bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Functional Recovery Among Older Survivors of Major Surgery
Authors: Becher Robert D. , Murphy Terrence E. , Gahbauer Evelyne A. , Leo-Summers Linda , Stabenau Hans F. , Gill Thomas M. 
Published: February 2019

Objective:
The objectives of the current study were 2-fold: first, to evaluate the incidence and time to recovery of premorbid function within 6 months of major surgery and second, to identify factors associated with functional recovery among older persons who survive a major surgery with increased disability.

Background:
Most older persons would not choose a surgical treatment resulting in persistently increased postsurgical disability, even if survival was assured. Potential predictors of functional recovery after major surgery have, however, not been well-studied among geriatric patients.

Methods:
It is a prospective longitudinal study of 754 community-living persons 70 years or older. The analytic sample included 266 person-admissions in which participants survived major surgery with increased disability and were monitored on a monthly basis for 6 months.

Results:
Of the 266 person-admissions assessed, 174 (65.4%) recovered to their presurgical level of function, with median time to recovery of 2 months (interquartile range, 1–3), whereas 16 (6.0%) died. Two factors were significantly associated with an increased likelihood of functional recovery: being nonfrail (hazard ratio 1.60; 95% confidence interval 1.03–2.51; P = 0.038) and having elective surgery (hazard ratio 1.72; 95% confidence interval 1.14–2.59; P = 0.009). Three factors were associated with a reduced likelihood of functional recovery: hearing impairment, greater increase in postsurgical disability in the month after hospital discharge, and years of education.

Conclusions:
Among older persons, nonfrailty and elective surgery were positively associated with functional recovery, whereas hearing impairment, greater increases in postsurgical disability, and years of education were associated with higher risk of protracted disability.
A Simple Method of Intracorporeal “W-shaped” Liver Retraction Technique for Minimally Invasive Gastric Cancer Surgery
Authors: Wang Chih-Jung , Chao Ying-Jui , Sy Edgar D. , Shan Yan-Shen 
Published: February 2019

Background:
Minimally invasive gastric cancer surgery requires an extended liver retraction in order to provide optimal operative view, working space for lymph node dissection, and esophageojejunal reconstruction. Ideally, it should avoid reposition of the retractor, additional skin incision or puncture, and liver parenchyma injury. Herein, we introduced an intracorporeal W-shaped liver retraction technique (W-LRT) for minimally invasive gastric cancer surgery without an additional incision or abodminal puncture.

Methods:
Between October 2013 and October 2016, the W-LRT was applied in 80 patients undergoing minimally invasive gastric cancer surgery. The W-LRT was performed using one 75 cm 3-0 monocryl suture with its end fixed to one hemoclip. The perioperative outcome was recorded.

Results:
The W-LRT was applied in 80 gastric cancer patients using either laparoscopic approach (N=69) or robotic approach (N=11). The mean age was 62.7±14 years and the mean body mass index (BMI) was 24.1±3.6 kg/m2. The time required for W-LRT was 5.6±5.2 minutes in laparoscopic approach and 6.2±4.7 minutes in robotic approach. This technique was successfully applied in all procedures and no other technique or additional instrument was required. Major complications developed in 7 patients (8.8%), classified as greater than Clavien-Dindo classification II; however, there was neither any intraoperative nor postoperative major complication related to W-LRT. The length of hospital stay was 9.1±4.4 days.

Conclusions:
In laparoscopic or robotic gastric cancer surgery, the W-LRT can provide excellent operative view during lymph node dissection and reconstruction of esophagojejunostomy and eliminate an additional skin incision or abdominal puncture.
The acute inflammatory response after trauma is heightened by frailty: A prospective evaluation of inflammatory and endocrine system alterations in frailty
Authors: Palmer James , Pandit Viraj , Zeeshan Muhammad , Kulvatunyou Narong , Hamidi Mohammad , Hanna Kamil , Fain Mindy , Nikolich-Zugich Janko , Zakaria El-Rasheid , Joseph Bellal 
Published: February 2019

BACKGROUND
Frailty is a geriatric syndrome characterized by decreased physiological reserves, increased inflammation, and decreased anabolic-endocrine response. The biomarkers associated with frailty are poorly understood in trauma. The aim of this study was to analyze the association between frailty and immune: IL-1β, IL-6, IL-2Rα, tumor necrosis factor (TNF)-α, and endocrine biomarkers: insulin-like growth factor-1 and growth hormone in trauma patients.

METHODS
We conducted a 1-year (2017–2018) prospective analysis of geriatric (≥65 years) trauma patients admitted to our Level I trauma center. Frailty was measured using the trauma-specific frailty index (TSFI) and blood samples were collected within 24 hours of admission. Patients were stratified into two groups: frail (TSFI > 0.25) and nonfrail (TSFI ≤ 0.25). We then measured the levels of immune and endocrine biomarkers by a colorimetric output that was read by a spectrophotometer (Quantikine ELISA). The outcome measures were the levels of the immune and endocrine markers in the two groups. Multivariable linear regression was performed.

RESULTS
A total of 100 geriatric trauma patients were consented and enrolled. The mean age was 77.1 ± 9.8 years and 34% were female. Thirty-nine (39%) patients were frail. Frail patients were more likely to present after falls (p = 0.01). There was no difference in age (p = 0.78), sex (p = 0.77), systolic blood pressure (p = 0.16), and heart rate (p = 0.24) between the two groups. Frail patients had higher levels of TNF-α (p = 0.01), IL-1β (p = 0.01), and IL-6(p = 0.01) but lower levels of growth hormone (p = 0.03) and insulin-like growth factor-1 (p < 0.04) compared with nonfrail patients. There was no difference in the level of IL-2Rα (p = 0.25). On regression analysis, frailty was positively correlated with the levels of proinflammatory biomarkers, that is, TNF- α, IL-1 β, and IL-6 and negatively correlated with endocrine biomarkers.

CONCLUSION
This study supports the association between frailty and immune and endocrine markers. Frailty acts synergistically with trauma in increasing the acute inflammatory response. Moreover, frail patients have lower levels of anabolic hormones. Understanding the inflammatory and endocrine response in frail trauma patients may result in better therapeutic strategies.
Effect of Timing and Complement Receptor Antagonism on Intragraft Recruitment and Protolerogenic Effects of Mesenchymal Stromal Cells in Murine Kidney Transplantation
Authors: Casiraghi Federica , Todeschini Marta , Azzollini Nadia , Cravedi Paolo , Cassis Paola , Solini Samantha , Fiori Sonia , Rota Cinzia , Karachi Aida , Carrara Camillo , Noris Marina , Perico Norberto , Remuzzi Giuseppe 
Published: February 2019

Background.
Mesenchymal stromal cells (MSCs) have protolerogenic effects in renal transplantation, but they induce long-term regulatory T cells (Treg)-dependent graft acceptance only when infused before transplantation. When given posttransplant, MSCs home to the graft where they promote engraftment syndrome and do not induce Treg. Unfortunately, pretransplant MSC administration is unfeasible in deceased-donor kidney transplantation.

Methods.
To make MSCs a therapeutic option also for deceased organ recipients, we tested whether MSC infusion at the time of transplant (day 0) or posttransplant (day 2) together with inhibition of complement receptors prevents engraftment syndrome and allows their homing to secondary lymphoid organs for promoting tolerance. We analyzed intragraft and splenic MSC localization, graft survival, and alloimmune response in mice recipients of kidney allografts and syngeneic MSCs given on day 0 or on posttransplant day 2. C3a receptor (C3aR) or C5a receptor (C5aR) antagonists were administered to mice in combination with the cells or were used together to treat MSCs before infusion.

Results.
Syngeneic MSCs given at day 0 homed to the spleen increased Treg numbers and induced long-term graft acceptance. Posttransplant MSC infusion, combined with a short course of C3aR or C5aR antagonist or administration of MSCs pretreated with C3aR and C5aR antagonists, prevented intragraft recruitment of MSCs and graft inflammation, inhibited antidonor T-cell reactivity, but failed to induce Treg, resulting in mild prolongation of graft survival.

Conclusions.
These data support testing the safety/efficacy profile of administering MSCs on the day of transplant in deceased-donor transplant recipients and indicate that complement is crucial for MSC recruitment into the kidney allograft.
Successful Single-kidney Transplantation in Adult Recipients Using Pediatric Donors Aged 8 to 36 Months: Comparable Outcomes With Those Using Pediatric Donors Aged >3 Years
Authors: Zhu Lan , Fu Cheng , Chen Song , Liu Bin , Du Dunfeng , Chang Sheng , Gong Nianqiao , Jiang Jipin , Chen Zhishui , Chen Gang 
Published: February 2019

Background.
Using pediatric donors for single-kidney transplantation (SKT) can increase the number of possible recipients. However, it is unclear when SKT involving small pediatric donors and adult recipients can safely be performed without compromising graft outcome.

Methods.
From 2013 to 2017, a total of 102 SKTs in adult recipients were performed in our center using pediatric donors aged <12 years. We compared the outcomes from donors aged 8 to 36 months (the small-kidney group [SKG], n = 46) and from donors aged 3 to 12 years (the big-kidney group [BKG], n = 56). The median follow-up time was 30 months in the SKG and 28 months in the BKG.

Results.
All patients achieved satisfactory renal function after transplantation, despite the fact that some patients (SKG, 19.6%; BKG, 28.6%) developed delayed graft function. One-year graft survival and death-censored graft survival in the SKG were 89.1% and 100%, respectively, comparable to the results in the BKG (92.9% and 98.2%). One year later, the graft and patient survival rates in both groups remained unchanged. Pulmonary infection was the main cause of death in patients with a functioning graft (SKG, 4 patients; BKG, 2 patients). Proteinuria occurred early in some patients (SKG, 30.4%; BKG, 19.6%) and decreased gradually within the first year posttransplantation.

Conclusions.
SKT from pediatric donors aged 8 to 36 months to selected adult recipients produced excellent intermediate-term outcomes, comparable with those when older pediatric donors were used. This study provides evidence to support a lower age limit for SKT from pediatric donors.
Analytical Validation of a Single-nucleotide Polymorphism-based Donor-derived Cell-free DNA Assay for Detecting Rejection in Kidney Transplant Patients
Authors: Altuğ Yücel , Liang Nathan , Ram Rosalyn , Ravi Harini , Ahmed Ebad , Brevnov Maxim , Swenerton Ryan K. , Zimmermann Bernhard , Malhotra Meenakshi , Demko Zachary P. , Billings Paul R. , Ryan Allison 
Published: February 2019

Background.
Early detection of rejection in kidney transplant recipients holds the promise to improve clinical outcomes. Development and implementation of more accurate, noninvasive methods to detect allograft rejection remain an ongoing challenge. The limitations of existing allograft surveillance methods present an opportunity for donor-derived cell-free DNA (dd-cfDNA), which can accurately and rapidly differentiate patients with allograft rejection from patients with stable organ function.

Methods.
This study evaluated the analytical performance of a massively multiplexed polymerase chain reaction assay that targets 13 962 single-nucleotide polymorphisms, characterized and validated using 66 unique samples with 1064 replicates, including cell line-derived reference samples, plasma-derived mixtures, and transplant patient samples. The dd-cfDNA fraction was quantified in both related and unrelated donor-recipient pairs.

Results.
The dd-cfDNA assay showed a limit of blank of 0.11%, a limit of detection and limit of quantitation of 0.15% for unrelated donors, and limit of blank of 0.23%, a limit of detection and limit of quantitation of 0.29% for related donors. All other metrics (linearity, accuracy, and precision) were observed to be equivalent between unrelated and related donors. The measurement precision of coefficient of variation was 1.8% (repeatability, 0.6% dd-cfDNA) and was <5% for all the different reproducibility measures.

Conclusions.
This study validates the performance of a single-nucleotide polymorphism-based massively multiplexed polymerase chain reaction assay to detect the dd-cfDNA fraction with improved precision over currently available tests, regardless of donor-recipient relationships.
Trends in the Medical Complexity and Outcomes of Medicare-insured Patients Undergoing Kidney Transplant in the Years 1998–2014
Authors: Lenihan Colin R. , Liu Sai , Montez-Rath Maria E. , Winkelmayer Wolfgang C. 
Published: February 2019

Background.
Graft and patient survival following kidney transplant are improving. However, the drivers of this trend are unclear. To gain further insight, we set out to examine concurrent changes in pretransplant patient complexity, posttransplant survival, and cause-specific hospitalization.

Methods.
We identified 101 332 Medicare-insured patients who underwent their first kidney transplant in the United States between the years 1998 and 2014. We analyzed secular trends in (1) posttransplant patient and graft survival and (2) posttransplant hospitalization for cardiovascular disease, infection, and cancer using Cox models with year of kidney transplant as the primary exposure of interest.

Results.
Age, dialysis vintage, body mass index, and the prevalence of a number of baseline medical comorbidities increased during the study period. Despite these adverse changes in case mix, patient survival improved: the unadjusted and multivariable-adjusted hazard ratios (HRs) for death in 2014 (versus 1998) were 0.61 (confidence interval [CI], 0.52-0.73) and 0.46 (CI, 0.39-0.55), respectively. For graft failure excluding death with a functioning graft, the unadjusted and multivariable adjusted subdistribution HRs in 2014 versus 1998 were 0.4 (CI, 0.25-0.55) and 0.45 (CI, 0.3-0.6), respectively. There was a marked decrease in hospitalizations for cardiovascular disease following transplant between 1998 and 2011, subdistribution HR 0.51 (CI, 0.43-0.6). Hospitalization for infection remained unchanged, while cancer hospitalization increased modestly.

Conclusions.
Medicare-insured patients undergoing kidney transplant became increasingly medically complex between 1998 and 2014. Despite this, both patient and graft survival improved during this period. A marked decrease in serious cardiovascular events likely contributed to this positive trend.
Urine Angiotensin II Signature Proteins as Markers of Fibrosis in Kidney Transplant Recipients
Authors: Mohammed-Ali Zahraa , Tokar Tomas , Batruch Ihor , Reid Shelby , Tavares-Brum Alexandre , Yip Paul , Cardinal Héloïse , Hébert Marie-Josée , Li Yanhong , Kim S. Joseph , Jurisica Igor , John Rohan , Konvalinka Ana 
Published: February 2019

Background.
Interstitial fibrosis/tubular atrophy (IFTA) is an important cause of kidney allograft loss; however, noninvasive markers to identify IFTA or guide antifibrotic therapy are lacking. Using angiotensin II (AngII) as the prototypical inducer of IFTA, we previously identified 83 AngII-regulated proteins in vitro. We developed mass spectrometry–based assays for quantification of 6 AngII signature proteins (bone marrow stromal cell antigen 1, glutamine synthetase [GLNA], laminin subunit beta-2, lysophospholipase I, ras homolog family member B, and thrombospondin-I [TSP1]) and hypothesized that their urine excretion will correlate with IFTA in kidney transplant patients.

Methods.
Urine excretion of 6 AngII-regulated proteins was quantified using selected reaction monitoring and normalized by urine creatinine. Immunohistochemistry was used to assess protein expression of TSP1 and GLNA in kidney biopsies.

Results.
The urine excretion rates of AngII-regulated proteins were found to be increased in 15 kidney transplant recipients with IFTA compared with 20 matched controls with no IFTA (mean log2[fmol/µmol of creatinine], bone marrow stromal cell antigen 1: 3.8 versus 3.0, P = 0.03; GLNA: 1.2 versus −0.4, P = 0.03; laminin subunit beta-2: 6.1 versus 5.4, P = 0.06; lysophospholipase I: 2.1 versus 0.6, P = 0.002; ras homolog family member B: 1.2 versus −0.1, P = 0.006; TSP1_GGV: 2.5 versus 1.9; P = 0.15; and TSP1_TIV: 2.0 versus 0.6, P = 0.0006). Receiver operating characteristic curve analysis demonstrated an area under the curve = 0.86 for the ability of urine AngII signature proteins to discriminate IFTA from controls. Urine excretion of AngII signature proteins correlated strongly with chronic IFTA and total inflammation. In a separate cohort of 19 kidney transplant recipients, the urine excretion of these 6 proteins was significantly lower following therapy with AngII inhibitors (P < 0.05).

Conclusions.
AngII-regulated proteins may represent markers of IFTA and guide antifibrotic therapies.
Renal Safety of Intravenous Gadolinium-enhanced MRI in Patients Following Liver Transplantation
Authors: Flynn Mary M. , Parekh Anjali N. , Parikh Mehul R. , Sood Akhil , Shaffer Katherine M. , Runge Thomas M. , Lipowska Anna M. , Perez Sebastian D. , Sakaria Sonali S. , Subramanian Ram M. 
Published: February 2019

Background.
Intravenous contrast-enhanced imaging is invaluable in diagnosing pathology following liver transplantation. Given the potential risk of contrast nephropathy associated with iodinated computed tomography contrast, alternate contrast modalities need to be examined, especially in the setting of renal insufficiency. The purpose of this study was to examine the renal safety of MRI with gadolinium following liver transplantation.

Methods.
The study involved a retrospective analysis of 549 cases of abdominal MRI with low-dose gadobenate dimeglumine in liver transplant recipients at a single center. For each case, serum creatinine values before and after the MRI were compared. In addition, cases were analyzed for the development of nephrogenic systemic fibrosis.

Results.
Pre-MRI creatinine values ranged from 0.32 to 6.57 mg/dL (median, 1.28 g/dL), with 191 cases having values ≥1.5 mg/dL (median, 1.86 g/dL). A comparison of the pre- and post-MRI creatinine values showed no significant difference, including those patients with pre-MRI values ≥1.5 mg/dL (mean change of −0.04 [95% confidence interval, −0.07 to −0.01; P = 0.004]). No cases of nephrogenic systemic fibrosis were noted.

Conclusions.
Our findings suggest that, irrespective of baseline renal function, MRI with gadobenate dimeglumine is a nonnephrotoxic imaging modality in liver transplant recipients. Importantly, this intravenous contrast-enhanced imaging modality can be considered in those posttransplant patients who have a contraindication to computed tomography contrast due to renal insufficiency.
The role of somatic mutational events in the pathogenesis of epilepsy
Authors: Iffland Philip H. , Crino Peter B. 
Published: February 2019

Purpose of review
There has been rapid progress in defining novel causative gene variants responsible for a large spectrum of human epilepsy syndromes and subtypes. Of particular interest is the discovery that somatic mutations, for example, noninherited mutations occurring in neuroglial progenitor cells during embryonic brain development, are highly linked to malformations of cortical development (MCD) such as focal cortical dysplasia (FCD) type II and hemimegalencephaly.

Recent findings
Somatic gene variants have been identified in genes encoding regulatory proteins within the mechanistic target of rapamycin (mTOR) signaling cascade and have thus comprised the group classified as mTORopathies. FCD II and hemimegalencephaly often result from mutations in identical genes suggesting that these are spectrum disorders. An exciting recent development has been the identification of somatic mutations causing both FCD Ia and nonlesional neocortical epilepsy.

Summary
Defining somatic gene mutations in brain tissue specimens has shed new light on how MCD form and the mechanisms of epileptogenesis associated with MCD. Trials of mTOR inhibitors in tuberous sclerosis complex have demonstrated that inhibition of mTOR activation in mTORopathies can reduce seizure frequency. New somatic mutations found for a variety of epilepsy syndromes may provide new targets for clinical therapeutics.
Educational attainment causally impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study in ~ 780,000 study participants
Authors: Rosoff Daniel B. , Lohoff Falk W. 
Published: February 2019

ABSTRACTBackgroundObservational studies suggest that lower educational attainment may be associated with risky alcohol consumption behaviors. However, these findings may be biased by confounding and reverse causality. Using two-sample Mendelian randomization (MR), we can determine whether education is causally related to alcohol consumption behaviors and alcohol dependence (AD).MethodsWe performed two-sample MR using summary statistics from recent genome-wide association studies (GWAS) in 784,726 study participants to assess the causal effects of educational attainment on alcohol consumption behaviors, including intake frequency, total weekly drinks, beverage preferences, whether alcohol is consumed with meals, as well as AD risk. Of 53 independent (linkage disequilibrium R2=0.001, kb distance<10,000) nucleotide polymorphisms (SNPs) that predict educational attainment, and after removal of palindromes with intermediate allele frequency, 51 were present in the alcohol consumption behaviors, and 44 were present in the AD GWAS. Complementary MR techniques accommodating different assumptions about genetic pleiotropy (inverse variance weighted (IVW), Egger, weighted median, and weighted mode MR) tested the sensitivity of our results.ResultsWe found strong evidence of a causal effect between years of education and alcohol consumption behaviors generally. Higher educational attainment decreased alcohol intake frequency (IVW odds ratio (ORIVW), 0.718, 95% CI, 0.673-0.765, PIVW=4.62E-24), as well as weekly distilled spirits intake (ORIVW, 0.874, 95% CI, 0.833-0.917, PIVW=3.91E-08), and weekly beer plus cider intake (ORIVW, 0.837, 95% CI, 0.805-0.869, P=5.58E-20), but increased weekly white wine (ORIVW, 1.220, 95% CI, 1.172-1.269, PIVW=7.96E-23), red wine (ORIVW, 1.227, 95% CI, 1.174-1.282, PIVW=6.67E-20), and fortified wine intake (ORIVW, 1.051, 95% CI, 1.027-1.075, PIVW] =1.87E-07). We also found evidence educational attainment reduced AD risk (ORIVW.508, 95% CI, .315-.819, PIVW=5.51E-03). We found no evidence for total weekly consumption (ORIVW.508, 95% CI,.315-.819, PIVW=5.51E-03). Consistency of results across complementary MR methods strengthens our causal inferences.ConclusionsOur findings show low educational attainment is causally associated with increased alcohol consumption frequency, increased preference for beer, cider, and spirits, and AD risk, indicating a potential mechanism explaining reported associations between educational attainment and adverse health outcomes, including cardiovascular disease. These findings suggest increased educational attainment might be a useful prevention strategy to reduce risky alcohol behaviors and AD.