bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors Related to Acute Radiation Dermatitis in Breast Cancer Patients After Radiotherapy: A Systematic Review and Meta-Analysis
Authors: Xie Yuxiu , Wang Qiong , Hu Ting , Chen Renwang , Wang Jue , Chang Haiyan , Cheng Jing 
Published: December 2021

BackgroundAcute radiation dermatitis (ARD) is the most common acute response after adjuvant radiotherapy in breast cancer patients and negatively affects patients’ quality of life. Some studies have reported several risk factors that can predict breast cancer patients who are at a high risk of ARD. This study aimed to identify patient- and treatment-related risk factors associated with ARD.MethodsPubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang literature databases were searched for studies exploring the risk factors in breast cancer patients. The pooled effect sizes, relative risks (RRs), and 95% CIs were calculated using the random-effects model. Potential heterogeneity and sensitivity analyses by study design, ARD evaluation scale, and regions were also performed.ResultsA total of 38 studies composed of 15,623 breast cancer patients were included in the analysis. Of the seven available patient-related risk factors, four factors were significantly associated with ARD: body mass index (BMI) ≥25 kg/m2 (RR = 1.11, 95% CI = 1.06–1.16, I2 = 57.1%), large breast volume (RR = 1.02, 95% CI = 1.01–1.03, I2 = 93.2%), smoking habits (RR = 1.70, 95% CI = 1.24–2.34, I2 = 50.7%), and diabetes (RR = 2.24, 95% CI = 1.53–3.27, I2 = 0%). Of the seven treatment-related risk factors, we found that hypofractionated radiotherapy reduced the risk of ARD in patients with breast cancer compared with that in conventional fractionated radiotherapy (RR = 0.28, 95% CI = 0.19–0.43, I2 = 84.5%). Sequential boost and bolus use was significantly associated with ARD (boost, RR = 1.91, 95% CI = 1.34–2.72, I2 = 92.5%; bolus, RR = 1.94, 95% CI = 1.82–4.76, I2 = 23.8%). However, chemotherapy regimen (RR = 1.17, 95% CI = 0.95–1.45, I2 = 57.2%), hormone therapy (RR = 1.35, 95% CI = 0.94–1.93, I2 = 77.1%), trastuzumab therapy (RR = 1.56, 95% CI = 0.18–1.76, I2 = 91.9%), and nodal irradiation (RR = 1.57, 95% CI = 0.98–2.53, I2 = 72.5%) were not correlated with ARD. Sensitivity analysis results showed that BMI was consistently associated with ARD, while smoking, breast volume, and boost administration were associated with ARD depending on study design, country of study, and toxicity evaluation scale used. Hypofractionation was consistently shown as protective. The differences between study design, toxicity evaluation scale, and regions might explain a little of the sources of heterogeneity.ConclusionThe results of this systematic review and meta-analysis indicated that BMI ≥ 25 kg/m2 was a significant predictor of ARD and that hypofractionation was consistently protective. Depending on country of study, study design, and toxicity scale used, breast volume, smoking habit, diabetes, and sequential boost and bolus use were also predictive of ARD.
A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine
Authors: Dong Ping , Wang Li , Xiao Liu , Yang Liu , Huang Rui , Li Lin 
Published: December 2021

BackgroundTotal thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in patients with low-risk DTC treated with TT or lobectomy but without RAI.MethodsWe performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6–24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.ResultsAt a median follow-up of 51 months (range 33–66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had structural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p&lt;0.001).ConclusionOur study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.
Comprehensive Analysis of m6A Regulators Characterized by the Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy and Chemotherapy
Authors: Yang Zhiqiang , Ming Xiaoping , Huang Shuo , Yang Minlan , Zhou Xuhong , Fang Jiayu 
Published: December 2021

BackgroundN6-Methyladenosine (m6A), which is a prevalent regulator of mRNA expression, has gathered increasing study interests. Though the role of m6A as being important in many biological processes (such as growth and proliferation of cancers) has been well documented, its potential role in tumor immune microenvironment (TIME) has rarely been analyzed.MethodsWe downloaded RNA expression, single nucleotide polymorphism (SNP), and copy number variation (CNV) data from The Cancer Genome Atlas (TCGA). We then curated 21 m6A regulators and clustered patients into three m6A subtypes and m6A-related gene subtypes and compared them based on overall survival (OS). The combination of CIBERSORT as well as ssGSEA quantified the infiltration levels of immune cells and immune-related functions. The m6A scores were determined by using principal component analysis (PCA) algorithm. Furthermore, we evaluate the correlation of m6A regulators with immune and response to therapy.ResultsThree m6A clusters were identified based on the TCGA-HNSCC cohort, and there were significant associations among them in overall outcomes and caner-related pathways. We found that three m6A clusters were consistent with three phenotypes: immune-inflamed, immune-dessert, and immune-excluded. HNSCC patients were divided into high– and low–m6A score groups based on the cutoff of m6A score. Patients with lower m6A score had better overall survival outcome. Further analysis indicated that patients with higher m6A score presented higher tumor mutation burden (TMB). In addition, patients in low–m6A score subgroup had high chemotherapeutics sensitivity. GEO cohort confirmed patients with low m6A score demonstrated significant overall survival advantages and clinical benefits. Low m6A score carry an increased neoantigen load, eliciting a response to immunotherapy, and its value in predicting survival outcomes of immunotherapy was also confirmed in three anti-PD-1 cohorts.ConclusionsOur study demonstrated that m6A regulators are closely related to TIME and the m6A score was an effective prognostic biomarker and predictive indicator for immunotherapy and chemotherapeutics. Comprehensive evaluation of m6A regulators in tumors will extend our understanding of TIME and effectively guide increasing study investigations on immunotherapy and chemotherapy strategies for HNSCC.
A Retrospective Analysis of Rituximab Treatment for B Cell Depletion in Different Pediatric Indications
Authors: Wennmann Merlin , Kathemann Simone , Kampmann Kristina , Ohlsson Sinja , Büscher Anja , Holzinger Dirk , Della Marina Adela , Lainka Elke 
Published: December 2021

Background: Rituximab (RTX) is used in cancer therapy as well as in the treatment of autoimmune diseases and alloimmune responses after transplantation. It depletes the disease-causing B cells by binding to the CD (cluster of differentiation) 20 antigen. We evaluate different pediatric treatment protocols (via fixed treatment schedule, B cell- or symptom-controlled) and their therapeutic effects.Methods: Demographic information, clinical and laboratory characteristics, and special laboratory values such as immunoglobulin G (IgG), CD19 positive B cells and Epstein-Barr viral load were retrospectively analyzed in children treated with RTX between 2008 and 2016.Results: Seventy-six patients aged 1 to 19 (median 13) years were treated with 259 RTX infusions. The spectrum of diseases was very heterogeneous. RTX led to a complete depletion of the B cells. The reconstitution time varied between patients and was dependent on the application schedule (median 11.8 months). Fourteen out of 27 (52%) patients developed hypogammaglobulinaemia. The risk of IgG deficiency was 2.6 times higher in children under 4 years of age than in olderones. In the last group IgG deficiency developed in only 38% of the cases (n = 8). Recurrent and severe infections were observed each in 11/72 (15%) patients. Treatment-related reactions occurred in 24/76 (32%) cases; however, treatment had to be discontinued in only 1 case. In 16/25 (76%), the Epstein-Barr viral load dropped below the detection limit after the first RTX infusion.Conclusion: RTX is an effective and well-tolerated drug for the treatment of oncological diseases as well as autoimmune and alloimmune conditions in children. B cell depletion and reconstitution varies both intra- und interindividually, suggesting that symptom-oriented and B cell-controlled therapy may be favorable. Treatment-related reactions, IgG deficiency and infections must be taken into account.
Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
Authors: Lodeweyckx Niels , Wouters Kristien , Ledeganck Kristien J. , Trouet Dominique 
Published: December 2021

Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition.Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model.Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat.Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.
Radiofrequency Ablation a Safe and Effective Treatment for Pediatric Benign Nodular Thyroid Goiter
Authors: Lin An-Ni , Lin Wei-Che , Cheng Kai-Lun , Luo Sheng-Dean , Chiang Pi-Ling , Chen Wei-Chih , Chen Yueh-Sheng , Wang Cheng-Kang , Kan Na-Ning , Su Yan-Ye 
Published: December 2021

Purpose: To evaluate the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules in pediatric patients.Materials and Methods: Twelve pediatric patients (11 female, 1 male; mean age 15.54 ± 2.8 years, range 10–19 years) with benign thyroid nodules (mean longest diameter 4.1 ± 1.4 cm, range 1.5–5.9 cm) treated by RFA from 2017 to 2020 were evaluated. The inclusion criteria for RFA therapy were (i) age &lt; 20 years; (ii) benign cytological confirmation by 2 separate ultrasound guided fine-needle aspiration cytology (FNAC) or core needle biopsies; (iii) pressure symptoms or cosmetic problems caused by thyroid nodules; (iv) absence of any sonographic suspicious feature; and (v) follow-up for &gt;6 months. Under local anesthesia, RFA was performed with the use of an RF generator and an 18-gauge internally cooled electrode. Volume changes in nodules on follow-up ultrasonography (US), changes in symptomatic and cosmetic scores, and complications arising during or after RFA were evaluated.Results: Mean follow-up period was 24.9 ± 13.9 months (range 6–43 months). At the last follow-up visits, volume of the nodule had decreased significantly (15.34 ± 11.52 mL vs. 4.07 ± 4.99 mL; P &lt; 0.05), whereas volume reduction rate was 74.31% ± 19.59%. Both cosmetic and compressive symptoms were also significantly improved (2.91 ± 0.79 vs. 0.92 ± 0.67 and 1.5 ± 1.93 vs. 0.17 ± 0.39; P &lt; 0.05). The mean number of ablation sessions was 1.4 ± 0.6 (range 1–3 sessions), and one of the patients suffered from transient vocal cord palsy which was spontaneously resolved 53 days later.Conclusions: RFA is a safe and effective treatment for benign thyroid nodules in pediatric patients, and can thus serve as an alternative treatment for thyroidectomy.
Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
Authors: Rypdal Veronika , Jørandli Sondre , Hemmingsen Dagny , Solbu Marit Dahl , Klingenberg Claus 
Published: December 2021

Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.
Increased Arterial Stiffness Is Associated With Reduced Diastolic Function in Youth With Obesity and Type 2 Diabetes
Authors: Madsen Nicolas L. , Haley Jessica E. , Moore Ryan A. , Khoury Philip R. , Urbina Elaine M. 
Published: December 2021

Background: Increased arterial stiffness is associated with diastolic dysfunction in adults. Data in youth are lacking, so we examined the impact of arterial stiffness on diastolic function in youth.Methods: We obtained diastolic function and augmentation index, pulse wave velocity, brachial artery distensibility, and carotid stiffness on 612 youth [10–24 years, 65% female, 38% normal weight, 36% obese, and 26% with type 2 diabetes mellitus (T2DM)]. Participants were classified as compliant (C) vs. stiff (S) arteries based on seven arterial stiffness parameters [Global Stiffness Index (GSI), S = GSI &gt; 4). Mean differences in covariates were evaluated by Student's t-tests. A stepwise regression analysis was performed to determine if GSI was an independent predictor of diastolic function.Results: Lower diastolic function and more adverse cardiovascular disease (CVD) risk factors were present in the S group (n = 67) than the C group (n = 545) (p &lt; 0.001). Covariates that were associated with diastolic dysfunction were higher GSI, male sex, higher body mass index (BMI), and systolic blood pressure (SBP) z-score (R2 = 0.18 to 0.25; p ≤ 0.05).Conclusion: Adverse diastolic function is seen in youth with increased arterial stiffness independent of CVD risk factors. Interventions to improve arterial stiffness prior to clinical onset of diastolic dysfunction are needed to prevent development of heart failure.
Endocan: A Novel Marker for Colchicine Resistance in Familial Mediterranean Fever Patients?
Authors: Omma Ahmet , Armaǧan Berkan , Güven Serdar Can , Sandıkçı Sevinç Can , Çolak Seda , Yücel Çiǧdem , Küçükşahin Orhan , Erden Abdulsamet 
Published: December 2021

Introduction: Familial Mediterranean fever (FMF) patients had 5–10% colchicine resistance. Although FMF attacks are characterized by acute phase elevation, there are no biomarkers that can show colchicine resistance yet. The serum endocan levels may elevate in inflammatory and auto-inflammatory diseases.Objectives: This study aimed to evaluate serum endocan levels in FMF patients according to whether attack and colchicine resistance or not and also compare them with classical acute phase reactants.Methods: In this single-center and cross-sectional study, a total of 111 FMF patients and 60 healthy individuals were enrolled. All patients' basic demographic and clinical data were recorded and blood samples were collected.Results: A total of 46 (41.4%) FMF patients had colchicine resistance. In comparison to the FMF patients according to colchicine response, colchicine resistance patients had a significantly higher median (IQR) endocan levels than colchicine responsive patients [36.98 ng/ml (97.41) vs. 13.57 ng/ml (27.87), p = 0.007], but there were no differences between in terms of median ESR and CRP levels. Inversely, serum endocan levels were similar during an attack and attack-free period in FMF patients, although ESR and CRP levels were significantly different. Interestingly, the highest serum endocan levels were in the control group.Conclusion: In conclusion, serum endocan levels were higher in colchicine resistance than colchicine responsive patients, but attack state had no effect on serum endocan levels in our study. Unlike ESR and CRP, serum endocan may be a novel biomarker for detection of colchicine resistance and distinguish the FMF attacks.
Case Report: Development of Type 1 Autoimmune Pancreatitis in an Adolescent With Ulcerative Colitis Mimicking Pancreatic Cancer
Authors: Choi Sujin , Lee Hae Jeong , Seo An Na , Bae Han Ik , Kwon Hyung Jun , Cho Chang Min , Lee So Mi , Choe Byung-Ho , Kang Ben 
Published: December 2021

Introduction: Autoimmune pancreatitis (AIP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) which is typically responsive to corticosteroid treatment.Case Presentation: We report a case of a 17-year-old male diagnosed with ulcerative colitis who subsequently developed acute pancreatitis. Blood tests demonstrated elevated pancreatic enzyme levels of amylase (1319 U/L) and lipase (809 U/L). Abdominal computed tomography revealed peripancreatic fat stranding and the presence of a perisplenic pseudocyst. Azathioprine and mesalazine were stopped as possible causes of drug-induced pancreatitis. However, pancreatic enzymes remained elevated and corticosteroid treatment was started. Despite corticosteroid therapy, amylase and lipase levels continued to increase. Infliximab was started due to a flare in gastrointestinal symptoms of ulcerative colitis. Follow-up abdominal ultrasonography revealed a pancreatic tail mass. Tumor markers, including CA 19-9, were elevated and atypical cells were seen on histological examination of an endoscopic ultrasonography-guided fine needle aspiration biopsy. Surgical pancreaticosplenectomy was performed for suspected pancreatic neoplasm. Surprisingly, histology revealed chronic pancreatitis with storiform fibrosis and infiltration of IgG4-positive cells, compatible with AIP type 1. Thereafter, pancreatic enzymes gradually decreased to normal levels and the patient has been in remission for 9 months on infliximab monotherapy.Conclusion: Pediatric gastroenterologists should keep in mind that AIP may develop during the natural course of pediatric IBD. Moreover, the development of pancreatic fibrosis may be non-responsive to corticosteroid treatment and mimic pancreatic neoplasia.