The role of extracorporeal membrane oxygenation in adult kidney transplant patients: A qualitative systematic review of literature.

BACKGROUND: A paucity of evidence exists regarding the risks and benefits of Extracorporeal Membrane Oxygenation (ECMO) in adult kidney transplantation. METHODS: This was a systematic review conducted from Jan 1, 2000 to April 24, 2020 of adult kidney transplant recipients (pre- or post- transplant) and donors who underwent veno-arterial or veno-venous ECMO cannulation. Death and graft function were the primary outcomes, with complications as secondary outcomes. RESULTS: Twenty-three articles were identified that fit inclusion criteria. 461 donors were placed on ECMO, with an overall recipient 12-month mortality rate of 1.3% and a complication rate of 61.5%, the majority of which was delayed graft function. Fourteen recipients were placed on ECMO intraoperatively or postoperatively, with infection as the most common indication for ECMO. The 90-day mortality rate for recipients on ECMO was 42.9%, with multisystem organ failure and infection as the ubiquitous causes of death. 35.7% of patients experienced rejection within 6 months of decannulation, yet all were successfully treated. CONCLUSIONS: ECMO use in adult kidney transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO mirrors that of recipients from standard criteria donors. The morbidity and mortality of recipients placed on ECMO are also similar to other patient populations requiring ECMO.

Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective.

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.

Pharmacological management of patients undergoing total pancreatectomy with auto-islet transplantation.

Chronic pancreatitis results in permanent parenchymal destruction of the pancreas gland leading to anatomical and physiological consequences for patients. Surgical management varies, and some patients require total pancreatectomy with autologous islet cell transplantation (TPIAT). Patients undergoing TPIAT require complex and diligent management after surgery. This encompasses the management of glucose control (endocrine function of the pancreas) and supplementing loss of exocrine function of the pancreas with digestive enzymes. Other areas of management include optimizing pain relief while reducing narcotic usage, providing antimicrobial prophylaxis, and reducing loss of islet cells by improving its integrity through anticoagulation and use of anti-inflammatory agents. Each aspect of care is unique to this population. However, comprehensive reviews on its pharmacological management are scarce. This review will discuss the available literature to date surrounding all aspects of pharmacological management of patients undergoing TPIAT.

Selection of parenchymal preserving or total pancreatectomy with/without islet cell autotransplantation surgery for patients with chronic pancreatitis.

BACKGROUND: The selection of surgery between parenchymal preserving (PPS) and total pancreatectomy (TP) with/without islet cell autotransplantation (IAT) for chronic pancreatitis (CP) patients varies based on multiple factors with a scarcity in literature addressing both at the same time. The aim of this manuscript is to present an algorithm for the surgery selection based on dominant area of disease, ductal dilatation, and glycemic control and compare outcomes. METHODS: From 2017 to 2021, CP patients offered surgery at a single institution were retrospectively evaluated. RESULTS: 51 patients underwent surgery (20 [39.2%] TPIAT, 4 [7.8%] TP, and 27 [52.9%] PPS - 9 Whipple procedures, 15 distal pancreatectomies, and 3 duct drainage procedures). No significant difference was observed in baseline characteristics or perioperative outcomes except median length of stay (8 days [IQR 6-10] vs. 13 days [IQR 9-15.5], p < 0.001), attributed to insulin requirement and education for TPIAT group. No differences in postoperative complications, such as clinically significant leak and intrabdominal fluid collection (3 [11.1%] vs 2 [10%], p = 1.0), hemorrhage (0 vs. 2 [10.0%], p = 0.2), delayed feeding (1 [3.7%] vs. 5 [25.0%], p = 0.07), or wound infection (4 [14.8%] vs. 0, p = 0.1) between PPS and TPIAT groups, respectively, were observed nor requirement of long-acting insulin at discharge (2 [15.4%] vs. 7 [43.8%], p = 0.1) for pre-operatively non-diabetic patients. No significant difference in weaning off narcotics and no mortality observed. CONCLUSION: The most appropriate selection of surgery based on the algorithm yields good and comparable outcomes.

Changing opportunities for liver transplant for patients with hepatocellular carcinoma.

INTRODUCTION: Aim was to study the early impact of acuity circle-based allocation implementation system on liver transplantation for hepatocellular carcinoma (HCC) patients. METHODS: We assessed characteristics of HCC and non-HCC deceased donor orthotopic liver transplants (OLT) in the year before (2/2019-2/2020) and after (3/2020-2/2021) introduction of the acuity circle policy using the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database. RESULTS: Total OLTs reduced from 6699 in the preacuity circle era to 6660 in the postacuity circle era (-.6%); this decrease is mostly driven by a decrease in HCC transplants (1529 to 1351; -11.6%). Six out of 11 regions had a reduction in the absolute number and percentage of HCC transplants with significant reductions in regions 2 (-37.8%, p < .001) and 4 (-28.3%, p = .001). DISCUSSION: The introduction of median model for end-stage liver disease (MELD) at transplant minus 3 (MMaT-3) exception points, has created differential opportunities for HCC patients, in low-MELD as opposed to high-MELD areas, despite having the same disease. This effect has become more prominent following the implementation of acuity circle-based allocation system. Ongoing investigation of these trends is needed to ensure that HCC patients are not disparately disadvantaged due to their location.

The role of extracorporeal membrane oxygenation in adult liver transplant patients: A qualitative systematic review of literature.

BACKGROUND: A paucity of evidence exists regarding risks and benefits of extracorporeal membrane oxygenation (ECMO) in adult liver transplantation. METHODS: This was a systematic review conducted from January 1, 2000 to April 24, 2020 of adult liver transplant recipients (pre- or post-transplant) and donors who underwent Veno-arterial or Veno-venous ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. RESULTS: Forty-one articles were identified that fit criteria. A total of 183 donors were placed on ECMO, with recipient complication profiles and mortality that mirrored rates from standard criteria donors. Sixty-one recipients were placed on ECMO intraoperatively or postoperatively. Most patients experienced at least one complication with infections as the most common cause and minimal complications specifically related to ECMO use. Multisystem organ failure (MSOF) and infections were more common among liver recipients who died compared to those who survived. Overall mortality at 90 days was 45.9%. Causes of death were most commonly MSOF and infections. CONCLUSIONS: ECMO use in adult liver transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO parallel that of recipients from standard criteria donors, and morbidity and mortality of recipients placed on ECMO are similar to other ECMO populations.

Type 3c: Understanding pancreatogenic diabetes.

ABSTRACT: Type 3c diabetes, also known as pancreatogenic diabetes, occurs when primary pancreatic disorders damage the pancreatic islets of Langerhans. Although often misdiagnosed as type 2 diabetes, type 3c diabetes is different in cause, clinical presentation, treatment, and prognosis. Patients with type 3c diabetes are more likely to experience complications and death related to hypoglycemic events. This article reviews the causes and management of type 3c diabetes, which is estimated to affect 5% to 10% of all patients with diabetes.

Challenges, highlights, and opportunities in cellular transplantation: A white paper of the current landscape.

Although cellular transplantation remains a relatively small field compared to solid organ transplantation, the prospects for advancement in basic science and clinical care remain bountiful. In this review, notable historical events and the current landscape of the field of cellular transplantation are reviewed with an emphasis on islets (allo- and xeno-), hepatocytes (including bioartificial liver), adoptive regulatory immunotherapy, and stem cells (SCs, specifically endogenous organ-specific and mesenchymal). Also, the nascent but rapidly evolving field of three-dimensional bioprinting is highlighted, including its major processing steps and latest achievements. To reach its full potential where cellular transplants are a more viable alternative than solid organ transplants, fundamental change in how the field is regulated and advanced is needed. Greater public and private investment in the development of cellular transplantation is required. Furthermore, consistent with the call of multiple national transplant societies for allo-islet transplants, the oversight of cellular transplants should mirror that of solid organ transplants and not be classified under the unsustainable, outdated model that requires licensing as a drug with the Food and Drug Administration. Cellular transplantation has the potential to bring profound benefit through progress in bioengineering and regenerative medicine, limiting immunosuppression-related toxicity, and providing markedly reduced surgical morbidity.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

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.

What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model.

Survivorship is a well-established concept in the cancer care continuum with a focus on disease recurrence, quality of life, and the minimization of competing risks for mortality; however, survivorship has not been well studied in liver transplantation (LT). We investigated what survivorship means to LT patients and identified motivations and coping strategies for overcoming challenges after LT. A total of 20 in-depth home interviews were conducted among adults 3 to 6 months after LT. Interviews were conducted by trained qualitative research experts and coded and analyzed using an inductive approach. A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a "second chance" at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%). LT recipients and caregivers identified multiple strategies to cope with post-LT challenges, including relying on a large network of community, spiritual, and virtual support. These findings informed a conceptual model of LT survivorship based on socioecological theory, which identified the following variables influencing survivorship: (1) pretransplant experiences, (2) individual attributes and challenges, (3) interpersonal relationships with caregivers and other social support, (4) community relationships, and (5) large-scale factors including neighborhood and financial issues. LT recipients identified themselves as survivors, and post-LT identities were greatly influenced by pre-LT experiences. These perspectives informed an in-depth conceptual model of survivorship after transplantation. We identified sources of motivation and coping strategies used in LT recovery that could be targets of survivorship interventions aimed at improving post-LT outcomes.

Characterization of extracellular vesicle miRNA identified in peripheral blood of chronic pancreatitis patients.

Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently, there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of EV as biomarkers for pancreatic health and/or as adjuvant therapy would make a difference in management of these patients. The aim of this study was to characterize the miRNA cargo of EV purified from the plasma of CP patients and compared to those of healthy participants. EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle tracking analysis was used to determine frequency and size, while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with EV miRNA cargo. ~ 30 miRNA species were identified to have significantly (p < 0.05) different expression in EV from individuals with CP compared to healthy individuals; ~ 40 miRNA were differentially expressed in EV from pre-diabetic versus non-diabetic CP patients. miR-579-3p, while exhibiting significantly lower (~ 16-fold) expression in CP compared to healthy and lower (~ 24-fold) in CP narcotic users compared to the non-users, is actually enriched (~ 32-fold) within EV in pre-diabetic CP patients compared to non-diabetic CP patients. A unique pattern was identified in female CP patients. These data support the prospect of using a plasma-derived EV cargo to assess pancreatic health and its therapeutic potential in CP patients.

Use of Continuous Glucose Monitoring for evaluation of hypoglycemia pre- and post-operatively for patients undergoing Total Pancreatectomy with Autologous Islet Cell Transplant.

INTRODUCTION: Total pancreatectomy with autologous islet transplant (TPAIT) is indicated for patients with chronic pancreatitis to improve quality of life while reducing complications from hypoglycemia. Continuous glucose monitoring (CGM) was used to assess overall islet function and the incidence of hypoglycemia pre- and post-operatively. METHODS: Nineteen patients who underwent TPAIT at a single center from 2018 to 2020 were included. Pre-operatively, patients were defined by diabetic status. HbA1c, stimulated C-peptide, and CGM were used to characterize glycemic function. RESULTS: Pre-operatively, three patients had diabetes, and 16 patients did not have diabetes. Eight out of 16 non-diabetic patients were insulin independent (50%). Of six non-diabetic patients with > 10% hypoglycemia on pre-operative CGM, 33% were insulin-independent post-operatively (P = .3). Of non-diabetic patients with ≥ 80% time in the euglycemic range, 62% were insulin-independent post-operatively (P = .2). For patients without diabetes, the median percent time in hypoglycemic range was reduced from 8% to 1% (P = .001). Delta C-peptide had a positive correlation with islet yield (P = .03). DISCUSSION: Conventional evaluation of TPAIT patients assesses primarily beta cell function. As pancreatogenic diabetes is concerning principally for the risk of hypoglycemia, assessment of alpha cell function can improve the quality of care. CGM better captures islet function and increases the identification of hypoglycemia.

The role of extracorporeal membrane oxygenation in pediatric abdominal transplant patients: A qualitative systematic review of literature.

BACKGROUND: Advances in ECMO have made it a useful adjunct in critically ill pediatric patients; however, a dearth of evidence exists regarding risks and benefits in pediatric abdominal transplantation. The purpose of this study was to perform a qualitative systematic review of outcomes in pediatric patients undergoing ECMO support pre- or post-abdominal organ transplantation. METHODS: This was a systematic review conducted from Jan 1, 1989, to April 24, 2020, via PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and ClinicalTrials.gov of all pediatric solid abdominal organ transplant recipients (pre- and post-transplant) and donors who underwent V-A or V-V ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. RESULTS: Fourteen articles were identified that fit criteria, with 88% being case reports. Three patients were donors placed on ECMO, with no mortality among the 8 recipients of organs from these donors. Nineteen recipients were placed on ECMO. All were liver transplants. Most patients experienced at least one complication (84%), with bleeding as the most common cause (44%). Mortality was 26%. Causes of death included multiorgan system failure (n = 3), heart failure (n = 1), Systemic inflammatory response syndrome (n = 1), abdominal compartment syndrome (n = 3), bleeding (n = 1), septic shock from aspergillus (n = 1), and hepatic artery thrombosis (n = 2). CONCLUSIONS: The data are poor on ECMO usage in pediatric abdominal transplantation. While complications were high, mortality did not appear to be related to ECMO usage and was relatively low given the severity of patient illness.

Portal flow dynamics after total pancreatectomy and autologous islet cell transplantation.

BACKGROUND: Portal vein thrombosis (PVT) is a serious complication of total pancreatectomy and autologous islet cell transplant (TPAIT); therefore, portal flow dynamics are monitored by Doppler ultrasound postoperatively. The practical value of scheduled Doppler ultrasound examinations and the relationship between portal vein velocity, liver function, and complications have not been clearly studied. METHODS: A retrospective review of 16 TPAIT was performed. Correlation analysis of portal vein velocity with indices of liver function, portal pressure, and volume of islet cells infused was conducted. RESULTS: There was no correlation between portal vein velocity and postoperative liver function tests (LFTs). Larger volume of islet cells infused and higher intraoperative portal pressure correlated with decreased postoperative portal flow. There was no significant difference in portal pressure, portal vein velocity, or LFTs between those with normal and abnormal pre-infusion liver histopathology. While no PVT occurred, there were two cases of postoperative bleeding related to anticoagulation. CONCLUSION: Segmental portal vein velocities are low in the setting of high tissue volume and portal pressure, but are not associated with variation in LFTs. Therefore, patient management in response to changes in velocities without clinical symptoms may be unnecessary.

The impact of post-transplant diabetes mellitus on liver transplant outcomes.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is common after liver transplantation (LT). Yet, how PTDM relates to graft outcomes and survival needs elucidation as more individuals are transplanted for nonalcoholic fatty liver disease (NAFLD). METHODS: This single-center, retrospective study of adult LT recipients (2003-2016) identified PTDM incidence and associations with graft steatosis, rejection, and post-LT patient survival. Multivariable analysis investigated predictors of PTDM. Kaplan-Meier curves depicted patient survival 5 years post-LT. RESULTS: Among 415 adult LT recipients, 23% had pre-LT DM and 13% were transplanted for NAFLD. PTDM incidence was 34.7%, 46.9%, and 56.2% and overall survival was 90%, 80.9%, and 71.7% at 1, 3, and 5 years, respectively. Over a third of non-NAFLD patients developed PTDM. Half of PTDM cases developed by 6 months and 75% by 12 months. The PTDM group had more rejection episodes compared to no PTDM (31.9% vs 21.8%, P = 0.055), with trends toward worse patient survival 5 years post-LT (log-rank test P = 0.254). Age was the only significant predictor of PTDM. CONCLUSIONS: Post-transplant diabetes mellitus occurs rapidly in the post-LT period and is a significant problem for both NAFLD and non-NAFLD LT recipients. Age is a significant risk factor for PTDM. Outcomes trended toward increased rejection and worse survival among PTDM individuals, suggesting the benefit of early strategies targeting glucose control.

Islet Transplantation in Children.

PURPOSE OF REVIEW: Transplantation of the islets of Langerhans or the pancreas aims to restore blood sugar control. We review both forms of transplantation in children. RECENT FINDINGS: Allogenic islet transplantation typically in to the liver via the portal vein may be a potential alternative to pancreas transplantation in the future. Autologous islet transplantation after total pancreatectomy is effective for debilitating symptoms of recurrent and chronic pancreatitis. Chronic pancreatitis in children is most often related to genetic mutations but is otherwise similar to adults with eventual exocrine and endocrine failure. Removal of the pancreas ameliorates pain, and islet transplantation preserves endocrine function to the extent allowed by the damage sustained by the pancreas from chronic inflammation. Despite the complexity of the operative procedure, the outcome of total pancreatectomy and autologous islet transplantation in children has been excellent including quality of life.

Visceral transplantation in patients with intestinal-failure associated liver disease: Evolving indications, graft selection, and outcomes.

Intestinal failure (IF)-associated liver disease (IFALD) is widely recognized as a lethal complication of long-term parenteral nutrition. The pathophysiology of IFALD is poorly understood but appears to be multifactorial and related to the inflammatory state in the patient with IF. Visceral transplant for IFALD includes variants of intestine, liver, or combined liver-intestine allografts. Graft selection for an individual patient depends on the etiology of IF, abdominal and vascular anatomy, severity of IFALD, and potential for intestinal rehabilitation. The past decade has witnessed dramatic improvement in the management of IFALD, principally due to improved lipid emulsion formulations and the multidisciplinary care of the patient with IF. As the recognition and treatment of IFALD continue to improve, the requirement of liver-inclusive visceral grafts appears to be decreasing, representing a paradigm shift in the care of the patient with IF. This review highlights the current indications, graft selection, and outcomes of visceral transplantation for IFALD.

Pancreatic cystosis in patients with cystic fibrosis: A qualitative systematic review.

BACKGROUND: Patients with cystic fibrosis (CF) and a CFTR gene mutation may present with a variety of pancreatic disorders. The presence of multiple macrocysts (>1 cm) replacing the entire pancreatic parenchyma is termed pancreatic cystosis. Lack of clear data makes clinical decision making challenging and controversial. The aim of this review is to perform a qualitative systematic analysis of the literature with intention to evaluate management plans. METHODS: Electronic databases MEDLINE, Embase, and Scopus were searched for relevant studies, and 19 studies describing patients with pancreatic cystosis were included and analyzed for clinical features and therapy offered. RESULTS: The data of 24 patients were collected from included studies. Eight cases (33%) had a documented CFTR gene mutation and 10 (42%) were symptomatic at presentation. Imaging modalities included ultrasound in 18 (75%), CT in 12 (50%), and MRI in 8 (33%) cases. An average size of the largest cyst was 5.4 cm. 6 (25%) patients were offered therapy that described surgical (3), endoscopic (1), or medical therapy (2). Surgeries offered included total pancreatectomy, partial pancreatic resection of uncertain extent, and complex cyst resection. Endoscopic treatment was cystogastrostomy. Novel medical treatment was utilized with Doxepin, Propantheline, and Clonidine, resulting in reduction in cyst size and overall clinical improvement. CONCLUSION: Patients with pancreatic cystosis should not be denied treatment when necessary. This literature review is the most comprehensive thus far of cystic fibrosis and pancreatic cystosis, and it did not provide identification of a definitive treatment plan or demonstrate contraindication to specific therapies.