bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients – A Proof-of-Concept Study
Authors: Kamath Megan , Shekhtman Grigoriy , Grogan Tristan , Hickey Michelle J. , Silacheva Irina , Shah Karishma S. , Shah Kishan S. , Hairapetian Adrian , Gonzalez Diego , Godoy Giovanny , Reed Elaine F. , Elashoff David , Bondar Galyna , Deng Mario C. 
Published: February 2022

BackgroundOver the last decade, expanding use of molecular diagnostics in heart transplantation has allowed implementation of non-invasive surveillance strategies for monitoring allograft health. The commercially available HeartCare platform combines the AlloMap gene expression profiling assay and the AlloSure donor-derived cell-free DNA test (dd-cfDNA). Beyond their established use for assessment of rejection, evidence is building for predictive utility, with the longitudinal AlloMap Variability score previously shown to correlate with the risk of future rejection, graft dysfunction, re-transplantation, or death. In this single-center, retrospective pilot study, we evaluated the performance of a novel AlloSure Variability metric in predicting mortality in a cohort of heart transplant recipients.MethodsSeventy-two adult heart transplant recipients with at least 3 concurrent AlloMap/AlloSure results were included. Demographic, clinical, imaging, and laboratory parameters were captured. Variability was defined as the standard deviation of longitudinal AlloMap/AlloSure results. A Cox multivariable adjusted proportional hazards model was used to evaluate the variability metrics as predictors of mortality. Associations between AlloMap/AlloSure variability and donor specific antibody (DSA) status were also assessed.ResultsA total of 5 patients (6.9%) died during a median follow-up of 480 days. In a univariate Cox proportional hazards model, higher AlloSure variability (HR 1.66, 95%CI 1.14 – 2.41), but not AlloMap variability or the cross-sectional AlloSure/AlloMap results was associated with increased mortality risk. Longitudinal AlloSure variability was also higher among patients with both preformed DSA and those developing de novo DSA.ConclusionOur results suggest that increased variability of dd-cfDNA in heart transplant patients is associated with both mortality risk and the presence of donor specific antibodies. These findings highlight the added value of longitudinal data in the interpretation of AlloMap/AlloSure scores in this population and open the door to larger studies investigating the utility of these metrics in shaping post-transplant clinical care paradigms.
Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: An Evidence-Based Analysis
Authors: Cao Dehong , Li Jinze , Lu You , Huang Yin , Chen Bo , Chen Zeyu , Shen Yinzhi , Liu Liangren , Wei Qiang 
Published: February 2022

BackgroundPeyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic.MethodsWe searched the Web of Science, PubMed, Embase, and ClinicalTrials.gov for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity.ResultsFour articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: −318.77, p &lt; 0.001) and PDSB (WMD: −1.20, p &lt; 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: −0.64, P = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, p &lt; 0.001].ConclusionsThe current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.
A Nomogram for Predicting Portal Hypertensive Gastropathy in Patients With Liver Cirrhosis: A Retrospective Analysis
Authors: Wang WenSheng , Mu ZhiYong , Zhu GuangXi , Wang Tao , Lai ShuJie , Guo Yan , Yin XinRu , Wen LiangZhi , Chen DongFeng 
Published: February 2022

BackgroundThere is an urgent need for non-invasive methods for predicting portal hypertensive gastropathy (PHG). This study aims to develop and validate a non-invasive method based on clinical parameters for predicting PHG in patients with liver cirrhosis (LC).MethodsThe overall survival (OS) and hepatocellular carcinoma (HCC)-free survival were evaluated in LC patients, both with and without PHG. A prediction model for PHG was then constructed based on a training dataset that contained data on 492 LC patients. The discrimination, calibration, and clinical utility of the predicting nomogram were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was conducted using a bootstrapping method, and further external validation using data on the 208 other patients.ResultsLC patients with PHG had a worse prognosis compared with those without PHG. A nomogram was constructed using clinical parameters, such as age, hemoglobin content, platelet count and Child-Pugh class. The C-index was 0.773 (95% CI: 0.730–0.816) in the training cohort, 0.761 after bootstrapping and 0.745 (95% CI: 0.673–0.817) in the validation cohort. The AUC values were 0.767, 0.724, and 0.756 in the training, validation and total cohorts, respectively. Well-fitted calibration curves were observed in the training and validation cohorts. Decision curve analysis demonstrated that the nomogram was clinically useful at a threshold of 15%.ConclusionThe nomogram constructed to predict the risk of developing PHG was found to be clinically viable. Furthermore, PHG is an independent risk factor for OS of LC, but not for the occurrence of HCC.
Serum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study
Authors: Hahn Robert G. , Yanase Fumitaka , Zdolsek Joachim H. , Tosif Shervin H. , Bellomo Rinaldo , Weinberg Laurence 
Published: February 2022

BackgroundThe Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery.MethodsWe performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed.ResultsThe median perioperative change in serum creatinine in the two groups was −19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th−75th percentiles, 0.09–1.98) to 0.35 (0.19–0.57) (mg/L)2 in the first group and rose from 0.57 (0.22–1.53) to 0.85 (0.67–2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2–11.7) μg2/mmol2 before surgery vs.6.9 (5.3–11.0) μg2/mmol2 after the surgery (P = 0.69).ConclusionIn the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.
Antibacterial Activity of Small Molecules Which Eradicate Methicillin-Resistant Staphylococcus aureus Persisters
Authors: Hamad Mohamad , Al-Marzooq Farah , Srinivasulu Vunnam , Omar Hany A. , Sulaiman Ashna , Zaher Dana M. , Orive Gorka , Al-Tel Taleb H. 
Published: February 2022

Graphical AbstractAntibacterial activity of small molecules which eradicate methicillin-resistant Staphylococcus aureus (MRSA) persisters.
Erythrocytes Are an Independent Protective Factor for Vascular Cognitive Impairment in Patients With Severe White Matter Hyperintensities
Authors: Tao Xi , Zhou Hang , Mo Danheng , Zhang Wenjie , Chang Zihan , Zeng Yiheng , Luo Yuqi , Wu Siyuan , Tang Wenjing , Yang Chen , Wang Qing 
Published: February 2022

Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH.Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels.Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047).Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.
Association Between Carotid Artery Perivascular Fat Density and Embolic Stroke of Undetermined Source
Authors: Hu Xiaohong , Chen Jianhui , Fu Huajun , Chen Yinjuan , Fan Daofeng , Chen Yangui , Shen Chaoxiong 
Published: February 2022

AimThis study aims to retrospectively evaluate the association between pericarotid inflammation and the presence of embolic stroke of undetermined source (ESUS).MethodsIn total, 126 patients with ESUS and 118 patients with ischemic stroke from large artery atherosclerosis (LAA) were enrolled. All the patients underwent brain MRI and a neck CT angiography (CTA) examination. Reviewers were blinded to infarct location and stroke cause. Paired t-tests assessed within-subjects differences in mean Hounsfield units (HUs) in carotid perivascular fat between the cerebral infarction side and contralateral side for ESUS and LAA ischemic stroke cases. The unpaired Student's t-test was used to assess between-subjects differences in mean HUs between ESUS and LAA ischemic stroke cases.ResultsIn both the ESUS cases and LAA ischemic stroke cases, the pericarotid fat density around the carotid artery ipsilateral to the stroke significantly increased compared with contralateral stroke position in both the groups (ESUS cases −56.31 ± 18.70 vs. −67.31 ± 20.01, p = 0.000; LAA ischemic stroke cases −51.62 ± 19.95 vs. −64.58 ± 22.68, p = 0.000). However, there was no significant difference in ipsilateral and contralateral positions to infarct between ESUS cases and LAA ischemic stroke cases (ipsilateral to infarct −56.31 ± 18.70 vs. −51.62 ± 19.95, p = 0.059; contralateral to infarct −67.31 ± 20.01 vs. −64.58 ± 22.68, p = 0.320).ConclusionWe found increased density in the fat surrounding carotid artery ipsilateral to stroke compared with contralateral in ESUS, suggesting the presence of an inflammatory reaction that extends beyond the vessel lumen in patients with ESUS with a risk factor profile similar to LAA strokes.
Endovascular Management of Vertebrobasilar Trunk Artery Large Aneurysms: Complications and Long-Term Results
Authors: Wu Qiaowei , Xu Shancai , Wang Chunlei , Ji Zhiyong , Li Yuchen , Sun Bowen , Meng Yuxiao , Shi Huaizhang , Wu Pei 
Published: February 2022

ObjectiveTo analyze the complications and long-term results of endovascular management of vertebrobasilar trunk large (≥10 mm) aneurysms (VBTLAs) and identify predictors of outcomes.MethodsBetween 2014 and 2020, 6,987 patients with intracranial aneurysms were referred to our center for aneurysm management and 2,224 patients have undergone the endovascular procedures. We retrospectively reviewed the database and identify all the patients with VBTLAs.ResultsA total of 62 VBTLAs were identified. The median aneurysm size was 13.4 mm [interquartile range (IQR) 11.5–18.7]. Among them, 24 aneurysms were treated with overlapping stent techniques, 18 aneurysms were treated with flow diversion, 14 aneurysms were treated with single stent-assisted coiling, and 6 aneurysms were treated with coiling alone. Ten patients were treated with parent artery occlusion or unilateral vertebral artery occlusion. Periprocedural complications were occurred in 7 (11.3%) patients. Clinical follow-up was obtained at the median of 27.5 months (IQR 15.3–58.5). The overall complication rate was 16.1% (10/62), including nine ischemic events and one hemorrhagic event. The combined disability and neurological mortality rate was 12.9% (8/62), with 4 (6.5%) deaths. The favorable outcome rate at follow-up was 87.1% (54/62). The complication-free cumulative survival rates at 1 and 5 years were 86.8 and 82.0%, respectively. The overall cumulative survival rates at 1 and 5 year were 96.5 and 89.8%, respectively. In the multivariate Cox regression analysis, longer procedure time (&gt;115 min) (P = 0.037) and ischemic onset (P = 0.005) predict complications. Angiography follow-up was available for 36 patients at the median of 6.0 months (IQR 6–12), with a complete occlusion rate of 77.8% (28/36). Two (5.6%) aneurysms were recanalized and subsequently received the retreatment. Subgroup analysis did not find any differences in the complete occlusion rate between endovascular strategies.ConclusionEndovascular management of VBTLAs has a reasonable safety profile with favorable 5-year cumulative survival rates and imaging outcomes at follow-up. Prolonged procedure and ischemic onset are associated with a high risk of overall complications.
Prognostic Analysis for Patients With Parathyroid Carcinoma: A Population-Based Study
Authors: Qian Bei , Qian Ying , Hu Longqing , Zhang Shoupeng , Mei Li , Qu Xincai 
Published: February 2022

BackgroundParathyroid carcinoma (PC) is a rare but often lethal malignancy for which staging system, prognostic indicators, and treatment guidelines are still not established. We aimed to explore the prognostic parameters and construct a nomogram for cancer-specific survival (CSS) of PC.MethodsA retrospective analysis of 604 PC patients in the SEER database from 2001 through 2018 was performed. All the cases were randomly assigned to the training cohort (n = 424) or the validation cohort (n = 180) at a ratio of 7:3. The Kaplan–Meier method and Cox regression model were applied to estimate the CSS and risk factors, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram in CSS were assessed by concordance index (C-index), the area under the curve (AUC) of receiver operating characteristics (ROC), and the calibration curve.ResultsAge at diagnosis &gt; 70 years [hazard ratio (HR): 3.55, 95% CI: 1.07–11.78, p = 0.039] and tumor size &gt; 35 mm (HR 4.22, 95% CI: 1.67–10.68, p = 0.002) were associated with worse CSS. Compared with distant metastasis, localized (HR 0.17, 95% CI: 0.06–0.47, p = 0.001) and regional lesions (HR 0.22, 95% CI: 0.07–0.66, p = 0.007) showed an improved CSS rate. Parathyroidectomy was the recommended treatment (p = 0.02). The C-index of the nomogram was 0.826, and the AUC for 5-, 10-, and 15-year CSS was 83.7%, 79.7%, and 80.7%, respectively. The calibration curve presented good agreement between prediction by nomogram and actual observation.ConclusionAge at diagnosis &gt; 70 years, tumor size &gt; 35 mm, and distant metastasis were independent risk factors for PC-specific mortality. Parathyroidectomy was currently the most recommended treatment for PC. This nomogram provided individualized assessment and reliable prognostic prediction for patients with PC.
The Sex Features of Patients With Solid Pseudopapillary Neoplasms of the Pancreas: A Retrospective Study
Authors: Wei Guangmin , Luo Qiong , Fang Jiankai , Li Xiaolou , Shi Yanhong , Li Yuqiong , Sun Liqi 
Published: February 2022

BackgroundSolid pseudopapillary neoplasms of the pancreas (SPNs) in male patients are more frequently reported. The aim of the study was to evaluate the sex features of SPN and the risk factors that predict tumor recurrence.MethodsFrom 2013 to 2019, patients who were pathologically confirmed to have SPNs were retrospectively reviewed. The baseline study parameters were compared between males and females. A logistic regression model was established to identify the independent risk factors for tumor recurrence.ResultsIn total, 221 patients were included in this study. Of them, 53 patients (24.0%) were males. Male patients were older than female patients (39.1 vs 31.6 years, P=0.001), and the tumor size in male patients was smaller than that in female patients (50.38 vs 39.65 mm, P=0.038). The preoperative imaging diagnostic accuracy was significantly higher in females than in males (70.5% vs 54%, P=0.02). SPNs in male patients tended to be misdiagnosed with other malignant tumors (37.7% vs 10.7%, P&lt;0.0001), with a more solid component observed in images (66.8% vs 24.7%, P&lt;0.0001). For immunohistochemical staining, the expression of beta catenin was significantly lower in male patients (P=0.002), and the expression of vimentin was the opposite (P=0.01). The overall survival rate and disease-free survival were not different. Based on multivariate analysis, older age [hazard ratio (HR)= 1.094, 95% confidence interval (CI): 1.005-1.190] and KI 67 index grade III (HR=12.029, 95% CI: 2.399-60.311) were independent risk factors for tumor recurrence.ConclusionThe clinical and imaging features of SPN in males were not in full accord with those in females; however, the differences did not influence prognosis.
Mirabegron in Overactive Bladder and Its Role in Exit Strategy After Botulinum Toxin Treatment in Children
Authors: Tan Denise Jia Yun , Weninger Julia , Goyal Anju 
Published: February 2022

PurposeMirabegron is a recent addition to the management options of overactive bladder (OAB) in children. The purpose of this study was to ascertain the role of Mirabegron in the treatment algorithm of therapy-resistant OAB especially after botulinum toxin.MethodsCase notes of all children receiving Mirabegron between July 2017 and February 2020 were reviewed.ResultsForty one children (21 females, 20 males), mean age 12.6 [8–17] years old, commenced Mirabegron: 35 idiopathic OAB, 6 neuropathic OAB. The mean duration of treatment was 20.7 [3–45] months. In total 24 (59%) had Mirabegron after partial/no response to anticholinergics, and 17 (41%) patients had Mirabegron subsequent to botulinum toxin A (BtA) as an exit strategy. In total 35 (85%) patients had combination therapy (Mirabegron and anticholinergics), and 6 (15%) patients had Mirabegron only. Fourteen (34%) had complete response, 17 (41%) had partial response, and 10 (24%) had no response. Side effects were reported in 7 (17%) patients with discontinuation necessitated in 3.ConclusionMirabegron when used alone or in combination with anticholinergics resulted in complete/partial response in 76% of anticholinergic therapy-resistant OAB. In addition to being an important step in treatment escalation after no/partial response to anticholinergics, it has a crucial role in the exit strategy for recurring symptoms after BtA wears off.