bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 3-month, Multicenter, Randomized, Open-label Study to Evaluate the Impact on Wound Healing of the Early (vs Delayed) Introduction of Everolimus in De Novo Kidney Transplant Recipients, With a Follow-up Evaluation at 12 Months After Transplant (NEVERWOUND Study)
Authors: Manzia Tommaso Maria , Carmellini Mario , Todeschini Paola , Secchi Antonio , Sandrini Silvio , Minetti Enrico , Furian Lucrezia , Spagnoletti Gionata , Pisani Francesco , Piredda Gian Benedetto , Cappelli Gianni , Tisone GIuseppe 
Published: July 2019

Background.
The risk of wound healing complications (WHCs) and the early use of mammalian target of rapamycin inhibitors after kidney transplantation (KT) have not been fully addressed.

Methods.
The NEVERWOUND study is a 3-month, multicenter, randomized, open-label study designed to evaluate whether a delayed (ie, 28 ± 4 d posttransplant) immunosuppression regimen based on everolimus (EVR) reduces the risk of WHC versus EVR started immediately after KT. Secondary endpoints were treatment failure (biopsy-proven acute rejection, graft loss, or death), delayed graft function, patient and graft survival rates, and renal function.

Results.
Overall, 394 KT recipients were randomized to receive immediate (N = 197) or delayed (N = 197) EVR after KT. At 3 months, WHC-free rates in the immediate EVR versus delayed EVR arm, considering the worst- and best-case scenario approach, were 0.68 (95% confidence interval [CI], 0.62-0.75) versus 0.62 (95% CI, 0.55-0.68) (log-rank P = 0.56) and 0.70 (95% CI, 0.64-0.77) versus 0.72 (95% CI, 0.65-0.78) (log-rank P = 0.77), respectively. The 3- and 12-month treatment failure rates, delayed graft function and renal function, and patient and graft survival were not different between the arms.

Conclusions.
The early introduction of EVR after KT did not increase the risk of WHC, showing good efficacy and safety profile.
Incidence, Predictors, and Impact on Survival of Long-term Cardiovascular Events After Liver Transplantation
Authors: Sastre Lydia , García Raquel , Gándara Julián-Gonzalo , Ruiz Pablo , Lombardo Julissa , Colmenero Jordi , Navasa Miquel , Crespo Gonzalo 
Published: July 2019

Background:
Information on the risk factors, particularly kidney function, and impact of long-term cardiovascular events (CVE) after liver transplantation (LT) remains scarce.

Methods:
This is a retrospective, single-center study that included consecutive LT recipients between 2007 and 2017. The incidence of CVE, their risk factors, and their impact on patient survival were investigated.

Results:
We included 627 LT recipients. The incidence of CVE was 8% and 20% at 12 and 60 months after LT, respectively. The independent risk factors of long-term (beyond 12 mo) CVE were age at LT (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.07), male gender (HR, 2.48; 95% CI, 1.21-5.05), history of pre-LT cardiovascular disease (HR, 2.19; 95% CI, 1.2-3.98), and immunosuppression with cyclosporine A (HR, 1.93; 95% CI, 1.14-3.3). In patients with pre-LT cardiovascular disease, creatinine levels 12 months after LT significantly impacted the risk of long-term CVE. Long-term CVE (HR, 2.12; 95% CI, 1.24-3.61), hepatitis C as the etiology of liver disease (HR, 2.18; 95% CI, 1.29-3.67), cytomegalovirus infection (HR, 1.89; 95% CI, 1.08-3.3), and donor age (HR, 1.02; 95% CI, 1.01-1.04) were independent factors associated with post-LT patient death.

Conclusions:
Age, male gender, cardiovascular disease before LT, and cyclosporine A were associated with the risk of long-term CVE. The impact of serum creatinine was restricted to patients with pre-LT cardiovascular disease. In these patients, preservation of kidney function early after LT may lessen the incidence of CVE, which are an independent predictor of post-LT death.
New Evidence Supporting Increased Use of Split Liver Transplantation
Authors: Perkins James D. , Dick Andre A. , Healey Patrick J. , Montenovo Martin I. , Biggins Scott W. , Sibulesky Lena , Reyes Jorge D. 
Published: July 2019

Background.
Young children and small-statured candidates are dying on liver candidate waitlists. The Organ Procurement and Transplantation Network and United Network for Organ Sharing have proposed a split liver (SL) variance encouraging transplant programs to split more livers to aid these smaller statured candidates.

Methods.
We evaluated the US experience of splitting donor livers during 2002–2016. The results of our analysis provide new evidence to support this variance.

Results.
During 2002–2016, SL grafts from 935 donors were transplanted into 1870 recipients. Controlling for recipient factors and using time period and program identification as random variables, a multivariable mixed Cox proportional hazards model for graft failure revealed that donor aged 3–10 years had a relative risk (RR) of 3.94 (2.86–5.44), and donor aged >30 years had a RR of 1.94 (1.59–2.35) for graft failure. Donor-to-recipient body surface area ratio <0.90 had a RR of 1.40 (1.13–1.75). Programs with experience transplanting <23 SLs had a RR of 1.43 (1.21–1.75). The same program transplanting both split segments had a RR of 1.38 (1.20–1.59).

Conclusions.
Splitting protocols based on these findings could improve graft survival after SL transplantation, which would encourage programs to opt into splitting more livers. The new protocols may consider donor age restrictions, necessary program experience, donor with body surface area appropriate for recipient, and improved logistical factors to share segments between transplant programs. The result would likely be a drastic reduction in liver waitlist deaths for young children and small-statured candidates.
Implementing a Ureteric Magnetic Stent in the Kidney Transplant Setting: Report of 100 Consecutive Cases
Authors: Capocasale Enzo , Cremaschi Elena , Valle Raffaele Dalla , Ferretti Stefania , Pellegrino Carlo , Iaria Maurizio , Puliatti Carmelo 
Published: July 2019

Background.
Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease. The double-J-stent has been used to prevent urological complications (UCs), but it requires cystoscopy extraction. The novel magnetic black star (MBS) stent provided with a customized retrieval device (9 or 15 Fr) has been developed to spare cystoscopy. Scope of the paper is to analyze MBS in 100 consecutive KTs.

Methods.
We report a retrospective analysis of 100 consecutive KT performed between April 2015 and September 2018 using MBS (4.8 Fr, 15 cm) to protect Lich-Gregoir ureteroneocystotomy. MBS was removed 4 weeks after KT by either the 9 Fr (61 cases) or the 15 Fr (39 cases) retrieval device.

Results.
Intraoperative MBS insertion was straightforward in all cases, and its extraction was carried out in the outpatient setting in 93 patients. Extraction time was <30 seconds in 45 out of 61 patients (73.8%) and in 38 out of 39 patients (97.4%) using the 9 Fr and the 15 Fr retrieval device, respectively. In 15 patients, MBS removal took between 30 seconds and 3 minutes. Only 2 cases required extraction by cystoscopy. We observed 2 UC (ureteric leak and stenosis), 8 urinary tract infections, and 9 stent-related symptoms. 7 patients experienced distressing pain according to Visual Analog Scale for Pain.

Conclusions.
In our cohort, MBS appeared to be safe and cost-effective. We advocate its routine implementation in KT because of an easy and comfortable extraction in the outpatient setting even by nondedicated staff, without detrimental impact on UC and urinary tract infection rates.
Do Social Determinants Define “Too Sick” to Transplant in Patients With End-stage Liver Disease?
Authors: Bababekov Yanik J. , Hung Ya-Ching , Chang David C. , Rickert Charles G. , Adler Joel T. , Bethea Emily , Pomfret Elizabeth A. , Pomposelli James J. , Yeh Heidi 
Published: July 2019

Background.
Delisting for being “too sick” to be transplanted is subjective. Previous work has demonstrated that the mortality of patients delisted for “too sick” is unexpectedly low. Transplant centers use their best clinical judgment for determining “too sick,” but it is unclear how social determinants influence decisions to delist for “too sick.” We hypothesized that social determinants and Donor Service Area (DSA) characteristics may be associated with determination of “too sick” to transplant.

Methods.
Data were obtained from the Scientific Registry of Transplant Recipients for adults listed and removed from the liver transplant waitlist from 2002 to 2017. Patients were included if delisted for “too sick.” Our primary outcome was Model for End-Stage Liver Disease (MELD) score at waitlist removal for “too sick.” Regression assessed the association between social determinants and MELD at removal for “too sick.”

Results.
We included 5250 delisted for “too sick” at 127 centers, in 53 DSAs, over 16 years. The mean MELD at delisting for “too sick” was 25.8 (SD ± 11.2). On adjusted analysis, social determinants including age, race, sex, and education predicted the MELD at delisting for “too sick” (P < 0.05).

Conclusions.
There is variation in delisting MELD for “too sick” score across DSA and time. While social determinants at the patient and system level are associated with delisting practices, the interplay of these variables warrants additional research. In addition, center outcome reports should include waitlist removal rate for “too sick” and waitlist death ratios, so waitlist management practice at individual centers can be monitored.
Metformin Attenuates Cyclosporine A-induced Renal Fibrosis in Rats
Authors: Lin Can-Xiang , Li Yan , Liang Shi , Tao Jun , Zhang Li-Sui , Su Yang-Fan , Huang Yun-Xi , Zhao Zong-Kai , Liu Shan-Ying , Zheng Jun-Meng 
Published: July 2019

Background.
The aim of the present study was to investigate the therapeutic potential of metformin in preventing cyclosporine A (CsA)-induced nephrotoxicity.

Methods.
Three groups of adult male Sprague-Dawley rats were treated with vehicle, CsA, and CsA + metformin for 4 weeks following 1 week on low sodium diet, respectively. At the end of treatment, all animals were euthanized, and the samples of kidney, urine, and blood were collected for functional, morphological, and molecular biological evaluation.

Results.
Metformin effectively prevented CsA-induced renal dysfunction with increased creatinine clearance rate and reduced blood urea nitrogen and serum creatinine, as well as less proteinuria in comparison to the CsA group. Morphologically, metformin ameliorated CsA-induced renal fibrosis and tissue collapse in the areas of arteries, glomeruli, and proximal tubules. We further demonstrated that the antifibrotic effects of metformin in kidneys treated with CsA were associated with decreased phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2).

Conclusions.
In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway.
Long-term Seroprotection of Varicella-zoster Immunization in Pediatric Liver Transplant Recipients
Authors: Verolet Charlotte M. , Pittet Laure F. , Wildhaber Barbara E. , McLin Valérie A. , Rodriguez Maria , Grillet Stéphane , Siegrist Claire-Anne , Posfay-Barbe Klara M. 
Published: July 2019

Background.
Chickenpox is a highly contagious vaccine-preventable disease that can lead to severe complications, especially in immunocompromised patients. Varicella-zoster virus (VZV) vaccine appears to be safe and immunogenic in pediatric solid organ transplant recipients, but there are few data on the long-term vaccine-induced seroprotection.

Methods.
In this prospective interventional study, we offered 2 doses of VZV vaccine to all eligible and nonseroprotected children seen 1 year after liver transplant. Vaccine responses were measured 1 month later and yearly thereafter. Vaccine safety was closely monitored. A supplementary dose was administered if protective levels were not reached/maintained.

Results.
Among 121 enrolled patients, 49 were vaccinated and followed during 5.5 years (interquartile range, 3.7-8.0). Their seroconversion rate reached 100% (97.5% confidence interval [CI], 92.7-100). Low VZV-antibody concentration (≤400 UI/L) after the first 1–2 dose/s was associated with the need for a supplementary dose (odds ratio, 15.0; 95% CI, 3.4-67.0, P = 0.001) and was given to 31% (15/47) of children at 1.1 year (interquartile range, 0.9-3.9). Although antibody concentrations declined during follow-up, 96% (95% CI, 86.0-99.5) of patients maintained protective antibody concentrations at a median of 5.5 years after vaccination. One breakthrough disease was identified.

Conclusions.
VZV immunization of pediatric solid organ transplant recipients confers sustained seroprotection.
Plasmacytoid Dendritic Cell–driven Induction of Treg Is Strain Specific and Correlates With Spontaneous Acceptance of Kidney Allografts
Authors: Oh Nicholas A. , O’Shea Thomas , Ndishabandi Dorothy K. , Yuan Qing , Hong Shuahuan , Gans Jared , Ge Jifu , Gibney Sean , Chase Catharine , Yang Chao , Rosales Ivy , Shinoda Kazunobu , Drew Benjamin , Kojima Lisa , Russell Paul S. , Madsen Joren C. , Colvin Robert B. , Alessandrini Alessandro 
Published: July 2019

Background.
DBA/2J kidney allografts, but not heart allografts, are spontaneously accepted indefinitely in C57BL/6 (B6) mice, through regulatory tolerance mechanism dependent on Foxp3+ cells. In contrast, B6 kidneys are rejected within a week in DBA/2J recipients. We hypothesized that the tolerogenic difference of the kidneys might be due to differences in number or function of plasmacytoid dendritic cells (pDCs), because these cells are potent inducers of Foxp3+ cells.

Methods.
pDCs from murine bone marrow, native kidneys, and spontaneously accepted kidney allografts were analyzed using flow cytometry and immunohistochemical staining. Naive T cells were cocultured with pDCs in specific strain combinations and analyzed for FoxP3 induction and functionality. MEK/ERK and NFκB inhibitors were used to assess the regulatory T-cell induction pathways. pDCs and T-cell cultures were adoptively transferred before heterotopic heart transplantation to assess allograft survival.

Results.
DBA/2J pDCs were more potent in inducing Foxp3+ in B6 T cells than the reverse combination, correlating with survival of the kidney allografts. Foxp3 induction by pDCs in vitro was dependent on pDC viability, immaturity, and class II MHC mismatch and blocked by MEK/ERK and NFκB inhibition. pDC-induced Foxp3+ T cells suppressed proliferation of B6 T cells in vitro, and adoptive transfer into B6 recipients 2 weeks before heterotopic DBA/2J heart transplantation resulted in prolonged allograft survival.

Conclusions.
These data suggest that pDC-induced regulatory T cells are dependent on downstream signaling effects and on strain-dependent, MHC class II disparity with naive T cells, which may explain organ- and strain-specific differences in spontaneous tolerance.
First European Case of Simultaneous Liver and Pancreas Transplantation as Treatment of Wolcott-Rallison Syndrome in a Small Child
Authors: Nordström Johan , Lundgren Markus , Jorns Carl , Fischler Björn , Arnell Henrik , Dlugosz Rafal , Sandberg John , Wennberg Lars , Nowak Greg 
Published: July 2019

Background.
The concept of organ transplantation as treatment for complex genetic conditions, including Wolcott-Rallison syndrome (WRS), continues to show promise. Liver transplantation is essential for survival of patients with WRS, and pancreas transplantation cures their type I diabetes mellitus.

Methods.
The recipient, a 3-year-old girl weighing 14 kg at the time of transplantation, suffered from major complications of WRS, including repetitive liver failure episodes and poorly controlled diabetes. The patient underwent a nonacute, combined, simultaneous liver and pancreas transplantation from a pediatric donor without using the en bloc technique.

Results.
Well-preserved graft functions at 2-year follow-up with normal liver and pancreas function.

Conclusions.
This is the first case report of simultaneous liver and pancreas transplantation as treatment of WRS in a small child in Europe. Two-year follow-up demonstrates that organ transplantation can halt life-threating recurrent liver failure episodes and cure type 1 diabetes.
Kidney After Liver Transplantation Matched-pair Analysis: Are Kidneys Allocated to Appropriate Patients to Maximize Their Survival?
Authors: Eerhart Michael J. , Reyes José A. , Leverson Glen E. , Danobeitia Juan S. , Blanton Casi L. , Zitur Laura J. , Chlebeck Peter J. , Fernandez Luis A. 
Published: July 2019

Background.
Kidney after liver transplantation (KALT) is the best therapeutic option for patients with end-stage renal disease after orthotopic liver transplantation (OLT). New allocation policies prioritize kidneys to patients in renal failure within the first year following OLT. There is little data on how kidney quality, measured by kidney donor profile index (KDPI), impacts KALT survival outcomes.

Methods.
The United Network for Organ Sharing database was queried for adult KALT recipients from 1988 to 2015 and compared to their paired kidney transplant alone (KTA) recipients. Seven hundred forty-five pairs were stratified into 3 KDPI subgroups and compared patient survival, graft survival, and death-censored graft survival among matched-paired recipients.

Results.
Overall, KTA recipients had superior patient and graft survival compared with the KALT group. KTA patient survival was superior for all 3 KDPI subgroups analysis. KTA graft survival was superior compared with KALT recipients of KDPI 21%–85% kidneys. Inferior graft half-life was observed in KALT versus KTA recipients with KDPI 21%–85% and >85%.

Conclusions.
From a utilitarian perspective, it is important that kidneys are allocated to recipients that are able to maximize their benefit from the full life of the organ. In KTA recipients, graft quality correlates directly to graft survival. However, in KALT patients receiving the matched-pair kidneys of the KTA recipients, patient mortality, rather than kidney quality, dictates graft survival significantly. As allocation practices continue developing, utilization of expanded criteria kidneys that better match anticipated patient and graft survival should be strongly considered to maximize the benefits of limited resources for the greatest number of patients.
Impact of a Mobile Health Intervention on Long-term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial
Authors: Geramita Emily M. , DeVito Dabbs Annette J. , DiMartini Andrea F. , Pilewski Joseph M. , Switzer Galen E. , Posluszny Donna M. , Myaskovsky Larissa , Dew Mary Amanda 
Published: July 2019

Background.
In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence.

Methods.
Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups’ nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics’ associations with nonadherence.

Results.
One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%–81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%–23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05).

Conclusions.
Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.
Ileostomy After Intestinal Transplantation: The First in Depth Report on Techniques, Complications, and Outcomes
Authors: Dumronggittigule Wethit , Venick Robert S. , Dubray B. John , Cheng Elaine C. , Duffy John P. , Marcus Elizabeth A. , Busuttil Ronald W. , Farmer Douglas G. 
Published: July 2019

Background.
Temporary ileostomy during intestinal transplantation (ITx) is the standard technique for allograft monitoring. A detailed analysis of the ITx ileostomy has never been reported.

Methods.
A retrospective review of a single-center ITx database was performed. The analysis was divided into ileostomy formation and takedown episodes.

Results.
One hundred thirty-five grafts underwent ileostomy formation, and 79 underwent ileostomy takedown. Median age at ITx was 7.7 years and weight was 23 kg. Allograft types were intestine (22%), liver/intestine (55%), multivisceral (16%), and modified multivisceral (7%). Sixty-four percent had 1-stage ITx, whereas 36% required 2-staged ITx. Final ileostomy types were end (20%), loop (10%), distal blowhole (59%), and proximal blowhole (11%). Ileostomy formation: Thirty-one grafts had complications (23%), including prolapse (26%), ischemia (16%), and parastomal hernia (19%). Twelve required surgical revision. There were no significant differences in graft type, ileostomy type, survival, and ileostomy takedown rate between grafts with and without complications. Colon inclusive grafts had higher complication rates (P = 0.002). Ileostomy takedown: Ileostomy takedown occurred at a median of 422 days post-ITx. Twenty-five complications occurred after 22 takedowns (28%), including small bowel obstruction (27%) and abscess (18%). Fifteen grafts required surgical correction. Recipients with complications had longer hospital stay (17 versus 9 d; P = 0.001) than those without complications. Graft type, ileostomy type, and survival were not different.

Conclusions.
The first of its kind analysis of the surgical ileostomy after ITx reveals that most recipients can undergo successful ileostomy formation/takedown, complication rates are significant but within an acceptable range, and complications do not affect survival. This study demonstrates that the routine use of transplant ostomies remains an acceptable practice after ITx. However, true analysis of risk and benefit will require a randomized control trial.