bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population enrichment for critical care trials: phenotypes and differential outcomes
Authors: Shankar-Hari Manu , Rubenfeld Gordon D. 
Published: July 2019

Purpose of review
Sepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials.

Recent findings
Many researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials.

Summary
Enrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.
Defining standard of practice: pros and cons of the usual care arm
Authors: Angriman Federico , Masse Marie-Hélène , Adhikari Neill K.J. 
Published: July 2019

Purpose of review
The aim of this review is to describe the use of usual care arms in randomized trials.

Recent findings
Randomization of patients to an experimental or a control arm remains paramount for the estimation of average causal effects. Selection of the control arm is as important as the definition of the intervention, and it might include a placebo control, specific standards of care, protocolized usual care, or unrestricted clinical practice. Usual care control arms may enhance generalizability, clinician acceptability of the protocol, patient recruitment, and ensure community equipoise, while at the same time introducing significant variability in the care delivered in the control group. This effect may reduce the difference in treatments delivered between the two groups and lead to a negative result or the requirement for a larger sample size. Moreover, usual care control groups can be subject to changes in clinician behavior induced by the trial itself, or by secular trends in time.

Summary
Usual care control arms may enhance generalizability while introducing significant limitations. Potential solutions include the use of pretrial surveys to evaluate the extent to which a protocolized control arm reflects the current standard of care and the implementation of adaptive trials.
How should we treat acinetobacter pneumonia?
Authors: Amaya-Villar Rosario , Garnacho-Montero José 
Published: July 2019

Purpose of review
To describe recent data about Acinetobacter baumannii pneumonia epidemiology and the therapeutic options including adjunctive nebulized therapy.

Recent findings

A. baumannii is a major cause of nosocomial pneumonia in certain geographic areas affecting mainly debilitated patients, with prolonged hospitalization and broad-spectrum antimicrobials. Inappropriate empirical treatment has clearly been associated with increased mortality in A. baumannii pneumonia. Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity. Colistin is the antimicrobial most widely used although polymyxin B is associated with less renal toxicity. It is clear that lung concentrations of polymyxins are suboptimal in a substantial proportion of patients. This issue has justified the use of combination therapy or adjunctive nebulized antibiotics. Current evidence does not allow us to recommend combination therapy for A. baumannii pneumonia. Regarding nebulized antibiotics, it seems reasonable to use in patients who are nonresponsive to systemic antibiotics or A. baumannii isolates with colistin minimum inhibitory concentrations close to the susceptibility breakpoints. Cefiderocol, a novel cephalosporin active against A. baumannii, may represent an attractive therapeutic option if ongoing clinical trials confirm preliminary results.

Summary
The optimal treatment for multidrug-resistant A. baumannii pneumonia has not been established. New therapeutic options are urgently needed. Well designed, randomized controlled trials must been conducted to comprehensively evaluate the effectiveness and safety of nebulized antibiotics for the treatment of A. baumannii pneumonia.
Therapeutic effect of lutein supplement on non-proliferative diabetic retinopathy
Authors: Ren Yong-bo , Qi Yan-xiu , Su Xing-jie , Luan He-qun , Sun Qi 
Published: July 2019

Abstract
This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR).
A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment.
Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group.
The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.
Prognostic role of C-reactive protein to albumin ratio in colorectal cancer
Authors: Wang Fan , Li Pei , Li Feng-sen 
Published: July 2019

Abstract

Objective:
This meta-analysis evaluates the prognosis value of C-reactive protein to albumin ratio (CAR) in colorectal cancer.

Methods:
Embase, PubMed, and Web of Science were searched. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used as effective values.

Results:
A total of 6 studies with 1942 patients were included in this study. Pooled results revealed that elevated pretreatment CAR was related with poorer overall survival (OS) (HR: 2.09, 95%CI: 1.78–2.45, P < .001) in colorectal cancer.

Conclusion:
Elevated CAR was associated with poor prognosis in colorectal cancer. Thus CAR might be used as a prognostic system and classification of colorectal patients in clinical potential.
Efficacy of prison-based cognitive behavioral rehabilitation intervention on violent sexual behaviors among sex offenders in Nigerian prisons
Authors: Nwokeoma Bonaventure N. , Ede Moses O. , Ugwuanyi Christian , Mezieobi Daniel , Ugwoezuonu Amanda U. , Amoke Chijioke , Egenti Nkechi T. , Nwosu Nneka , Oforka Theresa O. , Victor-Aigbodion Vera , Offordile Edmund E. , Ezeh Ngozi E. , Eze Celestine O. , Eluu Patrick E. , Ugwuanyi Benedict E. , Uzoagba Ngozi C. , Ugwonna Grace O. , Chukwu Chinyere Loveth , Amadi Kingley C. , Eseadi Chiedu 
Published: July 2019

Abstract

Background/Objective:
Evidence showed that reoffending habits are increasing among offenders with violent sexual behaviors. Given the recidivism rates, a psychotherapeutic intervention becomes imperative. This study examined the efficacy of prison-based cognitive behavioral rehabilitation intervention (PCBRI) on violent sexual behaviors among sex offenders in Nigerian prisons.

Method:
A total of45 participants were the sample size. Compulsive Sexual Behavior Inventory and Hypersexual Behavior Inventory were employed in assessing the participants at 3 points. Using a simple random allocation sequence, 23 participants were exposed to PCBRI programme and 22 participants allocated to control condition. The data obtained were analyzed using repeated measures 2-way analysis of variance.

Results:
Results indicated a significant effect of the treatment on violent sexual behaviors among sex offenders in Nigerian prisons exposed to the PCBRI programme when compared to the no-intervention group. Result also showed a significant interaction effect of time and group on sex offenders with violent sexual behaviors. Follow-up tests showed significant decrease in violent sexual behaviors after 6 months for the PCBRI group in comparison to the control group.

Conclusion:
This study concluded that PCBRI approach is a type of psychotherapy that reduces violent sexual behaviors among sex offenders in Southeast Nigeria.
Correction of labial tubercle defect in repaired bilateral cleft lips using bilateral vermilion musculomucosal sliding flaps
Authors: Liang Yun , Yang Yusheng , Wu Yilai 
Published: July 2019

Abstract

Rationale:
Insignifificant, asymmetrical or lack of labial tubercle often occurs after cleft lip surgery due to improper treatment of vermilion tissue. Especially in the cases of bilateral cleft lip, because of short front lip and insuffificient vermilion tissue, the median vermilion depression often occurs after surgery, forming a “whistling” deformity. The object of this study is to verify the outcomes of patients with median labial tubercle detects after treatment with bilateral vermilion musculomucosal sliding flflaps (VMSF).

Patient concerns:
Six patients with median labial tubercle defect after bilateral cleft lip repair from March 2015 to May 2017 were enrolled in our department and subjected to bilateral lip deformity correction under general anesthesia.

Diagnoses:
Secondary deformity of bilateral cleft lip forming a “whistling” deformity were diagnosed in all the patients.

Interventions:
Bilateral VMSF were designed and used to reconstruct the median labial tubercles by sliding downward so as to eliminate the whistling deformity.

Outcomes:
During the 10 to 37 months of follow-up, the reconstructed vermilion tubercles had stable morphology showing no whistling deformity and the overall lip shapes were satisfactory.

Lessons:
Reconstructing MVTD and eliminating whistling deformity using the scar tissues that need to be removed previously on the vermilion musculomucosa has achieved stable and satisfactory results and is worthy of clinical application.
Upregulation of microRNA-191 can serve as an independent prognostic marker for poor survival in prostate cancer
Authors: Liu Jing-bo , Yan Yong-ji , Shi Jing , Wu Ya-bing , Li Yan-feng , Dai Lin-feng , Ma Xue-tao 
Published: July 2019

Abstract
MicroRNA-191 (miR-191) has been identified as being upregulated in several types of cancers, and plays the role of oncogene. The expression of miR-191 has been found to be upregulated in prostate cancer tissues as well as cell lines. In this study, we analyzed the correlation of miR-191 expression with clinicopathologic factors and prognosis in prostate cancer.
Prostate cancer tissue samples and adjacent normal prostate tissue samples were collected from 146 patients who underwent laparoscopic radical prostatectomy between April 2013 and March 2018. Student two-tailed t-test was used for comparisons of 2 independent groups. The relationships between miR-191 expression and different clinicopathological characteristics were evaluated using the Chi-squared test. Kaplan–Meier survival plots and log-rank tests were used to assess the differences in overall survival of the different subgroups of prostate cancer patients.
miR-191 expression was significantly higher in prostate cancer tissues compared with normal adjacent prostate tissues (P < .001). miR-191 expression was observed to be significantly correlated with Gleason score (P < .001), pelvic lymph node metastasis (P = .006), bone metastases (P < .001), and T stage (P = .005). Kaplan–Meier analysis showed that patients with higher levels of miR-191 had significantly poorer survival than those with lower expression of this miRNA in prostate cancer patients (log rank test, P = .011). Multivariate analysis revealed that miR-191 expression (hazard ratio [HR] = 2.311, 95% confidence interval, [CI]: 1.666–9.006; P = .027) was independently associated with the overall survival of prostate cancer patients.
Our results demonstrated that miR-191 might serve as an independent prognostic indicator for prostate cancer patients.
Autologous hematopoietic stem cell transplantation for human immunodeficiency virus associated gastric Burkitt lymphoma
Authors: Junfeng Lu , Lina Ma , Xinyue Chen 
Published: July 2019

Abstract

Rationale:
HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored.

Patient concerns:
A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month.

Diagnosis:
HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL.

Interventions:
Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation.

Outcomes:
The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection

Lessons:
The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.
Diagnostic accuracy of different computer-aided diagnostic systems for malignant and benign thyroid nodules classification in ultrasound images
Authors: Liu Ruisheng , Li Huijuan , Liang Fuxiang , Yao Liang , Liu Jieting , Li Meixuan , Cao Liujiao , Song Bing 
Published: July 2019

AbstractObjective:The aim of this study was to determine the diagnostic accuracy of different computer-aided diagnostic (CAD) systems for thyroid nodules classification.Methods:A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. Literature selection and data extraction were conducted by 2 independent reviewers. Numerical values for sensitivity and specificity were obtained from false negative (FN), false positive (FP), true negative (TN), and true positive (TP) rates, presented alongside graphical representations with boxes marking the values and horizontal lines showing the confidence intervals (CIs). Summary receiver operating characteristic (SROC) curves were applied to assess the performance of diagnostic tests. Data were processed using Review Manager 5.3 and Stata 15. The methodological quality of included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.Trial registration number:PROSPERO CRD42019132540
The erector spinae plane block for effective analgesia after lung lobectomy
Authors: Bang Seunguk , Chung Kyudon , Chung Jihyun , Yoo Subin , Baek Sujin , Lee Sang Mook 
Published: July 2019

Abstract

Rationale:
The thoracic epidural block and thoracic paravertebral block are widely used techniques for multimodal analgesia after thoracic surgery. However, they have several adverse effects, and are not technically easy. Recently, the erector spinae plane block (ESPB), an injected local anesthetic deep to the erector spinae muscle, is a relatively simple and safe technique.

Patient concerns:
Three patients were scheduled for video assisted thoracoscopic lobectomy with mediastinal lymph node dissection. All the patients denied any past medical history to be noted.

Diagnoses:
They were diagnosed with primary adenocarcinoma requiring lobectomy of lung.

Interventions:
The continuous ESPB was performed at the level of the T5 transverse process. The patient was received the multimodal analgesia consisted of oral celecoxib 200 mg twice daily, intravenous patient-controlled analgesia (Fentanyl 700 mcg, ketorolac 180 mg, total volume 100 ml), and local anesthetic (0.375% ropivacaine 30 ml with epinephrine 1:200000) injection via indwelling catheter every 12 hours for 5 days. Additionally, we injected a mixture of ropivacaine and contrast through the indwelling catheter for verifying effect of ESPB and performed Computed tomography 30 minutes later.

Outcomes:
The pain score was maintained below 3 points for postoperative 5 days, and no additional rescue analgesics were administered during this period. In the computed tomography, the contrast spread laterally from T2-T12 deep to the erector spinae muscle. On coronal view, the contrast spread to the costotransverse ligament connecting the rib and the transverse process. In the 3D reconstruction, the contrast spread from T6-T10 to the costotransverse foramen.

Lessons:
Our contrast imaging data provides valuable information about mechanism of ESPB from a living patient, and our report shows that ESPB can be a good option as a multimodal analgesia after lung lobectomy.
Association of CTLA-4 tagging polymorphisms and haplotypes with hepatocellular carcinoma risk
Authors: Yang Jing , Liu Jiaochun , Chen Yu , Tang Weifeng , Liu Chao , Sun Yuling , Chen Jianping 
Published: July 2019

Abstract
It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC).
In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit.
We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04–1.85; P = .028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08–1.89; P = .012). After using Bonferroni correction, this association remained (P = .012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypes might increase the risk of HCC risk (P = .018, <.001, and .017, respectively). However, we found that CTLA4 Trs16840252A rs231775Grs3087243Trs733618 decreased the risk of HCC (P = .020).
Our results suggest that the CTLA-4 rs3087243 G>A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations.
Effects of febuxostat on renal function in patients with chronic kidney disease
Authors: Lin Tsu-Chen , Hung Lie Yee , Chen Ying-Chun , Lo Wei-Cheng , Lin Chun Hung , Tam Ka-Wai , Wu Mei-Yi 
Published: July 2019

Abstract

Background/Objective:
Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia.

Methods:
We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I2 tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant.

Results:
Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups.

Conclusions:
The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.
Evaluating the tumor biology of lung adenocarcinoma: A multimodal analysis
Authors: Kim Ki Hwan , Ryu Seong-Yoon , Lee Ho Yun , Choi Joon Young , Kwon O. Jung , Kim Hong Kwan , Shim Young Mog 
Published: July 2019

Abstract
We evaluated the relationships among functional imaging modality such as PET-CT and DW-MRI and lung adenocarcinoma pathologic heterogeneity, extent of invasion depth, and tumor cellularity as a marker of tumor microenvironment.
In total, 74 lung adenocarcinomas were prospectively included. All patients underwent 18F-fluorodeoxyglucose (FDG) PET-CT and MRI before curative surgery. Pathology revealed 68 stage I tumors, 3 stage II tumors, and 3 stage IIIA tumors. Comprehensive histologic subtyping was performed for all surgically resected tumors. Maximum standardized uptake value (SUVmax) and ADC values were correlated with pathologic grade, extent of invasion, solid tumor size, and tumor cellularity.
Mean solid tumor size (low: 1.7 ± 3.0 mm, indeterminate: 13.9 ± 14.2 mm, and high grade: 30.3 ± 13.5 mm) and SUVmax (low: 1.5 ± 0.2, indeterminate: 3.5 ± 2.5, and high grade: 15.3 ± 0) had a significant relationship with pathologic grade based on 95% confidence intervals (P = .01 and P < .01, respectively). SUVmax showed a strong correlation with tumor cellularity (R = 0.713, P < .001), but was not correlated with extent of invasion (R = 0.387, P = .148). A significant and strong positive correlation was observed among SUVmax values and higher cellularity and pathologic grade. ADC did not exhibit a significant relationship with tumor cellularity.
Intratumor heterogeneity quantification using a multimodal-multiparametric approach might be effective when tumor volume consists of a real tumor component as well as a non-tumorous stromal component.