bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Relationship of Genetically Predicted Serum Micronutrients Levels With Sarcopenia: A Mendelian Randomization Study
Authors: Sha Tingting , Li Wei , He Hongyi , Wu Jing , Wang Yilun , Li Hui 
Published: June 2022

ObjectivesPrevious observational studies have suggested associations between concentrations of several circulating micronutrients and sarcopenia. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. Therefore, we aimed to examine the causal effects of the levels of genetically predicted serum micronutrients on sarcopenia.MethodsSingle nucleotide polymorphisms (SNPs) were chosen from large-scale genome-wide association studies of participants only with European descent and were used as genetic instruments for the levels of 10 serum micronutrients (calcium, magnesium, selenium, copper, iron, zinc, Vitamin A, Vitamin B12, Vitamin D, and Vitamin E). Sarcopenia was defined by referencing to the 2019 definition given by the European Working Group on Sarcopenia in Older People (EWGSOP). A two-sample Mendelian randomization (MR) analysis was carried out to examine the associations between the levels of genetically predicted serum micronutrients and the risk of sarcopenia. Then, sensitivity analyses (including weighted median, MR-Egger and leave-one-out sensitivity analyses) were performed to evaluate the robustness of study findings. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs) per one standard deviation (SD) increase in the exposures.ResultsA total of 378,635 UK Biobank participants, including 572 participants who were identified with sarcopenia, were included in this study. The iron status was shown to have a clear effect on the risk of sarcopenia based on MR analyses. The per one SD increment in the genetically-determined serum iron level corresponded to a 53% increase in the risk of sarcopenia (OR = 1.53, 95% CI: 1.31–1.78, P = 0.001). The exclusion of SNPs of the circulating iron level (i.e., rs1799945 SNP, rs1800562 SNP or rs855791 SNP) did not attenuate the magnitude of the signal in MR analysis. There was little evidence supporting the associations between other remaining micronutrients and sarcopenia.ConclusionsAn increased risk of sarcopenia was observed with a genetically higher concentration of iron, suggesting that iron may play a role in the occurrence or development of sarcopenia.
Dosing Pattern and Early Cumulative Dose of Liposomal Irinotecan in Metastatic Pancreatic Cancer: A Real-World Multicenter Study
Authors: Su Yung-Yeh , Chiang Nai-Jung , Li Chung-Pin , Yen Chia-Jui , Yang Shih-Hung , Chou Wen-Chi , Chen Jen-Shi , Chiu Tai-Jan , Chen Yen-Yang , Chuang Shih-Chang , Bai Li-Yuan , Chiu Chang-Fang , Peng Cheng-Ming , Chan De-Chuan , Chiu Sz-Chi , Yang Yi-Hsin , Shan Yan-Shen , Chen Li‐Tzong 
Published: June 2022

IntroductionThis multicenter, real-world cohort study aimed to evaluate the effectiveness of early cumulative dose administration and dosing pattern of liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (mPDAC).Material and MethodsThe electronic medical records of mPDAC patients treated with nal-IRI+5-FU/LV in nine participating centers were manually reviewed. To accommodate to the NAPOLI-1 study population, only patients with an Eastern Cooperative Oncology Group Performance Score of 0–1 were included. The survival impact of the relative 6-week cumulative dose and dosing pattern (standard vs. reduced starting dose, with and without further dose modification) were investigated.ResultsOf the 473 included patients, their median overall survival (mOS) was 6.8 [95% CI, 6.2–7.7] months. The mOS of patients who received a relative 6-week cumulative dose of &gt;80%, 60%–80%, and &lt;60% were 7.9, 8.2, and 4.3 months, respectively (p&lt;0.0001). Their survival impact remained significant after covariate adjustment using Cox regression. The mOS was 8.0–8.2 months in patients with a standard starting dose with and without early dose modification, and 9.3 and 6.7 months in those who had a reduced starting dose with and without escalation in the subsequent treatment, respectively. The incidence of grade 3–4 neutropenia and diarrhea was 23.3% and 2.7%, respectively.ConclusionOur results support the use of nal-IRI+5-FU/LV in gemcitabine-refractory mPDAC and suggest that a lower starting dose followed by a re-escalation strategy could achieve clinical outcomes comparable to those with standard starting doses in real-world practice.
Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms
Authors: Castelo-Branco Luis , Cardenas-Rojas Alejandra , Rebello-Sanchez Ingrid , Pacheco-Barrios Kevin , de Melo Paulo S. , Gonzalez-Mego Paola , Marduy Anna , Vasquez-Avila Karen , Costa Cortez Pablo , Parente Joao , Teixeira Paulo E. P. , Rosa Gleysson , McInnis Kelly , Caumo Wolnei , Fregni Felipe 
Published: June 2022

IntroductionFibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables.Materials and MethodsIn this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity.ResultsFifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = −0.5, p = 0.009).ConclusionOur results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.
Continuous Renal Replacement Therapy in Pediatric Patients With Acute Kidney Injury After Liver Transplantation
Authors: Sun Yan , Gao Sinan , Wang Xingqiang , Yu Lixin , Xu Min , Gao Wei , Sun Chao , Wang Bing 
Published: June 2022

ObjectiveThis study aimed to explore the clinical application of continuous renal replacement therapy (CRRT) in pediatric patients with acute kidney injury (AKI) after liver transplantation.MethodsPediatric patients who underwent liver transplantation were retrospectively investigated. Those who developed AKI within 1 year after the surgery were included and divided into a CRRT group and a non-CRRT group. The perioperative conditions and postoperative complications of the two groups were compared along with the prognoses of the groups to analyze the high-risk factors of the postoperative CRRT.Results189 (36.91%) patients developed AKI within 1 year after the liver transplantation surgery. There were 18 patients in the CRRT group and 171 in the non-CRRT group. The differences in the preoperative conditions were not statistically significant between the two groups. Compared with the non-CRRT group, patients in the CRRT group had significantly longer transplantation times, higher volumes of intraoperative hemorrhage, and increased incidence of postoperative unscheduled surgery, postoperative primary nonfunction of the transplanted liver, secondary liver transplantation, hepatic artery occlusion, and intestinal fistula (P &lt; 0.05). Moreover, the proportion of patients in AKI stage 3 is higher in the CRRT group (83.33%) than that in the non-CRRT group (11.11%), P &lt; 0.001. The median time to initiate CRRT was 10 days postoperatively, the median number of CRRT treatments per patient was 2 times, the average duration of each CRRT treatment was 10.1 h, and the average rate of the decrease in blood creatinine per treatment was 25.6%. Results of multivariate logistic regression analysis showed that AKI stage 3 [OR=40.000, 95%CI (10.598, 150.969), P = 0.016], postoperative unscheduled surgery [OR=6.269, 95%CI (3.051, 26.379), P = 0.007], and hepatic artery occlusion [OR = 17.682, 95%CI (1.707, 40.843), P = 0.001] were recognized as risk factors for postoperative AKI with CRRT therapy. The one- and two-year survival rates were 72.22% and 72.22% in the CRRT group, respectively; and 97.08% and 96.49% in the non-CRRT group, accordingly. There were statistically significant differences in the one- and two-year survival rates between the two groups (P &lt; 0.001).ConclusionThe incidence of AKI after liver transplantation in pediatric patients was high. Patients with AKI stage 3, hepatic artery occlusion, and underwent unscheduled surgery postoperatively were with a high likelihood of receiving CRRT, which was related to a lower one- and two-year survival rates. CRRT effectively improved the one- and two-year survival rates.
First Identification of Rare Exonic and Deep Intronic Splice-Altering Variants in Patients With Beta-Sarcoglycanopathy
Authors: Xie Zhiying , Sun Chengyue , Liu Chang , Chu Xujun , Gang Qiang , Yu Meng , Zheng Yiming , Meng Lingchao , Li Fan , Xia Dongliang , Wang Li , Li Ying , Deng Jianwen , Lv He , Wang Zhaoxia , Zhang Wei , Yuan Yun 
Published: June 2022

BackgroundThe precise genetic diagnosis of a sarcoglycanopathy or dystrophinopathy is sometimes extremely challenging, as pathogenic non-coding variants and/or complex structural variants do exist in DMD or sarcoglycan genes. This study aimed to determine the genetic diagnosis of three patients from two unrelated families with a suspected sarcoglycanopathy or dystrophinopathy based on their clinical, radiological, and pathological features, for whom routine genomic detection approaches failed to yield a definite genetic diagnosis.MethodsMuscle-derived reverse transcription-polymerase chain reaction analysis and/or TA cloning of DMD, SGCA, SGCB, SGCD, and SGCG mRNA were performed to identify aberrant transcripts. Genomic Sanger sequencing around the aberrant transcripts was performed to detect possible splice-altering variants. Bioinformatic and segregation studies of the detected genomic variants were performed in both families.ResultsIn patients F1-II1 and F1-II2, we identified two novel pathogenic compound heterozygous variants in SGCB. One is a deep intronic splice-altering variant (DISV), c.243 + 1558C &gt; T in intron 2 causing the activation of an 87-base pair (bp) pseudoexon, and the other one is a non-canonical splicing site variant, c.243 + 6T &gt; A leading to the partial intron inclusion of 10-bp sequence. A novel DISV, c.243 + 1576C &gt; G causing a 106-bp pseudoexon activation, and a nonsense variant in SGCB were identified in compound heterozygous state in patient F2-II1. Unexpectedly, the predicted nonsense variant, c.334C &gt; T in exon 3, created a new donor splice site in exon 3 that was stronger than the natural one, resulting in a 97-bp deletion of exon 3 (r.333_429del).ConclusionThis is the first identification of rare exonic and DISVs in the SGCB gene.
Prevention of Radiodermatitis With Topical Chinese Herbal Medicine: A Systematic Review and Meta-Analysis
Authors: Yu Hui-Bo , Han Bao-Jin , Cao Hui-Juan 
Published: June 2022

Objectives: Topical Chinese herbal medicine (TCHM) is widely used to prevent radiodermatitis in patients who receive radiation therapy in China. However, evidence regarding its efficacy remains limited. The purpose of the review is to evaluate the effects of TCHM in preventing radiodermatitis.Methods: The protocol of this review was registered in PROSPERO (CRD42020220620). Relevant clinical trials were identified (from January 1, 2010, to April 24, 2022) through 11 electronic databases, including PubMed, SpringerLink, Proquest, the Cochrane Central Register of Controlled Trials, Scopus, the ProQuest Dissertation &amp; Theses Global, PsycINFO, Applied Social Sciences Index and Abstracts, the Chinese National Knowledge Infrastructure Databases, Wangfang Data Knowledge Service Platform, and the Chongqing VIP Chinese Science and Technology Periodical Database. The quality of the included trials was assessed through a risk of bias assessment using Version 2 of the Cochrane risk-of-bias tool (RoB 2.0). We included RCTs that compared TCHM single used or as adjunctive treatment with routine drugs, conventional therapy, or placebo for cancer patients who are about to start radiation therapy and do not possess any type of dermatitis or skin lesions at that time. Primary outcomes of interest were the incidence of radiodermatitis and the grade of radiodermatitis according to the RTOG (Radiation Therapy Oncology Group). Secondary outcomes included the recovery time of skin and mucosa, the occurrence time of radiodermatitis, the radiation dose, quality of life, and adverse events. Data were summarized using risk ratio (RR) calculations and 95% confidence intervals (CI) for binary outcomes or mean difference (MD) with 95% CI for continuous outcomes. Certainty of the evidence was assessed according to the GRADE criteria.Results: In this review, 38 randomized controlled trials (RCTs) were included. Risk of bias assessment through RoB 2.0 showed that two studies were rated as low risk, two studies were rated as high risk, and the rest were rated as having some concerns. Compared with routine drugs, TCHM may have an advantage in reducing RTOG grading (RR = 0.46, 95%CI 0.35–0.60), decreasing the recovery time of radiodermatitis (MD = −2.35, 95%CI 3.58 to −1.12 days), delaying the occurrence of radiodermatitis (MD = 2.36, 95%CI 1.74–2.98), and improving the quality of life of patients (RR = 1.46, 95%CI 1.03–2.06). Compared with conventional therapy, TCHM may also have an advantage in decreasing the grade of RTOG (RR = 0.28, 95%CI 0.21–0.38).Conclusion: Current low evidence revealed that TCHM may have better efficacy in the prevention of radiodermatitis; however, more high-quality RCTs are still warranted to testify this conclusion.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020220620), identifier (PROSPERO 2020 CRD42020220620).
A Prescribing Cascade of Proton Pump Inhibitors Following Anticholinergic Medications in Older Adults With Dementia
Authors: Trenaman Shanna C. , Harding Austin , Bowles Susan K. , Kirkland Susan A. , Andrew Melissa K. 
Published: June 2022

Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events.Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia.Method: The cohort was comprised of Nova Scotia Seniors’ Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis.Results: We identified 28,952 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97–0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74–0.91]), or to be men (OR 0.74, 95%CI [0.67–0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29–1.58]).Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors’ Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades.
Genetic Polymorphisms in CYP2C19 Cause Changes in Plasma Levels and Adverse Reactions to Anlotinib in Chinese Patients With Lung Cancer
Authors: Tan Tingfei , Han Gongwei , Cheng Ziwei , Jiang Jiemei , Zhang Li , Xia Zitong , Wang Xinmeng , Xia Quan 
Published: June 2022

Background: Anlotinib is a small molecular multi-targeting tyrosine kinase inhibitor. Growing evidence indicates that treatment efficacy, and toxicity varies considerably between individuals. Therefore, this study aimed to investigate the relationship between cytochrome P450 (CYP450) gene polymorphisms, drug concentrations, and their adverse reactions in anlotinib-treated patients with lung cancer.Methods: We enrolled 139 patients with lung cancer, treated with anlotinib. Twenty loci in the following five genes of the CYP450 family were genotyped: CYP450 family 3 subfamily A member 5 (CYP3A5), 3 subfamily A member 4 (CYP3A4), 2 subfamily C member 9 (CYP2C9), 2 subfamily C member 19 (CYP2C19), and 1 subfamily A member 2 (CYP1A2). Data on adverse reactions were collected from patients, and plasma anlotinib concentrations were measured.Results: There were significant variances in plasma trough concentration (3.95–52.88 ng/ml) and peak plasma concentration (11.53–42.8 ng/ml) following administration of 8 mg anlotinib. Additionally, there were significant differences in the plasma trough concentration (5.65–81.89 ng/ml) and peak plasma concentration (18.01–107.18 ng/ml) following administration of 12 mg anlotinib. Furthermore, for CYP2C19-rs3814637, the peak plasma concentrations of mutant allele T carriers (TT+CT) were significantly higher than those of wildtypes (CC). For CYP2C19-rs11568732, the peak plasma concentrations of the mutant allele G carriers (GT+GG) were significantly higher than those of the wild-type (TT). More importantly, the incidence rates of hypertension and hemoptysis (peripheral lung cancer) with TT+CT in rs3814637 and GT+GG in rs11568732 were significantly higher than those with CC and TT.Conclusions: The plasma trough and peak concentrations varied significantly for both 8 and 12 mg of anlotinib. Single-nucleotide polymorphisms in CYP2C19 are significantly associated with hypertension, hemoptysis, and anlotinib peak concentrations. Polymorphisms in CYP450 may explain inter-individual differences in anlotinib-related adverse reactions.
Discordant Spirometry and Impulse Oscillometry Assessments in the Diagnosis of Small Airway Dysfunction
Authors: Lu Lifei , Peng Jieqi , Zhao Ningning , Wu Fan , Tian Heshen , Yang Huajing , Deng Zhishan , Wang Zihui , Xiao Shan , Wen Xiang , Zheng Youlan , Dai Cuiqiong , Wu Xiaohui , Zhou Kunning , Ran Pixin , Zhou Yumin 
Published: June 2022

Background and objective: Spirometry is commonly used to assess small airway dysfunction (SAD). Impulse oscillometry (IOS) can complement spirometry. However, discordant spirometry and IOS in the diagnosis of SAD were not uncommon. We examined the association between spirometry and IOS within a large cohort of subjects to identify variables that may explain discordant spirometry and IOS findings.Methods: 1,836 subjects from the ECOPD cohort underwent questionnaires, symptom scores, spirometry, and IOS, and 1,318 subjects were examined by CT. We assessed SAD with R5-R20 &gt; the upper limit of normal (ULN) by IOS and two of the three spirometry indexes (maximal mid-expiratory flow (MMEF), forced expiratory flow (FEF)50%, and FEF75%) &lt; 65% predicted. Multivariate regression analysis was used to analyze factors associated with SAD diagnosed by only spirometry but not IOS (spirometry-only SAD) and only IOS but not spirometry (IOS-only SAD), and line regression was used to assess CT imaging differences.Results: There was a slight agreement between spirometry and IOS in the diagnosis of SAD (kappa 0.322, p &lt; 0.001). Smoking status, phlegm, drug treatment, and family history of respiratory disease were factors leading to spirometry-only SAD. Spirometry-only SAD had more severe emphysema and gas-trapping than IOS-only SAD in abnormal lung function. However, in normal lung function subjects, there was no statistical difference in emphysema and gas-trapping between discordant groups. The number of IOS-only SAD was nearly twice than that of spirometry.Conclusion: IOS may be more sensitive than spirometry in the diagnosis of SAD in normal lung function subjects. But in patients with abnormal lung function, spirometry may be more sensitive than IOS to detect SAD patients with clinical symptoms and CT lesions.