bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parathyroid Changes After RAI in Patients With Differentiated Thyroid Carcinoma
Authors: Xiao Liu , Zhang Wenjie , Zhu Hongmei , Wang Yueqi , Liu Bin , Huang Rui , Li Lin 
Published: May 2021

ObjectiveThe purpose of this study was to investigate parathyroid hormone (PTH), serum calcium, phosphorus, and 25-hydroxyvitamin D (25-OH-VD) changes before and after radioactive iodine (RAI) in differentiated thyroid carcinoma (DTC) patients at different time points.MethodsA total of 259 DTC patients who received RAI were prospectively enrolled. We evaluated PTH, serum calcium, phosphorus, and 25-OH-VD levels at baseline pre-RAI, five days, six weeks, and six months post-RAI, respectively. We analyzed the risk factors of hypocalcemia at five days post-RAI.ResultsThe mean PTH, serum calcium and phosphorus values decreased five days post-RAI compared with pre-RAI (PTH 4.18 ± 1.23 pmol/L vs. 3.95 ± 1.41 pmol/L; calcium 2.27 ± 0.09 mmol/L vs. 2.20 ± 0.11 mmol/L; phosphorus 1.25 ± 0.17 vs. 0.98 ± 0.20 mmol/L, P &lt; 0.05), and the differences were statistically significant. The mean 25-OH-VD levels did not significantly decrease at five days post-RAI. 21.2% (55/259) of patients had hypocalcemia at five days post-RAI, and all of them were given oral calcium supplements. At six weeks post-RAI, all of the above parameters were higher than those at five days post-RAI. Multivariate regression analysis showed that baseline pre-RAI serum calcium &lt; 2.27 mmol/L, PTH &lt; 4.18 pmol/L and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia at five days post-RAI.ConclusionFor DTC patients with normal PTH and serum calcium levels at pre-RAI, their PTH, serum calcium, and phosphorus levels decreased at five days post-RAI. About one-fifth of patients could have hypocalcemia at five days post-RAI. Lower baseline pre-RAI serum calcium and PTH levels and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia five days post-RAI.
Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life
Authors: Odumade Oludare A. , Plotkin Alec L. , Pak Jensen , Idoko Olubukola T. , Pettengill Matthew A. , Kollmann Tobias R. , Ozonoff Al , Kampmann Beate , Levy Ofer , Smolen Kinga K. 
Published: May 2021

BackgroundHuman adenosine deaminases (ADAs) modulate the immune response: ADA1viametabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.MethodsIn a subgroup of the EPIC002-study, clinical data and plasma samples were collected from 540 Gambian infants at four time-points: day of birth; first week of life; one month of age; and four months of age. Concentrations of total extracellular ADA, ADA1, and ADA2 were measured by chromogenic assay and evaluated in relation to clinical data. Plasma cytokines/chemokine were measured across the first week of life and correlated to ADA concentrations.ResultsADA2 demonstrated a steady rise across the first months of life, while ADA1 concentration significantly decreased 0.79-fold across the first week then increased 1.4-fold by four months of life. Males demonstrated significantly higher concentrations of ADA2 (1.1-fold) than females at four months; newborns with early-term (37 to &lt;39 weeks) and late-term (≥41 weeks) gestational age demonstrated significantly higher ADA1 at birth (1.1-fold), and those born to mothers with advanced maternal age (≥35 years) had lower plasma concentrations of ADA2 at one month (0.93-fold). Plasma ADA1 concentrations were positively correlated with plasma CXCL8 during the first week of life, while ADA2 concentrations correlated positively with TNFα, IFNγ and CXCL10, and negatively with IL-6 and CXCL8.ConclusionsThe ratio of plasma ADA2/ADA1 concentration increased during the first week of life, after which both ADA1 and ADA2 increased across the first four months of life suggesting a gradual development of Th1/Th2 balanced immunity. Furthermore, ADA1 and ADA2 were positively correlated with cytokines/chemokines during the first week of life. Overall, ADA isoforms demonstrate robust ontogeny in newborns and infants but further mechanistic studies are needed to clarify their roles in early life immune development and the correlations with sex, gestational age, and maternal age that were observed.
Association of Circulating Vascular Endothelial Growth Factor Levels With Autoimmune Diseases: A Systematic Review and Meta-Analysis
Authors: Zhan Haoting , Li Haolong , Liu Chenxi , Cheng Linlin , Yan Songxin , Li Yongzhe 
Published: May 2021

BackgroundAutoimmune diseases (ADs) are characterized by immune-mediated tissue damage, in which angiogenesis is a prominent pathogenic mechanism. Vascular endothelial growth factor (VEGF), an angiogenesis modulator, is significantly elevated in several ADs including rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). We determined whether circulating VEGF levels were associated with ADs based on pooled evidence.MethodsThe analyses included 165 studies from the PubMed, EMBASE, Cochrane Library, and Web of Science databases and fulfilled the study criteria. Comparisons of circulating VEGF levels between patients with ADs and healthy controls were performed by determining pooled standard mean differences (SMDs) with 95% confidence intervals (CIs) in a random-effect model using STATA 16.0. Subgroup, sensitivity, and meta-regression analyses were performed to determine heterogeneity and to test robustness.ResultsCompared with healthy subjects, circulating VEGF levels were significantly higher in patients with SLE (SMD 0.84, 95% CI 0.25–1.44, P = 0.0056), RA (SMD 1.48, 95% CI 0.82–2.15, P &lt;0.0001), SSc (SMD 0.56, 95% CI 0.36–0.75, P &lt;0.0001), Behcet’s disease (SMD 1.65, 95% CI 0.88–2.41, P &lt;0.0001), Kawasaki disease (SMD 2.41, 95% CI 0.10–4.72, P = 0.0406), ankylosing spondylitis (SMD 0.78, 95% CI 0.23–1.33, P = 0.0052), inflammatory bowel disease (SMD 0.57, 95% CI 0.43–0.71, P &lt;0.0001), psoriasis (SMD 0.98, 95% CI 0.62–1.34, P &lt;0.0001), and Graves’ disease (SMD 0.69, 95% CI 0.20–1.19, P = 0.0056). Circulating VEGF levels correlated with disease activity and hematological parameters in ADs.ConclusionCirculating VEGF levels were associated with ADs and could predict disease manifestations, severity and activity in patients with ADs.Systematic Review RegistrationPROSPERO, identifier CRD42021227843.
A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial
Authors: Wu Zhuoxi , Zhao Peng , Peng Jing , Fang Liang , Ding Jinping , Yan Guangming , Wang Yang , Zhu Jing , Wang Dongting , Li Yang , Chen Zhengqiong , Zhang Qingling , Deng Qiangting , Duan Guangyou , Zuo Zhiyi , Li Hong 
Published: May 2021

Background: Postpartum depression (PPD) is a severe psychiatric disorder. Its risk is associated with the cesarean section (CS). Currently, there are few early intervention strategies for these women with PPD who underwent CS.Methods: This was a parallel-group randomized controlled trial of singleton pregnant women who underwent elective CS in a tertiary referral hospital in China from October, 2017 to September, 2019. After operation, patients received randomly tramadol patient-controlled intravenous analgesia (PCIA; 4 mg/ml; TRA group), hydromorphone PCIA (0.04 mg/ml; HYD group), or ropivacaine patient-controlled epidural analgesia (PCEA; 1.5 mg/ml; ROP group) for 48 h in a 1:1:1 ratio. Total blinding during hospitalization was not feasible due to differences between the PCEA and PCIA treatments. All investigators who performed the follow-up were blinded to the group assignment.Outcomes: A total of 1,230 patients were enrolled for eligibility. Intention-to-treat analysis showed reduced incidence of PPD in the TRA group (n = 27 [6.6%]) than that in the HYD (10.2%, OR 1.62, 95% CI 0.98~2.68; p = 0.059) and ROP groups (10.5%, OR 1.66, 95% CI 1.01~2.75; p = 0.046) at 4 weeks post-operation, however, the difference was not statistically significant (Bonferroni corrected p = 0.118, p = 0.098, respectively). Subgroup analysis in high-risk women (preoperative Edinburgh Postpartum Depression Scale [EPDS] ≥10) showed a significantly lower incidence of PPD in the TRA group (16.5%) than in the HYD (32.6%) and ROP groups (30.9%) (Bonferroni corrected p = 0.022 and p = 0.038, respectively). The per-protocol analysis yielded similar results. Reported adverse events (AEs) were mostly mild. None of the women or infant discontinued treatment due to AEs.Conclusions: Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03309163?term=ETPPD&amp;draw=2&amp;rank=1; ClinicalTrials.gov (NCT03309163).
Blood Microsampling to Monitor Metabolic Profiles During Physical Exercise
Authors: Nix Cindy , Hemmati Maryam , Cobraiville Gaël , Servais Anne-Catherine , Fillet Marianne 
Published: May 2021

Monitoring approaches and technical improvements are key factors to improve a sportsman’s health, training, and recovery after an injury. In this study, a targeted metabolomics approach using microsampling with hemaPEN® was developed to measure changes in blood concentrations of nine amino acids and four organic acids before, during, and after exercise. The aim of this research project was to investigate if a reliable monitoring of metabolite levels during sports activity can be achieved by collecting one drop of whole blood at different time points. A hemaPEN device is an easy-to-use and noninvasive microsampling technique designed to collect four accurate and precise blood volumes simultaneously (10.96 µl). Twenty healthy volunteers between 19 and 30 years of age were included in this study. Physical activity consisted in running as fast as possible 1,600 m after 400 m warm-up. One drop of blood was collected at five time points: before exercise, after 800-m running, after 1,600 m, and 30 min and 60 min after finishing the exercise. The influence of physical activity on metabolite levels was evaluated using two ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) methods. Analytical performance criteria such as metabolite stability, method precision, trueness, and accuracy were found to be satisfactory. Expected significant metabolic changes were identified for lactic acid, main TCA cycle intermediates, and some amino acids (e.g., creatinine, choline, and taurine). This preliminary study performed on a small cohort demonstrated a high interest of using microsampling for fluxomics analysis, not only to collect quickly and easily biological samples during sports events but also because it is much easier to store and to process the samples than classical plasma/serum samples obtained by venipuncture. The present results open new avenue for fluxomics analysis in the context of health care.
A Combined Long Noncoding RNA Signature as a Candidate Prognostic Biomarker for Ovarian Cancer
Authors: Li Hui , Wang Shuoer , Yao Qianlan , Liu Yan , Yang Jing , Xu Lun , Yang Gong 
Published: May 2021

AimsDysregulated long noncoding RNAs (lncRNAs) contributing to ovarian cancer (OC) development may serve as prognostic biomarker. We aimed to explore a lncRNA signature to serve as prognostic biomarker of OC.MethodsUnivariate Cox regression was conducted on the lncRNA expression dataset from the TCGA cohort, and 246 genes significantly associated with survival were retained for building a model. A random forest survival model was carried out, and a model was developed using 6 genes with the highest frequency. The selected genes were applied in a Cox multivariate regression model for prognostic prediction by calculating the risk score. We also used CCK-8, EdU, and colony formation assays to validate the function of these lncRNAs in OC cells.ResultsThis study confirmed that the 6-lncRNA combined signature was related to OC prognosis. Systematic analysis demonstrated that lncRNA-associated genes were enriched in oncogenic signalling pathways. Five out of the 6 lncRNAs participated in OC proliferation.ConclusionWe established a 6-lncRNA combined signature for OC prognosis, which may serve as powerful prognostic biomarker for OC after further validation.
Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma
Authors: Huang Jingjun , Huang Wensou , Guo Yongjian , Cai Mingyue , Zhou Jingwen , Lin Liteng , Zhu Kangshun 
Published: May 2021

ObjectivesTo classify hepatocellular carcinoma (HCC) recurrence patterns after radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) combined with RFA (TACE-RFA) and analyze their risk factors and impacts on survival.MethodsWe retrospectively evaluated the medical records of HCC patients who underwent RFA or TACE-RFA from January 2006 to December 2016. HCC recurrences were classified into four patterns: local tumor progression (LTP), intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence. Risk factors, overall survival (OS), and post-recurrence survival of each pattern were evaluated.ResultsA total of 249 patients with a single, hepatitis-B virus (HBV)-related HCC ≤ 5.0 cm who underwent RFA (HCC ≤ 3.0 cm) or TACE-RFA (HCC of 3.1-5.0 cm) were included. During follow-up (median, 53 months), 163 patients experienced HCC recurrence: 40, 43, 62 and 18 patients developed LTP, intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence, respectively; the median post-recurrence survival was 49, 37, 25 and 15 months, respectively (P &lt; .001); the median OS was 65, 56, 58 and 28 months, respectively (P &lt; .001). Independent risk factors for each pattern were as follows: tumor sized 2.1-3.0 cm undergoing RFA alone and insufficient ablative margin for LTP, periportal tumor and non-smooth tumor margin for intra-segmental recurrence, HBV-DNA ≥ 2000 IU/mL for extra-segmental recurrence, and periportal tumor and α-fetoprotein ≥ 100 ng/mL for aggressive recurrence. Recurrence pattern (P &lt; .001) and Child-Pugh class B (P = .025) were independent predictors for OS.ConclusionsBased on our classification, each recurrence pattern had different recurrence risk factors, OS, and post-recurrence survival.
Risk of Cardiac Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-Analysis
Authors: Hu Jiexuan , Tian Ruyue , Ma Yingjie , Zhen Hongchao , Ma Xiao , Su Qiang , Cao Bangwei 
Published: May 2021

BackgroundWe performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy.MethodsEligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1).ResultsAmong 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08–14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1–5 myocardial disease (OR 5.09, 95% CI: 1.11–23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1–5 arrhythmology (OR 2.49, 95% CI: 1.30–4.78, p = 0.289).ConclusionsOur meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.
Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators
Authors: Byun Hwa Kyung , Chang Jee Suk , Jung Minkyu , Koom Woong Sub , Chung Kee Yang , Oh Byung Ho , Roh Mi Ryung , Kim Kyung Hwan , Lee Choong-Kun , Shin Sang Joon 
Published: May 2021

BackgroundImmune checkpoint blocker (ICB) has shown significant clinical activity in melanoma. However, there are no clinically approved biomarkers to aid patient selection. We aimed to identify patients with advanced or metastatic melanoma who are likely to benefit from ICB monotherapy using easily accessible clinical indicators.Materials and MethodsWe retrospectively reviewed the records of 134 patients with advanced or metastatic melanoma who received ICB monotherapy between 2014 and 2018. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were determined using Cox regression analysis.ResultsDuring the median follow-up of 13.7 months, the median OS and PFS were 18.4 and 3.4 months, respectively. Visceral/central nervous system (CNS) metastasis (OS: adjusted hazards ratio [HR], 1.82; p=.014; PFS: HR, 1.59; p=.024), lymphopenia (&lt;1000 cells/µL) within 3 months (OS: HR, 1.89, p=.006; PFS: HR, 1.70; p=.010), and elevated baseline lactate dehydrogenase (LDH) level (OS: HR, 2.61; p&lt;.001; PFS: HR, 2.66; p&lt;.001) were independent prognostic factors for both poor OS and PFS. Development of immune-related adverse events (irAE; e.g., hypothyroidism or vitiligo) within 6 months showed a trend toward better OS in multivariable analysis (HR, 0.37; p=.058). Patients with normal LDH levels and no visceral/CNS metastasis had a substantially better OS than the others (median, 40.4 vs. 13.6 months; p&lt;.001). Among others, patients who developed irAE within 6 months achieved long-term OS (median, 43.6 vs. 13.1 months; p=.008). A decision tree was suggested using four risk factors, and the risk stratification provided significant distinction between the survival curves.ConclusionThe four easily accessible clinical indicators associated with better treatment outcomes after ICB monotherapy in patients with advanced or metastatic melanoma were LDH level, the extent of disease, lymphopenia, and irAE. The combined use of these indicators can be clinically useful in improving risk stratification of patients treated with ICB monotherapy.
The SELFIE 2.0 project (SELF assessment for the therapeutic appropriateness in people with diabetes): proposals to impro­vethe approach to therapeutic intensification in patients with type 2 diabetes with inadequate metabolic control
Authors: Rossi, M.C.  
Published: May 2021

The SELFIE project (SELF assessment for therapeutic appropriateness in people with diabetes) was designed to collect the perceptions and opinions of 60 diabetologists in 12 territorial meetings. The objective was to launch the debate between experts through a structured discussion procedure to identify the main “barriers to intensification” of diabetes treatment (first phase) and the “possible solutions” (second phase). The discussion took into account that DPP4-inhibitors prescription still requires a “therapeutic schedule” in Italy. So, the specific barriers of 8 different profiles (phenotypes) of patients with inadequate metabolic control, classified in terms of age, renal function and treatment with one or more glucose-lowering drugs were highlighted. This article summarizes the results of the second phase. Optimizing / simplifying drug therapy, establishing a therapeutic alliance with the patient, involving a caregiver to act on motivation / communication with the patient, improving organizational aspects, reducing bureaucracy and stimulating the doctor’s attitude to change are the key points that emerged as crucial for overcoming clinical inertia. Implementation of these solutions based on their applicability to the different phenotypes was debated though standardized discussion procedures. Implementing these solutions, monitoring their adoption and measuring the results obtained in the short- and long term, simultaneously focusing on the training of patients and healthcare professionals, is a challenge for the entire diabetes community, to improve the care provided and the clinical outcomes. KEY WORDS type 2 diabetes; glycemic targets; therapeutic inertia; DPP-IV inhibitors; professional education.
Telemedicine and digital narrative medicine for the customization of the diagnostic-therapeutic path at the time of COVID 19
Authors: Agrusta, M.  
Published: May 2021

The Covid-19 issues have placed the telemedicine into the limelight, for its ability to reach remote patients affected by COVID-19, offering them support, expert advice, home hospitalization. At the same time, it gives the many fragile patients, who should be submitted to therapeutic checks or adjustments, the opportunity to be followed appropriately, avoiding travelling and associated risks of contagion. The current situation has accelerated its use in diabetological care: but with the risk of reducing the medical-patient empathic relationship. Narrative Medicine (NBM) integrates with Evidence-Based Medicine (EBM) and, taking into account the plurality of perspectives, makes clinical-care decisions more complete, personalized, effective and appropriate. The stories told by patient and by those who take care, are an essential element of contemporary medicine, based on the active participation of the subjects who are involved in the choices. People, through their own stories, become protagonists of the process of care”. The ability of mixing the technology achievements with the humanistic vision of the care process characterizes DNM, the first digital platformentirely designed for the development of narrative medicine projects in the clinical practice. It was conceived by a team of anthropologists and psychologists with the advice of doctors and experts in narrative medicine of OMNI the Observatory of Narrative Medicine Italy. The DNM features aim to maximize the potential of the digital process, at the same time preserving patient privacy and health data confidentiality. KEY WORDS telemedicine; narrative medicine; digital narrative medicine.