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This study aimed to elucidate the interactions between osteosarcoma (OS) and M1 macrophages infiltrated into the tumor microenvironment and to explore the underlying mechanisms whereby M1 macrophages influence the growth of OS, so that novel treatments of OS can be developed. A transwell co-culture system, an indirect conditioned medium culture system and two orthotopic bearing OS models were established to assess for the interplay between M1 macrophages and OS. We found that the co-culture of M1 macrophages with OS cells significantly inhibited the growth of the tumor cells by inducing apoptosis. Furthermore, HSPA1L secreted by M1 macrophages exerted this anti-tumor effect through the IRAK1 and IRAK4 pathways. LGALS3BP secreted by OS cells bound to the ligand LGALS3 on M1 macrophages and thereby induced the secretion of Hspa11 via Akt phosphorylation. In vivo experiments demonstrated that the culture supernatant of OS-stimulated M1 macrophages significantly inhibited the growth of OS, whereas silencing Lgals3bp promoted the progression of OS. In conclusion, OS modifies the phenotype of tumor-associated macrophages (TAMs) and thereby influences the apoptosis of OS cells through soluble factors. The modulation of TAMs may be a promising and effective therapeutic approach in OS. [ABSTRACT FROM AUTHOR]

Background: Fibroblast activation protein (FAP) in pancreatic ductal adenocarcinoma (PDAC) is closely related to the prognosis and treatment of patients. Accurate preoperative FAP expression can better identify the population benefitting from FAP-targeting drugs.Purpose: To develop and validate a machine learning classifier based on noncontrast MRI for the preoperative prediction of FAP expression in patients with PDAC.Study Type: Retrospective cohort study.Population: Altogether, 129 patients with pathology-confirmed PDAC undergoing MR scan and surgical resection; 90 patients in a training cohort, and 39 patients in a validation cohort. FIELD STRENGTH/SEQUENCE/3T: Breath-hold single-shot fast-spin echo T2-weighted sequence and unenhanced and noncontrast T1-weighted fat-suppressed sequences.Assessment: FAP expression was quantified using immunohistochemistry. For each patient, 1409 radiomics features were extracted from T1- and T2-weighted images and reduced using the least absolute shrinkage and selection operator logistic regression algorithm. A multilayer perceptron (MLP) network classifier was developed using the training and validation set. The MLP network classifier performance was determined by its discriminative ability, calibration, and clinical utility.Statistical Tests: Kaplan-Meier estimates, student's t-test, the Kruskal-Wallis H test, and the chi-square test, univariable regression analysis, receiver operating characteristic curve, and decision curve analysis were used.Results: A log-rank test showed that the survival of patients with low FAP expression (24.43 months) was significantly longer (P < 0.05) than that in the FAP-high group (13.50 months). The prediction model showed good discrimination in the training set (area under the curve [AUC], 0.84) and the validation set (AUC, 0.77). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the training set were 75.00%, 79.41%, 0.77, 0.86, and 0.66, respectively, whereas those for the validation set were 85.00%, 63.16%, 0.74, 0.71, and 0.80, respectively.Data Conclusions: The MLP network classifier based on noncontrast MRI can accurately predict FAP expression in patients with PDAC.Evidence Level: 2 TECHNICAL EFFICACY: Stage 2. [ABSTRACT FROM AUTHOR]

Background: After activation of the Hospital Readmission Reduction Program (HRRP) in 2012, hospitals nationwide experimented broadly with the implementation of Transitional Care (TC) strategies to reduce hospital readmissions. Although numerous evidence-based TC models exist, they are often adapted to local contexts, rendering large-scale evaluation difficult. Little systematic evidence exists about prevailing implementation patterns of TC strategies among hospitals, nor which strategies in which combinations are most effective at improving patient outcomes. We aimed to identify and define combinations of TC strategies, or groups of transitional care activities, implemented among a large and diverse cohort of U.S. hospitals, with the ultimate goal of evaluating their comparative effectiveness.Methods: We collected implementation data for 13 TC strategies through a nationwide, web-based survey of representatives from short-term acute-care and critical access hospitals (N = 370) and obtained Medicare claims data for patients discharged from participating hospitals. TC strategies were grouped separately through factor analysis and latent class analysis.Results: We observed 348 variations in how hospitals implemented 13 TC strategies, highlighting the diversity of hospitals' TC strategy implementation. Factor analysis resulted in five overlapping groups of TC strategies, including those characterized by 1) medication reconciliation, 2) shared decision making, 3) identifying high risk patients, 4) care plan, and 5) cross-setting information exchange. We determined that the groups suggested by factor analysis results provided a more logical grouping. Further, groups of TC strategies based on factor analysis performed better than the ones based on latent class analysis in detecting differences in 30-day readmission trends.Conclusions: U.S. hospitals uniquely combine TC strategies in ways that require further evaluation. Factor analysis provides a logical method for grouping such strategies for comparative effectiveness analysis when the groups are dependent. Our findings provide hospitals and health systems 1) information about what groups of TC strategies are commonly being implemented by hospitals, 2) strengths associated with the factor analysis approach for classifying these groups, and ultimately, 3) information upon which comparative effectiveness trials can be designed. Our results further reveal promising targets for comparative effectiveness analyses, including groups incorporating cross-setting information exchange. [ABSTRACT FROM AUTHOR]

Objective: Evaluate associations between orange juice (OJ) consumption and anthropometric parameters.Design: Prospective cohort study assessing the association between OJ intake and changes in BMI and height-for-age Z-score (HAZ) using mixed linear regression.Setting: 2004-2008, USA.Participants: Children from the Growing Up Today Study II (n 7301), aged 9-16 years at enrollment.Results: OJ consumption was positively associated with 2-year change in HAZ in girls (mean (se)): 0·03 (0·01) for non-consumers, 0·03 (0·02) for 1-3 glasses/month, 0·06 (0·01) for 1-6 glasses/week and 0·09 (0·02) for ≥1 glass/d after full adjustment (Ptrend = 0·02). However, OJ consumption was not associated with 2-year change in BMI percentile (kg/m2, mean (se)): -0·44 (0·36) for non-consumers, 0·20 (0·41) for 1-3 glasses/month, -0·04 (0·34) for 1-6 glasses/week and -0·77 (0·62) for ≥1 glass/d in girls, Ptrend = 0·81; -0·94 (0·53) for non-consumers, -1·68 (0·52) for 1-3 glasses/month, -0·81 (0·38) for 1-6 glasses per week and -1·12 (0·61) for ≥1 glass/d in boys, Ptrend = 0·49.Conclusion: OJ consumption was favourably associated with height growth but unrelated to excess weight gain. OJ may be a useful alternative to whole fruit in the event that whole fruit intake is insufficient. [ABSTRACT FROM AUTHOR]

Study Question: Should women with X chromosome abnormalities (XCAs) be recommended to have embryos selected by both morphological and cytogenetic assessment through preimplantation genetic testing (PGT) rather than morphological assessment only in conventional IVF/ICSI treatment?Summary Answer: PGT is not a preferred recommendation for women with XCAs in the absence of other PGT indications.What Is Known Already: XCAs are the most frequent sort of chromosomal aberrations in infertile women. Patients with a complete or partial absence of one X chromosome, diagnosed as Turner Syndrome (TS), demonstrate low spontaneous pregnancy rates (5-7%) and high miscarriage rates (22.8-30.8%), as well as high chances of birth defects (20%). PGT is known to improve pregnancy rates and decrease the incidence of miscarriage in couples with chromosomal aberrations such as Robertsonian and reciprocal translocations and Klinefelter Syndrome.Study Design, Size, Duration: A retrospective cohort study was conducted with 394 women with XCAs and undergoing their first oocyte retrieval and first embryo transfer cycle from June 2011 to August 2019 in the Reproductive Hospital Affiliated to Shandong University.Participants/materials, Setting, Methods: Pregnancy outcomes were compared between the conventional IVF/ICSI group (n = 284) and the PGT group (n = 110) in the first fresh or frozen embryo transfer cycle for each woman with XCAs. Three platforms were applied in PGT: fluorescence in situ hybridisation (FISH, n = 34), array comparative genomic hybridisation (aCGH, n = 24) and next-generation sequencing (NGS, n = 51). The embryo aneuploidy rate and distribution of embryonic chromosomal aberrations revealed by aCGH or NGS were analysed and stratified by maternal age and type of XCAs to assess the effect of maternal XCAs on embryo karyotypes.Main Result and the Role Of Chance: The live birth rate (LBR) per embryo transfer was similar between the PGT group and IVF/ICSI group both in the first cycle of fresh or frozen embryo transfer respectively (39.13% in PGTFISH vs 42.58% in IVF/ICSI, Padj=0.558; 66.67% in PGTFISH vs 52.08% in PGTaCGH/NGS vs 53.06% in IVF/ICSI, Padj=0.756), as was the clinical pregnancy rate (60.87% in PGTFISH vs 50.97% in IVF/ICSI, Padj =0.672; 88.89% in PGTFISH vs 58.33% in PGTaCGH/NGS vs 69.39% in IVF/ICSI, Padj =0.480) and the pregnancy loss rate (35.71% in PGTFISH vs 16.46% in IVF/ICSI, Padj =0.136; 12.50% in PGTFISH vs 10.71% in PGTaCGH/NGS vs 23.53% in IVF/ICSI, Padj =0.352). The rates of maternal and neonatal complications were also comparable between the PGT and IVF/ICSI groups with fresh and frozen transfers respectively (10.00% vs 8.85%, P = 1.000; 21.74% vs 14.55%, P = 0.272). Intriguingly, the distribution of embryonic chromosome abnormalities was more frequent on autosomes 22 (20.39%), 21 (18.45%) and 16 (17.47%), compared with the X chromosome (8.73%).Limitations, Reasons For Caution: Selection bias is an inherent drawback of a retrospective study. First, our participants hosted 4.84% X chromosome mosaicism with few typical somatic anomalies of TS. Second, the incidences of history of recurrent miscarriage and abnormal offspring in the PGT group were higher than in IVF/ICSI group although binary logistic regression analysis was performed to attenuate the modifying effect of confounding factors. Third, FISH performed in this study only used X/Y probes and lacked the reference of autosome, which might have resulted in misdiagnosis and bias. Finally, intrinsic disadvantages could not be totally avoided due to the retrospective nature of this study.Wider Implication Of the Findings: In the current study, comparable pregnancy outcomes were revealed among a large cohort of women with XCAs undergoing their first cycles of PGT or conventional IVF/ICSI treatment. Moreover, the X chromosome abnormality was illustrated to cause no higher frequency of aberrations in embryos. Our data provided perspectives for genetic and reproductive counselling to XCAs individuals and their families.Study Funding/competing Interest(s): This work was supported by National Research and Development Plan (2016YFC1000604 and 2017YFC1001100), the National Natural Science Foundation of China (81701406), Shandong Science Fund for Distinguished Young Scholars (JQ201720), Taishan Scholars Program for Young Experts of Shandong Province (tsqn20161069) and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523 and 2016WS0368). There is no conflict of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Patients with intracranial atherosclerotic disease (ICAD) have a high frequency of stroke recurrence. However, there has been little investigation into the prognostic value of higher-resolution magnetic resonance imaging (HR-MRI).Purpose: To investigate the use of intracranial atherosclerotic plaques features in predicting risk of recurrent cerebrovascular ischemic events using HR-MRI.Study Type: Prospective.Population: Fifty-eight patients with acute/subacute stroke (N = 46) or transient ischemic attack (N = 12).Field Strength/sequence: A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and T2-weighted fast spin echo sequences with 0.31 x 0.39 mm2 in-plane resolution, twice (with >3 months between scans) following the initial event.Assessment: Patients were also followed clinically for recurrent ischemic events for up to 48 months or until a subsequent event occurred. The degree of stenosis, plaque burden (PB), minimal lumen area (MLA), and contrast enhancement ratio were assessed at each scanning session and the percentage change of each over time was calculated.Statistical Tests: Univariable and multivariable Cox regression analyses were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for predicting recurrent events.Results: The mean time interval between baseline and follow-up MRI scans was 6.2 ± 4.1 months. After the second MRI scan, 20.7% of patients (N = 12) had experienced ipsilateral recurrent TIA/stroke within 10.9 ± 9.2 months. Univariable analyses showed that baseline triglyceride, percentage change of PB, and progression of PB were significantly associated with recurrent events (all P < 0.05). Multivariable Cox regression indicated that progression of PB (HR, 6.293; 95% CI, 1.620-24.444; P < 0.05) was a significant independent imaging feature for recurrent ischemic events.Data Conclusion: Progression of PB was independently associated with recurrent ischemic cerebrovascular events. HR-MRI may help risk stratification of patients at risk of recurrent stroke.Level Of Evidence: 2 TECHNICAL EFFICACY: Stage 4. [ABSTRACT FROM AUTHOR]

Study Question: Is it possible to establish a new in-vitro activation (IVA) protocol for infertility treatment?Summary Answer: A new IVA procedure is an efficient and easily performed approach for infertility treatment of patients with diminished ovarian reserve (DOR).What Is Known Already: IVA of primordial follicles with or without stimulators has been developed to treat patients with primary ovarian insufficiency (POI) successfully. However, the efficiency of the procedure is still very low. There is a requirement to optimize the protocol with increased efficiency for clinical application.Study Design, Size, Duration: Newborn mouse ovaries were used to establish a new 1-h IVA protocol with the mechanistic target of rapamycin (mTOR) stimulator phosphatidic acid (PA, 200 µM) and the phosphatidylinositol-3-kinase (PI3K) stimulator 740Y-P (250 µg/ml); a prospective observational cohort study in POI patients was performed on 15 POI patients and 3 poor ovarian response (POR) patients in three different centers of reproductive medicine in China.Participants/materials, Setting, Methods: One-third of ovarian cortex was removed and processed into bigger strips (1 × 1 cm2, 1-2 mm thickness). Strips were then sutured back after treatment. The new approach only requires one laparoscopic surgery.Main Results and the Role Of Chance: Follicular activation and development increased in cultured mouse and human ovarian tissues after 1 h of stimulator treatment. Compared with tiny ovarian cortex pieces (1 × 1 mm2), large ovarian strips (1 × 1 cm2) showed the lowest apoptotic signals after incubation. We applied the orthotropic transplantation procedure with large strips in the clinic, and 9 of 15 POI patients showed at least one-wave follicular growth during the monitoring period. One patient was reported with one healthy delivery after natural conception and another patient with a healthy singleton delivery after IVF. All the contacted patients (n = 13) responded with no side effects on their health 2-4 years after IVA procedure.Limitations, Reasons For Caution: Further clinical trials with a large number of well-defined patients are required to compare different IVA protocols. A long-term follow-up system should be set up to monitor patient's health in the future cohort study.Wider Implications Of the Findings: By using stimulators, the findings in the study provide a more efficient IVA protocol for the treatment of patients with DOR. It requires only one laparoscopic surgery and thus minimizes patients' discomfort and costs. This strategy could be useful for patients diagnosed with POI and desire pregnancy as soon as possible after the operation.Study Funding/competing Interest(s): This work was supported by the National Key Research and Development Program of China (2018YFC1003703 and 2018YFC1004203); the National Natural Science Foundation of China (81871221); Co-construction of Provincial Department (201601006). The authors have no conflict of interest to disclose.Trial Registration Number: ChiCTR2000030872. [ABSTRACT FROM AUTHOR]

Background: Intracranial atherosclerotic plaque causing mild luminal stenosis might lead to acute ischemic events. However, the difference between culprit and nonculprit lesions is unclear, as are the factors associated with favorable treatment outcomes.Purpose: To quantify characteristics of intracranial atherosclerosis with mild luminal stenosis and to identify factors associated with lesion type (culprit or nonculprit) and with clinical outcomes.Study Type: Prospective POPULATION: 293 patients who had acute stroke with mild luminal stenosis (<50%) in the middle cerebral or basilar artery.Field Strength/sequence: 3.0 T higher resolution magnetic resonance imaging (hrMRI) of intracranial arteries and whole brain MR images.Assessment: Morphological and compositional analysis of plaques was performed. This included assessment of plaque volume, plaque burden, remodeling ratio, eccentricity, intraplaque hemorrhage, and enhancement ratio. Clinical outcomes were assessed according to the modified Rankin Scale (mRS) at day 90, with a favorable outcome being defined as a 90-day mRS ≤2.Statistical Tests: The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by a logistic regression model.Results: Hypertension (OR 5.2; 95% CI 2.6-10.3; P < 0.05) and hrMRI enhancement ratio (OR 2.7; 95% CI 1.4-5.1; P < 0.05) were independently associated with lesion type. Patients without hypertension had significantly more (P < 0.05) favorable outcomes (124/144) than patients with hypertension (97/149). Most hypertensive patients without any previous blood pressure control (54/63) had a favorable outcome. However, these patients were significantly younger (P < 0.05) than those with adequate blood pressure control. After adjusting for all significant characteristics, hypertension duration (OR 1.19; 95% CI 1.09-1.29; P < 0.05), hypertension management (OR 2.49; 95% CI 1.18-5.26; P < 0.05), and enhancement ratio (OR 0.01; 95% CI 0.001-0.157; P < 0.05) were found to be independent high-risk factors for outcome prediction. DATA CONCLUSION: hrMRI provided incremental value over traditional risk factors in identifying higher risk intracranial atherosclerosis with mild luminal stenosis.Level Of Evidence: 2 TECHNICAL EFFICACY: Stage 2. [ABSTRACT FROM AUTHOR]

The macroeconomic environment has been shown to affect health-care service utilization. We examined the relationship between unemployment rate and service intensity among a nationally representative sample of primary care office visits from Medicare patients by merging data from the 2006-2012 National Ambulatory Medical Care Survey with unemployment data from the Bureau of Labor Statistics. Multispecialty practices demonstrated increases in the number of electrocardiogram tests prescribed and the number of return appointments scheduled. In contrast, single-specialty practices did not respond on those margins and instead increased the likelihood of administering diagnostic and screening examinations. We found no significant relationship between unemployment rates and the number of laboratory and imaging services, magnetic resonance imaging use, referrals, or medication prescribing. These results were robust to controlling for extensive visit characteristics and county-, year-, and month-fixed effects. Our results suggest that physicians responded to the Great Recession by changing their practice behavior. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral nerve hyperexcitability syndrome (PNHS) is characterized by muscle fasciculations and spasms. Nerve hyperexcitability and after-discharges can be observed in electrophysiological studies. Autoimmune mechanisms play a major role in the pathophysiology of primary PNHS.Methods: We retrospectively conducted a case-control study recruiting patients with clinical and electrophysiological features of PNHS. Control patients were diagnosed with other neuronal or muscular diseases. Contactin-associated protein2 (CASPR2) and leucine-rich glioma-inactivated1 (LGI1) antibodies were examined.Results: A total of 19 primary PNHS patients and 39 control patients were analyzed. The most common symptoms for the case group were fasciculations (11/19) and muscle spasms (13/19). Case group patients were likely to demonstrate electrodiagnostic findings of nerve hyperexcitability (17/19) and after-discharges in the tibial nerve (19/19). We found high prevalence of CASPR2 (9/19) and LGI1 (6/19) antibodies in the case group.Discussion: Primary PNHS patients were likely to show after-discharges in the tibial nerve. The pathogenesis of PNHS is autoimmune CASPR2 and LGI1 antibodies are possible pathogenic antibodies for primary PNHS. [ABSTRACT FROM AUTHOR]

• The first clinical isolate of mcr-3.1-positive MDR Salmonella Choleraesuis. • Complete sequence of a transferable plasmid with mcr-3.1 contained in a prophage. • Plasmid pXXB210 contained resistance genes for six classes of antimicrobials. [ABSTRACT FROM AUTHOR]

Background and Purpose: Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies.Experimental Approach: The effects of chronic unpredictable mild stress (CUMS) on wild-type (WT) and TLR4-/- mice were examined. Antidepressant-like effects of arctigenin were tested using the CUMS-induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co-immunoprecipitation assays.Key Results: The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4-/- mice, compared with WT mice. Arctigenin exhibited antidepressant-like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways.Conclusions and Implications: Arctigenin has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression. [ABSTRACT FROM AUTHOR]

Objectives: To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management.Study Design: In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization.Main Outcome Measures: The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity.Findings: We recruited 39,446 women in intervention (N = 20,264) and control clusters (N = 19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p = 0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p = 0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p = 0·74) or morbidity (1·12 [0·57, 2·16]; p = 0·77); early (0·95 [0·82-1·09]; p = 0·46) or late neonatal deaths (1·23 [0·97-1·55]; p = 0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p = 0·40). Improvements in outcome rates were observed with 4-7 (p = 0·015) and ≥8 (p < 0·001) (vs. 0) CLIP contacts.Interpretation: The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening.Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337). [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound-guided fine-needle aspiration is associated with the accurate determination of tumor grade. However, because it is an invasive procedure there is a need to explore alternative noninvasive procedures.Purpose: To develop and validate a noncontrast radiomics model for the preoperative prediction of nonfunctional pancreatic neuroendocrine tumor (NF-pNET) grade (G).Study Type: Retrospective, single-center study.Subjects: Patients with pathologically confirmed PNETs (139) were included.Field Strength/sequence: 3T/breath-hold single-shot fast-spin echo T2 -weighted sequence and unenhanced and dynamic contrast-enhanced T1 -weighted fat-suppressed sequences.Assessment: Tumor features on contrast MR images were evaluated by three board-certified abdominal radiologists.Statistical Tests: Multivariable logistic regression analysis was used to develop the clinical model. The least absolute shrinkage and selection operator method and linear discriminative analysis (LDA) were used to select the features and to construct a radiomics model. The performance of the models was assessed using the training cohort (97 patients) and the validation cohort (42 patients), and decision curve analysis (DCA) was applied for clinical use.Results: The clinical model included 14 imaging features, and the corresponding area under the curve (AUC) was 0.769 (95% confidence interval [CI], 0.675-0.863) in the training cohort and 0.729 (95% CI, 0.568-0.890) in the validation cohort. The LDA included 14 selected radiomics features that showed good discrimination-in the training cohort (AUC, 0.851; 95% CI, 0.758-0.916) and the validation cohort (AUC, 0.736; 95% CI, 0.518-0.874). In the decision curves, if the threshold probability was 0.17-0.84, using the radiomics score to distinguish NF-pNET G1 and G2/3, offered more benefit than did the use of a treat-all-patients or treat-none scheme.Data Conclusion: The developed radiomics model using noncontrast MRI could help differentiate G1 and G2/3 tumors, to make the clinical decision, and screen pNETs grade.Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1124-1136. [ABSTRACT FROM AUTHOR]

Background Context: Open-door laminoplasty often results in postoperative complications such as loss of cervical lordosis, limitations of cervical motion, and axial symptoms. However, current modified laminoplasty techniques such as muscle-sparing type or spinous process splitting technique are not as effective as expected.Purpose: To evaluate the radiological and clinical outcomes of C3 laminectomy combined with modified unilateral laminoplasty (preservation of posterior muscle-ligament complex and reconstruction of the midline structures) versus traditional open door laminoplasty in treating cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament.Study Design: Retrospective case-control study.Patient Sample: One hundred and eleven patients with multilevel cord compression and myelopathic symptoms.Outcome Measures: The outcome parameters were operation time, blood loss volume, complications, osseous fusion status, C0-C2 and C2-C7 Cobb angles, T1 slope, cervical sagittal vertical axis (cSVA), cervical curvature index (CCI), range of motion (ROM), cross-sectional area (CSA) of the semispinalis cervicis, axial symptoms, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI).Methods: We matched 37 patients who underwent modified laminoplasty with 74 patients treated by traditional open door laminoplasty (ratio, 1:2) according to age, sex, body mass index, compromised level, and radiographic characteristics. Preoperative and postoperative cervical parameters, namely, the C2-C7 Cobb angle, ROM, and CCI were measured on X-ray films. The CSA of the semispinalis cervicis was assessed on magnetic resonance images, and osseous fusion status of the hinge side and the osteotomy site was evaluated by computed tomography. We used the JOA and VAS scores, and the NDI to evaluate clinical outcomes.Results: The average follow-up period in the modified group was 24.1 months (range, 18-37 months) compared with 24.7 months (range, 18-38 months) in the control group. At the final follow-up, C0-C2 Cobb angle, T1 slope, and cSVA increased in the control group and were unchanged in the modified group. The C2-C7 Cobb angle decreased significantly in the control group and did not change in the modified group. ROM and CCI loss rate did not change in the modified group but decreased significantly in the control group. The CSA loss in the semispinalis cervicis was 222.90±79.56 mm2 in the control group and 49.11±75.93 mm2 in the modified group, with a significant difference (p<.001). The final CSA of the semispinalis cervicis at C2 and C4-C7 levels showed no significant difference in the modified group and decreased significantly in the control group compared with preoperation. Changes in the C2-C7 Cobb angle and cSVA were both correlated with the CSA loss of the semispinalis cervicis (r=0.282, p=.003; r=0.267, p=.005, respectively). Moreover, the CSA loss of the semispinalis cervicis also correlated with the CCI loss rate and the changes in ROM (r=0.312, p=.001; r=0.287, p=.002, respectively). Clinical outcomes such as VAS and NDI scores, improved significantly more in the modified group versus the controls (p<.001 and p=.005, respectively), while JOA scores improved similarly in both groups (p=.132). The incidence of axial symptoms was significantly lower in the modified group versus controls (5.4% vs 9.5%, respectively; p=.023).Conclusions: C3 laminectomy combined with modified unilateral laminoplasty is effective for treating patients with multilevel cord compression. This modified technique reconstructs the midline structures and may lead to improved alignment and less axial pain. [ABSTRACT FROM AUTHOR]

Background: Predictors besides symptoms of obstruction indicating small bowel stenosis are little known.Aims: To detect predictors of small bowel stenosis in balloon-assisted enteroscopy.Methods: Over a 6-year period, 461 patients had enteroscopy for suspected small intestinal disease. Details of clinical manifestations, medical history, demographic characteristics, findings of examinations, information on enteroscopy, and treatment were retrospectively collected based on medical records. Small bowel stenosis was defined as stricture that over-tube cannot go through in enteroscopy. Univariate and multivariate analyses were performed to identify predictors for small bowel stenosis.Results: A total of 314 patients had definite diagnosis after enteroscopy, imaging modalities, and/or even surgical exploration. They were included in this study for analyses. Mean age for them was 48.2 years old (range 15-81 years). Small bowel stenosis was present in 59 patients (18.8%). Analyses showed that CT/MRI indicating stenosis was significantly associated with severe stenosis (p = 0.014) but insignificant related to general stenosis (p = 0.097). Predictive factors that accompanied stenosis were age ≥ 60 years (OR = 2.1, 95% CI 1.1-4.0), underweight (BMI ≤ 18.5) (OR = 3.4, 95% CI 1.4-8.4), symptoms of obstruction (OR = 3.6, 95% CI 1.8-7.4), and overt small bowel bleeding (OR = 0.5, 95% CI 0.2-0.9).Conclusions: Small bowel stenosis more tended to occur to patients with symptoms of obstruction, no overt small bowel bleeding, age ≥ 60 years, or underweight. [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment.Study Design: The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (<4 h) or non-urgently (<24 h), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts.Main Outcome Measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity.Results: All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p = 0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p < 0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p = 0.072).Conclusions: As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka. [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment.Study Design: The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts.Main Outcome Measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity.Results: 15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033).Interpretation: As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial.Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate regional neural activity and regulation of patterns in the reorganized neural network of obesity and explore the correlation between brain activities and eating behavior.Methods: A total of 23 individuals with obesity and 23 controls with normal weight were enrolled. Functional magnetic resonance imaging (fMRI) data were acquired using 3.0-T MRI. Amplitude of low-frequency fluctuation and functional connectivity (FC) analyses were conducted using Data Processing Assistant for resting-state fMRI and Resting-State fMRI Data Analysis Toolkit (REST).Results: The group with obesity showed increased amplitude of low-frequency values in left fusiform gyrus/amygdala, inferior temporal gyrus (ITG), hippocampus/parahippocampal gyrus, and bilateral caudate but decreased values in right superior temporal gyrus. The group with obesity showed increased FC between left caudate and right superior temporal gyrus, left fusiform gyrus/amygdala and left ITG, right caudate and left fusiform gyrus/amygdala, and right caudate and left hippocampus/parahippocampal gyrus. Dutch Eating Behavior Questionnaire-Emotional scores were positively correlated with FC between left hippocampus/parahippocampal gyrus and right caudate but negatively correlated with FC between left fusiform gyrus/amygdala and left ITG.Conclusions: The study indicated the reorganized neural network presented as a bilateral cross-regulation pattern across hemispheres between reward and various appetite-related functional processing, thus affecting emotional and external eating behavior. These results could provide further evidence for neuropsychological underpinnings of food intake and their neuromodulatory therapeutic potential in obesity. [ABSTRACT FROM AUTHOR]

Objective: Adverse childhood experiences (ACEs) are associated with poor adult health and immune dysregulation. The impact of ACEs on patients with autoimmune disease is unknown. The present study was undertaken to compare the prevalence of ACEs in patients with systemic lupus erythematosus (SLE) to a population-based survey estimate and to investigate relationships between ACEs and SLE outcomes.Methods: Data derived from the California Lupus Epidemiology Study (CLUES), a sample of adult patients with SLE. Participants completed a 10-item ACE questionnaire covering 3 domains (abuse, neglect, household challenges). We estimated ACE prevalence in 269 CLUES participants compared to geographically matched respondents from the 2015 California Behavioral Risk Factor Surveillance System (BRFSS), which was standardized to CLUES participant characteristics (age, sex, race/ethnicity). We examined associations of patient-reported and physician-assessed health status measures with overall ACE levels and domains using multivariable linear regression, controlling for sociodemographics, nephritis, and juvenile-onset SLE.Results: Although specific domains varied, overall ACE levels were similar for CLUES and BRFSS respondents. Among SLE patients, 63.2% had ≥1 ACE, and 19.3% had ≥4. ACEs were more prevalent in those who were older, women, Latino or African American, and without college degrees, but not in those with lupus nephritis. In adjusted models, higher ACE levels and ACE domains were associated with worse patient-reported SLE activity, depression, and health status but were not significantly associated with physician-assessed SLE activity, damage, or severity.Conclusion: Given the association between ACE levels and important patient-reported outcomes in SLE, our study reinforces the need for prevention of ACEs in childhood and for clinical interventions to promote resilience among adults who have experienced ACEs. [ABSTRACT FROM AUTHOR]

Background: Data are scarce on sexually transmitted infection (STI) treatment-seeking behavior among men who have sex with men (MSM) in China. The purpose of the study was to characterize the first response to STI symptoms, treatment-seeking behavior, and its associated factors among MSM in China.Methods: A cross-sectional study with convenience sampling design was conducted in 13 cities from April to July 2017. Face-to-face interviews were conducted to collect information on demographics, STI symptoms, and treatment-seeking behavior. Logistic regression analysis was conducted to evaluate variables associated with not seeking treatment.Results: Among 3925 recruited participants, 628 (16.0%) reported STI symptoms in the past 12 months and were included in the analysis. Upon or after being notified of the symptoms, MSM sought help from various sources or self-tested using rapid testing kits. Only 322(51.3%) went to see a doctor in clinic. In multiple logistic regression analyses, younger age, lower income, less STI knowledge (adjusted odds ratio [AOR], 1.8; 95% confidence interval [CI], 1.2-2.5), not knowing own STI risk (AOR, 1.8; 95% CI, 1.2-2.7), no symptoms of anogenital ulcers (AOR, 2.3; 95% CI, 1.3-3.8) or anogenital warts (AOR, 2.4; 95% CI, 1.6-3.7), no syphilis testing in the past 12 months (AOR, 2.1; 95% CI, 1.5-3.0) were associated with higher probability of not seeking treatment in clinics.Conclusions: We found a high prevalence of STI symptoms among MSM and only half sought treatment. Prevention efforts should promote STI education, testing, and adequate treatment-seeking behavior. [ABSTRACT FROM AUTHOR]

Purpose: The interferon regulatory factor 2 (IRF-2) acted as a tumor suppressor. We inspected IRF-2 as a predictor of prognosis in gastric cancer (GC) patients and tried to find out the potential molecular mechanism.Methods: In this study, the association between IRF-2 expression and clinical or prognosis significance was investigated in 86 pairs of tumor and the adjacent normal gastric tissues from GC patients. After establishing the stable cell lines, the Transwell assays were deduced to evaluate the malignancy of tumor. Then, microarray assay was carried out and the GO/KEGG pathway analyses were conducted to identify IRF-2's target gene. The relationship between IRF-2 and matrix metalloproteinases 1 (MMP-1) was also investigated by the immunohistochemistry in 15 pairs of tumor and adjacent normal gastric tissues.Results: We found that IRF-2 expression level in GC was significantly correlated with the prognosis of the patients. Transwell assays suggested an impaired ability of invasion and migration in IRF-2-overexpressed GC cells and a progressive malignant phenotype in IRF-2-knockdown GC cells. Ninety differentially expressed genes were found between IRF-2-overexpressed GC cells and its normal control sets by microarray. We demonstrated that MMP-1 was canonical in the network of differentially expressed genes by GO and KEGG pathway analysis and its expression level was markedly decreased in IRF-2-overexpressed cells of MKN-45 and increased in IRF-2-knockdown cells of SGC-7901. The expression of MMP-1 was inversely correlated with IRF-2 in GAC TMA specimens.Conclusion: IRF-2 may inhibit GC progression by down-regulating MMP-1 level. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether weight change could influence the risks of colorectal cancer (CRC) and mortality. This study aimed to quantify the associations between full-spectrum changes in body mass index (BMI) and the risks of colorectal cancer (CRC) incidence, cancer-related and all-cause mortality among midlife to elder population.Methods: A total of 81,388 participants who were free of cancer and aged 55 to 74 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening program were involved. The percentage change of BMI was calculated as (BMI in 2006 - BMI at baseline)/BMI at baseline, and was categorized into nine groups: decrease (≥ 15.0%, 10.0-14.9%, 5.0-9.9%, 2.5-4.9%), stable (decrease/increase < 2.5%), increase (2.5-4.9%, 5.0-9.9%, 10.0-14.9%, ≥ 15.0%). The associations between percentage change in BMI from study enrolment to follow-up (median: 9.1 years) and the risks of CRC and mortality were evaluated using Cox proportional hazard regression models.Results: After 2006, there were 241 new CRC cases, 648 cancer-related deaths, and 2361 all-cause deaths identified. Overall, the associations between BMI change and CRC incidence and cancer-related mortality, respectively, were not statistically significant. Compared with participants whose BMI were stable, individuals who had a decrease in BMI were at increased risk of all-cause mortality, and the HRs were 1.21 (95% CI: 1.03-1.42), 1.65 (95% CI: 1.44-1.89), 1.84 (95% CI: 1.56-2.17), and 2.84 (95% CI: 2.42-3.35) for 2.5-4.9%, 5.0-9.9%, 10.0-14.9%, and ≥ 15.0% decrease in BMI, respectively. An L-shaped association between BMI change and all-cause mortality was observed. Every 5% decrease in BMI was associated with a 27% increase in the risk of all-cause mortality (HR = 1.27, 95% CI: 1.22-1.31, p < 0.001). The results from subgroups showed similar trends.Conclusions: A decrease in BMI more than 5% shows a significantly increased risk of all-cause mortality among older individuals; but no significant association between increase in BMI and all-cause mortality. These findings emphasize the importance of body weight management in older population, and more studies are warranted to evaluate the cause-and-effect relationship between changes in BMI and cancer incidence/mortality. [ABSTRACT FROM AUTHOR]

Study Design: A prospective and controlled study of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery.Objective: Assessment of dexmedetomidine added to preemptive ropivacaine infiltration for the relief of postoperative pain after lumbar fusion surgery.Summary Of Background Data: Single local anesthetic preemptive wound infiltration for the relief of postoperative pain does not translate into major or consistent clinical benefits after lumbar fusion surgery. Dexmedetomidine added to local anesthetics prolonged the duration of blockade and enhanced the analgesic in peripheral nerve block. The effect of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery for the relief of postoperative pain has yet not been studied.Methods: Fifty-seven patients with elective posterior lumbar fusion were randomly divided into two groups. Five minutes before incision, the skin and subcutaneous tissues were injected with 20 mL 0.5% ropivacaine in group R (n = 28) and 20 mL 0.5% ropivacaine and 1 ug/kg of dexmedetomidine in group RD (n = 29) in two divided doses (i.e., 10 mL per side of the incision line). After the operation, all patients received intravenous morphine for analgesia. The total morphine consumption, the time of first analgesic demand, numbers of PCA analgesia, Visual Analog Scale, and postoperative adverse effects were collected.Results: In group RD, cumulative morphine dose and numbers of PCA analgesia in group RD were significantly reduced, the time of first analgesic demand was significantly delayed compared to the group R. Visual Analog Scale in group RD showed a marked reduction at 8 hours, 12 hours, 16 hours after operation and less patients in group RD experienced postoperative nausea or vomiting compared to the group R.Conclusion: The addition of dexmedetomidine to preemptive ropivacaine wound infiltration provided a superior analgesic effect, reduced postoperative morphine consumption, and prolonged the time of the first analgesic demand with no serious side effects.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background and Aims: Glypican-1 (GPC1), a cell-surface heparan sulfate proteoglycan, promotes the pathogenesis of many human cancers. This study focuses on the role of GPC1 in the promotion of cell proliferation and motility in esophageal squamous cell carcinoma (ESCC).Methods: The expression and distribution of GPC1 were measured in tumor tissues from 248 ESCC patients using immunohistochemical (IHC) assays. Cell counting (kit-8), flow cytometry, Transwell, wound healing, IHC, and Western blotting assays were performed to examine the molecular mechanisms that underlie how GPC1 enhances cell proliferation and motility.Results: The level of GPC1 was higher in ESCC tumor samples than in para-tumor tissues (IHC score: 5.42 ± 2.15 vs. 0.86 ± 0.96). Ectopic overexpression of GPC1 in EC9706 cells promoted cell growth and the G1/S phase transition; conversely, GPC1 knockdown in Eca109 cells attenuated cell proliferation and induced G2/M phase arrest. In addition, GPC1 upregulation enhanced ESCC cell motility and induced epithelial mesenchymal transition (EMT), as demonstrated by the aberrant expression of EMT markers. Mechanistically, we demonstrated that GPC1 increased levels of p-Akt and β-catenin and reduced PTEN expression in ESCC.Conclusions: Our study indicated that GPC1 promotes the aggressive proliferation of ESCC cells by regulating the PTEN/Akt/β-catenin pathway. GPC1 may be a promising target for ESCC treatment. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic utility of quantitative parameters which generated in different regions of interests (ROIs) of benign and malignant breast lesions using contrast-enhanced sonography(CEUS).Materials and Methods: 130 patients were evaluated with contrast harmonic imaging after the injection of a bolus dose of 4.8 ml SonoVue (Bracco Sp A, Milan, Italy). Quantitative analyses using the TIC were performed in two types of ROI (manually tracing the whole lesions and using 3-mm rectangular sampling frames to depict local lesions).Wash in slope (WIS), rise time (RT), time to peak (TTP),peak intensity (PI),strengthening intensity (SI),wash out slope(WOS) and mean transit time(MTT) were investigated in each ROI, SI includes the strengthening intensity of the lesion itself(SIs) and its strengthening intensity relative to the reference area(SIr).Results: Pathologic analysis showed 52 benign and 78 malignant lesions. There were significant differences in the quantitative parameters obtained by the two ROI types (P < 0.05). There were significant differences between benign and malignant lesions in the WIS-e(P < 0.05), TTP-e(P < 0.05), and SIr-e (P < 0.05) for the manual ROI. Significant differences were found between benign and malignant lesions in the WIS-l(P < 0.05), TTP-l(P < 0.05), PI-l(P < 0.05), SIs-l(P < 0.05), and SIr-l (P < 0.05) for the 3-mm ROI. The regression equation obtained by ROI-e was P = 1/[1 + e-(2.65-0.184TTP-e)]. The regression equation obtained by ROI-l was P = 1/[1 + e-(2.472+0.024SIr-l-0.279TTP-l)]. There was statistically significant difference in the diagnostic efficacy between the two ROI types (P < 0.05).Conclusions: CEUS quantitative analysis has a certain value in the diagnosis of benign and malignant breast lesions. The ROI type which depicts local lesions can better reflect the hemodynamic characteristics of the lesions. [ABSTRACT FROM AUTHOR]

Introduction: Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterized by progressive wasting of muscles for which the disease-monitoring tools are still deficient.Methods: We performed muscle MRI of the lower limbs in 32 LGMD2A patients and 21 controls. The modified Mercuri scale was employed to evaluate the degree of fatty infiltration.Results: Severe fatty infiltration in the long head of biceps femoris (modified Mercuri scale 3.99) and sparing of extensor digitorum longus (modified Mercuri scale 0.17) were observed. The sensitivity and specificity of this pattern in diagnostic testing was 76.00% and 90.48%, respectively. A comprehensive clinical and MRI evaluation revealed that progressive fatty infiltration in the upper leg correlated well with disease progression, but neither calf involvement nor muscle strength deterioration showed a good correlation.Discussion: The selective involvement pattern is potentially useful for LGMD2A diagnosis. Upper leg muscle MRI is a sensitive evaluation method for monitoring disease progression. Muscle Nerve 58: 536-541, 2018. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study which examined the effects of lifestyle intervention in maternal gestational diabetes mellitus (GDM) on the growth pattern of newborns before two years of age. In the research, a population-based randomized controlled trial (RCT) was carried out in Tianjin, China. The study compared the effectiveness of intensive care (IC) against usual care (UC) on adverse pregnancy results in patients with GDM.

Background: Infection with hepatitis B virus (HBV) in pregnant women may be a threat for both mothers and fetuses. This study was performed to explore the impact of maternal HBV carrier status on pregnancy outcomes.Methods: We conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University between January 1, 2012 and September 30, 2015. A consecutive sample of 21,004 pregnant women, 513 asymptomatic HBV carriers and 20,491 non-HBV controls, was included in this study. The main outcomes of interest were selected pregnancy outcomes including miscarriage, stillbirth, preterm birth (PTB), gestational diabetes (GDM), intrahepatic cholestasis of pregnancy (ICP), preterm premature rupture of the membrane (PPROM), low birth weight (LBW), small for gestational age (SGA) and Apgar scores. The incidence of adverse pregnancy outcomes between asymptomatic HBV carriers and non-HBV controls were compared using the chi-square test and logistic regression. P values were two sided, and P <0.05 was considered to indicate statistical significance.Results: The incidences of stillbirth, PTB, GDM, ICP, PPROM, LBW, and SGA were similar between the HBV carrier and non-HBV groups. The proportion of miscarriage was significantly higher among the HBV carriers than the controls (9.36% vs 5.70%; P <0.001). After using multivariate modelling to adjust for possible socio-demographical variables and obstetric complications, women with HBV carrier status were still more likely to have miscarriage (adjusted OR 1.71, 95% CI 1.23-2.38). In addition, the incidences of other maternal and neonatal outcomes were similar between the two groups.Conclusion: Maternal HBV carrier status may be an independent risk factor for miscarriage and careful surveillance is warranted. [ABSTRACT FROM AUTHOR]

Objective: Deciding on public funding for pharmaceuticals on the basis of value for money is now widespread. We suggest that evidence-based assessment of value has restricted the availability of medicines in Australia in a way that reflects the relative bargaining power of government and the pharmaceutical industry. We propose a simple informal game-theoretic model of bargaining between the funding agency and industry and test its predictions using a logistic multiple regression model of past funding decisions made by the Pharmaceutical Benefits Advisory Committee in Australia.Method: The model estimates the probability of a drug being recommended for subsidy as a function of incremental cost per quality-adjusted life-year (QALY), as well as other drug and market characteristics. Data are major submissions or resubmissions from 1993 to 2009 where there was a claim of superiority and evidence of a difference in quality of life. Independent variables measure the incremental cost per QALY, the cost to the public budget, the strength and quality of the clinical and economic evidence, need as measured by severity of illness and the availability of alternative treatments, whether or not a resubmission, and newspaper reports as a measure of public pressure. We report the odds ratio for each variable and calculate the ratio of the marginal effect of each variable to the marginal effect of the cost per QALY as a measure of the revealed willingness to pay for each of the variables that influence the decision.Results: The results are consistent with a bargaining model where a 10,000 Australian dollar ($A) fall in value (increase in cost per QALY) reduces the average probability of public funding from 37 to 33% (95% CI 34-32). If the condition is life threatening or the drug has no active comparator, then the odds of a positive recommendation are 3.18 (95% CI 1.00-10.11) and 2.14 (95% CI 0.95-4.83) greater, equivalent to a $A33,000 and a $A21,000 increase in value (fall in cost per QALY). If both conditions are met, the odds are increased by 4.41 (95% CI 1.28-15.24) times, equivalent to an increase in value of $A46,000. Funding is more likely as time elapses and price falls, but we did not find clear evidence that public or corporate pressure influences decisions.Conclusion: Evidence from Australia suggests that the determinants of public funding and pricing decisions for medicines reflect the relative bargaining power of government and drug companies. Value for money depends on the quality of evidence, timing, patient need, perceived benefit and opportunity cost; these factors reflect the potential gains from striking a bargain and the risk of loss from not doing so. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia is characterized by maternal systemic inflammation and coagulation activation, akin to the sepsis syndrome. Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) may modify disease progression to safely prolong pregnancies and improve perinatal outcomes. Both maternal and perinatal risks are highest remote from term.Study Design: Open-label, single arm safety and efficacy trial of rhAPC in consenting pregnant women with severe early-onset preeclampsia. Disease severity-matched rhAPC-naïve controls were identified from an existing database. An additional six women were recruited as biomarker controls.Main Outcome Measures: Primary safety outcome: incidence of peripartum bleeding; primary efficacy outcome: duration of pregnancy after enrolment.Results: Twelve (31.6%) of 38 eligible women consented; 3 did not receive the infusion due to staffing. Therefore, 9 women received rhAPC (24 μg/kg/hr for ≤96 h antenatally). No safety issues were identified. There was a marginal prolongation in eligibility-to-delivery intervals for women receiving rhAPC (Mantel-Cox p = 0.052; Gehan-Breslow-Wilcoxon p = 0.049). Compared with both the pre-infusion phase in the rhAPC-treated women themselves and with fullPIERS rhAPC-naïve women, rhAPC was associated with increased urine output during the infusion (6/9 vs 1/9 had urine output >100 mL/h during the infusion, Fisher's exact p = 0.003).Conclusions: These data support further investigation of APC in women with severe early-onset preeclampsia; recombinant and purified human APC is available. In addition, these data will inform the design and implementation of randomized controlled trials aiming to modify and/or moderate the proinflammatory and proacoagulant state of preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: Laparoscopic splenectomy (LS) is relatively contraindicated in cirrhotic portal hypertension (CPH) patients with complicating hypersplenic splenomegaly (HS). This study aimed to evaluate the effectiveness and safety of incorporation of iodized oil and gelatin sponge embolization to conventional splenic artery embolization (cSAE) with coiling in CPH/HS patients undergoing LS.Patients and Methods: Between April 2012 and March 2014, eligible CPH/HS patients (n = 56) were assigned to preoperative modified SAE (mSAE) with LS (mSAE+LS group, n = 16), cSAE with LS (cSAE+LS group, n = 20) or LS alone (LS group, n = 20). Main outcome measures included frequency of conversion to laparotomy, operative time, intraoperative bleeding, and transfusion.Results: The three groups had similar baseline characteristics (all P > .05). mSAE and cSAE similarly decreased LS conversion frequency (mSAE+LS versus cSAE+LS versus LS, 0.0% versus 10.0% versus 30.0%, P = .030) and operative time (155 ± 23 minutes versus 170 ± 26 minutes versus 221 ± 42 minutes, P < .001) compared with LS alone. mSAE significantly reduced bleeding (178 ± 22 mL versus 250 ± 27 mL versus 328 ± 67 mL, P < .001) compared with cSAE and LS alone. The three groups had similar postoperative recovery times and surgical morbidities (all P > .05).Conclusions: In CPH/HS patients, preoperative SAE reduced LS conversion frequency and reduced operative time compared with LS alone, while mSAE further decreased volume of blood loss. [ABSTRACT FROM AUTHOR]

By sequence analysis of 16S rRNA, flaB, p66, and glpQ, we identified Borrelia miyamotoi in 1 of 4 Père David deer (n = 43) seropositive for Borrelia spp. and 1.2% (3/244) of Haemaphysalis longicornis ticks from Dafeng Elk National Natural Reserve, China. Future studies should assess Borrelia pathogenesis in deer. [ABSTRACT FROM AUTHOR]

Background: In response to urban-rural disparities in healthcare resources, China recently launched a healthcare reform with a focus on improving rural care during the past decade. However, nationally representative studies comparing medical care and patient outcomes between urban and rural areas in China during this period are not available.Methods and Results: We created a nationally representative sample of patients in China admitted for ST-segment-elevation myocardial infarction in 2001, 2006, and 2011, using a 2-stage random sampling design in 2 urban and 3 rural strata. In China, evidence-based treatments were provided less often in 2001 in rural hospitals, which had lower volume and less availability of advanced cardiac facilities. However, these differences diminished by 2011 for reperfusion therapy (54% in urban versus 57% in rural; P=0.1) and reversed for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (66% versus 68%; P=0.04) and early β-blockers (56% versus 60%; P=0.01). The risk-adjusted rate of in-hospital death or withdrawal from treatment was not significantly different between urban and rural hospitals in any study year, with an adjusted odds ratio of 1.13 (0.77-1.65) in 2001, 0.99 (0.77-1.27) in 2006, and 0.94 (0.74-1.19) in 2011.Conclusions: Although urban-rural disparities in evidence-based treatment for myocardial infarction in China have largely been eliminated, substantial gaps in quality of care persist in both settings. In addition, urban hospitals providing more resource-intensive care did not achieve better outcomes.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883. [ABSTRACT FROM AUTHOR]

Object: To assess the effect of auricular points treatment combined with acupoints application on patient with constipation after lung cancer surgery.Methods: Design and participants: This is a single-center randomized controlled trial. Totally 341 after lung cancer surgery patients were randomly assigned into the experimental group (n = 174) and the control group (n = 167). The control group received routine nursing care, which was included psychological support, diet instruction, and post-operative activities guidance. The experimental group received auricular points treatment combined with acupoints application therapy in addition to the routine nursing care. All the patients had defecation within 3 days after operation. The characteristics of the stool were recorded, and the progress and performance of the incidence of constipation was recorded in two groups.Results: The incidence of constipation in the control group was higher than that in the experimental group (P < 0.001). Moreover, the stool characteristics of experimental group were better than it in the control group by rank-sum test (P = 0.047).Conclusion: On the basis of routine measures to prevent constipation after lung cancer surgery, auricular point sticking combined with acupoint application therapy can effectively decrease the incidence of postoperative constipation. [ABSTRACT FROM AUTHOR]

Background: Joint salvage surgery for patients with juxtaarticular osteosarcoma remains challenging, especially when the tumor invades the epiphysis. Because patients are surviving longer with current chemotherapy regimens, it is advantageous to retain native joints if possible, especially in young patients. However, the results using joint-preserving tumor resections in this context have not been well characterized.Questions/purposes: (1) What are the functional outcomes after limb salvage surgery at a minimum of 3 years? (2) What are the oncologic outcomes? (3) Is joint salvage surgery for epiphyseal tumors associated with an increased risk of local recurrence compared with metaphyseal tumors not invading the epiphysis? (4) What are the complications associated with joint salvage surgery?Methods: Between 2004 and 2013, we treated 117 patients with juxtaarticular osteosarcoma; of those, 43 (38%) were treated with joint salvage surgery, and 41 (95%) of the 43 patients are included in our study. The other two (5%) were lost to followup before 3 years (mean, 4.4 years; range, 3-11 years,). During the period in question, we generally performed joint salvage surgery in these patients when they had a favorable response to chemotherapy, did not have a pathologic fracture or extrusion of the tumor into the joint, and did not have a whole-epiphyseal osteolytic lesion, a large mass, or obvious neurovascular involvement. This report is a followup of an earlier study; the current study includes an additional nine patients, and additional followup of a mean of 19 months for the patients included in the earlier report. We ascertained overall survival and survival free from local recurrence which was estimated using the Kaplan-Meier method, functional status of the limb which was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system, and recorded reconstructive complications including infection, fracture, skin necrosis, and nonunion. We compared oncologic and functional outcomes between patients with (n = 28) and without tumor extension to epiphysis (n =13). We also compared oncologic and functional outcomes among patients with different adjuvant treatments including microwave ablation (n = 11), cryoablation (n = 12), and navigation-assisted osteotomy (n = 5). Complications were tallied using records from our institutional database.Results: The overall Kaplan-Mayer survival rate was 82% (95% CI, 104-128 months) at 5 years. The overall Kaplan-Meier survivorship from local recurrence was 91% at 5 years (95% CI, 115-133 months). Three patients had a local recurrence, but none had local recurrence in or close to the remaining epiphysis. The MSTS scores ranged from 22 to 30 points, with a median of 28. There were no differences in survival rate, local recurrence, or MSTS scores between patients with a tumor that did not invade the epiphysis and those in whom the tumor did invade the epiphysis. There were differences in MSTS scores among patients with epiphyseal tumor extension in which different adjuvant techniques, including microwave ablation, cryoablation, and navigation-assisted osteotomy, were used. Additional surgical procedures were recorded for 10 patients (24%). Osteonecrosis of the residual epiphysis was detected 13 patients (31%).Conclusions: Our findings suggest it is possible to salvage joints in selected patients with juxtaarticular osteosarcoma around the knee. The patients who have a favorable response to chemotherapy are the best candidates for this approach. Future studies might explore the role of adjuvant techniques of microwave ablation and cryoablation, particularly when the tumor invades the epiphysis, and whether resections can be facilitated with navigation.Level Of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in TNFSF4 and ANKRD55 genes have been shown to be associated with several autoimmune diseases, although whether these genes are susceptibility genes for dermatomyositis/polymyositis (DM/PM) has, to date, not been reported. This study aimed to investigate the potential associations of these SNPs with DM/PM in a Chinese Han population. Five SNPs in TNFSF4 (rs2205960, rs844644, and rs844648) and ANKRD55 (rs6859219, rs7731626) genes were genotyped using the SequenomMassArray system in 2297 Chinese individuals. In total, 1017 DM/PM patients and 1280 gender-matched healthy controls were genotyped. No significant associations were observed in DM/PM patients for the five SNPs analyzed. The association between SNPs and interstitial lung disease (ILD) was also investigated. Both DM-ILD (Pc=0.030, OR = 0.65, 95% CI: 0.47–0.88) and DM/PM-ILD (Pc = 0.015, OR = 0.67, 95% CI: 0.51–0.87) exhibited a significant association with the rs7731626-A allele. Rs7731626-A was less frequently found in DM-ILD and DM/PM-ILD patients compared with healthy controls. This is the first study to demonstrate a positive association between ANKRD55 polymorphism and DM-ILD and DM/PM-ILD. A decreased frequency of rs7731626-A in DM-ILD and DM/PM-ILD patients suggests that the A variant may be protective against DM/PM-ILD. [ABSTRACT FROM AUTHOR]

We investigated the association between platelet-to-lymphocyte ratio (PLR) and clinical outcomes (including all-cause mortality, recurrent myocardial infarction, heart failure, serious cardiac arrhythmias and ischemic stroke) in patients with ST-segment elevation myocardial infarction (STEMI). Based on PLR quartiles, 5886 patients with STEMI were categorized into 4 groups: <98.8 (n = 1470), 98.8 to 125.9 (n = 1474), 126.0 to 163.3 (n = 1478), >163.3 (n = 1464), respectively. We used Cox proportional hazards models to examine the relation between PLR and clinical outcomes. Mean duration of follow-up was 81.6 months, and 948 patients (16.1%) died during follow-up. The lowest mortality occurred in the lowest PLR quartile group (P = 0.006), with an adjusted hazard ratio of 1.18 (95% confidence interval [CI], 1.04-1.55), 1.31 (95% CI, 1.18-1.64), and 1.59 (95% CI, 1.33-1.94) in patients with PLR of 98.8 to 125.9, 126.0 to 163.3, >163.3, respectively. Higher levels of PLR were also associated with recurrent myocardial infarction (Ptrend = .023), heart failure (Ptrend = .018), and ischemic stroke (Ptrend = .043). In conclusion, a higher PLR was associated with recurrent myocardial infarction, heart failure, ischemic stroke, and all-cause mortality in patients with STEMI. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]

Background: Catheter-related bladder discomfort (CRBD) is a common distressing symptom complex during the postoperative period, especially after urologic procedures with a relatively greater size urinary catheter. In this study, we will enroll male patients undergoing elective prostate surgery with urinary catheterization under general anesthesia, and we will compare the efficacy of pudendal nerve block (PNB) and intravenous tramadol in CRBD prevention.Methods/design: This trial is a prospective, randomized controlled trial that will test the superiority of bilateral PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg for CRBD prevention. A total of 94 male patients undergoing elective prostate surgery with urinary catheterization after anesthesia induction will be randomized to receive either bilateral PNB with 0.33 % ropivacaine (the PNB group) or intravenous tramadol 1.5 mg/kg (the tramadol group) after the completion of surgery. The primary outcome is the incidence of CRBD. The most important secondary outcome is the severity of postoperative CRBD, and other secondary outcomes include Numeric Rating Scale (NRS) score for postoperative pain; incidence of postoperative side effects such as postoperative nausea/vomiting, sedation, dizziness, and dry mouth; postoperative requirement for tramadol as a rescue treatment for CRBD and sufentanil as a rescue analgesic for postoperative pain; and NRS score for acceptance of an indwelling urinary catheter.Discussion: This trial is planned to test the superiority of PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg. It may provide a basis for a new clinical practice for the prevention of CRBD.Trial Registration: ClinicalTrials.gov identifier NCT02683070 . Registered on 11 February 2016. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer.Methods: Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes.Results: A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11-1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55-0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66-0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26-0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92-1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70-1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90-1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71-1.03, P = 0.09).Conclusions: This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Studies investigating the relationship between maternal tea drinking and risk of preterm birth have reached inconsistent results.Methods: The present study analyzed data from a birth cohort study including 10,179 women who delivered a singleton live birth were conducted in Lanzhou, China between 2010 and 2012.Results: Drinking tea (OR = 1.36, 95 % CI: 1.09-1.69), and specifically green (OR = 1.42, 95 % CI: 1.08-1.85) or scented tea (OR = 1.61, 95 % CI: 1.04-2.50), was associated with an increased risk of preterm birth. Drinking tea was associated with both moderate preterm (OR = 1.41, 95 % CI: 1.12-1.79) and spontaneous preterm birth (OR = 1.41, 95 % CI: 1.09-1.83). Risk of preterm birth increased with decreasing age of starting tea drinking (<20 years, OR = 1.60, 95 % CI: 1.17-2.20) and increasing duration (p for trend < 0.01). The relationship between tea drinking and preterm birth is modified by both maternal age (p < 0.05) and gestational weight gain (p < 0.05).Conclusions: Despite conflicting findings in the previous literature, we saw a significant association with maternal tea drinking and risk of preterm birth in our cohort. More studies are needed both to confirm this finding and to elucidate the mechanism behind this association. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH). Methods: This was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. Results: After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups ( P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group ( P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 ( P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment ( P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment ( P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. Conclusion: The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding. [ABSTRACT FROM AUTHOR]

Background: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02).Conclusions: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. [ABSTRACT FROM AUTHOR]

Background: This paper explores the importance of electronic medical records (EMR) for predicting 30-day all-cause non-elective readmission risk of patients and presents a comparison of prediction performance of commonly used methods.Methods: The data are extracted from eight Advocate Health Care hospitals. Index admissions are excluded from the cohort if they are observation, inpatient admissions for psychiatry, skilled nursing, hospice, rehabilitation, maternal and newborn visits, or if the patient expires during the index admission. Data are randomly and repeatedly divided into fitting and validating sets for cross validations. Approaches including LACE, STEPWISE logistic, LASSO logistic, and AdaBoost, are compared with sample sizes varying from 2,500 to 80,000.Results: Our results confirm that LACE has moderate discrimination power with the area under receiver operating characteristic curve (AUC) around 0.65-0.66, which can be improved to 0.73-0.74 when additional variables from EMR are considered. These variables include Inpatient in the last six months, Number of emergency room visits or inpatients in the last year, Braden score, Polypharmacy, Employment status, Discharge disposition, Albumin level, and medical condition variables such as Leukemia, Malignancy, Renal failure with hemodialysis, History of alcohol substance abuse, Dementia and Trauma. When sample size is small (≤5000), LASSO is the best; when sample size is large (≥20,000), the predictive performance is similar. The STEPWISE method has a slightly lower AUC (0.734) comparing to LASSO (0.737) and AdaBoost (0.737). More than one half of the selected predictors can be false positives when using a single method and a single division of fitting/validating data.Conclusions: True predictors can be identified by repeatedly dividing data into fitting/validating subsets and referring the final model based on summarizing results. LASSO is a better alternative to the STEPWISE logistic regression, especially when sample size is not large. The evidence for adequate sample size can be explored by fitting models on gradually reduced samples. Our model comparison strategy is not only good for 30-day all-cause non-elective readmission risk predictions, but also applicable to other types of predictive models in clinical studies. [ABSTRACT FROM AUTHOR]

Background: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors' offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be accelerated.Methods/design: Project ACHIEVE focuses on diverse Medicare populations such as individuals with multiple chronic diseases, patients with low health literacy/numeracy and limited English proficiency, racial and ethnic minority groups, low-income groups, residents of rural areas, and individuals with disabilities. During the first phase, we will use focus groups to identify the transitional care outcomes and components that matter most to patients and caregivers to inform development and validation of assessment instruments. During the second phase, we will evaluate the comparative effectiveness of multi-component care transitions programs occurring across the U.S. Using a mixed-methods approach for this evaluation, we will study historical (retrospective) and current and future (prospective) groups of patients, caregivers and providers using site visits, surveys, and clinical and claims data. In this natural experiment observational study, we use a fractional factorial study design to specify comparators and estimate the individual and combined effects of key transitional care components.Discussion: Our study will determine which evidence-based transitional care components and/or clusters most effectively produce patient and caregiver desired outcomes overall and among diverse patient and caregiver populations in different healthcare settings. Using the results, we will develop concrete, actionable recommendations regarding how best to implement these strategies. Finally, this work will provide tools for hospitals, community-based organizations, patients, caregivers, clinicians and other stakeholders to help them make informed decisions about which strategies are most effective and how best to implement them in their communities.Trial Registration: Registered as NCT02354482 on clinicaltrials.gov on 1/29/2015. [ABSTRACT FROM AUTHOR]

Introduction: The anti-IgE therapy omalizumab is currently licensed for the treatment of moderate to severe allergic asthma and chronic idiopathic urticaria. Owing to limitations in the use of omalizumab, a need exists for optimized anti-IgE therapies to broaden clinical indications and patient populations, and to improve dosing schedules. The objective of this phase I, randomized, placebo/omalizumab-controlled, first-in-human, dose-escalation study was to evaluate the pharmacokinetics, pharmacodynamics, and safety of the high-affinity, anti-IgE therapy MEDI4212 in non-Japanese and Japanese subjects with atopy and/or diagnostic IgE ≥ 30 IU/mL.Methods: Subjects with atopy and/or baseline IgE ≥ 30 IU/mL were randomized to a single dose of subcutaneous (5, 15, 60, 150, or 300 mg) or intravenous (300 mg) MEDI4212, subcutaneous omalizumab, or placebo. Following administration, pharmacokinetic, pharmacodynamic [IgE (free and total), and cellular FcεRI expression], and safety assessments were made.Results: MEDI4212 rapidly suppressed free serum IgE to a greater extent than omalizumab; however, recovery of free IgE to baseline in MEDI4212-dosed subjects was rapid when compared with the slow and gradual recovery seen in omalizumab-dosed individuals. The loss of IgE suppression corresponded with a rapid decrease of serum MEDI4212. FcεRI expression on dendritic cells and basophils was reduced following MEDI4212 dosing. MEDI4212 was well tolerated by subjects; adverse events were generally of low severity and no subjects discontinued due to adverse events.Conclusions: The increased potency of MEDI4212 may be of clinical interest for individuals with high-diagnostic IgE levels where more extensive IgE suppression is required for clinical response. However, the modest duration of free IgE suppression below the target concentration noted with MEDI4212 in this study suggests limited potential for dosing schedule advantages over omalizumab.Funding: MedImmune.Trial Registration: ClinicalTrials.gov identifier, NCT01544348. [ABSTRACT FROM AUTHOR]

Background and Purpose: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products.Experimental Approach: Intracellular calcium measurements and patch clamp recordings were made from cell lines. Compounds were generated by synthetic chemistry.Key Results: Through a screen of natural products used in traditional Chinese medicines, the flavonol galangin was identified as an inhibitor of lanthanide-evoked calcium entry in TRPC5 overexpressing HEK 293 cells (IC50 0.45 μM). Galangin also inhibited lanthanide-evoked TRPC5-mediated current in whole-cell and outside-out patch recordings. In differentiated 3T3-L1 cells, it inhibited constitutive and lanthanide-evoked calcium entry through endogenous TRPC5-containing channels. The related natural flavonols, kaempferol and quercetin were less potent inhibitors of TRPC5. Myricetin and luteolin lacked effect, and apigenin was a stimulator. Based on structure-activity relationship studies with natural and synthetic flavonols, we designed 3,5,7-trihydroxy-2-(2-bromophenyl)-4H-chromen-4-one (AM12), which inhibited lanthanide-evoked TRPC5 activity with an IC50 of 0.28 μM. AM12 also inhibited TRPC5 activity evoked by the agonist (-)-Englerin A and was effective in excised outside-out membrane patches, suggesting a relatively direct effect. It inhibited TRPC4 channels similarly, but its inhibitory effect on TRPC1-TRPC5 heteromeric channels was weaker.Conclusions and Implications: The data suggest that galangin (a natural product from the ginger family) is a TRPC5 inhibitor and that other natural and synthetic flavonoids contain antagonist or agonist capabilities at TRPC5 and closely related channels depending on the substitution patterns of both the chromone core and the phenyl ring. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the population pharmacokinetics (PKs) of subcutaneous (SC) and intravenous (IV) trastuzumab in early breast cancer (EBC), assess the impact of covariates on trastuzumab PK, and evaluate fixed (nonweight-based) dosing for the SC regimen administrated via handheld syringe.Methods: Serum trastuzumab concentrations from 595 patients with HER2-positive EBC in the HannaH study (fixed 600 mg SC trastuzumab or weight-based IV trastuzumab) were analyzed using nonlinear mixed-effects modeling. Multiple logistic regression was used to assess the exposure-response relationships between PK, efficacy [pathologic complete response (pCR)], and safety [grade ≥3 adverse events (AEs)].Results: Trastuzumab PK was described by a two-compartment model with parallel linear and nonlinear elimination and first-order SC absorption, with a bioavailability of 77 %. Estimated total clearance (CL) values were 0.18-0.22 L/day for steady-state trough/peak concentrations of 75-148 µg/mL; the estimate for central volume of distribution was 2.9 L. Body weight and alanine transaminase, while showing significant effects on PK, only explained 8% of the variability in CL. Exposure-response analyses showed no relationship between PK, pCR, and grade ≥3 AEs for either regimen.Conclusion: A fixed 600 mg SC dose of trastuzumab provides the desired exposure, with steady-state trough concentrations (35-123 μg/mL for the 5th-95th percentiles) above the historical target concentration of 20 μg/mL for efficacy. Fixed dosing is further supported by lack of an exposure-response relationship between PK, pCR, and grade ≥3 AEs. No dose adjustment per patient factors is required within the ranges studied. [ABSTRACT FROM AUTHOR]

Background: Catheter-related bladder discomfort (CRBD) is common in male patients under general anesthesia, and it may cause patient agitation and exacerbated postoperative pain. In this study, we will enroll male patients undergoing elective surgery with urinary catheterization after anesthetic induction and compare the efficacy of a dorsal penile nerve block (DPNB) and intravenous tramadol for the prevention of CRBD.Methods/design: This trial is a prospective, open-label, randomized controlled trial that will test the superiority of a dorsal penile nerve block with 0.33% ropivacaine to the use of intravenous tramadol 1.5 mg/kg for CRBD prevention. A total of 60 male patients undergoing elective surgery with urinary catheterization after anesthetic induction will be randomized to receive either DPNB with 0.33% ropivacaine (DPNB group) or intravenous tramadol 1.5 mg/kg (TRAM group) after the completion of surgery but before extubation. The primary outcome is the incidence and severity of CRBD. Secondary outcomes include Visual Analog Score (VAS) for postoperative pain, number of patients requiring sulfentanil after operation, acceptance of an indwelling urinary catheter after extraction of the catheter, and postoperative side effects, which include postoperative nausea/vomiting (PONV), vertigo, sedation, drowsiness, and dry mouth.Discussion: For CRBD prevention, this trial is planned to test the superiority of a dorsal penile nerve block with 0.33% ropivacaine to the use of intravenous tramadol 1.5 mg/kg. The results will provide new insight into the mechanism of CRBD and new clinical practice for the prevention of CRBD.Trial Registration: The registration number is NCT01721031, which was assigned by the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov) on 27 October 27. [ABSTRACT FROM AUTHOR]