bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Blockers for traumatic brain injury: A systematic review and meta-analysis
Authors: Ding Huaqiang , Liao Luoxing , Zheng Xiaomei , Wang Qisheng , Liu Zhi , Xu Guanghui , Li Xing , Liu Liang 
Published: January 2021

BACKGROUND
Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).
β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI.

METHODS
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes.

RESULTS
Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30–0.51; I
2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09–2.80; I
2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55–1.50; I
2 = 25.9%; p = 0.702).

CONCLUSION
This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Human Metapneumovirus and Parainfluenza Virus Infections in Lung Transplant Recipients: The Effects on Lung Allograft and Clinical Outcomes
Authors: Permpalung Nitipong , Sait Afrah S. , Bazemore Katrina , Avery Robin K. , Mathew Joby , Shah Pali D. 
Published: January 2021

Background.
Human metapneumovirus (HMPVi) and parainfluenza virus (PIVi) infections are common community-acquired infections in lung transplant recipients (LTRs), but data are extremely limited.

Methods.
A retrospective study including all LTRs at the Johns Hopkins Hospital during July 2010–June 2019 with positive HMPV and PIV polymerase chain reaction respiratory specimens was performed.

Results.
Thirty-one HMPV- and 53 PIV-infected LTRs were identified. LTRs with HMPVi and PIVi had similar baseline characteristics, infection parameters, treatment allocation, and allograft function outcomes. Among entire cohort, 31.6% had chronic allograft dysfunction (CLAD) stage progression within 1 y postinfections (29.2% versus 35.5% for PIVi versus HMPVi, respectively, P = 0.56). In forced expiratory volume in 1 s percent (FEV1%) trajectory analysis showed steadily decline of FEV1 across time among CLAD stage progressors from both viruses. FEV1% decline ≥10% at 90 d had adjusted hazard ratio for CLAD stage progression of 18.4 (4.98-67.76) and 4.6 (1.36-15.34) for PIVi and HMPVi, respectively. PIVi caused higher donor-specific antigen development (11.8% versus 3.2%, P = 0.18) and 1-y mortality (9.4% versus 0%, P = 0.11), compared with HMPVi, even though the results were not statistically significant. Ribavirin did not show protective effect, and mycophenolate discontinuation during infection did not increase risk of CLAD stage progression.

Conclusions.
One-third of HMPV- and PIV-infected LTRs developed CLAD stage progression within 1 y. The lack of early lung function recovery may predict long-term CLAD progression.
Longer Distance From Dialysis Facility to Transplant Center Is Associated With Lower Access to Kidney Transplantation
Authors: Whelan Adrian M. , Johansen Kirsten L. , McCulloch Charles E. , Adelmann Dieter , Niemann Claus U. , Roll Garrett R. , Siyahian Salpi , Grimes Barbara , Ku Elaine 
Published: January 2021

Background.
Rates of kidney transplantation vary substantially across dialysis facilities in the United States. Whether distance between the dialysis facility and transplant center associates with variations in transplantation rates has not been examined.

Methods.
We performed a retrospective study of adults treated with dialysis between 2005 and 2015, according to the US Renal Data System. We examined the association between distance from dialysis facility to transplant center and time to kidney transplantation (primary outcome) and waitlist registration (secondary outcome) using Fine-Gray models. We also performed sensitivity analyses using the distance from each patient’s dialysis facility to the nearest transplant center as the predictor so that patients who were never registered on the waitlist (and therefore would not have a transplant center) could be included.

Results.
In total, 178 885 waitlisted patients were included for our primary analysis. As distance between dialysis facility and transplant center increased, lower hazard of transplantation (subhazard ratio [HR], 0.92; 95% confidence interval [CI], 0.91-0.94, if distance was 10 to <50 miles; sub-HR, 0.90; 95% CI, 0.88-0.92, if distance ≥50 miles compared with <10 miles) was noted. We also found a weak association between longer distance and hazard of waitlist registration (sub-HR, 0.96; 95% CI, 0.94-0.97, if distance was ≥50 miles versus <10 miles). Findings were similar in sensitivity analyses using distance between dialysis facility and the nearest transplant center (N = 1 149 721).

Conclusions.
Patients receiving dialysis in facilities located further away from transplant centers have lower hazard of kidney transplantation. Developing strategies to address barriers to transplantation in patients receiving dialysis at facilities located far away from a transplant center may help improve disparities in transplantation rates.
Hyponatremia Is Associated With Increased Mortality in Children on the Waiting List for Liver Transplantation
Authors: Bezinover Dmitri , Nahouraii Lauren , Sviatchenko Alexandr , Wang Ming , Kimatian Steven , Saner Fuat H. , Stine Jonathan G. 
Published: January 2021

Background.
Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT).

Methods.
A retrospective analysis of the united network for organ sharing/organ procurement transplantation network database on pediatric LT performed between 1988 and 2016 was conducted. Hyponatremia was defined as a serum sodium of 130 mEq/L or below. Subjects were divided into 2 age groups: I (0–6 y old) and II (7–18 y old). Patient survival before and after LT, as well as graft survival, were compared in patients with and without hyponatremia. Multivariable Cox proportional hazards models were constructed for perioperative mortality.

Results.
Data from 6606 children were available for analysis of waiting list mortality, and 4478 for postoperative mortality. The prevalence of hyponatremia at the time of registration was 2.8% and 3.7% at the time of LT. Waiting list mortality in patients with hyponatremia was significantly higher in group I (P < 0.001) but not in group II (P = 0.09). In group I, the relative risk of mortality adjusted to pediatric end-stage liver disease score was significantly associated with hyponatremia (P < 0.001). A sodium level below 130 mEq/L (hazard ration [HR] = 1.7), younger age (group I) (HR = 2.01), and need for dialysis (HR = 2.3) were independent predictors for increased waiting list mortality. There was no difference in overall postoperative patient or graft survival related to hyponatremia.

Conclusions.
Hyponatremia is associated with increased waiting list mortality for pediatric LT candidates, particularly in younger children. Future studies examining incorporation of age-specific serum sodium levels into organ allocation policies in children seems warranted based on our findings.
Pancreatic Islet Changes in Human Whole Organ Pancreas Explants: What Can Be Learned From Explanted Samples?
Authors: Dumbill Richard , Laurenson-Schafer Hannah , Sharples Edward J. , Barnes James , Mittal Shruti , Friend Peter J. , Clark Anne 
Published: January 2021

Background.
Whole pancreas transplantation (Tx) is a successful treatment for type 1 diabetes resulting in independence from antidiabetic therapies. Transplant-related factors contributing to pancreatic islet failure are largely unknown; both recurring insulitis and pancreatitis have been implicated. The aim was to determine if cellular changes in islets and exocrine tissue are evident early in Tx, which could contribute to eventual graft failure using well-preserved tissue of grafts explanted from largely normoglycemic recipients.

Methods.
Histological specimens of explants (n = 31), Tx duration 1 day–8 years (median 29 d), cold ischemia time 7.2–17.3 hours (median 11.1 h), donor age 13–54 years (median 38 y) were examined; sections were labeled for inflammation, islet amyloidosis, and tissue fibrosis, and morphometry performed on immunolabeled insulin and glucagon positive islet cells. Data were related to clinical details of donor, recipient, and features of Tx.

Results.
Islet inflammation consistent with recurrent insulitis was not seen in any sample. Insulin-labeled islet cell proportion decreased with donor age (P < 0.05) and cold ischemia (P < 0.01) in explants from 26 normoglycemic patients; glucagon-labeled area proportion increased with cold ischemia (P < 0.05). Clinical pancreatitis was the explant reason in 12 of 28 normoglycemic cases. Exocrine fibrotic area/pancreas was variable (0.7%–55%) and unrelated to clinical/pathological features. Islet amyloid was present in 3 normoglycemic cases (donor ages 58, 42, and 31 y; Tx duration 8 y, 31 and 33 d, respectively). In 1 patient receiving antidiabetic therapy, the insulin-labeled area was reduced but with no evidence of islet inflammation.

Conclusions.
Explant histological changes after short-term Tx are similar to those seen in type 2 diabetes and occur in the absence of immunologic rejection without causing hyperglycemia. This suggests that factors associated with Tx affect islet stability; persistent deterioration of islet integrity and exocrine tissue fibrosis could impact on sustainability of islet function.
Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients
Authors: Plazak Michael E. , Gale Stormi E. , Reed Brent N. , Hammad Sara , Ton Van-Khue , Kaczorowski David J. , Madathil Ronson J. , Ravichandran Bharath 
Published: January 2021

Background.
Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT.

Methods.
This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications.

Results.
Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction).

Conclusions.
This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.
Impact of Subclinical Borderline Inflammation on Kidney Transplant Outcomes
Authors: Seifert Michael E. , Agarwal Gaurav , Bernard Miriam , Kasik Ellen , Raza S. Sikandar , Fatima Huma , Gaston Robert S. , Hauptfeld-Dolejsek Vera , Julian Bruce A. , Kew Clifton E. , Kumar Vineeta , Mehta Shikha , Ong Song , Rosenblum Frida , Towns Graham , Mannon Roslyn B. 
Published: January 2021

Background.
Surveillance biopsies permit early detection of subclinical inflammation before clinical dysfunction, but the impact of detecting early subclinical phenotypes remains unclear.

Methods.
We conducted a single-center retrospective cohort study of 441 consecutive kidney transplant recipients between 2015 and 2018 with surveillance biopsies at 6 months post-transplant. We tested the hypothesis that early subclinical inflammation (subclinical borderline changes, T cell-mediated rejection, or microvascular injury) is associated with increased incidence of a composite endpoint including acute rejection and allograft failure.

Results.
Using contemporaneous Banff criteria, we detected subclinical inflammation in 31%, with the majority (75%) having a subclinical borderline phenotype (at least minimal inflammation with mild tubulitis [>i0t1]). Overall, subclinical inflammation was independently associated with the composite endpoint (adjusted hazard ratio, 2.88; 1.11-7.51; P = 0.03). The subgroup with subclinical borderline inflammation, predominantly those meeting the Banff 2019 i1t1 threshold, was independently associated with 5-fold increased hazard for the composite endpoint (P = 0.02). Those with concurrent subclinical inflammation and subclinical chronic allograft injury had worse outcomes. The effect of treating subclinical inflammation was difficult to ascertain in small heterogeneous subgroups.

Conclusions.
Subclinical acute and chronic inflammation are common at 6 months post-transplant in kidney recipients with stable allograft function. The subclinical borderline phenotype with both tubulitis and interstitial inflammation was independently associated with poor long-term outcomes. Further studies are needed to elucidate the role of surveillance biopsies for management of allograft inflammation in kidney transplantation.
Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19?
Authors: Eftekhar Seyed Parsa , Kazemi Sohrab , Barary Mohammad , Javanian Mostafa , Ebrahimpour Soheil , Ziaei Naghmeh 
Published: January 2021

AbstractBackgroundHydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause Torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin.MethodsThis was a retrospective cohort study. 172 patients with COVID-19 included, hospitalized at hospitals of Babol University of Medical Sciences between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment.Results83.1% of patients received hydroxychloroquine plus azithromycin vs 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4. The mean of post-treatment QTc interval in the monotherapy group was shorter than the mean of post-treatment QTc interval in the combination therapy group but it had no significant statistical difference (462.5 ± 43.1 milliseconds vs 464.3 ± 59.1 milliseconds;P= 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, 14 patients did not continue therapy after 4 days.ConclusionHospitalized patients treated with hydroxychloroquine with or without azithromycin, had no significant difference in prolongation of QT interval and outcome. But the number of patients with prolonged QT intervals in this study emphasizes careful cardiac monitoring during therapy; especially in high-risk patients.
Natural Progression of Routine Laboratory Markers following Spinal Trauma: A Longitudinal, Multi-Cohort Study
Authors: Bourguignon Lucie , Vo Anh Khoa , Tong Bobo , Geisler Fred , Mach Orpheus , Maier Doris , Kramer John L.K. , Grassner Lukas , Jutzeler Catherine R. 
Published: January 2021

ABSTRACTObjectiveTo track and quantify the natural course of hematological markers over the first year following spinal cord injury.MethodsData on hematological markers, demographics, and injury characteristics were extracted from medical records of a clinical trial (Sygen) and an ongoing observational cohort study (Murnau Study). The primary outcomes were concentration/levels/amount of commonly collected hematological markers at multiple time-points. Two-way ANOVA and mixed-effects regression techniques were used to account for the longitudinal data and adjust for potential confounders. Trajectories of hematological markers contained in both data sources were compared using the slope of progression.ResultsAt baseline (≤ 2 weeks post-injury), most hematological markers were at pathological levels, but returned to normal values over the course of six to twelve months post-injury. The baseline levels and longitudinal trajectories were dependent on injury severity. More complete injuries were associated with more pathological values (e.g. hematocrit, ANOVA test; Chisq = 77.10, df = 3, adjusted p-value<0.001, and Chisq = 94.67, df = 3, adjusted p-value<0.001, in the Sygen and Murnau studies, respectively). Comparing the two databases revealed some differences in the hematological markers, which are likely attributable to differences in study design, sample size, and standard of care.ConclusionsDue to trauma-induced physiological perturbations, hematological markers undergo marked changes over the course of recovery, from initial pathological levels that normalize within a year. The findings from this study are important as they provide a benchmark for clinical decision making and prospective clinical trials. All results can be interactively explored on the Haemosurveillance website (https://jutzelec.shinyapps.io/Haemosurveillance/).Code availabilityhttps://github.com/jutzca/Systemic-effects-of-Spinal-Cord-Injury
University students and staff able to maintain low daily contact numbers during various COVID-19 guideline periods
Authors: Trickey Adam , Nixon Emily , Christensen Hannah , Finn Adam , Thomas Amy , Relton Caroline , Montgomery Clara , Hemani Gibran , Metz Jane , Walker Josephine G. , Turner Katy , Kwiatkowska Rachel , Sauchelli Sarah , Danon Leon , Brooks-Pollock Ellen 
Published: January 2021

AbstractIntroductionUK universities re-opened in September 2020, despite the on-going coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November. COVID-19 can spread rapidly in university-settings, and students’ adherence to social distancing measures is critical for controlling transmission.MethodsWe measured university staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020-03/07/2020), relaxed guidance period (04/07/2020-13/09/2020), “rule-of-six” period (14/09/2020-04/11/2020), and the second lockdown (05/11/2020-25/11/2020).Results722 staff (4199 responses) (mean household size: 2.6) and 738 students (1906 responses) (mean household size: 4.5) were included in the study. Contact number decreased with age. Staff in single-person households reported fewer contacts than individuals in 2-and 3-person households, and individuals in 4-and 5-person households reported more contacts.For staff, daily contacts were higher in the relaxed guidance and “rule-of-six” periods (means: 3.2 and 3.5, respectively; medians: 3) than the post-first lockdown and second lockdown periods (means: 4.5 and 5.4, respectively; medians: 2). Few students responded until 05/10/2020, after which the median student contacts was 2 and the mean was 5.7, until the second lockdown when it dropped to 3.1.DiscussionUniversity staff and students responded to national guidance by altering their social contacts. The response in staff and students was similar, suggesting that students are able to adhere to social distancing guidance while at university.
Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24
Authors: Karunamuni Roshan A. , Huynh-Le Minh-Phuong , Fan Chun C. , Thompson Wesley , Lui Asona , Martinez Maria Elena , Rose Brent S. , Mahal Brandon , Eeles Rosalind A. , Kote-Jarai Zsofia , Muir Kenneth , Lophatananon Artitaya ,   UKGPCS collaborators, Tangen Catherine M. , Goodman Phyllis J. , Thompson Ian M. , Blot William J. , Zheng Wei , Kibel Adam S. , Drake Bettina F. , Cussenot Olivier , Cancel-Tassin Géraldine , Menegaux Florence , Truong Thérèse , Park Jong Y. , Lin Hui-Yi , Taylor Jack A. , Bensen Jeannette T. , Mohler James L. , Fontham Elizabeth T.H. , Multigner Luc , Blanchet Pascal , Brureau Laurent , Romana Marc , Leach Robin J. , John Esther M. , Fowke Jay H. , Bush William S. , Aldrich Melinda C. , Crawford Dana C. , Cullen Jennifer , Petrovics Gyorgy , Parent Marie-Élise , Hu Jennifer J. , Sanderson Maureen , Mills Ian G. , Andreassen Ole A. , Dale Anders M. , Seibert Tyler M. ,   The PRACTICAL Consortium
Published: January 2021

AbstractWe previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. Genotypic data were obtained from PRACTICAL consortium for 6,253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with performance of PHS46+African. A calibration factor (CF) was formulated using estimated Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our dataset with 1000 Genomes, we identified statistically significant associations between continental and calibration groupings. In conclusion, we identified PCs within 8q24 SNP window that were strongly associated with performance of PHS46+African. Further research to improve clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry