bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Hepcidin-25 and Risk of Mortality in Patients on Peritoneal Dialysis
Authors: Zhong Zhong , Luo Dan , Luo Ning , Li Bin , Fu Dongying , Fan Li , Li Zhijian , Chen Wei , Mao Haiping 
Published: June 2021

Background: Increased serum hepcidin-25 level is associated with excess mortality in hemodialysis patients. However, there is a dearth of published information about its predictive effect for survival in patients on peritoneal dialysis (PD). The purpose of this study is to evaluate the association of serum hepcidin-25 with the risk of mortality in PD patients.Methods: Serum hepcidin-25 level was measured using an enzyme-linked immunosorbent assay in a prospective cohort study of PD patients with stored serum samples at baseline. Multivariate linear regression model was used to determine clinical characteristics associated with serum hepcidin-25 concentration. We evaluated the relationship between serum hepcidin-25 and all-cause mortality using a Cox proportional hazards model and the relationship between hepcidin-25 and cardiovascular (CV) and infection-related deaths using competing-risks regression models.Results: In total, 513 PD patients were included in this study. The median serum hepcidin-25 level was 40.9 (17.9–85.9) ng/mL. Body mass index and serum ferritin were positively correlated with serum hepcidin-25 levels. During a median follow-up period of 64.1 months, 122 (24%) patients died, including 61 (50%) CV deaths and 32 (26%) infection-related deaths. In multivariable analysis, patients with the highest tertile of serum hepcidin-25 had a greater risk of all-cause [adjusted hazard ratio (aHR) 1.85, 95% confidence interval (95%CI), 1.14 to 3.00, P = 0.013] and infection-related mortality (adjusted subdistribution hazard ratio [aSHR], 2.61; 95%CI, 1.01 to 6.76, P = 0.049) when compared with those in the second tertile. However, no significant relationship was observed between serum hepcidin-25 and CV mortality.Conclusions: Higher baseline serum hepcidin-25 level was associated with increased risk for all-cause and infection-related mortality in PD patients.
Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature
Authors: Hammer Arthur , Borruat François-Xavier 
Published: June 2021

Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients.Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms “HIV,” “AIDS,” “ritonavir,” “didanosine,” “maculopathy,” “retinopathy,” “visual loss,” and “toxicity” to retrieve the appropriate literature on the subject.Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treatment. Patient 2: A 55-year-old man complained of slowly progressive peripheral visual field constriction for the past 5 years. History disclosed didanosine therapy for 13 years, however, stopped 4 years before the onset of visual symptoms. No alteration of therapy was offered to patient 2 as didanosine therapy was interrupted 9 years previously. Since 2011, 11 cases of ritonavir maculopathy have been reported in the literature. Relentless worsening of vision was reported in 3/7 patients despite cessation of ritonavir therapy. Didonasine peripheral retinopathy was first described in 1992, and a total of 24 patients have been reported since. Relentlessly progressive peripheral retinopathy was diagnosed despite the previous cessation of therapy in 14 patients.Conclusion: Ritonavir causes a slowly progressive atrophic maculopathy, and didanosine toxicity results in a relentlessly progressing peripheral atrophic retinopathy. The relentless progression of both toxic retinopathies reflects permanent alterations of the retinal metabolism by these medications. Both ritonavir and didanosine toxic retinopathies are rare events, but their clinical presentation is highly specific.
Trunk Impairment as a Predictor of Activities of Daily Living in Acute Stroke
Authors: Ishiwatari Masahiro , Honaga Kaoru , Tanuma Akira , Takakura Tomokazu , Hatori Kozo , Kurosu Akihiro , Fujiwara Toshiyuki 
Published: June 2021

Background and purpose: Trunk function plays a key role in performing activities of daily living (ADL) including locomotion and sitting. Sitting and ADL should be performed as early as possible especially during the acute phase of stroke rehabilitation. Therefore, this study aimed to assess trunk function among patients with acute stroke using the Trunk Impairment Scale (TIS) and to predict its functional outcomes.Methods: Overall, 67 patients with acute stroke (i.e., within 2 days of occurrence of the stroke) were included. The following clinical assessment items were obtained within 48 h after stroke onset and on the day before discharge from the hospital. Trunk function was examined using TIS and Trunk Control Test (TCT). The motor function of the upper and lower extremities was assessed using the stroke impairment assessment set motor (SIAS-M) score, and ADL was assessed using functional independence measure motor (FIM-M) items.Results: Multiple regression analysis was performed using the stepwise regression method, using the total FIM-M score following discharge as the dependent variable and age, TIS, TCT, SIAS-M, and FIM-M within 48 h after stroke onset as the independent variables. Age, TIS, and FIM-M within 48 h after stroke onset were selected as the input variables and showed a high-adjusted determination coefficient (R2 = 0.79; P &lt; 0.001).Conclusion: TIS is a reliable method for evaluating trunk control function and is an early predictor of ADL among patients with acute stroke.
Gait Difficulties and Postural Instability in Adrenoleukodystrophy
Authors: Godbole Neha P. , Sadjadi Reza , DeBono Madeline A. , Grant Natalie R. , Kelly Daniel C. , James Peter F. , Stephen Christopher D. , Balkwill M. David , Lewis Richard F. , Eichler Florian S. 
Published: June 2021

Background: Gait and balance difficulties are among the most common clinical manifestations in adults with X-linked adrenoleukodystrophy, but little is known about the contributions of sensory loss, motor dysfunction, and postural control to gait dysfunction and fall risk.Objective: To quantify gait and balance deficits in both males and females with adrenoleukodystrophy and evaluate how environmental perturbations (moving surfaces and visual surrounds) affect balance and fall risk.Methods: We assessed sensory and motor contributions to gait and postural instability in 44 adult patients with adrenoleukodystrophy and 17 healthy controls using three different functional gait assessments (25 Foot Walk test, Timed Up and Go, and 6 Minute Walk test) and computerized dynamic posturography.Results: The median Expanded Disability Status Scale score for the patient cohort was 3.0 (range 0.0–6.5). Both males and females with adrenoleukodystrophy showed impairments on all three functional gait assessments relative to controls (P &lt; 0.001). Performance on walking tests and Expanded Disability Status Scale scores correlated with incidence of falls on computerized dynamic posturography, with the 25 Foot Walk being a moderately reliable predictor of fall risk (area under the ROC curve = 0.7675, P = 0.0038).Conclusion: We demonstrate that gait difficulties and postural control deficits occur in patients with adrenoleukodystrophy, albeit at an older age in females. Postural deficits were aggravated by eyes closed and dynamic conditions that rely on vestibular input, revealing challenges to the interplay of motor, sensory and vestibular circuitry in adrenoleukodystrophy.
Early High Efficacy Treatment in Multiple Sclerosis Is the Best Predictor of Future Disease Activity Over 1 and 2 Years in a Norwegian Population-Based Registry
Authors: Simonsen Cecilia Smith , Flemmen Heidi Øyen , Broch Line , Brunborg Cathrine , Berg-Hansen Pål , Moen Stine Marit , Celius Elisabeth Gulowsen 
Published: June 2021

Background: Moderate and high efficacy disease modifying therapies (DMTs) have a profound effect on disease activity. The current treatment guidelines only recommend high efficacy DMTs for patients with highly active MS. The objective was to examine the impact of initial treatment choice in achieving no evidence of disease activity (NEDA) at year 1 and 2.Methods: Using a real-world population-based registry with limited selection bias from the southeast of Norway, we determined how many patients achieved NEDA on moderate and high efficacy DMTs.Results: 68.0% of patients who started a high efficacy DMT as the first drug achieved NEDA at year 1 and 52.4% at year 2 as compared to 36.0 and 19.4% of patients who started a moderate efficacy DMT as a first drug. The odds ratio (OR) of achieving NEDA on high efficacy drugs compared to moderate efficacy drugs as a first drug at year 1 was 3.9 (95% CI 2.4–6.1, p &lt; 0.001). The OR for high efficacy DMT as the second drug was 2.5 (95% CI 1.7–3.9, p &lt; 0.001), and was not significant for the third drug. Patients with a medium or high risk of disease activity were significantly more likely to achieve NEDA on a high efficacy therapy as a first drug compared to moderate efficacy therapy as a first drug.Conclusions: Achieving NEDA at year 1 and 2 is significantly more likely in patients on high-efficacy disease modifying therapies than on moderate efficacy therapies, and the first choice of treatment is the most important. The immunomodulatory treatment guidelines should be updated to ensure early, high efficacy therapy for the majority of patients diagnosed with MS.
Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder
Authors: Godel Michel , Andrews Derek S. , Amaral David G. , Ozonoff Sally , Young Gregory S. , Lee Joshua K. , Wu Nordahl Christine , Schaer Marie 
Published: June 2021

BackgroundRecent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.Materials and MethodsWe used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n= 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD,n= 9; typical development,n= 8; non-typical development,n= 3).ResultsASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.LimitationsOur study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples.ConclusionThese preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.
Therapeutic Effect and Cost-Benefit Analysis of Three Different Nutritional Schemes for Esophageal Cancer Patients in the Early Post-operative Period
Authors: Huang Chen , Liang Xinyu , Du Shanshan , He Jie , Bai Qian , Feng Xiaoqing , Liu Xiaoqing , Tian Xu , Wang Jian 
Published: June 2021

Objective: To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery.Methods: We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [n = 98 (32.1%)], WPJN group [n = 95 (31.1%)], and PPN group [n = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared.Results: The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups (p &lt; 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group (p &lt; 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group (p &lt; 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group (p &lt; 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups (p &lt; 0.001).Conclusion: Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.
An Applicable Inflammation-Joined and Nutrition-Related Prognostic Indicator in Patients With Colorectal Cancer
Authors: Wu Guo , Liu Jungang , Liu Haizhou , Jin Lan , Huang Xiaoliang , Mo Xianwei , Zhong Huage , Li Yanhua , Zhang Yawei , Tang Weizhong 
Published: June 2021

PurposeThis study aimed to elucidate the prognostic significance of a novel inflammation-joined and nutrition-related clinicopathological marker for colorectal cancer (CRC).MethodsVarious factors from preoperative fasting blood samples from 2471 patients with CRC were retrospectively analyzed. Factors related to prognosis were evaluated using univariate and multivariate analyses. The Kaplan–Meier method was used to generate survival curves, while the log-rank test was used to measure survival differences between groups.ResultsUnivariate analysis revealed that C-reactive protein (CRP)/mean corpuscular volume (MCV) ratio, TNM stage, differentiation, right-sided tumor, age, carcinoembryonic antigen (CEA) level, and CRP level were significantly associated with poor prognosis in CRC. In contrast, adjuvant chemotherapy is regarded as a protective factor. Elevation of CRP/MCV ratio (odds ratio [OR]: 1.535, 95% confidence interval [CI]: 1.121–2.104, P = 0.008), TNM stage (OR: 2.747, 95% CI: 2.175–3.469, P &lt; 0.001), and differentiation (OR, 1.384; 95% CI, 1.150–1.666; P = 0.001) were prognostic risk factors in the multivariate analyses. Subgroup analysis showed that CRP/MCV, TNM staging system, and differentiation also independently affected survival in patients with lymph node-positive CRC. The nomogram based on these three indicators showed that CRP/MCV had a greater prognostic value and clinical significance for lymph node-positive patients with poorly differentiated tumors at the late stage.ConclusionA novel nomogram using the clinicopathologic index of inflammation and nutrition was constructed to predict the prognosis of CRC. Early interventions should be emphasized for advanced-stage patients with severe inflammation and poor nutritional status.
Diagnostic Accuracy of the ADNEX Model for Ovarian Cancer at the 15% Cut-Off Value: A Systematic Review and Meta-Analysis
Authors: Huang Xiaotong , Wang Ziwei , Zhang Meiqin , Luo Hong 
Published: June 2021

ObjectivesTo evaluate the diagnostic accuracy of the ADNEX model for ovarian cancer at the 15% cut-off value.MethodsStudies on the identified diagnosis of the ADNEX model for ovarian cancer published in PubMed, Embase, the Cochrane Library and Web of Science databases from January 1st, 2014 to February 20th, 2021 were searched. Two researchers independently screened the retrieved studies and extracted the basic features and parameter data. The quality of the eligible studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2, and the result was summarized by Review Manager 5.3. Meta-Disc 1.4 and STATA 16.0 were used in statistical analysis. Heterogeneity of this meta-analysis was calculated. Meta-regression was performed to investigate the potential sources of heterogeneity. Sensitivity analysis and Deek’s funnel plot analysis were conducted to evaluate the stability and publication bias, respectively.Results280 studies were initially retrieved through the search strategy, and 10 eligible studies were ultimately included. The random-effects model was selected for data synthesis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the summary receiver operating characteristic curve were 0.92 (95% CI: 0.89–0.94), 0.82 (95% CI: 0.78–0.86), 5.2 (95% CI: 4.1–6.4), 0.10 (95% CI: 0.07–0.13), 54.0 (95% CI: 37.0–77.0) and 0.95 (95% CI: 0.91–0.95). Meta-regression based on study design, country, enrollment and blind method was not statistically significant. This meta-analysis was stable with no obvious publication bias.ConclusionsThe ADNEX model at the 15% cut-off had high diagnostic accuracy in identifying ovarian cancer.
Developing Placebos for Clinical Research in Traditional Chinese Medicine: Assessing Organoleptic Properties of Three Dosage Forms (Oral Liquid, Capsule and Granule)
Authors: Xiao Mengli , Ying Jiake , Zhao Yang , Li Qingna , Zhao Yingpan , Gao Rui , Lu Fang 
Published: June 2021

Background: The successful application of randomized, double-blind placebo-controlled studies requires maximum blinding. Organoleptic properties of the placebo should be similar to the drug, making it difficult to distinguish between the two. The uniqueness of traditional Chinese medicine (TCM) preparations makes it challenging to prepare placebo. Evaluation of the TCM placebo simulation effect can determine whether the preparation of placebo can be genuinely blind in clinical trials. There is still a lack of well-established methods to evaluate TCM placebos. Hence, this study aimed to explore the evaluation methodology of TCM placebo simulation.Methods: An independent evaluation method and three comparative evaluation methods were proposed, and three dosage forms (oral liquid, capsule, and granule) were tested. The independent evaluation, in which each person was given an experimental drug or a placebo, gave an overall assessment of organoleptic properties in a blind state. We comparatively evaluated the similarity in organoleptic properties between the experimental drug and placebo. According to different distribution methods, we divided comparative evaluation methods into three. In method 1, the evaluator was given the experimental drug and placebo and was told that there must be a placebo among them. In method 2, each evaluator was randomly assigned to the combination group or two investigational drugs group. In method 3, the evaluator was assigned to a set of three coded samples, numbered by random three-digit numbers, each different, two of which were identical, and the two samples were equally frequent.Results: In the independent evaluation, there was no difference between TCM placebo and experimental drugs in a blind state at the level of p = 0.05. Even though the comparative evaluation methods enabled identification of potential differences between the two samples, methods 2 and 3 were better than method 1 in eliminating psychological factors. Also, in method 3, the completely random method combined with the blind method eliminated the subjectivity and objectivity bias and improved the experiment’s credibility compared with the previous two methods.Conclusion: Regardless of the methods that could evaluate the placebo’s simulated effect in actual clinical trials, we suggest that independent evaluation and comparative evaluation (method 3) should be combined to reflect better whether the placebo is truly blind.
A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects
Authors: Huang Kai , Que Linling , Ding Ying , Chu Nannan , Qian Zhenzhong , Shi Yunfei , Qin Wei , Li Zhenni , Chen Yuanxin , Gu Xianghong , Wang Jiakun , Zhang Lin , Zhang Jisheng , Zhu Xiangyang , Yang Yongmin , Tang Yuan , He Qing 
Published: June 2021

Objective: This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects.Methods: A single-center, randomized, double-blind, single-dose, parallel trial was performed in 84 Chinese healthy male subjects who randomly (1:1) received a single intravenous infusion of 1 mg/kg HOT-1010 or Avastin® for 90 min and followed up for 85 days. Serum concentrations of bevacizumab were analyzed by enzyme-linked immunosorbent assay. Primary pharmacokinetic parameters, Cmax, AUC0-t and AUC0-∞, were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed.Results: A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 91.81–103.64%, 85.19–95.39% and 85.04–95.36%, which were all within the bioequivalence margin. Treatment-emergent adverse events were reported in 27 (65.9%) subjects in HOT-1010 group and 23 (56.1%) subjects in Avastin® group. Most TEAEs were mild or moderate. No TEAEs, Serious Adverse Events or deaths leading to discontinuation was reported. Subjects were all tested negative for Anti-drug Antibody.Conclusion: HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html, CTR20181610.