Epidemiology and Costs of Sepsis in the United States—An Analysis Based on Timing of Diagnosis and Severity Level

Objectives: To characterize the current burden, outcomes, and costs of managing sepsis patients in U.S. hospitals. Design: A retrospective observational study was conducted using the Premier Healthcare Database, which represents ~20% of U.S. inpatient discharges among private and academic hospitals. Hospital costs were obtained from billing records per the cost accounting method used by each hospital. Descriptive statistics were performed on patient demographics, characteristics, and clinical and economic outcomes for the index hospitalization and 30-day readmissions. Setting: Sepsis patient hospitalizations, including inpatient, general ward, and ICU (intermediate and/or step-down). Patients: Adults over 18 years old with a hospital discharge diagnosis code of sepsis from January 1, 2010, to September 30, 2016. Interventions: None. This was a retrospective observational study of deidentified data. Measurements and Main Results: The final study cohort consisted of 2,566,689 sepsis cases, representing patients with a mean age of 65 years (50.8% female). Overall mortality was 12.5% but varied greatly by severity (5.6%, 14.9%, and 34.2%) for sepsis without organ dysfunction, severe sepsis, and septic shock, respectively. Costs followed a similar pattern increasing by severity level: $16,324, $24,638, and $38,298 and varied widely by sepsis present at admission ($18,023) and not present at admission ($51,022). Conclusions: The highest burden of incidence and total costs occurred in the lowest severity sepsis cohort population. Sepsis cases not diagnosed until after admission, and those with increasing severity had a higher economic burden and mortality on a case-by-case basis. Methods to improve early identification of sepsis may provide opportunities for reducing the severity and economic burden of sepsis in the United States. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. This research was conducted at Premier, Inc. Supported, in part, by Beckman Coulter, Inc. Drs. Paoli and Dr. Reynolds are both employees of and hold stock in Beckman Coulter, Inc./Danaher Corp. (parent company of Beckman Coulter). Dr. Sinha is an employee of Premier, Inc., which received funding to conduct the research project. Dr. Gitlin is an employee of BluePath Solutions, which received funding to conduct the research project, and his institution received funding from Danaher Corp., Diagnostics & Life Science Platforms. Drs. Sinha's and Crouser's institutions received funding from Beckman Coulter, Inc. Dr. Crouser has received support from Beckman Coulter, Inc. as a scientific consultant and as principal investigator of a clinical trial investigating a novel sepsis biomarker, and his institution also received funding from the National Institutes of Health and Foundation for Sarcoidosis Research Address requests for reprints to: Carly J. Paoli, PharmD, MPH, Global Health Economics & Reimbursement, Danaher Corp., Diagnostics & Life Science Platforms | Beckman Coulter, 250 S. Kraemer Blvd, Brea, CA 92822. E-mail: cjworden@beckman.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Assessment of Lung Aeration and Recruitment by CT Scan and Ultrasound in Acute Respiratory Distress Syndrome Patients

Objectives: Lung ultrasound is commonly used to evaluate lung morphology in patients with acute respiratory distress syndrome. Aim of this study was to determine lung ultrasound reliability in assessing lung aeration and positive end-expiratory pressure–induced recruitment compared with CT. Design: Randomized crossover study. Setting: University hospital ICU. Patients: Twenty sedated paralyzed acute respiratory distress syndrome patients: age 56 years (43–72 yr), body mass index 25 kg/m2 (22–27 kg/m2), and PaO2/FIO2 160 (113–218). Interventions: Lung CT and lung ultrasound examination were performed at positive end-expiratory pressure 5 and 15 cm H2O. Measurements and Main Results: Global and regional Lung Ultrasound scores were compared with CT quantitative analysis. Lung recruitment (i.e., decrease in not aerated tissue as assessed with CT) was compared with global Lung Ultrasound score variations. Global Lung Ultrasound score was strongly associated with average lung tissue density at positive end-expiratory pressure 5 (R2 = 0.78; p

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Elevated Risk of Cancer Following Solid Organ Transplant in Childhood: A Population-based Cohort Study

Background Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients. Methods We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death. Results A total of 951 recipients (kidney n=400, liver n=283, heart n=218, lung n=36, multiorgan/small bowel n=14) were compared to 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio 32.9; 95% CI 26.6-40.8). Risk was highest in the first year posttransplant (aHR 176; 95% CI 117-264), but remained elevated beyond 10 years (aHR 10.8; 95% CI 6.3-18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR 93.1; 95% CI 59.6-145.2). Conclusions Childhood transplant recipients have a 30-times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population. *Corresponding Author Contact Information: Rulan S. Parekh, MD, MS., FRCPC, Nephrologist, Division of Nephrology, Associate Chief, Clinical Research, Scientist, Child Health Evaluative Sciences, Research Institute, Professor, Faculty of Medicine, Institute of Medical Sciences and Dalla Lana School of Public Health, University of Toronto, Peter Gilgan Centre for Research & Learning, The Hospital for Sick Children (SickKids), 686 Bay Street, Child Health Evaluative Sciences, 11th floor, Toronto, ON, Canada, M5G 0A4, Phone: 416-813-7654 ext. 328042, Fax: 416-813-5979. Email: rulan.parekh@sickkids.ca AUTHORSHIP A.K., S.D., S.J.K., P.C.N., and R.S.P participated in the study design. A.K., S.D., S.G., and P.C.N. participated in the data analysis. A.K., S.D., J.S.D., P.C.N., and R.S.P drafted the manuscript. All authors read and approved the final manuscript. DISCLOSURES The authors declare no conflicts of interest. FUNDING Dr. Rulan S. Parekh received funding from the Transplant & Regenerative Medicine Centre (TRMC) Catalyst Grant at The Hospital for Sick Children, Ashley's Angels Catwalk and the Canadian Institutes of Health Research (CIHR) for the completion of this study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Regional Variation in Utilization and Outcomes of Liver Allografts from Donors with High Body-Mass Index and Graft Macrosteatosis: A Role for Liver Biopsy

Background Obesity, defined as a body mass index ≥30 kg/m2 (hBMI), is a growing epidemic worldwide and is associated with multiple comorbidities. hBMI individuals account for an increasing portion of potential liver donors. Here we evaluate trends in the utilization and outcomes of hBMI donors on a national and regional level and the potential role of liver biopsy in donor evaluation. Methods UNOS STAR database was evaluated for deceased donor liver transplants between 2006 and 2016 across 11 OPTN regions. hBMI donors were compared to lower BMI counterparts and evaluated for biopsy rates, utilization rates and allograft outcomes. Univariate and multivariable analyses were performed. Results 77 050 potential donors were identified and 60 200 transplants were evaluated. Utilization rates for hBMI donors was 66.1% versus 78.1% for lower BMI donors (p

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Renal Revival; the Hidden Benefit of Antirejection Medications

No abstract available

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Reduced Risk of BK Polyomavirus Infection in HLA-B51 Positive Kidney Transplant Recipients

Background Identification of specific HLA alleles and T cell epitopes that influence the course of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), including development of BKPyV-associated nephropathy (BKPyVAN), can be useful for patient risk stratification and possibly vaccine development. Methods In a retrospective cohort of 407 living kidney donor-recipient pairs, donor and recipient HLA class I and II status were correlated with the occurrence of recipient BKPyV viremia and BKPyVAN in the first year after KTx. Relevant HLA alleles were systematically analyzed for candidate peptide epitopes in silico. Results While none of the 78 HLA alleles analyzed increased the risk of BKPyV viremia and BKPyVAN, a considerable reduction of BKPyV viremia and BKPyVAN cases was observed in HLA-B51 positive KTx recipients. Multivariate analysis showed that HLA-B51-positivity, found in 36 recipients (9%), reduced the risk of viremia approximately five-fold (HR 0.18, 95% CI: 0.04 – 0.73, p = 0.017). Four HLA-B51-restricted putative cytotoxic T lymphocyte epitopes were identified, including a previously described HLA-B supermotif-containing peptide (LPLMRKAYL), encoded by 2 relevant T-antigens (Small T and Large T) and previously shown to be highly immunogenic. Conclusions In conclusion, HLA-B51-positive kidney transplant recipients were less susceptible to BKPyV infection, which might be explained by efficient presentation of a particular BKPyV-derived immunogenic peptide. Authorship The author's specific contributions are as follows: HFW and MCWF initiated the study. HFW, ACMK, JWdF, JIR, FHJC and MCWF designed the study. HFW, CSdB, GWH and JIR collected the samples and gathered the data. CSdB performed the serological tests and the PCR assays. HFW analysed the data. EWvZ and GWH provided statistical support. HFW, ACMK, JWdF, JIR, FHJC, and MCWF interpreted the data. HFW and MCWF drafted the manuscript, and designed the figures and tables. All authors reviewed and approved the final report. Disclosure The authors declare no conflicts of interest Funding This study was supported by the Dutch Kidney Foundation, grant 13A1D302. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Impact of Deceased Donor Liver Extraction Time on Early Allograft Function in Adult Liver Transplant Recipients

Background In liver transplantation, both cold- and warm ischemia time are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known. Methods We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time and the donor risk index. Results Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score. (Coefficient 0.018, 95%CI 0.004 to 0.03, P = 0.012; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time and donor risk index had a significant effect on early graft function. Conclusions We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation. Correspondence information: Dieter Adelmann, MD, PhD, Department of Anesthesia & Perioperative Care, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA, dieter.adelmann@ucsf.edu Authorship: D.A., G.R.R., and C.U.N. drafted the study protocol. C.U.N. obtained Institutional Review Board approval D.A., M.T. and R.P.K. collected patients' data D.A. performed the statistical analysis D.A., G.R.R., S.S., L.J.B, R.P.K. and C.U.N. prepared the manuscript. Disclosures: The authors declare no conflicts of interest Funding: This study was supported by departmental funds. (Department of Anesthesia and Perioperative Care San Francisco, University of California, San Francisco, CA) Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cell Spray Transplantation of Stem Cells for Ischemic Cardiomyopathy – How effective are dispersed droplets?

No abstract available

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Cell Spray Transplantation of Adipose-Derived Mesenchymal Stem Cell Recovers Ischemic Cardiomyopathy in a Porcine Model

Background Allogeneic adipose-derived mesenchymal stem cells (ADSC) are promising cell sources for cell therapy to treat ischemic cardiomyopathy (ICM). We hypothesized that ADSC transplantation via the new cell spray method may be a feasible, safe, and effective treatment for ICM. Methods Human ADSCs were acquired from white adipose tissue. Porcine ICM models were established by constriction of the left anterior descending coronary artery. ADSCs were spread over the surface of the heart via cell spray in fibrinogen and thrombin solutions. The cardiac function was compared to that of the control group. Results ADSCs were successfully transplanted forming a graft-like gel film covering the infarct myocardium. Premature ventricular contractions were rarely detected in the first 3 days after transplantation. Echocardiography and magnetic resonance imaging revealed improved cardiac performance of the ADSC group at 4 and 8 weeks after transplantation. Systolic and diastolic parameters were significantly greater in the ADSC group at 8 weeks after transplantation. Histological examination showed significantly attenuated left ventricular remodeling and a greater vascular density in the infarct border area in the ADSC group. Moreover, the coronary flow reserve was maintained, and expression levels of angiogenesis-related factors in the infarct border and remote areas were significantly increased. Conclusion Spray method implantation of allogenic ADSCs can improve recovery of cardiac function in a porcine infarction model. This new allogenic cell delivery system may help to resolve current limitations of invasiveness and cost in stem cell therapy. Corresponding author: Yoshiki Sawa, MD, PhD, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan, E-mail: sawa-p@surg1.med.osaka-u.ac.jp, TEL: +81-6-6879-3154/FAX: +81-6-6879-3163 Author contributions D.M. participated in research design performance of research, analyzed data, and wrote the article. S.Y., K.K., H.K., and H.N. performed research and analyzed data. K.I. and J.H. participated in performing PET.(helped with some experiments) S.S., S.F., T.U., and K.T. reviewed all data and article. S.M. and Y.S.participated in research design, writing of the article and reviewed all data and article. All authors have met the following criteria: drafting the work or revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Disclosure This study was supported by Rohto Pharmaceutical Co., Ltd. Dr. Sawa serves as an advisor for the sponsor. Dr. Sawa and Dr. Miyagawa received a speaking fee from the sponsor. Ms. Kawai, Mr. Kurata, and Mr. Nishida receive a salary from the sponsor where they are employees. The sponsor had no control over the interpretation, writing, or publication of this work. The terms of this arrangement have been reviewed and approved by Osaka University in accordance with its policy on objectivity in research. Funding This work was supported by the Department of Advanced Stem Cell Therapy (Rohto Pharmaceutical Co. Ltd.). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Vascularized Plexus Allotransplantation: A New Hope in Brachial Plexus Palsy?

No abstract available

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Vascularized Brachial Plexus Allotransplantation – An Experimental Study in Brown Norway and Lewis Rats

Background Brachial plexus injuries are devastating. Current reconstructive treatments achieve limited partial functionality. Vascularized brachial plexus allotransplantation could offer the best nerve graft fulfilling the like-with-like principle. In this experimental study, we assessed the feasibility of rat brachial plexus allotransplantation and analyzed its functional outcomes. Methods A free vascularized brachial plexus with a chimeric compound skin paddle flap based on the subclavian vessels was transplanted from a Brown Norway rat to a Lewis rat. This study has 2 parts. Protocol I aimed to develop the vascularized brachial plexus allotransplantation-model (VBP-allo). Four groups are compared: no reconstruction, VBP-allo with and without Cyclosporine-A (CsA) immunosuppression, VBP autotransplantation (VBP-auto). Protocol II compared the recovery of the biceps muscle and forearm flexors when using all 5, 2 (C5+C6) or 1 (isolated C6) spinal nerve as the donor nerves. The assessment was performed on week 16 and included muscle weight, functionality (grooming tests, muscle strength), electrophysiology and histomorphology of the targeted muscles. Results Protocol I showed, the VBP-allo with CsA immunosuppression was electrophysiologically and functionally comparable to VBP-auto and significantly superior to negative controls and absent immunosuppression. In Protocol II, all groups had a comparable functional recovery in the biceps muscle. Only with 5 donor nerves did the forearm show good results compared with only 1 or 2 donor nerves. Conclusions This study demonstrated a useful vascularized complete brachial plexus allotransplantation rodent model with successful forelimb function restoration under immunosuppression. Only the allotransplantation including all 5 roots as donor nerves achieved a forearm recovery. Corresponding Author: David Chwei-Chin Chuang, M.D., Professor, Department of Plastic Surgery, Chang Gung Memorial Hospital, No.5, Fu-Shing St., Taoyuan, Taiwan, Tel.: 886-3-3281200, Ext 3355, Fax: 886-3-3972681, E-mail: dccchuang@gmail.com Authorship Author's specific contributions 1. Participated in research design: David Chwei-Chin Chuang 2. Participated in the writing of the paper: Tommy Nai-Jen Chang, Bassem W Daniel, Kuang-Te Chen, Johhny Chuieng-Yi Lu 3. Participated in the performance of the operation and the sample collection: Tommy Nai-Jen Chang, Kuang-Te Chen, Catherine Hernon 4. Contributed new reagents or analytic tools: Bassem W Daniel, David Chwei-Chin Chuang 5. Participated in data analysis: Tommy Nai-Jen Chang, Catherine Hernon, Mark Shafarenko, Yen-Lin Huang Disclosure The authors hereby declare that they have no conflict of interest in any products used/tested in this study and have nothing to declare. Financial Disclosure: This study was supported by a grant from the Ministry of Science and Technology Taiwan (NSC94-2314-B-182A-176) and the Chang Gung Memorial Hospital, Linkou, Taiwan (CMRPG3A0441-3). None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this article. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Is recipient HLA-B51 status protective for the risk of BK infection after kidney transplantation?

No abstract available

https://ift.tt/2NQUmhd

Downregulation of Long Noncoding RNA HOTAIR and EZH2 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Breast Cancer Cells

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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A pyridoindole antioxidant SMe1EC2 regulates contractility, relaxation ability, cation channel activity, and protein-carbonyl modifications in the aorta of young and old rats with or without diabetes mellitus

Abstract

We studied the effects of treatment with SMe1EC, a hexahydropyridoindole antioxidant, on vascular reactivity, endothelial function, and oxidonitrosative stress level of thoracic aorta in young and old rats with or without diabetes mellitus. The rats were grouped as young control (YC 3 months old), old control (OC 15 months old), young diabetic (YD), old diabetic (OD), young control treated (YCT), old control treated (OCT), young diabetic treated (YDT), and old diabetic treated (ODT). Diabetes was induced by streptozotocin injection and subsequently SMe1EC2 (10 mg/kg/day, p.o.) was administered to YCT, OCT, YDT, and ODT rats for 5 months. In young and old rats, diabetes resulted in hypertension, weight loss, hyperglycemia, and hypertriglyceridemia, which were partially prevented by SMe1EC2. SMe1EC2 also inhibited the diabetes-induced increase in aorta levels of AGEs (advanced glycosylation end-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine), 3-NT (3-nitrotyrosine), and RAGEs (receptors for AGEs). The contractions of the aorta rings to phenylephrine (Phe) and KCL did not significantly change, but acetylcholine (ACh) and salbutamol relaxations were reduced in OC compared to YC rats. Diabetes induction increased Phe contractions in YC and OC rats, KCL contractions in YC rats, and did not cause further inhibition in already inhibited ACh and salbutamol relaxations in OC rats. We have achieved the lowest levels of ACh relaxation in YD rats compared to other groups. SMe1EC2 did not change the response of aorta to ACh, salbutamol and Phe in YC rats, and ameliorated ACh relaxations in OC and YD but not in OD rats. In YDT and ODT rats, increased Phe and KCL contractions, high blood pressure, and impaired salbutamol relaxations were amended by SMe1EC2. Phe contractions observed in YD and OD rats as well as KCl contractions observed in OC rats were the lowest levels when the rats were treated with SMe1EC2. When the bath solution was shifted to cyclopiazonic acid (CYP) or CYP plus Ca²⁺-free medium, the contraction induced by a single dose of Phe (3 × 10⁻⁶ M) was more inhibited in YD and OD than in YC but not in OC rats. In SMe1EC2-treated rats, neither the presence of CFM nor CFM plus CYP exhibited a significant change in response of aorta to a single dose of Phe. These findings suggest that α1-adrenergic receptor signaling is activated in both age groups of diabetic rats, diabetes activates K⁺-depolarization and calcium mobilization via Ca_V especially in the aorta of young rats, and sensitizes the aorta of old rats to the regulating effect of SMe1EC2. ACh relaxations were inhibited in YC rats, increased in OC rats and unchanged in YD and OD rats when aortic rings pretreated with TEA, an inhibitor of calcium-activated K⁺ channels (K_Ca), or 4-aminopyridine (4-AP), an inhibitor of voltage-sensitive K⁺ channels (K_V). ACh relaxations were inhibited in YCT, OCT, and YDT rats in the presence of 4-AP or TEA. In ODT rats, 4-AP did not change ACh relaxation but TEA inhibited. These findings suggest that the contribution of K_v and K_Ca to ACh relaxation is likely upregulated by SMe1EC2 when the relaxations were inhibited by aging or diabetes. We conclude that SMe1EC2 might be a promising agent for aging and diabetes related vascular disorders.

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Pinnacle EMS 2018 Quick Take: The power of collaboration for EMS leaders

Jay Fitch, Ph.D., tells Pinnacle leaders that collaboration with colleagues and frenemies is critical to greater operational success

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circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346

Abstract

Backgroud

Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown.

Methods

We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC.

Results

Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346.

Conclusions

Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.

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Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA

Abstract

Background

Currently, resistance to tyrosine kinase inhibitors, such as gefitinib, has become a major obstacle in improving the clinical outcome of patients with metastatic and advanced-stage esophageal squamous cell carcinoma (ESCC). While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the roles of lncRNAs within extracellular vesicles (exosomes) are largely unknown. Therefore, we investigated the involvement and regulatory functions of potential lncRNAs enclosed in exosomes during formation of chemoresistance in human ESCC.

Methods

Gefitinib-resistant cell lines were established by continuously grafting TE1 and KYSE-450 cells into gefitinib-containing culture medium. LncRNA microarray assay followed by RT-qPCR were used to verify the differential expression of lncRNA Prostate Androgen-Regulated Transcript 1 (PART1) between gefitinib resistant and parental cell lines. RNA fluorescence in situ hybridization (FISH) was used to investigate whether extracellular PART1 could be incorporated into exosomes and transmitted to recipient cells. Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of lncRNA PART1 in ESCC cells. A signal transduction reporter array, bioinformatics analysis, western blotting, and immunofluorescence were carried out to verify the regulation of PART1 and its downstream Bcl-2 signaling pathway.

Results

lncRNA PART1 was upregulated in gefitinib-resistant cells when compared to parental ESCC cells. It was found that STAT1 can bind to the promoter region of lncRNA PART1, resulting in its activation. Knockdown of lncRNA PART1 potently promoted the gefitinib-induced cell death, while elevated PART1 promoted gefitinib resistance by competitively binding to miR-129 to facilitate Bcl-2 expression in ESCC cells. In addition, extracellular PART1 could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating gefitinib resistance. Clinically, high levels of serum lncRNA PART1 in exosome were associated with poor response to gefitinib treatment in ESCC patients.

Conclusions

LncRNA PART1 promotes gefitinib resistance by regulating miR-129/Bcl-2 pathway, and may serve as a therapeutic target for ESCC patients.

https://ift.tt/2mL9AIU

Clinical management of quadriplegia in low and middle-income countries: a patients road to physiotherapy, prostheses and rehabilitation

Here we discuss the follow-up case of a 27-year-old male patient from rural Philippines, who was neglected by local health services after losing all four of his limbs as a result of a high-voltage electrical accident. The case follows the patient's road to accessing prostheses, rehabilitation health services and physiotherapy. Significant disparities were found between the government health services and the private sector with respect to quality, accessibility and affordability. Access to affordable healthcare is a basic human right that must be a priority for low-income and middle-income countries.

https://ift.tt/2AkDAEW

Successful management of persistent distressing neuropsychiatric symptoms by clozapine in a patient suffering from dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia associated with poor prognosis and high carers' burden. Neuropsychiatric symptoms worsen this prognosis and are a high source of distress for service users and their carers. However, there is currently insufficient evidence to support the pharmacological and non-pharmacological management of these symptoms. Acetylcholinesterase inhibitors are the first-line pharmacological option, but challenging risky behaviours may persist despite their use. Antipsychotic medications are indicated in such clinical scenarios, but there is very limited evidence to support the efficacy and safety of these medications for managing neuropsychiatric symptoms in DLB. Hence, we report an individual with DLB with severe distressing persistent visual hallucinations and agitation. After multiple treatment options had failed, clozapine was successfully initiated with substantial improvement in both clinical and functional outcomes. Further studies are warranted for evaluating the efficacy of clozapine in managing neuropsychiatric symptoms in DLB.

https://ift.tt/2mNvgny

Linezolid-induced pancytopenia

Linezolid is a bacteriostatic antibiotic of the Oxazolidinone class; it works by inhibiting the initiation of protein synthesis on bacterial ribosomes. Due to its excellent bioavailability after oral dosing, it has become an important tool in combating multi-drug-resistant bacteria including glycopeptide-resistant enterococci and methicillin-resistant Staphylococcus aureus. Side effects are multiple and potentially serious. We report the case of an 87-year-old man who developed pancytopenia secondary to a 6-week course of linezolid. Withdrawal of the antibiotic was decided as the treatment and resolution of the pancytopenia was evident within 2 weeks. Clinicians should be aware of this side effect of linezolid therapy and that weekly full blood count monitoring is paramount.

https://ift.tt/2AeJSWV

Calvarial osteomyelitis and intracranial extension post-Mohs micrographic surgery

Mohs micrographic surgery (MMS) is a specialised micrographic technique used for the treatment of locally invasive skin cancers. Despite being a relatively low risk surgery, the overall complication rates range between 1.6% and 3%. Common complications include postoperative haemorrhage, haematoma formation, wound infection, wound dehiscence and flap/graft necrosis. Osteomyelitis after dermatological cancer surgery is exceedingly rare. There have only been two cases of osteomyelitis in association with Mohs surgery reported in the literature to date. Here, we describe an epidemiologically atypical patient who initially presented with fever and altered mental status and later found to have calvarial osteomyelitis, intracranial abscess (empyema) and meningoencephalitis as a result of Mohs surgery. Although rare, it is a predictable side effect postsurgery, and prevention of such complications are critical to decrease morbidity and mortality in patients undergoing MMS.

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Neurogenic pulmonary oedema complicating a lateral medullary infarct

Neurogenic pulmonary oedema (NPO) is a rare clinical syndrome of pulmonary oedema occurring secondary to an insult of the central nervous system (CNS). The exact aetiology of this disorder is unknown. NPO can be fatal and poor awareness and identification of this entity, particularly in terms of misdiagnosis as primary pulmonary or cardiac disease, can result in suboptimal management and outcomes. We describe the presentation and management of a 68-year-old woman with an acute left lateral medullary stroke complicated by pulmonary oedema. The likely aetiology is discussed, and important learning points are highlighted.

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Symptomatic pulmonary restriction secondary to diaphragmatic eventration and megacolon in adult

Description 

A 70-year-old woman with a medical history significant for toxic megacolon secondary to Clostridium difficile infection treated 40 years prior with partial colectomy and known diaphragmatic eventration presents with a 3-day history of progressive shortness of breath and dyspnoea on exertion. The patient had never previously been symptomatic nor suffered blunt trauma and had a strong personal conviction to avoid surgery. CT imaging revealed a massive left diaphragmatic displacement containing spleen, stomach and colon with mediastinal shift, compression of the left lung and a pericardial effusion (figure 1). Due to persistent tachycardia and presence of pericardial effusion on CT, a transthoracic echocardiogram was obtained, which demonstrated a large pericardial effusion concerning for tamponade physiology. The patient developed supraventricular tachycardia for which cardiology was consulted and two doses of adenosine were administered with resolution. The patient was upgraded to surgical intensive care and taken to the operating...

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Vessel wall enhancement by gadolinium-enhanced MRI in a patient with delayed stenosis after mechanical thrombectomy

Description 

Delayed stenosis of targeted vessels is a reported complication of stent retriever-based mechanical thrombectomy.1 We report a case of delayed stenosis with MRI findings that may be related to the underlying stenotic mechanism.

A 46-year-old woman was brought to our hospital with sudden left hemiparesis and unilateral spatial neglect. MRI revealed occlusion of the right middle cerebral artery (MCA) and acute cerebral infarction (figure 1A,B). Emergent mechanical thrombectomy was performed with one stent retriever pass following two aspiration catheter passes, and a red thrombus was retrieved (figure 1C,D). We thought that an embolism had caused the vessel occlusion as no abnormalities were visualised at the occluded site on day 2 (figure 1E). Despite detailed examinations, we could not determine the embolic source during the patient's hospitalisation, so we administered low-dose aspirin. She was discharged on day 46.

https://ift.tt/2AeK0pn

Indapamide-induced bilateral choroidal effusion in pseudophakic patient.

We describe a case of indapamide-induced bilateral choroidal effusion, first time reported in pseudophakic patient, associated with no change in visual acuity and stable refraction.

A 70-year-old man was referred for ophthalmic assessment, with binasal visual field defect for 2 days. He had been started on treatment with indapamide 3 weeks earlier. His ophthalmic history included bilateral cataract surgery and intraocular lens implant. Fundal examination revealed bilateral choroidal effusions; B-scan ultrasonography was used to measure the extent of the choroidal detachment and the anterior chamber depth. Discontinuation of indapamide resulted in spontaneous resolution of choroidal effusion after 3 days. Our case is the first in the literature that describes bilateral choroidal effusion induced by indapamide in a pseudophakic patient. The lack of myopic shift likely resulted in a later presentation, enhancing the theory that lens thickening and/or accommodative spasm may play a crucial role in pathophysiology.

https://ift.tt/2OjKm0R

Spontaneous disenclavation of phakic intraocular iris claw lens

Description 

A 35-year-old male patient came to the outpatient department with sudden onset painless diminution of vision and diplopia in RE since last 3 days. The vision was 20/200 in the RE and 20/20 in the LE. The patient was a known case of myopia with history of phakic eye iris claw intraocular lens (IOL) of both eyes done 12 years back. There was no history of trauma. His best-corrected visual acuity in the right eye was 20/20 with –3DS, –0.50DC x 90 in the OD. The intraocular pressure in the OD was 13 mm Hg and 15 mm Hg in the OS. On slit lamp examination nasal disenclavation of the iris claw lens was noted, the edge of which was bisecting the non-dilated pupillary plane. The IOL was hanging inferiorly with the optic touching the corneal endothelium inferiorly and with the other end fixed at the 9 o'clock position (figure 1). The cornea...

https://ift.tt/2AaHalb

POEMS syndrome: diagnostic delay and successful treatment with lenalidomide, cyclophosphamide and prednisone followed by autologous peripheral stem cell transplantation

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare systemic disease, often unrecognised in the primary care setting. POEMS syndrome is associated with plasma cell dyscrasias and upregulation of vascular endothelial growth factor leading to systemic oedema, papilloedema and pulmonary hypertension. A wide constellation of presenting symptoms often leads to late diagnosis. Unrecognised and untreated disease rapidly leads to death from neuropathic exhaustion or cardiopulmonary failure. Treatment is extrapolated from other plasma cell dyscrasias such as multiple myeloma. Autologous peripheral blood stem cell transplantation (PBSCT) is often an important component of treatment. There is no established standard of care for POEMS syndrome. Therapies include lenalidomide, bortezomib and targeted monoclonal antibodies. We present a patient with POEMS syndrome who achieved rapid complete response to triple therapy consisting of lenalidomide, cyclophosphamide and prednisone, followed by high-dose chemotherapy and PBSCT.

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Book review—Rosai and Ackerman’s surgical pathology-2 volume set, 11th edition

https://ift.tt/2LqN5Yw

Consideraciones acerca de la interpretación de la escala de Zarit en cuidadores de pacientes con esquizofrenia

José Miguel Ribé Buitrón, Carles Pérez Téstor, Raquel Muros Guijarro, Cristina Nofuentes García
Aten Primaria.2018;50:443-4

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Julian Tudor Hart (1927-2018): referente mundial indiscutible de atención primaria

Joan Gené Badia, Amando Martín Zurro
Aten Primaria.2018;50:385-6

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Confiamos en nuestra fuerza

Yolanda Ortega Vila, Albert Casasa Plana
Aten Primaria.2018;50:387

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https://ift.tt/2mL31pK

El sistema sanitario, la atención primaria y la salud pública

Andreu Segura Benedicto
Aten Primaria.2018;50:388-9

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https://ift.tt/2Akx80G

Evaluación de los cuidados recibidos por pacientes con enfermedades crónicas

Leyre Adrián-Arrieta, Juan Manuel Casas Fernández de Tejerina
Aten Primaria.2018;50:390-7

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https://ift.tt/2mNzzzv

Actitudes sexistas y reconocimiento del maltrato en parejas jóvenes

Vanesa García-Díaz, Alberto Lana-Pérez, Ana Fernández-Feito, Carolina Bringas-Molleda, Luis Rodríguez-Franco, F. Javier Rodríguez-Díaz
Aten Primaria.2018;50:398-405

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https://ift.tt/2AeAvpV

Valoración desde atención primaria del manejo del hipertenso en atención especializada (estudio DERIVA-DOS)

Nieves Martell-Claros, Alberto Galgo Nafría, María Abad-Cardiel, Beatriz Álvarez-Álvarez, José Antonio García Donaire, Emilio Márquez-Contreras, Ángel Molino-González
Aten Primaria.2018;50:406-13

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Aplicación de la Escala de Tabaquismo para Atención Primaria (ETAP) en la práctica clínica

M.P. González Romero, F.J. Cuevas-Fernández, I. Marcelino-Rodríguez, V.J. Covas, M.C. Rodríguez Pérez, A. Cabrera de León, A. Aguirre-Jaime
Aten Primaria.2018;50:414-21

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https://ift.tt/2AeAouv

Prevalencia de hipovitaminosis D y factores asociados en la edad infantojuvenil

Teodoro Durá-Travé, Fidel Gallinas-Victoriano, María Jesús Chueca-Guindulain, Sara Berrade-Zubiri, Paula Moreno-Gónzalez, María Malumbres-Chacón
Aten Primaria.2018;50:422-9

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Utilidad y fiabilidad de la ecografía clínica abdominal en medicina familiar (2): grandes vasos, bazo, nefrourológica y ginecológica

Ignacio Manuel Sánchez Barrancos, Francisco José Guerrero García, María del Carmen Rico López, Vicente Fernández Rodríguez, Tomás Vegas Jiménez, Rafael Alonso Roca, Daniel Domínguez Tristancho
Aten Primaria.2018;50:430-42

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https://ift.tt/2AeAYsb

Asociación de diabetes respecto a variables sociodemográficas, hipertensión, hipercolesterolemia y enfermedad periodontal

Miguel Ángel Tapias Ledesma, Patricia Tapias Martínez, Leonor Martín-Pero Muñoz, Juan Carlos Muñoz García
Aten Primaria.2018;50:445-6

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Considerations on the effectiveness of educational strategies in outcomes related to workplace violence

Maiara Bordignon, Inês Monteiro
Aten Primaria.2018;50:446-7

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Picaduras de insecto diagnosticadas inicialmente como varicela

Daniel Morgado-Carrasco, Constanza Riquelme-Mc Loughlin, Pilar Iranzo
Aten Primaria.2018;50:448-9

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https://ift.tt/2AezBd1

mTOR Complex 1 Implicated in Aphid/Buchnera Host/Symbiont Integration

Obligate nutritional endosymbioses are arguably the most intimate of all interspecific associations. While many insect nutritional endosymbioses are well studied, a full picture of how two disparate organisms, a bacterial endosymbiont and a eukaryotic host, are integrated is still lacking. The mTOR pathway is known to integrate nutritional conditions with cell growth and survival in eukaryotes. Characterization and localization of amino acid transporters in aphids suggest the mTOR pathway as point of integration between an aphid host and its amino acid-provisioning endosymbiont Buchnera aphidicola. The mTOR pathway is unannotated in aphids and unstudied in any nutritional endosymbiosis. We annotated mTOR pathway genes in two aphid species, Acyrthosiphon pisum and Myzus persicae, using both BLASTp searches and Hidden Markov Models. Using previously collected RNAseq data we constructed new reference transcriptomes for bacteriocyte, gut, and whole insect tissue for three lines of M. persicae. Annotation of the mTOR pathway identified homologs of all known invertebrate mTOR genes in both aphid species with some duplications. Differential expression analysis showed that genes specific to the amino acid-sensitive mTOR Complex 1 were more highly expressed in bacteriocytes than genes specific to the amino acid-insensitive mTOR Complex 2. Almost all mTOR genes involved in sensing amino acids showed higher expression in bacteriocytes than in whole insect tissue. When compared to gut, the putative glutamine/arginine sensing transporter ACYPI000333, an ortholog of SLC38A9, showed 6.5 times higher expression in bacteriocytes. Our results suggest that the mTOR pathway may be functionally important in mediating integration of Buchnera into aphid growth and reproduction.

https://ift.tt/2OlRDxc

Transcriptome Analysis of Four Arabidopsis thaliana Mediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation

The Mediator complex is a central component of transcriptional regulation in Eukaryotes. The complex is structurally divided into four modules known as the head, middle, tail and kinase modules, and in Arabidopsis thaliana, comprises 28-34 subunits. Here, we explore the functions of four Arabidopsis Mediator tail subunits, MED2, MED5a/b, MED16, and MED23, by comparing the impact of mutations in each on the Arabidopsis transcriptome. We find that these subunits affect both unique and overlapping sets of genes, providing insight into the functional and structural relationships between them. The mutants primarily exhibit changes in the expression of genes related to biotic and abiotic stress. We find evidence for a tissue specific role for MED23, as well as in the production of alternative transcripts. Together, our data help disentangle the individual contributions of these MED subunits to global gene expression and suggest new avenues for future research into their functions.

https://ift.tt/2AfsMYX

BGGE: A New Package for Genomic-Enabled Prediction Incorporating Genotype x Environment Interaction Models

One of the major issues in plant breeding is the occurrence of genotype x environment (GE) interaction. Several models have been created to understand this phenomenon and explore it. In the genomic era, several models were employed to improve selection by using markers and account for GE interaction simultaneously. Some of these models use special genetic covariance matrices. In addition, the scale of multi-environment trials is getting larger, and this increases the computational challenges. In this context, we propose an R package that, in general, allows building GE genomic covariance matrices and fitting linear mixed models, in particular, to a few genomic GE models. Here we propose two functions: one to prepare the genomic kernels accounting for the genomic GE and another to perform genomic prediction using a Bayesian linear mixed model. A specific treatment is given for sparse covariance matrices, in particular, to block diagonal matrices that are present in some GE models in order to decrease the computational demand. In empirical comparisons with Bayesian Genomic Linear Regression (BGLR), accuracies and the mean squared error were similar; however, the computational time was up to five times lower than when using the classic approach. Bayesian Genomic Genotype x Environment Interaction (BGGE) is a fast, efficient option for creating genomic GE kernels and making genomic predictions.

https://ift.tt/2OoUN3k

Prognostic significance of tumor-infiltrating B cells and plasma cells in human cancer

There is abundant evidence that tumor-infiltrating CD8+ T cells contribute positively to anti-tumor immunity; however, the role of tumor-infiltrating B cells (TIL-B) and plasma cells (PC) remains controversial, leading to differing opinions about whether immunotherapies should be designed to enhance or inhibit these cells. Through a comprehensive PubMed search, we reviewed publications with cohorts of 50 or more cases in which the prognostic value of TIL-B/PC was assessed by immunohistochemistry and/or gene expression analysis. Sixty-nine studies representing 19 cancers met our review criteria. The large majority of studies assessed TIL-B by immunohistochemical detection of CD20. Of these, 50.0% reported a positive prognostic effect for CD20+ TIL-B, whereas the remainder found a neutral (40.7%) or negative (9.3%) effect. These differences in prognostic effect were not attributable to cancer type, other clinicopathological factors, or differing technical approaches. The prognostic significance of TIL-B/PC was generally concordant with that of CD3+ and/or CD8+ T cells, and the prognostic effect of T cells was generally stronger when TIL-B and/or PC were also present. Additionally, 21 studies inferred the presence of TIL-B/PC from gene expression data, and a large majority reported a positive prognostic effect. While more studies are required involving additional cancer types and independent patient cohorts, the weight of evidence supports a positive role for TIL-B and PC in anti-tumor immunity, suggesting that enhancement of these responses should be considered in the design of cancer immunotherapies.

https://ift.tt/2JVnUaY

Blocking monocytic myeloid-derived suppressor cell function via anti-DC-HIL/GPNMB antibody restores the in vitro integrity of T-cells from cancer patients

Purpose: Blocking the function of myeloid-derived suppressor cells (MDSCs) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL monoclonal antibody (mAb) as a MDSC-targeting cancer treatment. Experimental Design: Metastatic cancer patients (n=198) were analyzed by flow-cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/lo MDSCs. Their suppressor function was assessed by in vitro co-culture with autologous T-cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the anti-tumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice. Results: Metastatic cancer patients had high blood levels of DC-HIL+ MDSCs compared to healthy controls. Anti-DC-HIL mAb reversed the in vitro function in ~80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T cell-derived IFN- in co-cultures. DC-HIL is not expressed by colorectal cancer cells, but by CD14+ cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of pre-established colon tumors by reducing MDSCs and increasing IFN--secreting T-cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb. Conclusions: Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL+ MDSCs.

https://ift.tt/2LugEZr

Cancer-Specific and General Nutritional Scores and Cancer Risk: Results from the Prospective NutriNet-Sante Cohort

Several national and international authorities have proposed nutritional and lifestyle recommendations with the aim of improving health of the general population. Scores of adherence to these recommendations can be calculated at the individual level. Here, we investigated the associations between four nutritional scores and overall, breast, prostate, and colorectal cancer risk in a large prospective population-based cohort: the cancer-specific World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) score, the Alternate Healthy Eating Index 2010 (AHEI-2010), a score based on adherence to the Mediterranean diet (MEDI-LITE), and the French National Nutrition Health Program-Guideline Score (PNNS-GS). This study included 41,543 participants aged ≥40 years from the NutriNet-Santé cohort (2009–2017). A total of 1,489 overall incident cancers were diagnosed. A one-point increment of the WCRF/AICR score was significantly associated with decreased overall [12%; 95% confidence interval (CI), 8%–16%; P < 0.0001], breast (14%; 95% CI, 6%–21%; P = 0.001), and prostate (12%; 95% CI, 0%–22%; P = 0.05) cancer risks. Hazard ratio for colorectal cancer risk was 0.86 (95% CI, 0.72–1.03; P = 0.09). The PNNS-GS score was associated with reduced colorectal cancer risk (P = 0.04) and AHEI-2010 was associated with reduced overall cancer risk (P = 0.03). The WCRF/AICR score performed best. Compared with other tested scores, it included a stronger penalty for alcohol, which is a major risk factor for several cancer sites. Better adherence to nutritional recommendations, especially those designed for cancer prevention, could substantially contribute to decreased cancer incidence.Significance: This large prospective population-based cohort study suggests that following dietary recommendations such as the ones proposed by the World Cancer Research Fund/American Institute for Cancer Research could significantly contribute to cancer prevention. Cancer Res; 78(15); 1–9. ©2018 AACR.

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Pinnacle EMS Quick Take: Why transitions of care are an important patient safety opportunity

Transitions of care are critical opportunities to communicate patient assessment and treatment information to other healthcare providers

https://ift.tt/2JYTYut

Pinnacle EMS Quick Take: EMS leaders challenged ‘to make tomorrow better than today’

John O'Leary, a survivor of 100 percent TBSA burn as a child, delivered an inspiring opening keynote to Pinnacle EMS conference attendees

https://ift.tt/2mN4Fr4

Pinnacle EMS Quick Take: Why transitions of care are an important patient safety opportunity

Transitions of care are critical opportunities to communicate patient assessment and treatment information to other healthcare providers

https://ift.tt/2JYTYut

Use of 2017 ACC/AHA Guidelines Would Increase HTN Prevalence

THURSDAY, July 26, 2018 -- Adoption of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines would increase the proportion of 45- to 75-year-olds labeled as having hypertension in the United States...

https://ift.tt/2uSoG3B

CDC: Salmonella-Tainted Melon Outbreak Appears to Be Over

THURSDAY, July 26, 2018 -- A Salmonella outbreak linked to melons and fruit salad mixes appears to be over, say officials at the U.S. Centers for Disease Control and Prevention. As of July 24, 2018, 77 people have been sickened across nine states...

https://ift.tt/2LP2rlL

Canada Updates Guidelines for Hepatitis C Virus Infection

THURSDAY, July 26, 2018 -- A guideline published in the June 4 issue of CMAJ, the journal of the Canadian Medical Association, provides updated evidence-based recommendations for the treatment of patients with chronic hepatitis C virus (HCV)...

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Focused Ultrasound May Briefly Open Blood-Brain Barrier

THURSDAY, July 26, 2018 -- A new approach to getting drugs through the blood-brain barrier in Alzheimer's patients shows early promise, according to a study published online July 25 in Nature Communications. The research was published to coincide...

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Assessing, Improving Patient Satisfaction Cuts Malpractice Risk

THURSDAY, July 26, 2018 -- Assessing and improving patient satisfaction can help physicians avoid being sued for malpractice, according to an article published in Physicians Practice. Avoiding malpractice suits is important for physicians across...

https://ift.tt/2LBrdJn

Computerised working memory‐based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis

European Journal of Neuroscience, Volume 48, Issue 1, Page 1691-1705, July 2018.


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Outcomes for Anaplastic Glioma Treated With Radiation Therapy With or Without Concurrent Temozolomide

Objectives: Postoperative management of anaplastic glioma remains without a clear standard of care—in this study we report outcomes for patients treated with radiotherapy (RT) with and without temozolomide (TMZ). Materials and Methods: We identified 71 consecutive patients with World Health Organization grade III glioma treated with either RT alone or with concurrent TMZ (RT+TMZ), between 2000 and 2013. Tumor histology was anaplastic astrocytoma in 42 patients, anaplastic oligodendroglioma in 25 patients, and anaplastic oligoastrocytoma in 4 patients. In total, 26 patients received RT and 45 received RT+TMZ. Adjuvant TMZ was administered to 12/26 (46.1%) patients who received RT and 42/45 (93.3%) patients who received RT+TMZ. Time-to-event endpoints included progression-free survival (PFS) and overall survival (OS). Results: Kaplan-Meier estimates revealed that patients receiving RT+TMZ followed by adjuvant TMZ had improved PFS (P=0.04) and OS (P=0.02) as compared with those receiving RT followed by adjuvant TMZ. Cox proportional hazards multivariate analysis revealed improved PFS and OS with RT+TMZ for all patients (PFS: hazard ratio [HR]=0.42, P=0.02; OS: HR=0.41, P=0.03) and for anaplastic astrocytoma patients (PFS: HR=0.35, P=0.03; OS: HR=0.26, P=0.01), regardless of whether patients received further adjuvant TMZ. Conclusions: These findings support the use of RT+TMZ in the postoperative management of grade III glioma, and suggest that there is a benefit to concurrent RT+TMZ that is independent of adjuvant monthly TMZ. Further investigation is warranted, both to prospectively validate the benefit of RT+TMZ, as well as to determine if an additional benefit truly exists for adjuvant TMZ following concurrent RT+TMZ.

https://ift.tt/2A9DoIC

Adjuvant External Radiation Impacts Outcome of Pelvis-limited Stage III Endometrial Carcinoma: A Multi-institutional Study

Background: Adjuvant therapy choice for women with FIGO stage III endometrial carcinoma (EC) is controversial. We investigate the comparative benefit of adjuvant chemotherapy (CT) alone, radiation therapy alone (RT) or in combination (chemotherapy and radiation therapy [CRT]) with respect to recurrence-free survival (RFS) and overall survival (OS) in women with pelvis-limited (PL) EC (stage IIIA, IIIB, and IIIC1). Materials and Methods: A multi-institutional database of 270 surgically staged women with PLEC was analyzed. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. Results: Median RFS and OS were 112 and 130 months, respectively, for the full cohort. Adjuvant treatment was CT in 21%, RT in 27%, and CRT in 47%. Age, year of treatment, grade, histology, and adjuvant treatment were significantly associated with RFS and OS on univariate analysis. PLEC patients receiving CT alone fared worse in terms of RFS (P=0.07 relative to RT and

https://ift.tt/2Abrkqu

Adjuvant Radiotherapy Versus Wait-and-See Strategy for Pathologic T3 or Margin-Positive Prostate Cancer: A Meta-Analysis

Objective: To conduct a meta-analysis of the randomized controlled trials (RCTs) comparing adjuvant radiotherapy (ART) to wait-and-see (WS) strategy in pathologic T3 or margin-positive prostate cancer. Methods: A comprehensive EMBASE, MEDLINE, https://ift.tt/1eXFYvm, and Cochrane Library search for RCTs of ART versus WS was done. Results were synthesized for metastasis-free, biochemical progression-free, clinical progression-free, hormone-free, and overall survival as well as gastrointestinal (GI) and genitourinary (GU) toxicities. Either random-effects model or fixed-effects model were used based on the test of heterogeneity. Results: Three RCTs (EORTC22911, SWOG8794, ARO96-02/AUO-AP09/95) were identified with 1737 patients. ART resulted in greater biochemical progression-free survival (hazard ratio [HR]=0.48, P

https://ift.tt/2mLgaPq

Appendix-derived Pseudomyxoma Peritonei (PMP): Molecular Profiling Toward Treatment of a Rare Malignancy

Objectives: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. Methods: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization). Results: Targeted sequencing of 47 genes detected variants in KRAS (81%), GNAS (74%), SMAD4 (16%), and ATM (16%). Mutations were found at low frequencies (n=1 to 2) in APC, BRAF, PIK3CA, MLH1, and TP53. GNAS and KRAS co-occurrence was found in 87%. Protein overexpression was found in epidermal growth factor receptor (83%), cyclooxygenase-2 (73%), cMET (63%), cKIT (58%), and platelet-derived growth factor receptor alpha (58%). Immune checkpoint expression was found in 36% (programmed cell death protein 1) and 18% (programmed death-ligand 1). Surrogate markers of cell proliferation were found at low rates (TLE3 23%, TOP2A 22%), consistent with the slow-growing biology of PMP. Phosophatase and tensin homolog was intact (wild type [100%]) and positive (immunohistochemistry [80%]). Patients exhibited stable microsatellite status and mismatch repair proficiency (93%). Importantly, multidrug resistance protein expression was elevated (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1), and irinotecan (TOPO1) chemosensitivities were detected at favorable rates: 93%, 87%, 77% and 65%, respectively. Conclusions: Molecular profiling by multiple platforms identified potential therapies for the nontargetable KRAS-mutated population. The role of cMET-targeted therapeutics and immune checkpoint inhibitors merits further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate efficacy to systemic treatment.

https://ift.tt/2A9Dz6K

Discord Among Radiation Oncologists and Urologists in the Postoperative Management of High-Risk Prostate Cancer

Objective: To query specialty-specific differences regarding postoperative radiotherapy (RT) for high-risk prostate cancer. Materials and Methods: Electronic mail survey of radiation oncologists (ROs) and urologists. We sought to maximize absolute response number to capture contemporary practice ethos. The outcome of interest was association between response and specialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression. Results: In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant radiotherapy (ART). ART or early salvage radiotherapy (SRT, with early SRT defined as that delivered at prostate-specific antigen

https://ift.tt/2AcAser

The Role of Radiotherapy in Early-stage Primary Diffuse Large B-Cell Lymphoma of the Waldeyer Ring: A Retrospective Cohort Study

Objectives: The role of radiotherapy (RT) in improving survival of patients with diffuse large B-cell lymphoma (DLBCL) of the Waldeyer ring (WR) remains controversial. Therefore, this retrospective cohort study aimed to determine the role of RT in the treatment of DLBCL of the WR as well as the effects of associated covariates. Materials and Methods: Patients (n=35) with stage I to II DLBCL of the WR who underwent treatment at our center between 1994 and 2010 were retrospectively investigated. All patients had histologic diagnosis and staging workup completed. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were analyzed. Variables with a P-value of 1 and age above 60 years were also found to negatively influence OS and EFS. Conclusions: RT was associated with improved OS and EFS in stage I to II DLBCL of the WR. Future prospective studies are required to confirm these findings.

https://ift.tt/2Abrk9Y

Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma

Objectives: Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. Materials and Methods: A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. Results: Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included. Multivariate analysis showed improved HPFS for PHP versus Y90 (P=0.004), PHP versus CE (P=0.02) but not for CE versus Y90. PFS was also significantly different: Y90 (54 d), CE (52 d), PHP (245 d), P=0.03. PHP treatment and lower tumor burden were significant predictors of prolonged PFS on multivariate analysis. Median OS from time of treatment was longest, but not significant, for PHP at 608 days versus Y90 (295 d) and CE (265 d), P=0.24. Only PHP treatment versus Y90 and lower tumor burden had improved OS on multivariate analysis (P=0.03, 0.03, respectively). Conclusions: HPFS and PFS were significantly prolonged in patients treated with PHP versus CE or Y90. Median OS in PHP patients was over double that seen in Y90 or CE patients but was significant only between PHP and Y90.

https://ift.tt/2Oi4tfK

Location and Grade of Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy After Negative Transrectal Ultrasound-guided Biopsy

Objectives: To determine the location and grade of prostate cancer diagnosed by transperineal template-guided mapping (TTMB) after negative transrectal ultrasound-guided (TRUS) biopsy. Materials and Methods: This analysis consisted of 1118 consecutive patients who underwent TTMB from January 2005 to August 2015. Eight hundred thirty-five underwent TTMB after at least 1 negative TRUS biopsy and 283 underwent TTMB as the first biopsy procedure. The study population was divided into cohorts based on the number of prior TRUS biopsy sessions (0, 1, 2, and ≥3). No patient underwent multiparametric magnetic resonance imaging. Differences in location and cancer grade detected on TTMB were evaluated as a function of the number of prior TRUS biopsies. Results: Of the 1118 patients, 679 were diagnosed with prostate cancer. This included 208, 325, 104, and 42 patients who underwent 0, 1, 2, and ≥3 prior TRUS biopsies. The incidence of cancer detection on TTMB decreased as the number of prior TRUS biopsies increased (73.5% vs. 62.4% vs. 51.7% vs. 37.2%, P

https://ift.tt/2AeKNXi

Suboptimal Compliance With National Comprehensive Cancer Network Melanoma Guidelines: Who Is at Risk?

Background: National Comprehensive Cancer Network (NCCN) melanoma treatment guidelines are based on best available literature. We evaluated NCCN excision margin and sentinel lymph node biopsy (SLNB) guideline adherence to identify patient populations at risk for suboptimal care. Methods: Retrospective review of prospectively maintained database of all patients who underwent operation for invasive melanoma from January 2005 to 2015. Results: In total, 865 patients underwent operation for 522 thin (60.3%), 268 intermediate-thickness (31.0%), and 75 thick (8.7%) melanomas. Tumor location was 349 extremity (40.4%), 348 trunk (40.2%), and 168 head/neck (19.4%). SLNB was performed in 422 patients (48.8%); 75 (17.8%) were positive, and 67 (15.9%) underwent therapeutic lymphadenectomy. A total of 154 lesions (17.8%) were ulcerated; 444 had mitotic rate ≥1 (51.3%). In total, 788 patients (91.1%) fulfilled both NCCN guidelines. Recommended surgical margins were achieved in 837 patients (96.8%) and SLNB was performed as appropriate in 806 patients (93.2%); 10 patients (1.2%) were deficient for both. Deficient margins and lack of SLNB were associated with increased invasion depth and head/neck location; deficient SLNB was associated with age 80 and above (P

https://ift.tt/2AiwBg6

Chemoradiation Versus Chemotherapy in Uterine Carcinosarcoma: Patterns of Care and Impact on Overall Survival

Objectives: Uterine carcinosarcoma (UCS) is a rare and aggressive cancer with poor survival. Our purpose was to evaluate the patterns-of-care and overall survival (OS) benefit of adjuvant chemoradiation (aCRT) compared with adjuvant chemotherapy (aCT) among UCS patients. Methods: A query was made in the National Cancer Database to identify patients with UCS diagnosed between 2004 and 2012. Factors predictive of OS were determined using univariate and multivariate Cox regression analysis, as well as Kaplan-Meier and log-rank analysis. Propensity-score matching was employed to decrease the potential influence of selection bias. Results: A total of 3538 patients were identified for analysis, consisting of 1787 patients (50.5%) receiving aCT and 1751 (49.5%) receiving aCRT. The median age of patients was 65 years. The majority of patients in our cohort were white (68.6%), on Medicare insurance (47.9%), with >5 cm tumor size (59.9%), and received a lymph node surgery (87.9%). The following factors were predictive of aCRT use: undergoing lymph node surgery (odds ratio, 1.59, P=0.01), and FIGO stage II (odds ratio, 1.71, P=0.01). Median survival for the aCT and aCRT groups was 24 months and 31.3 months, respectively. When compared with aCT alone, aCRT was associated with a benefit in OS on multivariate analysis (hazard ratio, 0.65, P

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Hepatotoxicity After Immune Checkpoint Inhibitor Therapy in Melanoma: Natural Progression and Management

Objective: To report the clinical features, treatment, and outcomes of patients with immune checkpoint inhibitor-induced hepatotoxicity. Patients and Methods: In this retrospective observational study, we identified patients with metastatic malignant melanoma seen in consultation and/or treated between March 2011 and March 2016. Hepatotoxicity was assessed using the Common Terminology Criteria for Adverse Events, v4.0. Results: Seventeen patients were identified as having any degree of hepatotoxicity by history (grade 1 to 4). Twelve of 17 were diagnosed after ipilimumab, 3 of 17 were diagnosed after pembrolizumab, and 2 of 17 after ipilimumab combined with nivolumab. Median time from first dose of immune therapy to hepatotoxicity was 52 days. Clinical symptoms were variable: asymptomatic, fatigue, myalgias, headache, abdominal pain, nausea, vomiting, confusion, and/or jaundice. Eight patients had concurrent adverse events including colitis, hypophysitis, pneumonitis, and/or rash. Immune therapy was discontinued in all patients except 3. The patients were most commonly treated with systemic corticosteroids such as prednisone. Immunosuppression was discontinued by taper over a median of 42 days; in 3 patients steroids had to be reinitiated based on clinical or laboratory worsening of liver tests. Normalization of liver tests was seen within a median of 31 days of immunosuppression initiation. One patient with grade 4 hepatotoxicity had normalization with the addition of cyclosporine. Conclusions: Melanoma patients treated with immune checkpoint inhibitors should be monitored regularly for hepatotoxicity. Treatment with discontinuation of therapy and initiation of corticosteroids is indicated with grade 3 or 4 hepatotoxicity. Cyclosporine may be beneficial in steroid-refractory hepatotoxicity.

https://ift.tt/2Ok8HDU

Third-line Salvage Chemotherapy for Recurrent Carcinoma of the Cervix is Associated With Minimal Response Rate and High Toxicity

Background: Metastatic and recurrent cervical cancer is rarely a curable disease. Systemic chemotherapy is typically recommended for treatment based on clinical trials in the first-line or second-line setting. Rare patients who progress through 2 salvage regimens will have the performance status, medical ability, and desire to continue cytotoxic therapy. For these patients, there are no data to provide effective counseling regarding expected response rates (RRs) and toxicities. We sought to review our experience with this patient population. Methods: A single institution review was performed of all patients treated for cervical cancer between January 1, 2000 and June 30, 2013. Eligible patients were those who received at least 3 unique salvage chemotherapy regimens following primary surgery or radiation. RRs, survival statistics and toxicities were evaluated. Results: Twenty-three of 710 (3.2%) patients treated for cervical cancer met eligibility criteria. Nineteen received 2 or more cycles of a third-line regimen and were assessed for response and progression-free survival. The remainder were included in analysis of overall survival and toxicity. The RR to third-line chemotherapy was 10% (1 complete, 1 partial). An additional 27% achieved stable disease. In total, 57% suffered a grade 3 or 4 toxicity. The progression-free survival from the beginning of third-line therapy was 3.8 months, and the overall survival was 7.4 months. Conclusions: Patients eligible to receive third-line chemotherapy for metastatic and recurrent cervical cancer can expect minimal benefit at the cost of significant toxicity. Quality of life considerations should be of paramount importance when counseling regarding the risks and benefits of further cytotoxic therapy.

https://ift.tt/2mLgaio

Impact of Concurrent Medication Use on Pancreatic Cancer Survival—SEER-Medicare Analysis

Objectives: Preclinical studies have suggested that non-antineoplastic medication use may impact pancreatic cancer biology. We examined the association of several medication classes on pancreatic cancer survival in a large medical claims database. Materials and Methods: Histologically confirmed pancreatic adenocarcinoma diagnosed between 2006 and 2009 were analyzed from the Surveillance, Epidemiology, and End Results-Medicare database with available part D data. Drug use was defined as having 2 prescriptions filled within 12 months of pancreatic cancer diagnosis. The following medication classes/combinations were analyzed: β-blocker, statin, insulin, metformin, thiazolidinedione, warfarin, heparin, β-blocker/statin, metformin/statin, and β-blocker/metformin. Multivariable Cox proportional hazard models adjusting for age, sex, race, stage at diagnosis, site of cancer, and Charlson comorbidity index were constructed to test the association between medication classes and overall survival. Results: A total of 13,702 patients were included in the study; median age 76 years, 42.5% males, 77.1% white. The most common anatomic site and stage at diagnosis were head of the pancreas (49.9%) and stage 4 (49.6%), respectively. Ninety-four percent of patients died in the follow-up period (median overall survival 5.3 mo). Multivariable Cox regression analysis showed that use of β-blockers, heparin, insulin, and warfarin were significantly associated with improved survival (P

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The Role of Definitive Radiotherapy in Craniopharyngioma: A SEER Analysis

Objective: Assess patterns of care in the management of craniopharyngioma, especially with respect to the use of radiation therapy (RT) alone (which has been understudied to date) as compared with gross total resection (GTR) and subtotal resection (STR) with adjuvant RT. Materials and Methods: The epidemiology, treatment modalities, and outcomes of patients with craniopharyngioma were studied using the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2012. Survival was compared between treatment groups using Kaplan-Meier analysis and log-rank tests. Results: In total, 1218 patients with craniopharyngioma were identified, with equal distribution across sex. There were bimodal incidence peaks, one 20 years old or below, and the other between 40 and 65 years. The majority of pediatric tumors with known histology were adamantinomatous type, which did not influence outcomes when adjusting for age (P=0.392). Overall survival/cause-specific death for patients that underwent RT, STR+RT, and GTR were not statistically different (P>0.05). There was improved survival between several modalities: RT only versus STR only (P=0.024), RT only versus observation (P=0.006), STR+RT versus observation (P=0.046), and GTR versus observation (P=0.046). Patients above 65 years old were more likely to undergo observation (P=0.002), with highest proportions of surgery (54%)/RT (21%) in the pediatric population. Multivariable analysis demonstrated that though age was associated with overall survival (P

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A Phase II Study of Ganetespib as Second-line or Third-line Therapy for Metastatic Pancreatic Cancer

Objectives: Heat shock protein 90 regulates multiple signaling proteins involved in key pathways of pancreatic cancer pathogenesis. Ganetespib binds to heat shock protein 90 and interferes with its binding to client proteins thus leading to inactivation and degradation of the signaling proteins that promote cancer progression. This phase II study was designed to evaluate the efficacy of ganetespib in patients with refractory metastatic pancreatic cancer (rMPC). Methods: Patients with rMPC received 175 mg/m2 ganetespib intravenously once weekly for 3 weeks in 4-week cycles. Primary endpoint was disease control rate at 8 weeks, with a goal of 70%. Secondary endpoints were progression-free survival, overall survival, and safety. Simon's 2-stage design was used to assess futility and efficacy. Ganetespib was considered inactive if ≤8 patients among the first 15 treated had disease control after 8 weeks of treatment. Results: Fourteen patients were treated on study. Grade 3 treatment-related toxicities were diarrhea, abdominal pain, fatigue, nausea, vomiting, and hyponatremia. Disease control rate at 8 weeks was 28.6%, and median progression-free survival and overall survival were 1.58 months and 4.57 months, respectively. Early stopping rules for lack of clinical efficacy led to study closure. Conclusions: Single-agent ganetespib was tolerable with only modest disease control in rMPC. This disease is resistant to chemotherapy, and given the emerging data in lung and rectal cancers, as well as in pancreatic cancer cell lines, suggesting improved activity of ganetespib in combination with cytotoxic agents, studies combining this agent with chemotherapy in rMPC are more likely to yield success.

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Influence of Extent of Lymph Node Evaluation on Survival for Pathologically Lymph Node Negative Non–Small Cell Lung Cancer

Objectives: Despite previous retrospective reports that the number of lymph nodes resected at curative intent surgery for lung cancer correlates with overall survival (OS), no consensus exists regarding the minimal nor optimal number of lymph nodes to resect at curative lung cancer surgery. Methods: We studied subjects in the Surveillance Epidemiology and End Results Database (SEER) diagnosed with non–small cell lung cancer between 2000 and 2011 who underwent either lobectomy or pneumonectomy and had pathologic negative nodal evaluation. We excluded patients with sublobar resection and/or no lymph node evaluation. We examined associations between number of lymph nodes evaluated and OS/lung cancer-specific survival by multivariable Cox regression; and predictors of evaluation of more lymph nodes. Results: Among the 33,463 patients in our sample, a median of 7 lymph nodes were evaluated. We found that lung cancer-specific survival and OS improved with increasing lymph node evaluation up to 16 to 18 lymph nodes (hazard ratio, 0.77 [95% confidence interval, 0.70-0.85] and 0.78 [95% confidence interval, 0.72-0.86], respectively). There was little additional improvement in outcomes with evaluation of >16 to 18 lymph nodes. Blacks, Hispanics, females, and patients from distinct geographical regions were less likely to have 16 or more lymph nodes evaluated. Conclusions: There was a consistently increasing survival benefit associated with a more extensive lymph node evaluation at lung cancer resection, up to 16 to 18 lymph nodes removed. The median number of nodes evaluated was, however, only 7, suggesting that setting a goal of ≥16 examined lymph nodes may lead to improved survival outcomes, and reduce disparities in care.

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Anterolateral Retroperitoneal Psoas-Sparing (Anterior To Psoas: ATP) Lumbar Interbody Fusion for Degenerative Spine and Adult Deformity: Surgical Technique and The Evidence

Publication date: Available online 26 July 2018

Source: Seminars in Spine Surgery

Author(s): Chadi Tannoury, Tony Tannoury

ABSTRACT

Corrective multilevel spinal surgeries are notorious for high complication rate. In effort to reduce morbidities, various minimally invasive surgical techniques have been described. Posterior interbody fusions, while familiar to most surgeons, are limited in their ability to address multilevel pathology. Contrastingly, anterior lumbar fusion is effective in correcting multilevel deformities, yet it is notorious for vascular injuries and often warrants the assistance of an exposure surgeon. Moreover, the attractive lateral transpsoas approach has been associated with catastrophic neurovascular and visceral complications. Therefore, a novel retroperitoneal anterolateral psoas sparing access will be presented as a promising alternative to the preexisting techniques.

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Sexual orientation-related disparities in employment, health insurance, healthcare access and health-related quality of life: a cohort study of US male and female adolescents and young adults

Objective

To investigate sexual orientation-related disparities in employment and healthcare, including potential contributions to health-related quality of life (HRQL).

Setting

Growing Up Today Study, a USA-based longitudinal cohort that began in 1996; predominantly composed of participants who are white and of middle-to-high socioeconomic positions.

Participants

9914 participants 18–32 years old at the most recent follow-up questionnaire.

Primary outcome measure

In 2013, participants reported if, in the last year, they had been unemployed, uninsured or lacked healthcare access (routine physical exam). Participants completed the EQ-5D-5L, a validated, preference-weighted measurement of HRQL. After adjusting for potential confounders, we used sex-stratified, log-binomial models to calculate the association of sexual orientation with employment, health insurance and healthcare access, while examining if these variables attenuated the sexual orientation-related HRQL disparities.

Results

Sexual minority women and men were about twice as likely as their respective heterosexual counterparts to have been unemployed and uninsured. For example, the risk ratio (95% CI) of uninsured bisexual women was 3.76 (2.42 to 5.85) and of unemployed mostly heterosexual men was 1.82 (1.30 to 2.54). Routine physical examination was not different across sexual orientation groups (p>0.05). All sexual minority subgroups had worse HRQL than heterosexuals (p<0.05) across the five EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Controlling for employment and health insurance did not substantially attenuate the existing sexual orientation-related HRQL disparities.

Conclusions

Research on sexual orientation-related disparities in employment and healthcare has often been limited to comparisons between cohabitating different-sex and same-sex adult couples, overlooking sexual minority subgroups (eg, bisexuals vs lesbians), non-cohabitating populations and young people. Less is known about sexual orientation-related disparities in HRQL including potential contributions from employment and healthcare. The current study documents that disparities in employment, health insurance and various HRQL dimensions are pervasive across sexual minority subgroups, non-cohabitating couples and youth in families of middle-to-high socioeconomic positions.

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L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile

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Primary Care Provider Practice Patterns and Barriers to Hepatocellular Carcinoma Surveillance

Low rates of hepatocellular carcinoma (HCC) surveillance are primarily due to provider-related process failures. However, few studies have evaluated primary care provider (PCP) practice patterns, attitudes, and barriers to HCC surveillance at academic tertiary care referral centers.

https://ift.tt/2OjIfdt

Risk of Colorectal Cancer in Patients with Acute Diverticulitis: a Systematic Review and Meta-Analysis of Observational Studies

We performed a systematic review and meta-analysis to assess the prevalence of colorectal cancer in patients with acute diverticulitis.

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Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study

Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most have been of insufficient size to identify heterogeneous associations with precision.

https://ift.tt/2OjIdST

Early Initiation of Tumor Necrosis Factor Antagonist-based Therapy for Patients with Crohn’s Disease Reduces Costs Compared With Late Initiation

Antagonists of tumor necrosis factor (TNF) are effective for induction and maintenance of remission of Crohn's disease (CD) and are generally prescribed when patients do not respond to conventional, less costly medical therapies. Early initiation of anti-TNF therapy reduced rates of surgery and dose escalation due to loss of response. However, these drugs are expensive, so studies are needed on the cost effectiveness of early initiation. We aimed to determine the cost effectiveness of initiating treatment early in the disease course (within 2 years of CD diagnosis) vs later in the disease course (more than 2 years after diagnosis).

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Role of immunotherapy in kidney cancer

Purpose of review To summarize current knowledge on promising immunotherapeutic agents and to provide a brief outline of current use of immunotherapeutic agents in patients with locally advanced or metastatic renal cell carcinoma (RCC). Recent findings Immunotherapy with mAbs directed against programed death cell protein 1, programed death-ligand 1 (PD-L1) and cytotoxic T-Lymphocyte Antigen 4 has become new first-line standard of care for moderate and poor-risk metastatic RCC patients. Similarly, the combination immune-oncology treatment and vascular endothelial growth factor (VEGF) mAbs also showed promising results in first-line therapy despite relative data immaturity. Finally, immune-oncology monotherapy (nivolumab) already represents second or third-line standard of care after tyrosine kinase inhibitor failure. Summary Combination immune-oncology therapy represents the standard of care for management of intermediate-to-poor risk clear cell metastatic RCC. In addition, combination of immune-oncology and anti-VEGF antibody represents a treatment option across all risk levels in patient with elevated PD-L1 expression. Finally, nivolumab is one of two ideal treatment options in second-line clear cell metastatic RCC patients. Correspondence to Sebastiano Nazzani, MD, Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Piazza Malan 1, San Donato Milanese, Italy. Tel: +39 3356274997; e-mail: sebastiano.nazzani@yahoo.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2FWWEea). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson’s disease

Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease

Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease, Published online: 26 July 2018; doi:10.1038/s41419-018-0848-7

Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease

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Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1

Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1

Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1, Published online: 26 July 2018; doi:10.1038/s41419-018-0868-3

Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1

https://ift.tt/2LEAUqs

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells, Published online: 26 July 2018; doi:10.1038/s41419-018-0854-9

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

https://ift.tt/2LzYCEj

Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity

Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity

Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity, Published online: 26 July 2018; doi:10.1038/s41419-018-0875-4

Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity

https://ift.tt/2LSNgIj

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer's disease

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer's disease, Published online: 26 July 2018; doi:10.1038/s41419-018-0886-1

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer's disease

https://ift.tt/2NNUEVR

Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells

Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells

Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells, Published online: 26 July 2018; doi:10.1038/s41419-018-0811-7

Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells

https://ift.tt/2uRhsNs

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways, Published online: 26 July 2018; doi:10.1038/s41419-018-0788-2

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

https://ift.tt/2LSAlpR

Familial Waldenström Macroglobulinemia

Familial clustering of Waldenström macroglobulinemia (WM) has been observed for nearly 6 decades. Family studies have provided seminal observations in delineating the phenotypic spectrum of WM susceptibility and confirming the importance of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (IgM MGUS) as a precursor condition for WM, providing the rationale for large population-based epidemiologic studies of IgM MGUS and WM, and providing both the basis and the material for ongoing genetic studies aimed at identifying WM predisposition genes. Together, these investigations may help elucidate the host factors underlying WM development.

https://ift.tt/2JZe7k7

Blocking cyclin-dependent kinase 4/6 during single dose vs. fractionated radiation therapy leads to opposite effects on acute gastrointestinal toxicity in mice

Pharmacological inhibition of CDK4/6 using palbociclib before a single dose of radiation ameliorates the GI-ARS, but it exacerbates the GI-ARS when given before and during fractionated radiation.

https://ift.tt/2LHwLSv

Patient and dosimetric predictors of genitourinary and bowel quality of life after prostate SBRT: Secondary analysis of a multi-institutional trial

We investigated associations between dosimetric parameters and quality of life (QOL) in patients treated with prostate SBRT on a prospective phase II trial. Rectal doses (e.g. Dmax) were significantly associated with decreased bowel QOL at both 1 month and 2 years. Patients with rectum Dmax greater than the median 37.4 Gy were more likely to have bowel symptoms at 2 years. Patient factors, but not bladder or urethral doses, were associated with urinary QOL.

https://ift.tt/2NPLs3w

Choosing the right through-the-scope clip: a rigorous comparison of rotatability, whip, open/close precision, and closure strength (with videos)

Many new through-the-scope (TTS) clips are available, and physicians often select clips based on physical characteristics and/or cost However, functional profiles may be equally important and have not been methodically assessed. We evaluated 5 commercially available clips: Resolution 360, Instinct, Quick Clip Pro, Dura Clip, and SureClip.

https://ift.tt/2mJE3qF

Calcium-rich foods that vegans can eat

Calcium provides many health benefits. Some people who are vegan, lactose intolerant, or who do not consume dairy products for other reasons wonder how to add more calcium to their diets. In this article, we describe the 18 best nondairy sources of this vital nutrient.

https://ift.tt/2v8P0Gh

Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin B12 Metabolism: Case Reports and Literature Review

We describe 2 children with cobalamin G disease, a disorder of vitamin B12 metabolism with normal serum B12 levels. They presented with megaloblastic anemia progressing rapidly to severe thrombotic microangiopathy. In infants presenting with acute thrombotic microangiopathy, cobalamin disorders should be considered early as diagnosis and targeted treatment can be lifesaving.

https://ift.tt/2A9JPeV

Ability to Identify Genuine Laughter Transcends Culture

People across cultures and continents are largely able to tell the difference between a fake laugh and a real one, according to research published in Psychological Science, a journal of the Association for Psychological Science.

For almost a decade, UCLA researcher Greg Bryant has studied the nature of laughter — and what it reveals about the evolution of human communication and cooperation. His latest study builds on a 2014 study he led indicating that people can discern when a laugh is genuine.

Working with the knowledge that laughter is a powerful and universal human "play signal" that allows people to predict behavior and affinity, Bryant and his coauthors expanded their previous research to include 884 study participants from the U.S. and 20 other countries, representing six continents.

For real laughter, researchers extracted laughs from recorded conversations between pairs of English-speaking, female friends. For the fake laughs, they took laughter produced by women who were asked to laugh on command. The recordings were edited for length and volume and played in random order to the study participants.

Across all societies, listeners were able to tell better than chance whether a laugh was "real" or "fake." But there was some variation. For example, Samoan listeners only got the right answer 56% of the time whereas Japanese listeners were able to get the correct answer 69% of the time.

Participants from smaller, less industrialized societies were more accurate in identifying fake laughs. Bryant said the result suggests that in places where deep and complex social relationships are critical to survival, people are more attuned to the emotional engagement of others, and more likely to use those signals to predict other people's behavior.

Can you identify which laughs are real? Check your answers below.





Bryant said volitional laughter and spontaneous laughter originate from different vocal production systems and have distinct acoustic features.

"We chose to use the words 'real' and 'fake' in our research because it taps into people's intuition," Bryant said. "Technically, all laughs are real — they are just produced by different vocal systems. We wanted to test whether or not this distinction is clear around the world."

Previous research by Bryant and others has found that real, spontaneous laughter has certain identifying qualities. During spontaneous laughter, the emotional vocal system produces qualities that signal "arousal" — higher pitch and volume, as well as faster bursts of non-articulate sounds and more non-tonal noise. These sounds carry subtle clues that a laugh is authentic.

On the other hand, volitional laughter is produced by a system in the brain that controls the tongue and lips, our instruments of speech.

"The specific brain circuit that controls our vocal organs has an imitative capacity," Bryant said. "With your speech system, you can make a lot of different noises, including crying, or laughter or a pain shriek. That's where volitional laughter comes from. Fake laughter is going to sound more like speech, and real laughter is not going to sound as much like speech."

Humans aren't the only animals that exhibit play vocalizations, Bryant said. But people are unique in using speech to mimic those spontaneous vocalizations.

Genuine laughter is perceived as a prosocial signal — an honest expression of affiliation, researchers believe. But, according to the paper, even fake laughter can be construed as a polite cooperative signal, especially in highly industrialized societies where anonymous interpersonal interactions informed by social status are common.

Another recent study Bryant conducted showed that people from around the world can tell when two people laughing together are friends or not, thanks to differences in the acoustic properties of laughter between friends versus laughter between strangers. And another recent project, yet to be published, has found that infants as young as 5 months old are attuned to these differences.

Collectively, Bryant's research suggests that humans have a sophisticated sensitivity to acoustic features that indicate emotional arousal, and that this skill serves a valuable evolutionary function in interpersonal cooperation.

In future research, Bryant hopes to study the sound of laughter across languages and cultures.

"We know people perceive laughter quite similarly across cultures," he said. "But we'd like to know more about how similar laughter sounds might be when produced by speakers of different languages."

All data have been made publicly available via Harvard Dataverse.

Want to know which of the tracks above contain real laughs? Answer: Laughs 1 and 2 are spontaneous, or "real." Laughs 3 and 4 are volitional, or "fake."

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