact of these lesions were unknown. Here, in a study of 39 human kidneys, we have identified that prolonged cold storage of human kidneys induces accumulation of fibrinogen within tubular epithelium. Restoration of normoxic conditions-either ex vivo during NMP or in vivo following transplant-triggered intravascular release of fibrinogen correlating with red blood cell aggregation and microvascular plugging. Combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs leading to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular-targeted nanoparticles. Our study suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential.

Background & Aim The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. Methods Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ⩾40 were followed for 30days or until the earliest occurrence of death or transplant. Results Of 65,776 waitlisted patients, 3.3% had MELD ⩾40 at registration, and an additional 7.3% had MELD scores increase to ⩾40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ⩾40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2–1.6) for patients with MELD 41–44, 2.6 (95% CI 2.1–3.1) for MELD 45–49, and 5.0 (95% CI 4.1–6.1) for MELD ⩾50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. Conclusions Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.

Transplant professionals recognize that the long-term follow-up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, as the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative that sets several priorities that we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long-term follow-up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow-up and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on a joint recognition and mission alignment between our transplant team and our hospital leadership, both of whom contribute resources, recognizing that supporting the long-term welfare of living donors is essential towards the goal of expanding living donor transplantation. This article is protected by copyright. All rights reserved.

Background and Aims Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW). Methods Fourteen small intestinal grafts were procured from deceased donors. HTK and UW were used for the vascular perfusion at the cross clamp, and UW, HTK, or Ringer Lactate were used for the luminal flush at the back table. Therefore, part of the same harvested intestine was stored in cold static storage and in continuous perfusion preservation (with intestinal perfusion unit) simultaneously. Histological samples were collected from the jejunum and ileum at different time points and different preservation conditions. The samples were collected before the initiation of cold storage (T0), after 8 hours of cold static (ST8), or after 8 hours of continuous perfusion preservation (PT8) (n = 161 samples). Blinded histological evaluation was conducted and ischemic damage was determined using the Park/Chiu scale. Results The ileum had less ischemic damage than the jejunum, regardless of using static or continuous perfusion preservation. There was no significantly ischemic damage difference between intestinal grafts flushed and perfused with UW or HTK. Conclusion The jejunum is more susceptible to ischemic injury than the ileum. UW and HTK are equivalent to preserve intestinal graft. This suggests that selective transplantation of ileum could reduce ischemia-related postoperative complications.

Background: The calcium-sensing receptor (CaSR) has been localized and characterized in numerous tissues throughout the body. In the mammalian gastrointestinal tract, the CaSR is known to act as a nutrient sensor and has recently been found to play a role in intestinal fluid and electrolyte balance. This study aims to demonstrate the functionality of the CaSR as a modulator of fluid secretion and absorption along the small intestine. Methods: Small intestine regions (proximal, middle, and distal) were isolated from Sprague Dawley rats and loaded into an ex vivo intestinal perfusion device that provides independent intraluminal and extraluminal (serosa/basolateral) perfusion. The regions were perfused with 5 mM and 7 mM of Ca2+, both in the presence and absence of forskolin (FSK), a potent secretagogue. Control experiments were conducted with intraluminal perfusate containing standard Ringer-HEPES buffer with a physiological concentration of Ca2+ (1 mM). A second set of comparison experiments was performed with intraluminal perfusates containing AC-265347, a CaSR activator and agonist, in the presence of FSK. In all experimental conditions, the intraluminal perfusate contained fluorescein isothiocyanate (FITC)-inulin, a nonabsorbable fluorescent marker of secretion and/or absorption. Intraluminal fluorescence signal was utilized as a measure of water movement at the start of the experiment and every 15 minutes for 90 minutes. Results: Under physiological conditions, increasing the concentration of Ca2+ in the luminal perfusate reduced intestinal fluid secretion in all regions. At a Ca2+ concentration of 7 mM, net fluid absorption was observed in all regions. In the presence of FSK, 5 mM Ca2+significantly decreased fluid secretion and 7 mM Ca2+ abolished FSK-induced fluid secretion. Intraluminal perfusion with 5 mM Ca2+ was as effective as AC-265347, in reducing secretagogue-induced fluid hypersecretion in the proximal and middle regions. Conclusion: This study concludes that apical CaSR is active along the small intestine. Its activation by Ca2+ and/or calcimimetics reduces fluid secretion in a dose-dependent manner, with higher Ca2+ concentrations, or application of a calcimimetic, leading to fluid absorption. We furthermore show that, in the presence of FSK, receptor activation abates FSK secretagogue-induced fluid secretion. This presents a new therapeutic target to address secretory diarrheal illnesses.

Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P

Benefits of belatacept-based immunosuppressive regimens in human immunodeficiency virus (HIV)-positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new-onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV-positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV-positive renal transplant recipient.

The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based.

In the field of transplantation, the demand for organs continues to increase and has far outpaced the supply. This ever-growing unmet need for organs calls for innovative solutions in order to save more lives. The development of new technologies in the field of biomedical engineering might be able to provide some solutions. With the advent of 3D bioprinting, the potential development of tissues or organ grafts from autologous cells might be within the reach in the near future. Based on the technology and platform used for regular 3D printing, 3D bioprinters have the ability to create biologically functional tissues by dispensing layer after layer of bioink and biogel that if left to mature with the proper environment will produce a functional tissue copy with normal metabolic activity. In the present day, 3D-bioprinted bladders, tracheal grafts, bone, and cartilage have proven to be functional after development and implantation in animal models and humans. Promising ongoing projects in different institutions around the world are focused on the development of 3D-bioprinted organs such as the livers and kidneys with integrated vasculature, in order for the tissue to be able to thrive once it has been transplanted. This review focuses on the background, the present, and the future of 3D bioprinting and its potential role in transplantation.

Kaposi sarcoma (KS) may rarely occur in transplant recipients through primary human herpesvirus-8 (HHV-8) infection from a seropositive donor. This report describes a patient who developed hepatic KS after receiving a split liver transplant from an HHV-8-positive donor. The recipient was treated with liposomal doxorubicin after reduction in immunosuppression led to acute cellular rejection. This treatment achieved regression of KS while preserving allograft function, demonstrating a successful therapeutic strategy for this malignancy.

Robotic assisted kidney transplant is the latest technical milestone in kidney transplant surgery. But, unlike other minimal invasive surgery, robotic kidney transplant has been slow to gain popularity despite the ergonomic advantage and lower wound complications, due to the costs involved, therefore questioning its true need in transplant surgery. Clearly the indications of robotic assisted kidney transplant are unclear, further debating its utility. Obesity in kidney transplant has been steadily growing, in accordance with the rising obesity rates worldwide. Obesity leads to poor outcomes after any general surgical procedure due to the higher incidence of complications, and subsequently, negatively impacts graft and patient survival after a kidney transplant. Therefore, some of obese patients can significantly benefit with a robotic kidney transplant and therefore justify its utility and cost. Robotic kidney transplant is not here to replace the open conventional surgery, but rather act as an alternative tool, reserved to benefit certain patients only.

The small intestine is one of the most ischemia-sensitive organs used in transplantation. To better preserve the intestinal graft viability and decrease ischemia-reperfusion injury, a device for extracorporeal perfusion was developed. We present the results for the first series of perfused human intestine with an intestinal perfusion unit (IPU). Five human intestines were procured for the protocol. (1) An experimental segment was perfused by the IPU delivering cold preservation solution to the vascular and luminal side continually at 4 oC for 8 h. (2) Control (jejunum and ileum) segments were preserved in static cold preservation. Tissue samples were obtained for histopathologic grading according to the Park/Chiu scoring system (0 = normal, 8 = transmural infarction). Jejunal experimental segments scored 2.2 with the Park/Chiu system compared to the control segments, which averaged 3.2. Overall scoring for ileum experimental and control segments was equal with 1.6. This data presents proof of concept that extracorporeal intestinal perfusion is feasible. The evidence shows that the IPU can preserve the viability of human intestine, and histopathologic evaluation of perfused intestine is favorable. Our early results can eventually lead to expanding the possibilities of intestinal preservation.

Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.

Purpose of review Liver allograft allocation has been a topic of hot debate for over a decade. New redistricting changes have been proposed by the Liver and Intestinal Transplant Committee to the existing United Network for Organ Sharing (UNOS) liver allocation policy. The basis of this new proposal is similar to the old one with an aim to distribute organs in a fair, efficient and equitable fashion. In this review, we plan to look in depth at the redistribution proposals thus far, their merits and how they may help patients who do not have adequate access to livers. Recent findings Many authors have criticized the proposed changes to organ distribution to reduce geographic disparity in access to liver transplantation. Our focus in this article is to bring forth the most recent literature and proposed changes in the current distribution system. We will also mention two other possible methods that have been proposed to redesign distribution using concentric circles and neighborhoods. In this article, we also look at the economics of the redistricting proposal and its effects on transplant centers. Summary The UNOS Liver and Intestinal Transplant Committee has recommended a proposal using the eight-district model with proximity circles and three additional Model for End-Stage Liver Disease (MELD) points with initial sharing MELD threshold of 25 as a starting point to reduce disparity in patient access to deceased donor livers for transplantation. This proposal has met with significant resistance because of concerns of cost, logistics and impact on existing transplant centers. Other methodologies have also been proposed that have the potential to significantly improve our current disparity of access to life-saving organs. Variation in the supply of donor organs vs. the demand or need for liver transplant by geography and the current defined areas of distribution drive this disparity. Cost benefits to the healthcare system in caring for patients with advanced stages of liver disease may outweigh increased costs of transportation and transplantation. The current allocation boundaries are not optimal for liver distribution, as modeled by all suggested solutions thus far. The need to identify a more optimal and equitable allocation/distribution system is paramount.