bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic value of MRI combined with ultrasound for lymph node metastasis in breast cancer
Authors: Cai Dechun , Lin Tong , Jiang Kailin , Sun Zhizhong 
Published: July 2019

Abstract

Background:
Early diagnosis and treatment of breast cancer are important to prevent fatal tumor progression. Axillary lymph node (ALN) status is the most significant prognostic factor for diagnosing overall survival in breast cancer patients. Axillary lymph node dissection (ALND) is regarded as the reference standard for determining ALN status. However, ALND is an invasive therapy with high morbidity and complications such as lymphedema, seroma and nerve injury. Comparatively, magnetic resonance imaging (MRI) and ultrasound are noninvasive and non-radiative techniques that are common imaging methods to diagnose breast cancer lymph node metastasis. Many studies have investigated the diagnostic value of MRI combined with ultrasound for breast cancer ALN metastasis, but the evidence has been insufficient to apply these modalities when diagnosing new patients.

Methods:
We will search electronic databases including PubMed, EMbase, The Cochrane Library, Chinese Biomedical Database, WangFang Database, and China National Knowledge Infrastructure. The language of studies is limited in English or Chinese. The final search includes articles published in June, 2018. Stata 14.0 software will be used for all statistical analyses, and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be utilized to evaluate the quality of the included studies. Meta-regression and subgroup analyses will be performed to explore heterogeneity, which will be derived from the different countries of origin of the included studies. Deeks’ funnel plot asymmetry test will be demonstrated the inexistence of publication bias.

Result:
This study will provide a rational synthesis of current evidences for magnetic resonance imaging combined with ultrasound for breast cancer.

Conclusion:
The conclusion of this study will provide evidence for the diagnostic value of MRI combined with ultrasound for lymph node metastasis in breast cancer.

Registration:
PROS-PERO CRD42019134474
Endoscopic papillary balloon dilation decreases the risk of bleeding in cirrhotic patients compared with endoscopic biliary sphincterotomy
Authors: Hung Tsung-Hsing , Tseng Chih-Wei , Chen Yen-Chun , Tseng Kuo-Chih , Hsieh Yu-Hsi , Tsai Chih-Chun 
Published: July 2019

Abstract
Although endoscopic papillary balloon dilation (EPBD) seems to cause fewer instances of bleeding, there are insufficient data to determine the optimal methods for decreasing the risk of bleeding in cirrhotic patients.
In this study, we compared the bleeding risks following endoscopic biliary sphincterotomy (EST) vs EPBD in cirrhotic patients and identified clinical factors associated with bleeding and 30-day mortality.
Taiwan's National Health Insurance Database was used to identify 3201 cirrhotic patients who underwent EST or EPBD between January 1, 2010, and December 31, 2013.
We enrolled 2620 patients receiving EST and 581 patients receiving EPBD. The mean age was 63.1 ± 13.9 years, and 70.4% (2252/3201) were men. The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding was higher among patients treated with EST than those treated with EPBD (EST vs EPBD: 3.5% vs 1.9%). Independent predisposing factors for bleeding included EST, renal function impairment, and antiplatelet or anticoagulant therapy. The overall 30-day mortality was 4.0% (127/3201). Older age, renal function impairment, hepatic encephalopathy, bleeding esophageal varices, ascites, hepatocellular carcinoma, biliary malignancy, and pancreatic malignancy were associated with higher risks for 30-day mortality.
To decrease post-ERCP hemorrhage, EPBD is the preferred method in patients with cirrhosis, especially for those who have renal function impairment or are receiving antiplatelet or anticoagulant therapy.
Identification of microRNA biomarkers in atrial fibrillation
Authors: Shen Nan-Nan , Zhang Zai-Li , Li Zheng , Zhang Chi , Li Hao , Wang Jia-Liang , Wang Jun , Gu Zhi-Chun 
Published: July 2019

Abstract

Background:
Atrial fibrillation (AF) is recognized as the most prevalent arrhythmia, and its subsequently serious complications of heart failure and thromboembolism always raise the social attention. To date, the molecular pathogenesis of AF has largely remained unclear. Publications of contemporary studies have evaluated individual miRNAs expression signatures for AF, and findings of different studies are inconsistent and not all miRNAs reported are actually important in the pathogenesis of AF.

Methods:
Medline, Embase, and Cochrane Library databases will be comprehensively searched (up to April 30, 2019) for studies identifying miRNA expression profiling in subjects with and without AF. Log10 odds ratios (logORs) and associated 95% confidence interval (95%CI) will be calculated using random-effects models. Subgroup analysis will be performed according to miRNA detecting methods, species, sample types, and ethnicities. Sensitivity analysis will be conducted to detect the robustness of the findings. The methodological quality of studies will be independently assessed using criteria adopted from the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Furthermore, bioinformatics analysis will be performed to identify the potential target genes in AF and the corresponding pathways of dysregulated miRNAs. Two reviewers will independently screen potential studies and extract data in a structured eligibility items, with any disagreements being resolved by consensus.

Results:
The present systematic review will identify potential biomarkers by pooling all differentially expressed miRNAs in AF studies, as well as to predict miRNA-target interactions and to identify the potential biometric functions using bioinformatics analysis.

Conclusions:
This systematic review and bioinformatics analysis will identify several miRNAs as potential biomarkers for AF, and explore the biological pathways regulated by the eligible miRNAs.

PROSPERO registration number:
CRD42019127594
Real-world experience with pembrolizumab in patients with advanced melanoma
Authors: Liu Frank Xiaoqing , Ou Wanmei , Diede Scott J. , Whitman Eric D. 
Published: July 2019

Abstract
Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.
Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan–Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.
Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18–84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03–39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8–29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7–5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).
These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.
Multi-route applications of tranexamic acid to reduce blood loss after total knee arthroplasty: a randomized controlled trial
Authors: Zhang Shenqi , Wang Chengbin , Shi Lei , Xue Qingyun 
Published: July 2019

Abstract

Background:
Perioperative bleeding during total knee arthroplasty (TKA) is an ongoing problem for surgeons. Intravenous or topical application of tranexamic acid (TXA) can effectively stop bleeding, but there is still no uniform standard for the best method of administration and dose.

Methods:
From October 2016 to September 2018, 218 patients with unilateral primary knee osteoarthritis requiring knee replacement were enrolled and randomly divided into four groups. Group 1 (n = 55) received intra-articular injection (IAI) of TXA and peri-articular injection (PAI) of placebo, group 2 (n = 55) received IAI of placebo and PAI of TXA, group 3 (n = 51) received IAI of TXA and PAI of TXA, and group 4 (n = 57) received double placebo (IAI of placebo and PAI of placebo). The demographic characteristics, surgical indices, hematological indices, wound healing history, and thromboembolic events were investigated.

Results:
Eight patients were lost to follow-up and 210 patients were included in the analysis. The median TBLs in patients who received IAI of TXA and PAI of placebo and those who received IAI of placebo and PAI of TXA were 470.81 ml and 481.54 ml, respectively. These TBL levels were significantly higher compared to those in patients who received IAI of TXA and PAI of TXA (359.18 ml, P ≤ .001), but significantly lower compared to those in patients who received the double placebo (522.71 ml, P ≤ .001). Compared to other groups, more patients in the double placebo group needed a blood transfusion (P = .013). In the short-term, the double placebo group had higher VAS pain scores and less ROM after surgery (P = .011 and P = .001, respectively). In the long-term (6-month follow-up), there were no significant differences in ROM, VAS, DVT, PE, or wound-related complications.

Conclusion:
The combined use of IAI and PAI of TXA can significantly reduce the TBL and the need for blood transfusion without delaying wound healing or increasing the risk of DVT and PE. In the short-term after surgery, this combined method reduces the pain VAS scores and improves the ROM; however, there are no long-term effects on VAS and ROM.
Efficacy and safety of dapagliflozin as monotherapy in patients with type 2 diabetes mellitus
Authors: Feng Miao , Lv Haihong , Xu Xia , Wang Jue , Lyu Wenyi , Fu Songbo 
Published: July 2019

Abstract

Background:
Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs.

Methods:
We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software.

Results:
Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: –0.60%; 95% confidence interval [CI]: –0.67%, –0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: –1.30 mmol/L; 95% CI: –1.52, –1.08; P < .00001), and body weight (WMD: –1.50 kg; 95% CI: –1.67, –1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001).

Conclusions:
Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.
Efficacy and safety of eradication therapy for elderly patients with helicobacter pylori infection
Authors: Kobayashi Satoshi , Joshita Satoru , Yamamoto Chikara , Yanagisawa Takumi , Miyazawa Takayuki , Miyazawa Megumi , Kubota Daisuke , Sato Junichi , Umemura Takeji , Tanaka Eiji 
Published: July 2019

Abstract

Helicobacter pylori (H. pylori) is the most prevalent chronic bacterial infection and is associated with chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Although eradication therapy is widely performed for H. pylori infection, adverse events (AEs) are of particular concern in the elderly. This study investigated the efficacy and safety of H. pylori eradication therapy for elderly patients.
Retrospective investigation of 1271 cases (median age: 61 years, 730 male) of H. pylori infection was performed to compare clinical indications and outcomes among the younger group (<65 years old), elderly group (65–74 years old), and super-elderly group (>75 years old).
Chronic gastritis (77.0%) and gastric and/or duodenal ulcer (16.4%) were the most frequent indications for eradication therapy in the cohort. The respective eradication and AE rates for the first and second treatment regimens were 92.1% (1044 of 1133 cases) and 9.1% (103 of 1133 cases) and 84.2% (123 of 146 cases) and 8.9% (13 of 146 cases). No significant differences were detected for eradication rate or AE frequency between the super-elderly group and the other groups. Prior to therapy, the super-elderly group had significantly less frequent chronic gastritis than the other groups but more frequent gastric or duodenal ulcer and post-gastric cancer treatment (all P < .001), indicating a reluctance for clinicians to treat very old patients, possibly due to unfounded concerns of complications.
Triple therapy for H. pylori eradication is effective and safe, even for elderly patients.
Occult papillary thyroid cancer presenting as cystic metastasis of the lateral neck
Authors: Schwaiger Karl , Koeninger Fabian , Wimbauer Julia , Heinrich Klemens , Gala-Kokalj Alexandra , Wechselberger Gottfried 
Published: July 2019

Abstract

Rationale:
Papillary thyroid cancer accounts for up to 85% of all cases of thyroid carcinoma. This disease entity is notorious for metastatic invasion of adjacent lymph nodes, including the cervical lymph nodes, potentially presenting as a growing lateral neck mass. However, these lesions tend to be recognized and diagnosed soon due to the palpable mass.

Patient concerns:
This report describes a very rare case of a huge slow-growing neck metastasis based on a 6 mm papillary thyroid microcarcinoma. This patient presented with a painless, but continuously growing right lateral neck mass. Aside from that, no specific complaints were mentioned.

Diagnosis:
The underlying cause of this patient's neck mass turned out to be an occult papillary thyroid microcarcinoma (Ø 6 mm) with metastatic invasion and subsequent cystic degeneration of cervical lymph nodes. Accurate diagnosis was made after surgical intervention through histopathological analysis.

Interventions:
The patient underwent complete resection of the cervical mass in conjunction with total thyroidectomy and right cervical neck dissection, followed by adjuvant iodine- and chemotherapy.

Outcome:
Margin free surgical resection without any postoperative complications could be achieved. The patient received iodine supplementation and remained free of recurrence during regular clinical follow-ups for 2 years. The therapy was curative.

Lessons:
This case report emphasizes the importance of a thorough diagnostic work-up including preoperative tissue sampling of any cervical neck mass, since a benign appearance on imaging does not exclude a malignant process.
Comprehensive analysis of competing endogenous RNA network and 3-mRNA signature predicting survival in papillary renal cell cancer
Authors: Zhu Xin , Tan Jianyu , Liang Zongjian , Zhou Mi 
Published: July 2019

Abstract
Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to exert significant roles in regulating the expression of mRNAs by sequestering and binding miRNAs. To elucidate the functional roles and regulatory mechanism of lncRNAs in papillary renal cell cancer (pRCC), we conducted a comprehensive analysis of ceRNA network and constructed a mRNA signature to predict prognosis of pRCC.
We collected mRNAs and lncRNAs expression profiles of 289 pRCC samples and 32 normal renal tissues, and miRNA expression profiles of 292 pRCC samples and 34 normal samples from The Cancer Genome Atlas (TCGA) database. Differential expressions of RNAs were evaluated by the “edgeR” package in R. Functional enrichment analysis of DEmRNA was performed by DAVID 6.8 and KEGG, while PPI network of top 200 DEmRNAs was conducted using the STRING database. The univariate and multivariate Cox regression were conducted to figure out the candidate DEmRNAs with predictive values in prognosis. Receiver operator characteristic (ROC) curve estimation was performed to achieve the area under the curve (AUC) of the ROC curve to judge mRNA-associated prognosic model. A ceRNA network was established relying on the basis of combination of lncRNA-miRNA interactions and miRNA-mRNA interactions.
A total of 1928 DEmRNAs, 981 DElncRNAs, and 52 DEmiRNAs were identified at significance level of |log2Fold Change |>2 and adjusted P-value < .01. A 3-mRNA signatures consisting of ERG, RRM2, and EGF was constructed to predict survival in pRCC. Moreover, a pRCC-associated ceRNA network was constructed, with 57 lncRNAs, 11 miRNAs, and 28 mRNAs.
Our study illustrated the regulatory mechanism of ceRNA network in papillary renal cancer. The identified mRNA signatures could be used to predict survival of pRCC.
Activated protein C in neuroprotection and malaria
Authors: Mosnier Laurent O. 
Published: July 2019

Purpose of review
Activated protein C (APC) is a homeostatic coagulation protease with anticoagulant and cytoprotective activities. Focusing on APC's effects in the brain, this review discusses three different scenarios that illustrate how APC functions are intimately affecting the physiology and pathophysiology of the brain.

Recent findings
Cytoprotective APC therapy holds promise for the treatment of ischemic stroke, and a recently completed trial suggested that cytoprotective-selective 3K3A-APC reduced bleeding in ischemic stroke patients. In contrast, APC's anticoagulant activity contributes to brain bleeding as shown by the disproportional upregulation of APC generation in cerebral cavernous malformations lesions in mice. However, too little APC generation also contributes to maladies of the brain, such as in case of cerebral malaria where the binding of infected erythrocytes to the endothelial protein C receptor (EPCR) may interfere with the EPCR-dependent functions of the protein C pathway. Furthermore, discoveries of new activities of APC such as the inhibition of the NLRP3-mediated inflammasome and of new applications of APC therapy such as in Alzheimer's disease and graft-versus-host disease continue to advance our knowledge of this important proteolytic regulatory system.

Summary
APC's many activities or lack thereof are intimately involved in multiple neuropathologies, providing abundant opportunities for translational research.
Neointimal hyperplasia: are fatty acid transport proteins a new therapeutic target?
Authors: Rekhi Umar , Piche Julia E. , Immaraj Linnet , Febbraio Maria 
Published: July 2019

Purpose of review
High-fat diets contribute to hyperlipidemia and dysregulated metabolism underlying insulin resistant states and cardiovascular diseases. Neointimal hyperplasia is a significant resulting morbidity. Increased fatty acid (FA) levels lead to dysfunctional endothelium, defined as activated, proinflammatory and prothrombotic. The purpose of this review is to assess the recent literature on the emerging concept that uptake of FA into many tissues is regulated at the endothelial level, and this in turn contributes to endothelial dysfunction, an initiating factor in insulin resistant states, atherosclerosis and neointimal hyperplasia.

Recent findings
Studies support the role of endothelial FA uptake proteins as an additional level of regulation in tissue FA uptake. These proteins include CD36, FA transport proteins, FA-binding proteins and caveolin-1. In many cases, inappropriate expression of these proteins can result in a change in FA and glucose uptake, storage and utilization. Accumulation of plasma FA is one mechanism by which alterations in expression of FA uptake proteins can lead to endothelial dysfunction; changes in tissue substrate metabolism leading to inflammation are also implicated.

Summary
Identification of the critical players and regulators can lead to therapeutic targeting to reduce endothelial dysfunction and sequela such as insulin resistance and neointimal hyperplasia.
The pathology of solid organ xenotransplantation
Authors: Rosales Ivy A. , Colvin Robert B. 
Published: July 2019

Purpose of review
The use of genetically modified pigs has resulted in prolonged xenograft organ survival, overcoming the initial barriers that lead to hyperacute rejection and immediate loss of the graft. The purpose of the present review is to revisit the xenogeneic response and the pathologic changes in the xenograft organ in the context of recent publications of large animal studies that highlight existing challenges.

Recent findings
Transgenic modifications that have included complement regulatory proteins and coagulation regulatory proteins have prolonged xenograft survival in pig to nonhuman primate kidneys, livers, and hearts. Modifications of immunosuppressive regimens such as the addition of mTOR inhibition and costimulatory blockade have also led to better outcomes. Antibody-mediated rejection and thrombotic microangiopathy persist as primary challenges to the field and require further systematic exploration.

Summary
The efforts to overcome the natural antibody response to xenoantigens are largely sufficient. There is great opportunity for designing immunosuppression protocols and for detecting early coagulopathies, complement activation, and donor-specific antibody response. With graft survival prolongation, there is also a greater need to understand mechanisms and to enhance diagnostic tools for pathologic evaluation.