Engineered Paper-Based Cell Culture Platforms

Abstract

Paper is used in various applications in biomedical research including diagnostics, separations, and cell cultures. Paper can be conveniently engineered due to its tunable and flexible nature, and is amenable to high-throughput sample preparation and analysis. Paper-based platforms are used to culture primary cells, tumor cells, patient biopsies, stem cells, fibroblasts, osteoblasts, immune cells, bacteria, fungi, and plant cells. These platforms are compatible with standard analytical assays that are typically used to monitor cell behavior. Due to its thickness and porous nature, there are no mass transport limitations to/from the cells in paper scaffolds. It is possible to pattern paper in different scales (micrometer to centimeter), generate modular configurations in 3D, fabricate multicellular and compartmentalized tissue mimetics for clinical applications, and recover cells from the scaffolds for further analysis. 3D paper constructs can provide physiologically relevant tissue models for personalized medicine. Layer-by layer strategies to assemble tissue-like structures from low-cost and biocompatible paper-based materials offer unique opportunities that include understanding fundamental biology, developing disease models, and assembling different tissues for organ-on-paper applications. Paper-based platforms can also be used for origami-inspired tissue engineering. This work provides an overview of recent progress in engineered paper-based biomaterials and platforms to culture and analyze cells.

Engineered paper-based cell culture platforms have been shown to be particularly promising for health diagnostics, tissue engineering, and personalized medicine. Here, a comprehensive overview of engineered paper-based biomaterials and platforms to culture and analyze cells is provided.

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Should We Manage All Septic Patients Based on a Single Definition? An Alternative Approach

No abstract available

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Twenty-Four-Hour Intensivist Staffing Is Not Beneficial for Patients

No abstract available

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Outcomes of Ventilated Patients With Sepsis Who Undergo Interhospital Transfer: A Nationwide Linked Analysis

Objectives: The outcomes of critically ill patients who undergo interhospital transfer are not well understood. Physicians assume that patients who undergo interhospital transfer will receive more advanced care that may translate into decreased morbidity or mortality relative to a similar patient who is not transferred. However, there is little empirical evidence to support this assumption. We examined country-level U.S. data from the Nationwide Readmissions Database to examine whether, in mechanically ventilated patients with sepsis, interhospital transfer is associated with a mortality benefit. Design: Retrospective data analysis using complex survey design regression methods with propensity score matching. Setting: The Nationwide Readmissions Database contains information about hospital admissions from 22 States, accounting for roughly half of U.S. hospitalizations; the database contains linkage numbers so that admissions and transfers for the same patient can be linked across 1 year of follow-up. Patients: From the 2013 Nationwide Readmission Database Sample, 14,325,172 hospital admissions were analyzed. There were 61,493 patients with sepsis and on mechanical ventilation. Of these, 1,630 patients (2.7%) were transferred during their hospitalization. A propensity-matched cohort of 1,630 patients who did not undergo interhospital transfer was identified. Interventions: None. Measurements and Main Results: The exposure of interest was interhospital transfer to an acute care facility. The primary outcome was hospital mortality; the secondary outcome was hospital length of stay. The propensity score included age, gender, insurance coverage, do not resuscitate status, use of renal replacement therapy, presence of shock, and Elixhauser comorbidities index. After propensity matching, interhospital transfer was not associated with a difference in in-hospital mortality (12.3% interhospital transfer vs 12.7% non–interhospital transfer; p = 0.74). However, interhospital transfer was associated with a longer total hospital length of stay (12.8 d interquartile range, 7.7–21.6 for interhospital transfer vs 9.1 d interquartile range, 5.1–17.0 for non–interhospital transfer; p

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Safety and Feasibility of Early Physical Therapy for Patients on Extracorporeal Membrane Oxygenator: University of Maryland Medical Center Experience

Objectives: To examine the feasibility and safety of mobilizing patients while on extracorporeal membranous oxygenation support. Design: Retrospective cohort study. Setting: Medical and Surgical ICUs in a large tertiary care hospital in the United States. Patients: Adults supported on extracorporeal membranous oxygenation from January 2014 to December 2015. Measurements and Main Results: We reviewed the medical records from physical therapy, perfusion, and intensivists to obtain the number and type of physical therapy interventions and discharge status; extracorporeal membranous oxygenation type and description of support, cannulation sites; and risk management details of adverse effects, if any. Of 254 patients supported on extracorporeal membranous oxygenation, 167 patients (66.7%) received a total of 607 physical therapy sessions while on extracorporeal membranous oxygenation support. In this cohort, 134 patients (80.2%) had at least one femoral cannula during physical therapy intervention. Sixty-six of the 167 patients (39.5%) were supported on extracorporeal membranous oxygenation with bifemoral cannulas, and 44 (26.3%) were on veno-arterial extracorporeal membranous oxygenation. A dual lumen catheter was only used in five cases. Twenty-five patients (15%) (13 bifemoral cases) participated in standing or ambulation activities. Seventy-five patients (68.8%) who were successfully weaned from extracorporeal membranous oxygenation were discharged to a rehabilitation facility; 26 patients (23.8%) went home. Three minor events (

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Significance of Mini Bronchoalveolar Lavage Fluid Amylase Level in Ventilator-Associated Pneumonia: A Prospective Observational Study

Objectives: Aspiration of oropharyngeal or gastric contents in intubated patients can lead to ventilator-associated pneumonia. Amylase in respiratory secretion has been reported as a possible marker of aspiration. We studied whether elevated α-amylase in mini bronchoalveolar lavage specimens can be suggestive of ventilator-associated pneumonia in intubated patients with high clinical suspicion. Design: Prospective single-center observational study. Setting: Department of Critical Care Medicine, tertiary care academic institute. Patients: Adult patients on mechanical ventilation for more than 48 hours with with clinically suspected ventilator-associated pneumonia as per defined criteria, admitted between December 2014 and May 2016. Methods: Mini bronchoalveolar lavage samples were collected within 72 hours of endotracheal intubation. Samples were sent for α-amylase level assay and quantitative culture. Ventilator-associated pneumonia was confirmed from mini bronchoalveolar lavage microbial culture of greater than or equal to 104 cfu/mL, and patients were divided into ventilator-associated pneumonia and no ventilator-associated pneumonia groups. Pre- and postintubation risk factors for aspiration were also noted. Results: The prevalence of ventilator-associated pneumonia was 64.9% among 151 patients in whom it was clinically suspected. Median (interquartile range) mini bronchoalveolar lavage α-amylase levels in ventilator-associated pneumonia and no ventilator-associated pneumonia groups on the day of study inclusion were 287 U/L (164–860 U/L) and 94 U/L (59–236 U/L), respectively (p

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Development and Validation of an Abbreviated Questionnaire to Easily Measure Cognitive Failure in ICU Survivors: A Multicenter Study

Objectives: To develop and validate an abbreviated version of the Cognitive Failure Questionnaire that can be used by patients as part of self-assessment to measure functional cognitive outcome in ICU survivors. Design: A retrospective multicenter observational study. Setting: The ICUs of two Dutch university hospitals. Patients: Adult ICU survivors. Interventions: None. Measurements and Main Results: Cognitive functioning was evaluated between 12 and 24 months after ICU discharge using the full 25-item Cognitive Failure Questionnaire (CFQ-25). Incomplete CFQ-25 questionnaires were excluded from analysis. Forward selection in a linear regression model was used in hospital A to assess which of the CFQ-25 items should be included to prevent a significant loss of correlation between an abbreviated and the full CFQ-25. Subsequently, the performance of an abbreviated Cognitive Failure Questionnaire was determined in hospital B using Pearson's correlation. A Bland-Altman plot was used to examine whether the reduced-item outcome scores of an abbreviated Cognitive Failure Questionnaire were a replacement for the full CFQ-25 outcome scores. Among 1,934 ICU survivors, 1,737 were included, 819 in hospital A, 918 in hospital B. The Pearson's correlation between the abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14) and the CFQ-25 was 0.99. The mean of the difference scores was –0.26, and 95% of the difference scores fell within +5 and –5.5 on a 100-point maximum score. Conclusions: It is feasible to use the abbreviated CFQ-14 to measure self-reported cognitive failure in ICU survivors as this questionnaire has a similar performance as the full CFQ-25. 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 (http://ift.tt/29S62lw). This work was performed at Radboud university medical center and University Medical Centre Utrecht. Drs. Wassenaar, de Reus, Donders, Schoonhoven, Pickkers, and van den Boogaard contributed in study concept and design. Drs. Cremer, van Dijk, de Lange, Slooter, and van den Boogaard contributed in acquisition of data. Drs. Wassenaar, de Reus, and Donders contributed in statistical analysis. Drs. Wassenaar, de Reus, and van den Boogaard contributed in analysis and interpretation of data. Drs. Wassenaar and de Reus contributed in drafting of the article. Drs. Donders, Schoonhoven, Cremer, de Lange, van Dijk, Slooter, Pickkers, and van den Boogaard contributed in critical revision of the article for important intellectual content. Drs. Pickkers and van den Boogaard contributed in study supervision. Dr. Schoonhoven contributed to study cosupervision. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Mark.vandenBoogaard@radboudumc.nl Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Association between serious psychological distress and nonparticipation in cancer screening and the modifying effect of socioeconomic status: Analysis of anonymized data from a national cross-sectional survey in Japan

BACKGROUND

It is unclear whether individuals who have serious psychological distress (SPD) are less likely to participate in screening tests for gastric cancer, lung cancer, and other types of cancer. Of the few studies that have examined the association between SPD and participation in cancer screening, none have reported modifying effects of educational, marital, or employment status.

METHODS

The authors analyzed a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan., including individuals aged <69 years who met the national program criteria for each type of cancer screening (colorectal, gastric, and lung cancers, n = 29,926; breast cancer, n = 15,423; and cervical cancer, n = 24,735). SPD was defined as a score of 13 or greater on the Kessler 6 scale. Logistic regression analyses were conducted to examine the association between SPD and participation in cancer screening, and multivariate analyses stratified by socioeconomic status also were conducted.

RESULTS

SPD was significantly associated with a lower odds ratio (OR) for participation in screening for colorectal cancer (OR, 0.743; 95% confidence interval [CI], 0.638-0.866), gastric cancer (OR, 0.823; 95% CI, 0.717-0.946), and lung cancer (OR, 0.691; 95% CI, 0.592-0.807). Only educational status significantly modified the effect of SPD on participation in these 3 types of cancer screening (P < .05).

CONCLUSIONS

Individuals with SPD, especially those with lower education levels, were less likely to participate in screening for colorectal, gastric, and lung cancers. Individuals with SPD should be encouraged and supported to participate in cancer screening tests. Cancer 2017. © 2017 American Cancer Society.

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Randomised clinical trial: yoga vs a low-FODMAP diet in patients with irritable bowel syndrome

Summary

Background

Irritable bowel syndrome is the most frequent gastrointestinal disorder. It is assumed that lifestyle interventions might be a rational treatment approach.

Aim

To examine the effect of a yoga-based intervention vs a low-FODMAP diet on patients with irritable bowel syndrome.

Methods

Fifty-nine patients with irritable bowel syndrome undertook a single-blind, randomised controlled trial involving yoga or a low-FODMAP diet for 12 weeks. Patients in the yoga group received two sessions weekly, while patients in the low-FODMAP group received a total of three sessions of nutritional counselling. The primary outcome was a change in gastrointestinal symptoms (IBS-SSS). Secondary outcomes explored changes in quality of life (IBS-QOL), health (SF-36), perceived stress (CPSS, PSQ), body awareness (BAQ), body responsiveness (BRS) and safety of the interventions. Outcomes were examined in weeks 12 and 24 by assessors "blinded" to patients' group allocation.

Results

No statistically significant difference was found between the intervention groups, with regard to IBS-SSS score, at either 12 (Δ = 31.80; 95%CI = −11.90, 75.50; P = .151) or 24 weeks (Δ = 33.41; 95%CI = −4.21, 71.04; P = .081). Within-group comparisons showed statistically significant effects for yoga and low-FODMAP diet at both 12 and 24 weeks (all P < .001). Comparable within-group effects occurred for the other outcomes. One patient in each intervention group experienced serious adverse events (P = 1.00) and another, also in each group, experienced nonserious adverse events (P = 1.00).

Conclusions

Patients with irritable bowel syndrome might benefit from yoga and a low-FODMAP diet, as both groups showed a reduction in gastrointestinal symptoms. More research on the underlying mechanisms of both interventions is warranted, as well as exploration of potential benefits from their combined use.

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Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma

Abstract

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OS—progression-free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression-free at 24 months post-ASCT (26 who died without disease progressions within 24 months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P = 0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9–30.2; P < 0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30 months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P < 0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.

Disease progression within 2 years and absence of CR at 30 months post-ASCT define new high-risk groups who should be ideally identified soon in order to be offered different therapeutic strategies, such as allogenic stem cell transplantation or novel drugs.

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Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer

Abstract

Few studies have been designed to investigate the incidence of postoperative pneumonia after radical gastrectomy and its effect on prognosis of these patients. Incidences of postoperative pneumonia after radical gastrectomy in our department between January 1996 and December 2014 were summarized. Their effects on prognosis were retrospectively analyzed using survival curves and Cox regression. A total of 5237 patients were included in this study, 767 (14.4%) of them had complications, including 383 cases of postoperative pneumonia (7.2%). The 5-year overall and disease-specific survival of patients with postoperative pneumonia were both lower than those without this complication (P < 0.001). Stratified analysis demonstrated that this difference existed in all Stage I, II, and III patients (log-rank, P < 0.05). Multivariate analysis revealed that age, neoadjuvant chemotherapy, tumor size, tumor stage, and postoperative pneumonia were independent risk factors for disease-specific survival. Postoperative pneumonia after radical gastrectomy is an independent risk factor for prognosis of gastric cancer patients, especially in stage III.

The study found that postoperative pneumonia after radical gastrectomy is an independent risk factor for prognosis of gastric cancer patients, especially in stage III. The prognoses of these pneumonic patients improve in the last decade.

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A Lumbosacral Plexopathy Compressed by Huge Uterine Myoma.

No abstract available

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Regional variation in the mechanical properties and fibre type composition of the rat extensor digitorum longus muscle

Abstract

Fibre type composition is heterogeneous and distribution varies spatially in many muscles, indicating there may be regional variation in recruitment and mechanical output. The rat extensor digitorum longus muscle is composed of predominantly fast-twitch fibres, and exhibits a gradient in phenotype, resulting in oxidative medial (areal composition 24.3% Type I/IIa) and glycolytic lateral (92.4% Type IIx/IIb) compartments. Here, we investigated the variation in mechanical performance between the medial and lateral compartments during isometric, isotonic and cyclical contractions. Isometric tetanic stress and force-velocity relationships were similar in both compartments, but isometric twitch kinetics were slower in the medial compared to the lateral compartment. The medial compartment also had a lower optimum cycle frequency for maximum net power generation (11 Hz vs. 15 Hz; P < 0.05) due to slower isometric kinetics, resulting in a lower level of activation and reduced net work generation at higher cycle frequencies, compared to the lateral compartment. The more oxidative, medial compartment had higher fatigue resistance, maintaining net power 26% longer than the lateral compartment. The predominant mechanisms underpinning the decrease in net power varied between the compartments, resulting from an increase in the work to extend the muscle and from a reduction in work during shortening in the medial and lateral compartments, respectively. Regional variation in mechanical performance and resistance to fatigue within a mixed muscle suggests a differential recruitment pattern is likely during locomotion, with the medial compartment being utilised during slow speed locomotion and the lateral compartment during burst activities.

This article is protected by copyright. All rights reserved

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Link: Fixed Dose PCC

this is how PCC should be given...

EMCrit by Scott Weingart.

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The utility of 68Ga-DOTATATE positron-emission tomography/computed tomography in the diagnosis, management, follow-up and prognosis of neuroendocrine tumors

Future Oncology, Ahead of Print.


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Allogeneic human double negative T cells as a novel immunotherapy for acute myeloid leukemia and its underlying mechanisms.

Purpose: To explore the potential of ex vivo expanded healthy donor derived allogeneic CD4 and CD8 double negative cells (DNTs) as a novel cellular immunotherapy for leukemia patients. Experimental Design: Clinical grade DNTs from peripheral blood of healthy donors were expanded and their anti-leukemic activity and safety were examined using flow-cytometry based in vitro killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays. Results:  Expanded DNTs from healthy donors target a majority(36/46) of primary AML cells including 9 chemotherapy-resistant patient samples in vitro and significantly reduce the leukemia load in patient-derived xenograft models in a DNT-donor unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, nor cause xenogeneic graft-versus-host disease in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFN which further increases NKG2D and DNAM-1 ligands expression on AML cells. IFN pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFN treatment is abrogated by NKG2D and DNAM-1 blocking antibodies. Conclusion: This study supports healthy donor-derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFN in selective targeting of AML by DNTs.

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Low PD-1 expression in Cytotoxic CD8+ Tumor infiltrating Lymphocytes Confers an Immune Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in Non Small Cell Lung Cancer (NSCLC), an extended analysis of PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Experimental Design Samples from resected adenocarcinoma (ADC 42) and squamous cell carcinoma (SCC 58) and from 26 advanced diseases (13 ADC, 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25 and Granzyme B TILs was immunohistochemically assessed. Results PD-L1 levels inversely correlated with N involvement although did not show a statistical significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC vs ADC in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8 pos lymphocytes lacking PD-1 inhibitory receptor had a longer Overall Survival (OS:HR=2.268, 95%CI 1.056-4.871,p=0.03). PD-1-to-CD8 ratio resulted a prognostic factor both on univariate (HR=1.952, 95%CI 1.34-3.12,p=0.001) and multivariate (HR=1.943, 95%CI 1.38-2.86,p=0.009) analysis. Moreover, low PD-1 incidence among CD8^pos cells was a distinctive feature of nivolumab treated patients showing clinical benefit with a prolonged Progression-Free Survival (PFS:HR=4.51, 95%CI 1.45-13.94,p=0.004). Conclusions In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1 negative effector T-lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC.

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Concurrent inhibition of Pim and FLT3 kinases enhances apoptosis of FLT3-ITD acute myeloid leukemia cells through increased Mcl-1 proteasomal degradation

Purpose:fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition. Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivo. Results: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines. AZD1208 co-treatment increased FLT3 inhibitor-induced apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G1 fraction, annexin V labeling, mitochondrial membrane potential and PARP and caspase-3 cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts and prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony formation. Mechanistically, AZD1208 and quizartinib co-treatment decreased expression of the anti-apoptotic protein Mcl-1. Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML. Conclusion: The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML.

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Prospective feasibility trial for genomics-informed treatment in recurrent and progressive glioblastoma

Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Methods: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome-sequencing and tumor RNA-sequencing was performed to identify molecular targets for potential matched therapy. A multi-disciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood brain barrier penetration of the indicated therapies, drug-drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome-sequencing was completed for all patients and RNA-sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression-free 21 months after surgery, three-times longer than the patient's previous time to progression. Analysis of matched non-enhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusion: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system (CNS)-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma.

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Pseudomyxoma pleuri as a Surgical Emergency: a Rare Case Report

Abstract

Pseudomyxoma pleuri is a rare condition and it mostly results from secondary involvement of an abdominal pathology. Massive pleural disease impedes cardiopulmonary functions and threatens life. We are reporting our experience about managing a middle-age lady with a known case of Pseudomyxoma peritonei, who presented to causality with progressive breathing difficulty in acute exacerbation and cardiopulmonary compromise.

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Conversion of PRPS hexamer to monomer by AMPK-mediated phosphorylation inhibits nucleotide synthesis in response to energy stress [Research Articles]

Tumors override energy stress to grow. However, how nucleotide synthesis is regulated under energy stress is unclear. We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS) 1 S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. Knock-in of non-phosphorylatable PRPS1/2 mutants, which have uninhibited activity, in brain tumor cells under energy stress exhausts cellular ATP and NADPH and increases ROS levels, thereby promoting cell apoptosis. The expression of those mutants inhibits brain tumor formation and enhances the inhibitory effect of the glycolysis inhibitor 2-deoxy-D-glucose on tumor growth. Our findings highlight the significance of recalibrating tumor cell metabolism by fine tuning nucleotide and NAD synthesis in tumor growth.

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FDA Disperses $22 Million for Rare Diseases [News in Brief]

Several grants will support clinical trials investigating novel treatments for rare cancers.

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NF-kB promotes ovarian tumorigenesis via classical pathways supporting proliferative cancer cells and alternative pathways supporting ALDH+ cancer stem-like cells

Understanding the mechanisms supporting tumor-initiating cells (TIC) is vital to combat advanced stage recurrent cancers. Here we show that in advanced ovarian cancers NF-kB signaling via the RelB transcription factor supports TIC populations by directly regulating the cancer stem-like associated enzyme aldehyde dehydrogenase (ALDH). Loss of RelB significantly inhibited spheroid formation, ALDH expression and activity, chemoresistance, and tumorigenesis in subcutaneous and intrabursal mouse xenograft models of human ovarian cancer. RelB also affected expression of the ALDH gene ALDH1A2. Interestingly, classical NF-kB signaling through the RelA transcription factor was equally important for tumorigenesis in the intrabursal model, but had no effect on ALDH. In this case, classical signaling via RelA was essential for proliferating cells, whereas the alternative signaling pathway was not. Our results show how NF-kB sustains diverse cancer phenotypes via distinct classical and alternative signaling pathways, with implications for improved understanding of disease recurrence and therapeutic response.

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Global metabolomic profiling of uterine leiomyomas

Global metabolomic profiling of uterine leiomyomas

British Journal of Cancer, Published online: 26 October 2017; doi:10.1038/bjc.2017.361

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Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer

Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer

British Journal of Cancer, Published online: 26 October 2017; doi:10.1038/bjc.2017.369

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Tetracycline use and risk of incident skin cancer: a prospective study

Tetracycline use and risk of incident skin cancer: a prospective study

British Journal of Cancer, Published online: 26 October 2017; doi:10.1038/bjc.2017.378

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Hybrid approach to laparoscopic decapsulation combined with splenic artery balloon occlusion in a patient with carbohydrate antigen 19-9 producing splenic cysts

Abstract

Introduction

Carbohydrate antigen 19-9 producing splenic cysts are relatively rare and usually occur in women and young individuals. This report describes the use of a novel splenic-preserving surgical approach in the hybrid operating room to reduce the risk of bleeding.

Materials and Surgical Technique

A 27-year-old woman presented at our hospital with a chief complaint of chest pain. CT showed an encapsulated left pleural effusion and multiple splenic cysts. The patient was diagnosed with carbohydrate antigen 19-9–producing splenic cysts and was treated with laparoscopic decapsulation. In the hybrid operating room, a balloon catheter was positioned in the splenic artery. Four ports were inserted into the abdomen, the cysts were punctured, and intracystic fluid was suctioned out. Combined splenic artery balloon occlusion was performed to control bleeding when the cyst wall was resected near the splenic parenchyma. Occlusion was performed to create intermittent blockage and consisted of 20-min ischemia and 5-min reperfusion. Then, the inner surface of the cyst wall was cauterized. The total operation time was 170 min (laparoscopic time, 110 min), and blood loss was 100 mL. There were no intraoperative or postoperative complications. The patient has remained healthy, with no recurrence for 8 months.

Discussion

Laparoscopic decapsulation for the treatment of splenic cysts can prevent life-threatening bacterial infections by preserving the spleen, but this can increase the risk of bleeding from the left splenic parenchyma. Combining splenic artery occlusion with laparoscopic decapsulation is a useful approach in the hybrid operating room.

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Robotic surgery for the upper gastrointestinal tract: Current status and future perspectives

Abstract

More than 4000 da Vinci Surgical Systems have been installed worldwide. Robotic surgery using the da Vinci Surgical System has been increasingly performed in the last decade, especially in urology and gynecology. The da Vinci Surgical System has not become standard in surgery of the upper gastrointestinal tract because of a lack of clear benefits in comparison with conventional minimally invasive surgery. We initiated robotic gastrectomy and esophagectomy for patients with upper gastrointestinal cancer in 2009, and we have demonstrated the potential advantages of the da Vinci Surgical System in reducing postoperative local complications after gastrectomy and recurrent laryngeal nerve palsy after esophagectomy. However, robotic surgery has the disadvantages of a longer operative time and higher costs than the conventional approach. In this review article, we present the current status of robotic surgery for gastric and esophageal cancer, as well as future perspectives on this approach, based on our experience and a review of the literature.

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Issue Information

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Transesophageal Echocardiography: Guidelines for Point-of-Care Applications in Cardiac Arrest Resuscitation

Cardiac arrest is one of the most challenging patient presentations managed by emergency care providers, and echocardiography can be instrumental in the diagnosis, prognosis, and treatment guidance in these critically ill patients. Transesophageal echocardiography has many advantages over transthoracic echocardiography in a cardiac arrest resuscitation. As transesophageal echocardiography is implemented more widely at the point of care during cardiac arrest resuscitations, guidelines are needed to assist emergency providers in acquiring the equipment and skills necessary to successfully incorporate it into the management of cardiac arrest victims.

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Validity and Reliability of the Verbal Numerical Rating Scale for Children Aged 4 to 17 Years With Acute Pain

The Verbal Numerical Rating Scale is the most commonly used self-report measure of pain intensity. It is unclear how the validity and reliability of the scale scores vary across children's ages. We aimed to determine the validity and reliability of the scale for children presenting to the emergency department across a comprehensive spectrum of age.

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Malpractice Claims: It’s a Crapshoot—Time to Stop the Self-Blame and Ask Different Questions

SEE RELATED ARTICLE, P. ■■■.

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Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease

Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels.

http://ift.tt/2gHbh79

What Is the Diagnostic Accuracy of Magnetic Resonance Imaging for Acute Appendicitis?

The authors included 30 studies with 2,665 patients. Of these, 12 focused on pregnant patients and 8 focused on pediatric patients. There was variability in the MRI technique studied, although nearly all studies included a combination of multiplanar T2-weighted imaging with and without fat suppression. The overall prevalence of appendicitis in the 30 included studies was 33% (880/2,665 patients). The meta-analysis of the diagnostic accuracy of MRI for acute appendicitis yielded a sensitivity of 96% (95% confidence interval [CI] 95% to 97%) and specificity of 96% (95% CI 95% to 97%).

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What Is the Utility of Noninvasive Ventilation in the Management of Acute Hypercapnic Respiratory Failure Associated With Chronic Obstructive Pulmonary Disease?

Authors included 17 randomized controlled trials comprising 1,264 patients from 697 citations retrieved from their initial literature search. Mean age of included patients was 66.8 years, and 65% of patients were men. Noninvasive ventilation decreased mortality, decreased need for intubation, and decreased length of hospital stay (Table). The number needed to treat for an additional beneficial outcome was 12 (95% confidence interval 9 to 23) for mortality benefit and 5 (95% confidence interval 5 to 6) for intubation.

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How Reliable Are Signs and Symptoms for Diagnosing Pneumonia in Pediatric Patients?

The initial literature search yielded 3,644 unique articles. Of these, 23 studies comprising 13,833 patients were included in this review. The study dates ranged from 1982 to 2017 and ranged in size from 78 to 2,829 patients. Two studies included preverbal children only, 10 included preverbal children aged 5 years and younger, 2 studies included children aged 6 years or younger, and 9 studies included a broad range of children from preverbal to adolescence. Eight of the 23 studies were conducted in North America, whereas the remaining 15 studies were conducted outside of North America.

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How Effective Is a Regional Nerve Block for Treating Pain Associated With Hip Fractures?

The search strategy identified 1,116 trials, of which 31 (1,760 total participants) met the inclusion criteria for this review. The trials took place in 20 countries, with publication dates extending from 1980 to 2016. The type of peripheral nerve block performed varied greatly in the studies, including type of nerve block (eg, femoral nerve block, fascia iliaca compartment block), duration of block (eg, single-shot block, continuous block), technique (eg, nerve stimulator, ultrasonographic guidance, landmark technique), and timing of nerve block (eg, preoperatively, intraoperatively, postoperatively).

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Measuring Anatomic Severity in Pediatric Appendicitis: Validation of the American Association for the Surgery of Trauma Appendicitis Severity Grade

To assess whether the American Association for the Surgery of Trauma (AAST) grading system accurately corresponds with appendicitis outcomes in a US pediatric population.

http://ift.tt/2yTwxkt

Nosocomial Transmission and Genetic Diversity of Rhinovirus in a Neonatal Intensive Care Unit

Rhinoviruses were detected as sole pathogens in 6 preterm infants who developed severe respiratory infections while hospitalized in a neonatal intensive care unit. We confirmed 2 nosocomial rhinovirus transmission episodes and describe the genetic diversity of rhinovirus strains that circulated simultaneously during a winter season.

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A Randomized Trial of Conditioned or Unconditioned Gases for Stabilizing Preterm Infants at Birth

To determine whether the use of heated-humidified gases for respiratory support during the stabilization of infants <30 weeks of gestational age (GA) in the delivery room reduces rates of hypothermia on admission to the neonatal intensive care unit (NICU).

http://ift.tt/2yRGtZT

Increasing Prevalence of Hepatitis C among Hospitalized Children Is Associated with an Increase in Substance Abuse

To evaluate the impact of substance abuse on pediatric hepatitis C virus (HCV) prevalence, we examined geographic and demographic data on inpatient hospitalizations in children with HCV.

http://ift.tt/2yTwpS1

Desquamating Rash in a Patient with Undiagnosed Netherton Syndrome

A 9-year-old girl presented with a 3-week history of a desquamating rash that affected ~20% of her body surface area. Physical examination revealed diffuse desquamative skin patches, of which the patches on the extremities showed a double border scale consistent with ichthyosis linearis circumflexa (Figure, A and B) and sparse, short hair on the patient's head (Figure, C). Laboratory studies were remarkable for an IgE level of 27 294 IU/mL (reference range 0-100). Collectively, these findings raised suspicion of a diagnosis of Netherton syndrome.

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Comparison of 36 Gy, 20 Gy or No Radiotherapy After Six Cycles of EBVP Chemotherapy and Complete Remission in Early Stage Hodgkin Lymphoma Without Risk Factors: Results of the EORTC–GELA H9-F Intergroup Randomized Trial

While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, radiotherapy dose and treatment with chemotherapy alone remain questionable. The noninferiority trial evaluates the feasibility of reducing the dose or omitting radiotherapy after chemotherapy.

http://ift.tt/2yVAGnR

MRI-guided adaptive radiotherapy; a “game changer” for prostate radiotherapy

Radiotherapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated alpha/beta ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator (linac) allows accurate soft tissue tracking with the capacity to re-plan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MR-only workflow and real-time adaptive planning.

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Multimodal Fluorescence and Bioluminescence Imaging Reveals Transfection Potential of Intratracheally Administered Polyplexes for Breast Cancer Lung Metastases

Human Gene Therapy , Vol. 0, No. 0.


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A Retrospective Study of the Cytokine Profile Changes in Mice with FVIII Inhibitor Development After Adeno-Associated Virus–Mediated Gene Therapy in a Hemophilia A Mouse Model

Human Gene Therapy , Vol. 0, No. 0.


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Treating first responder mental health, addiction, PTSD and suicide

A new fire/EMS-specific treatment facility caters to specific job-related trauma while making first responders feel at home

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Tetracycline use and risk of incident skin cancer: a prospective study

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Global metabolomic profiling of uterine leiomyomas

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Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer

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Treating first responder mental health, addiction, PTSD and suicide

This article first appeared on FireRehab.com, sponsored by Masimo. By Daniel Martynowicz, EMS1 Contributor Most in the fire/EMS community have a harrowing story of death, destruction and despair. These stories usually involve heartbreak and pain – not just for the victims involved, but also for the first responders tasked with restoring order to the chaos, perfusion to the pulseless, and hope ...

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Numerical Methods for Polyline-to-Point-Cloud Registration with Applications to Patient-Specific Stent Reconstruction

Summary

We present novel numerical methods for Polyline-to-Point-Cloud Registration and their application to patient-specific modeling of deployed coronary artery stents from image data. Patient-specific coronary stent reconstruction is an important challenge in computational hemodynamics and relevant to the design and improvement of the prostheses. It is an invaluable tool in large-scale clinical trials that computationally investigate the effect of new generations of stents on hemodynamics and eventually tissue remodeling. Given a point cloud of strut positions, which can be extracted from images, our stent reconstruction method aims at finding a geometrical transformation that aligns a model of the undeployed stent to the point cloud. Mathematically, we describe the undeployed stent as a polyline, which is a piecewise linear object defined by its vertices and edges. We formulate the nonlinear registration as an optimization problem whose objective function consists of a similarity measure, quantifying the distance between the polyline and the point cloud, and a regularization functional, penalizing undesired transformations. Using projections of points onto the polyline structure, we derive novel distance measures. Our formulation supports most commonly used transformation models including very flexible nonlinear deformations. We also propose two regularization approaches ensuring the smoothness of the estimated nonlinear transformation. We demonstrate the potential of our methods using an academic 2D example and a real-life 3D bioabsorbable stent reconstruction problem. Our results show that the registration problem can be solved to sufficient accuracy within seconds using only a few number of Gauss-Newton iterations. This article is protected by copyright. All rights reserved.

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Factors affecting the self-rated health of elderly individuals living alone: a cross-sectional study

In Japan, the number of elderly individuals living alone is continuing to increase as society ages. Although studies have considered quality of life, life expectancy, and gender differences in elderly individu...

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Acceptability of smartphone text- and voice-based ecological momentary assessment (EMA) methods among low income housing residents in New York City

This study aimed to evaluate the acceptability of smartphone-based text message- and voice-based ecological momentary assessment (EMA) methods among a sample of low-income housing residents in New York City. U...

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Prevalence of overweight and obesity among type 2 diabetic patients attending diabetes clinics in northern Tanzania

To determine the prevalence of overweight and obesity among patients with type 2 diabetes who are attending diabetes clinics in northern Tanzania.

http://ift.tt/2zGGsqR

Health-related quality of life of mothers of children with congenital heart disease in a sub-Saharan setting: cross-sectional comparative study

While the Health Related Quality of Life of the children with congenital heart defects is primarily affected, caring for a child with birth defect has an impact on the family's quality of life as well. Underst...

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Achieving community-based postpartum follow up in eastern Uganda: the field experience from the MamaMiso Study on antenatal distribution of misoprostol

Advance provision of misoprostol to women during antenatal care aims to achieve broader access to uterotonics for the prevention of postpartum hemorrhage. Studies of this community-based approach usually invol...

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Ultra high-field SWI of the substantia nigra at 7T: reliability and consistency of the swallow-tail sign

The loss of the swallow-tail sign of the substantia nigra has been proposed for diagnosis of Parkinson's disease. Aim was to evaluate, if the sign occurs consistently in healthy subjects and if it can be relia...

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Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice

Summary

Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac-)5-aminosalicylic acid (5-ASA) urinalysis by High-Performance Liquid Chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily IBD care. Twenty-nine patients (51.7% male, mean age 52 ± 11 yrs) were included (median FU 9 months) and collected weekly spot urine samples. We found large variation in spot (Nac-)5-ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion spot (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD care.

http://ift.tt/2iCYXJe

Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor

A protocol for the synthesis, purification, and characterization of a ruthenium-based inhibitor of mitochondrial calcium uptake is presented. A procedure to evaluate its efficacy in permeabilized mammalian cells is demonstrated.

http://ift.tt/2zHrf8O

Social cytopathology: Building a stronger cytopathology community through social media

Social media use can enhance education, networking, and collaboration in cytopathology. It can increase the impact of cytopathologists and elevate the understanding of cytopathology specifically and pathology in general among patients, colleagues, and the general public.

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High-grade urothelial carcinoma in urine cytology with jet black and smooth or glassy chromatin

BACKGROUND

Some high-grade urothelial carcinomas (UCs) in urine cytology can have jet black, smooth, or glassy chromatin, but to the authors' knowledge, the incidence and criteria for diagnosis are not well described. The current study was performed to define the incidence and appearance of high-grade UC in urine cytology in cytospin preparations with jet black and smooth or glassy chromatin.

METHODS

Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade UCs and 101 malignant UCs) were reviewed.

RESULTS

Cases with malignant cells with jet black and smooth or glassy chromatin were identified in a total of 60 cases (59.4% of all malignancies). These comprised 18 carcinoma in situ cases, 28 high-grade papillary UCs, 8 invasive UCs, 3 squamous cell carcinomas, 2 adenocarcinomas, and 1 melanoma. Of the 93 high-grade UCs, 51 (54.8%) had cells with either jet black and smooth or glassy chromatin. These cells were the only type of malignant cell in 6 of 101 cases (5.9%). All cases had at least 50 cells with jet black nuclei. Nuclei with jet black and smooth chromatin often were smaller than normal urothelial cells, often but not always elongate, had irregular nuclear outlines including pointed areas, and usually were accompanied by necrosis. Cells with glassy chromatin often were larger than normal urothelial cells, had rounder but still irregular nuclei, and also had frequent necrosis.

CONCLUSIONS

Malignant urothelial cells in urine cytology with jet black chromatin are common and can be diagnosed as "positive for malignancy" based on their irregular nuclear outline, increased cellularity (≥50 abnormal cells), and frequent necrosis. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle

Here we present a detailed protocol to detect both senescent and pluripotent stem cells in the skeletal muscle upon injury while inducing in vivo reprogramming. This method is suitable for evaluating the role of cellular senescence during tissue regeneration and reprogramming in vivo.

http://ift.tt/2yMn3Yy

Comparative risks of diabetes-related complications of basal insulins: a longitudinal population-based cohort of type 1 diabetes 1999-2013 in Taiwan

Abstract

Aim

We compared the effects of basal insulins: long-acting insulin analogues versus intermediate/long-acting human insulin, on diabetes-related complications in type 1 diabetes.

Methods

1,188 type 1 diabetes newly on long-acting insulin analogues or intermediate/long-acting human insulin were identified in 2004-2008 and followed until death or 2013. Clinical outcomes included acute (i.e., hyperglycemia, hypoglycemia) and chronic (i.e., nephropathy, retinopathy, neuropathy, cardiovascular diseases) complications. Diabetes-related complications were measured as a composite outcome which included acute and chronic complications. Cox proportional hazards models were used to assess the time to event hazard. Three propensity score (PS) methods were applied to adjust for baseline imbalances between basal insulin groups, including PS-matching approach (as main analysis), standardized mortality ratio weighting (SMRW), and inverse probability of treatment weighting (IPTW).

Results

Long-acting insulin analogues versus intermediate/long-acting human insulin had a lower risk for a composite of diabetes-related complications (adjusted hazards ratios; aHRs [95% CI]: 0.782 [0.639-0.956], 0.743 [0.598-0.924], and 0.699 [0.577-0.846] according to the PS-matching approach, SMRW, and IPTW, respectively). Compared to intermediate/long-acting human insulin, using long-acting insulin analogues had a lower hypoglycemia risk: aHRs (95% CI): 0.681 (0.498-0.930), 0.662 (0.466-0.943), and 0.639 (0.471-0.867) from PS-matching approach, SMRW, and IPTW, respectively. No statistical differences between two types of insulin on individual chronic complications were found.

Conclusion

A trend of lower diabetes-related complications associated with long-acting insulin analogues versus intermediate/long-acting human insulin was observed. Reduced hypoglycemia risk with long-acting insulin analogues was confirmed in this real-world study.

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Is Tranexamic acid exposure related to blood loss in hip arthroplasty? A Pharmacokinetic-Pharmacodynamic study.

Aims

Tranexamic acid (TXA) is an antifibrinolytic agent, decreasing blood loss in hip arthroplasty. This study investigated the relationship between TXA exposure markers, including the time above the in vitro threshold reported for inhibition of fibrinolysis (10 mg.L^-1), and perioperative blood loss.

Methods

Data were obtained from a prospective, double-blind, parallel-arm, randomised superiority study in hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of TXA followed by a continuous infusion of either TXA 1 g or placebo over 8 h. A population pharmacokinetic study was conducted to quantify TXA exposure.

Results

In total, 827 TXA plasma concentrations were measured in 166 patients. A two-compartment model fitted the data best, total body weight determining interpatient variability in the central volume of distribution. Creatinine clearance accounted for interpatient variability in clearance. At the end of surgery, all patients had TXA concentrations above the therapeutic target of 10 mg.L^-1. The model-estimated time during which TXA concentration was above 10 mg.L^-1 ranged from 3.3 h to 16.3 h. No relationship was found between blood loss and either the time during which TXA concentration exceeded 10 mg.L^-1, or the other exposure markers tested (maximum plasma concentration, area under the concentration-time curve).

Conclusion

In hip arthroplasty, TXA plasma concentrations were maintained above 10 mg.L^-1 during surgery and for a minimum of 3 h with a preoperative 1 g dose of TXA. Keeping TXA concentrations above this threshold up to 16 h conferred no advantage as regards blood loss.

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Water extract of Rumex crispus prevents bone loss by inhibiting osteoclastogenesis and inducing osteoblast mineralization

Rumex crispus root has traditionally been used in Asian medicine for the treatment of hemorrhage and dermatolosis. The aim of this study was to explore the pharmaceutical effects of wa...

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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening

Here, we present the detailed protocol adopted in the BioMILD screening trial to perform the circulating microRNA signature classifier test for early lung cancer detection.

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Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

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Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population

Objective

Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs.

Design

We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology.

Results

Age-standardised incidence of MPs in patients aged 50–74 years doubled from 5.4 in 1982–2002 to 10.9 per 100 000 in 2003–2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after firs

t-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982–2002) to 1.2% (2003–2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024).

Conclusion

Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.

http://ift.tt/2gEkoFA

Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions on mTORC1 and mTORC2 signalling

Objective

The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver.

Design and results

We generated an inducible liver-specific Reptin knockout (Repin^LKO) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia. This was associated with decreased hepatic mTOR protein abundance. Further experiments in primary hepatocytes demonstrated that Reptin maintains mTOR protein level through its ATPase activity. Unexpectedly, loss or inhibition of Reptin induced an opposite effect on mTORC1 and mTORC2 signalling, with: (1) strong inhibition of hepatic mTORC1 activity, likely responsible for the reduction of hepatocytes cell size, for decreased de novo lipogenesis and cholesterol transcriptional programmes and (2) enhancement of mTORC2 activity associated with inhibition of the gluconeogenesis transcriptional programme and hepatic glucose production. Consequently, the role of hepatic Reptin in the pathogenesis of insulin resistance (IR) and non-alcoholic fatty liver disease consecutive to a high-fat diet was investigated. We found that Reptin deletion completely rescued pathological phenotypes associated with IR, including glucose intolerance, hyperglycaemia, hyperlipidaemia and hepatic steatosis.

Conclusion

We show here that the AAA +ATPase Reptin is a regulator of mTOR signalling in the liver and global glucido-lipidic homeostasis. Inhibition of hepatic Reptin expression or activity represents a new therapeutic perspective for metabolic syndrome.

http://ift.tt/2i7hxW9

Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice

Objective

Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c⁺ proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development.

Design

vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr^-/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH.

Results

Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c⁺ and CD11c^– macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c⁺ ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes.

Conclusion

ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.

http://ift.tt/2gEklJU

Texas school district partners with fire department for EMT academy

By EMS1 Staff PFLUGERVILLE, Texas — A school district teamed up with a fire department to launch the first-ever EMT academy in the area for high school seniors. Statesman reported that six high school seniors from Connally High School and Hendrickson High School began participating in the academy as a result of a partnership between the Pflugerville school district and Pflugerville Fire Department ...

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Fla. fire department to add ballistic armor to ambulance

Gainesville Fire Rescue plans to add ballistic protection to the ambulance's front, sides and back to protect against handgun-caliber bullets

http://ift.tt/2zRVyKT

Biosurfactant from a marine bacterium disrupts biofilms of pathogenic bacteria in a tropical aquaculture system

Abstract

Bacterial infections are major constraints in aquaculture farming. These pathogens often adapt to the biofilm mode of growth and resist antibiotic treatments. We have used a non-toxic glycolipid biosurfactant (BS-SLSZ2) derived from a marine epizootic bacterium Staphylococcus lentus to treat aquaculture associated infections in an eco-friendly manner. We found that BS-SLSZ2 contained threose, a four carbon sugar as the glycone component, and hexadecanoic and octadecanoic acids as the aglycone components. The critical micelle concentration (CMC) of the purified glycolipid was 18 mg mL^–1. This biosurfactant displayed anti-adhesive activity and inhibited biofilm formation by preventing initial attachment of cells onto surfaces. The biosurfactant (at a concentration of 20 μg) was able to inhibit Vibrio harveyi and Pseudomonas aeruginosa biofilms by 80.33 ± 2.16 and 82 ± 2.03%, respectively. At this concentration it was also able to disrupt mature biofilms of V. harveyi (78.7 ± 1.93%) and P. aeruginosa (81.7 ± 0.59%). The biosurfactant was non-toxic towards Artemia salina. In vivo challenge experiments showed that the glycolipid was effective in protecting A. salina nauplii against V. harveyi and P. aeruginosa infections. This study highlights the significance of marine natural products in providing alternative biofilm controlling agents and decreasing the usage of antibiotics in aquaculture settings.

http://ift.tt/2i6XM0S

Soil texture-depending effects of doxycycline and streptomycin applied with manure on the bacterial community composition and resistome

Abstract

Veterinary antibiotics, bacteria carrying antibiotic resistance determinants located on mobile genetic elements and nutrients are spread on agricultural soil using manure as fertilizer. However, systematic quantitative studies linking antibiotic concentrations and antimicrobial resistance genes (ARGs) in manure and the environment are scarce but needed to assess environmental risks.In this microcosm study, a sandy and a loamy soil were mixed with manure spiked with streptomycin or doxycycline at five concentrations. Total-community DNA was extracted on days 28 and 92, and the abundances of ARGs (aadA, strA, tet(A), tet(M), tet(W), tet(Q), sul1, qacE/qacEΔ1) and class 1 and 2 integron integrase genes (intI1 and intI2) were determined by qPCR relative to 16S rRNA genes. Effects on the bacterial community composition were evaluated by denaturing gradient gel electrophoresis of 16S rRNA gene amplicons.Manure application to the soils strongly increased the relative abundance of most tested genes. Antibiotics caused further enrichments which decreased over time and were mostly seen at high concentrations. Strikingly, effects on relative gene abundances and soil bacterial community composition were more pronounced in sandy soil. The concept of defining antibiotic threshold concentrations for environmental risk assessments remains challenging due to the various influencing factors.

http://ift.tt/2gGxD93

Impact of land use change and soil organic carbon quality on microbial diversity in soils across Europe

Abstract

Land use and their change have dramatic consequences for above-ground biodiversity, but their impact on soil microbial communities is poorly understood. In this study, soils from 19 European sites representing conversion of croplands to grasslands or forests and of grasslands to croplands or forests were characterized for microbial abundance and bacterial diversity. The abundance of Bacteria and Fungi but not Archaea responded to land use change. Site was the major determinant of the soil bacterial community structure, explaining 32% of the variation in 16S rRNA gene diversity. While the quantity of soil organic carbon (SOC) only explained 5% of the variation, SOC when differentiated by its quality could explain 22%. This was similar to the impact of soil pH (21%) and higher that of land use type (15%). Croplands had the highest bacterial diversity. Converting croplands to grassland caused an increase of Verrucomicrobia; croplands to forest increased Rhizobiales but decreased Bacteroidetes and Nitrospirae; and grasslands to cropland increased Gemmatimonadetes but decreased Verrucomicrobia and Planctomycetes. Network analysis identified associations between particular SOC fractions and specific bacterial taxa. We conclude that land use-related effects on soil microorganisms can be consistently observed across a continental scale.

http://ift.tt/2i7wzLl

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and cours...

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Incorporation of Treatment Response, Tumor Grade and Receptor Status Improves Staging Quality in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Abstract

Background

Improved staging systems that better predict survival for breast cancer patients who receive neoadjuvant chemotherapy (NAC) by accounting for clinical pathological stage plus estrogen receptor (ER) and grade (CPS+EG) and ERBB2 status (Neo-Bioscore) have been proposed. We sought to evaluate the generalizability and performance of these staging systems in a national cohort.

Methods

The National Cancer Database (2006–2012) was reviewed for patients with breast cancer who received NAC and survived ≥90 days after surgery. Four systems were evaluated: clinical/pathologic American Joint Committee on Cancer (AJCC) 7th edition, CPS+EG, and Neo-Bioscore. Unadjusted Kaplan–Meier analysis and adjusted Cox proportional hazards models quantified overall survival (OS). Systems were compared using area under the curve (AUC) and integrated discrimination improvement (IDI).

Results

Overall, 43,320 patients (5-year OS 76.0, 95% confidence interval [CI] 75.4–76.5%) were included, 12,002 of whom had evaluable Neo-Bioscore. AUC at 5 years for CPS+EG (0.720, 95% CI 0.714–0.726) and Neo-Bioscore (0.729, 95% CI 0.716–0.742) were improved relative to AJCC clinical (0.650, 95% CI 0.643–0.656) and pathologic (0.683, 95% CI 0.676–0.689) staging. Both CPS+EG (IDI 7.2, 95% CI 6.6–7.7%) and Neo-Bioscore (IDI 9.8, 95% CI 8.0–11.6%) demonstrated superior discrimination when compared with AJCC clinical staging at 5 years. Comparison of CPS+EG with Neo-Bioscore yielded an IDI of 2.6% (95% CI 0.9–4.5%), indicating that Neo-Bioscore is the best staging system.

Conclusions

In a heterogenous national cohort of breast cancer patients treated with NAC and surgery, the incorporation of chemotherapy response, tumor grade, ER status, and ERBB2 status into the staging system substantially improved on the AJCC TNM staging system in discrimination of OS. Neo-Bioscore provided the best staging discrimination.

http://ift.tt/2yOAxTM

Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma

Abstract

Background

Recently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables.

Methods

The study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined.

Results

Most of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator.

Conclusion

Tumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients.

http://ift.tt/2ksvnmN

Risk Factors for Lateral Neck Recurrence of N0/N1a Papillary Thyroid Cancer

Abstract

Background

Current guidelines advocate no prophylactic dissection of the lateral neck compartment for papillary thyroid carcinoma (PTC) without clinical evidence of lateral neck metastasis (cN1b). However, lateral neck recurrence can affect patient treatment outcomes and quality of life. Therefore, this study examined the risk factors for lateral neck recurrence after the definitive treatment of PTC without cN1b.

Methods

The study enrolled 1928 consecutive patients who underwent total thyroidectomy between 2006 and 2012 for PTC without cN1b. Logistic regression analysis was used to identify the relationship of clinicopathologic factors with lateral neck recurrence. Uni- and multivariate Cox-proportional hazards regression analyses were used to identify factors predictive of lateral neck recurrence-free survival (LRFS).

Results

During a median follow-up period of 94 months (range, 24–133 months), lateral neck recurrence occurred in 47 patients (2.4%). Binary logistic regression showed that tumor size (>2 cm), multifocality, clinical central neck metastasis (cN1a), number of positive lymph nodes (LNs, >5), and LN ratio (>0.5) were significantly associated with lateral neck recurrence (P < 0.05). Multivariate analyses showed that multifocality (hazards ratio [HR], 2.338; 95% confidence interval [CI], 1.126–4.858; P = 0.023), cN1a (HR, 5.301; 95% CI, 2.416–11.630; P < 0.001), LN ratio (HR, 2.628; 95% CI, 1.228–5.626; P = 0.013), extranodal extension (HR, 2.570; 95% CI, 1.063–6.213; P = 0.036), and MACIS (distant metastasis, patient age, completeness of resection, local invasion and tumour size) score (HR, 2.513; 95% CI, 1.211–5.216; P = 0.013) were independent factors for LRFS.

Conclusions

Lateral neck recurrence after thyroidectomy is predicted by the clinicopathologic factors of multifocality, cN1a, LN ratio, extranodal extension, and MACIS score in N0/N1a PTC patients.

http://ift.tt/2gJRbwK

Association Between Patient Satisfaction and Short-Term Outcomes After Major Cancer Surgery

Abstract

Objective

The aim of this study was to investigate whether patient satisfaction, as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, is associated with short-term outcomes after major cancer surgery.

Materials and Methods

We first used national Medicare claims to identify patients who underwent a major extirpative cancer surgery from 2011 to 2013. Next, we used Hospital Compare data to assign the HCAHPS score to the hospital where the patient underwent surgery. We then performed univariate statistical analyses and fit multilevel logistic regression models to evaluate the relationship between excellent patient satisfaction and short-term cancer surgery outcomes for all surgery types combined and then by each individual surgery type.

Results

We identified 373,692 patients who underwent major cancer surgery for one of nine cancers at 2617 hospitals. In both unadjusted and adjusted analyses, hospitals with higher proportions of patients reporting excellent satisfaction had lower complication rates (p < 0.001), readmissions (p < 0.001), mortality (p < 0.001), and prolonged length of stay (p < 0.001) than hospitals with lower proportions of satisfied patients, but with modest differences. This finding held true broadly across individual cancer types for complications, mortality, and prolonged length of stay, but less so for readmissions.

Conclusions

Hospital-wide excellent patient satisfaction scores are associated with short-term outcomes after major cancer surgery overall, but are modest in magnitude.

http://ift.tt/2yNhd9b

Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma

Abstract

Background

Preoperative serum inflammatory markers have been correlated with outcome after resection of hepatocellular carcinoma (HCC), but studies have had conflicting results. This study aimed to evaluate the association of six inflammatory markers with recurrence-free survival (RFS), overall survival (OS), and microvascular invasion (MVI), a well-known prognostic factor.

Methods

This study investigated 370 patients who underwent resection of HCC from 1992 to 2016, retrospectively evaluating their inflammatory indices and individual components including their neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase-to-neutrophil ratio index (ANRI). Uni- and multivariate analyses were performed to evaluate these markers for RFS, OS, and MVI.

Results

The median RFS was 23 months, and the median OS was 60 months. Factors independently associated with worse RFS were higher PLR and alpha-fetoprotein level, male gender, and the presence of MVI as well as multiple nodules. Factors independently associated with worse OS were higher PLR and international normalized ratio, male gender, older age, presence of MVI and multiple nodules, larger tumor, presence of cirrhosis, and absence of steatosis. The study identified MVI in 47% of the patients. Lower level of albumin, higher level of alpha-fetoprotein, and larger tumor on preoperative imaging were independently associated with MVI.

Conclusions

This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

http://ift.tt/2gJQZxw

Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials

Abstract

Purpose

This study was designed to determine invasive cancer upstaging rates at surgical excision following vacuum-assisted biopsy of ductal carcinoma in situ (DCIS) among women meeting eligibility for active surveillance trials.

Methods

Patients with vacuum-assisted, biopsy-proven DCIS at a single center from 2008 to 2015 were retrospectively reviewed. Imaging and pathology reports were interrogated for the imaging appearance, tumor grade, hormone receptor status, and presence of comedonecrosis. Subsequent surgical reports were reviewed for upstaging to invasive disease. Cases were classified by eligibility criteria for the COMET, LORIS, and LORD DCIS active surveillance trials.

Results

Of 307 DCIS diagnoses, 15 (5%) were low, 95 (31%) intermediate, and 197 (64%) high nuclear grade. The overall upstage rate to invasive disease was 17% (53/307). Eighty-one patients were eligible for the COMET Trial, 74 for the LORIS trial, and 10 for the LORD Trial, although LORIS trial eligibility also included real-time, multiple central pathology review, including elements not routinely reported. The upstaging rates to invasive disease were 6% (5/81), 7% (5/74), and 10% (1/10) for the COMET, LORIS, and LORD trials, respectively. Among upstaged cancers (n = 5), four tumors were Stage IA invasive ductal carcinoma and one was Stage IIA invasive lobular carcinoma; all were node-negative.

Conclusions

DCIS upstaging rates in women eligible for active surveillance trials are low (6–10%), and in this series, all those with invasive disease were early-stage, node-negative. The careful patient selection for DCIS active surveillance trials has a low risk of missing occult invasive cancer and additional studies will determine clinical outcomes.

http://ift.tt/2gLAUaI

Predictors of Bowel Function in Long-term Rectal Cancer Survivors with Anastomosis

Abstract

Background

Bowel function in long-term rectal cancer survivors with anastomosis has not been characterized adequately. We hypothesized that bowel function is associated with patient, disease, and treatment characteristics.

Methods

The cohort study included Kaiser Permanente members who were long-term (≥5 years) rectal cancer survivors with anastomosis. Bowel function was scored using the self-administered, 14-item Memorial Sloan-Kettering Cancer Center Bowel Function Index. Patient, cancer, and treatment variables were collected from the electronic medical chart. We used multiple regression to assess the relationship of patient- and treatment-related variables with the bowel function score.

Results

The study included 381 anastomosis patients surveyed an average 12 years after their rectal cancer surgeries. The total bowel function score averaged 53 (standard deviation, 9; range, 31–70, higher scores represent better function). Independent factors associated with worse total bowel function score included receipt of radiation therapy (yes vs. no: 5.3-unit decrement, p < 0.0001), tumor distance from the anal verge (≤6 cm vs. >6 cm: 3.2-unit decrement, p < 0.01), and history of a temporary ostomy (yes vs. no: 4.0-unit decrement, p < 0.01). One factor measured at time of survey was also associated with worse total bowel function score: ever smoking (2.3-unit decrement, p < 0.05). The regression model explained 20% of the variation in the total bowel function score.

Conclusions

Low tumor location, radiation therapy, temporary ostomy during initial treatment, and history of smoking were linked with decreased long-term bowel function following an anastomosis. These results should improve decision-making about surgical options.

http://ift.tt/2yNfXmE

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

Abstract

Background

The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis.

Methods

We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay.

Results

Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12–2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24–3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77-6.40; P < 0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival.

Conclusions

These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.

http://ift.tt/2gLKN8j

Radioactive Seed Localization Versus Wire-Guided Localization for Nonpalpable Breast Cancer: A Cost and Operating Room Efficiency Analysis

Abstract

Background

This study aimed to compare the cost and resource use between our first-year experience using breast-conserving surgery (BCS) with radioactive seed localization (RSL) and the previous-year standard practice of BCS with wire-guided localization (WGL) for patients with nonpalpable breast cancer at a large Canadian tertiary center.

Methods

For this retrospective cohort study, data for BCS cases with RSL was collected from 1 April 2015 to 31 March 2016 and for BCS cases with WGL from 1 April 2014 to 31 March 2015.

Results

The study compared 153 WGL patients with 194 RSL patients. The two groups had no significant demographic differences. The average cost per patient for RSL, including opportunity costs, was $250.90 versus $1130.41 for WGL. Dedicated allocated radiology appointments to RSL increased (9 per day), and fewer radiologists were required for these procedures per day. Patients were transported to the operating room more quickly for RSL procedures (120 vs. 254 min; p < 0.001). Fewer vasovagal reactions occurred after insertion of RSL versus WGL (p = 0.05). No significant differences were observed in terms of surgical time, specimen volume, positive margins, or margin reexcision rates. No significant differences in postoperative complication rates were observed.

Conclusions

In this study, RSL had lower costs than WGL, allowed for more efficient use of radiology scheduling and resources, and had shorter wait times for patients on their day of surgery. In addition, RSL led to fewer vasovagal reactions at insertion. Therefore, RSL should be used instead of WGL given the reduced cost, decreased need of human resources, improved efficiency, and potential benefits to the patient experience.

http://ift.tt/2yNNZaB

Transoral Resection of Human Papillomavirus (HPV)-Positive Squamous Cell Carcinoma of the Oropharynx: Outcomes with and Without Adjuvant Therapy

Abstract

Background

With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma.

Methods

A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4).

Results

The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1–102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01–0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02–0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02–2.57) or overall survival (HR 0.18; 95% CI 0.01–2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6–20.6).

Conclusions

Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.

http://ift.tt/2yOA0Bg

A Review of Thoracic and Mediastinal Cytoreductive Techniques in Advanced Ovarian Cancer: Extending the Boundaries

Abstract

The aim of this study was to review the surgical and clinical outcomes of intrathoracic and mediastinal surgical cytoreduction in stage IV epithelial ovarian cancer (EOC). Relevant articles were identified from MEDLINE and EMBASE. Only analyses or reports that described actual intrathoracic cytoreduction via pleurectomy and/or resection of cardiophrenic/mediastinal lymph nodes were included. Imaging articles that merely described thoracic tumor patterns were excluded. A total of nine studies were identified, the oldest originating in 2007. Procedures described were transdiaphragmatic resection of cardiophrenic lymph nodes and pleural disease (n = 5) and video-assisted thoracoscopic and mediastinal tumorectomies including pleurectomy (n = 4). The number of operated patients ranged between 1 and 30 with complete cytoreduction rates ranging between 68 and 100%. No surgical deaths directly related to the thoracic cytoreduction were reported and only one patient (1/30) experienced a postoperative complication in terms of a pneumothorax. None of the studies presented a direct comparison of survival to patients with thoracic disease who did not undergo thoracic cytoreduction, and therefore the survival benefit of thoracic cytoreduction could not be quantified. In conclusion, thoracic cytoreduction in advanced EOC seems feasible and with acceptable morbidity while offering a better understanding of the extent of disease and hence allowing the tailoring of intraabdominal resections. Nevertheless, its direct impact on patients' survival by a potential overruling of a more adverse tumor biology remains to be established in larger-scale prospective and ideally randomized trials.

http://ift.tt/2gMwCQe

Negative Impact of Skeletal Muscle Wasting After Neoadjuvant Chemotherapy Followed by Surgery on Survival for Patients with Thoracic Esophageal Cancer

Abstract

Background

Skeletal muscle wasting during curative treatment is an important issue faced by esophageal cancer patients. However, it has not been clarified whether skeletal muscle change during neoadjuvant chemotherapy followed by surgery adversely affects prognosis. This study aimed to determine the relation between skeletal muscle change and survival for patients with advanced esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery.

Methods

This study retrospectively analyzed 66 patients with thoracic esophageal cancer who had undergone neoadjuvant chemotherapy followed by esophagectomy. The study investigated the correlation between the change in the total muscle cross-sectional area at the third lumbar vertebra before and 4 months after surgery as well as the postoperative recurrence and overall survival (OS).

Results

Of the 66 patients, 39 (59%) showed a skeletal muscle decrease from baseline to 4 months after esophagectomy. The change in the skeletal muscle index from baseline to 4 months after surgery was −1.2 cm²/m². Multivariable analysis showed that nonsquamous cell carcinoma subtype (hazard ratio [HR] 2.57; p = 0.029), pathologic stage (HR 5.73; p < 0.01), and skeletal muscle wasting (HR per 1 unit decrease in skeletal muscle index, 1.16; p = 0.015) were the independent prognostic factors associated with worse OS. Additionally, pathologic stage (HR 6.03; p < 0.01) and skeletal muscle wasting (HR per 1 unit decrease in skeletal muscle index, 1.11; p = 0.048) also were found to be independent prognostic factors associated with worse recurrence-free survival.

Conclusions

The study findings suggest that skeletal muscle wasting from baseline has a negative impact on cancer recurrence and survival.

http://ift.tt/2yOzMKq

Flat Epithelial Atypia on Core Biopsy and Upgrade to Cancer: a Systematic Review and Meta-Analysis

Abstract

Background

No consensus exists on whether flat epithelial atypia (FEA) diagnosed percutaneously should be surgically excised. A systematic review and meta-analysis of the frequency of upgrade to cancer or an atypical ductal hyperplasia (ADH) at surgical excision of FEA was performed.

Methods

Embase, MEDLINE, Scopus, and Web of Science databases from January 2003 to November 2015 were searched. The inclusion criteria required a manuscript in English with original data on FEA diagnosed percutaneously, data including the presence or absence of other concurrent high-risk lesions, and data including outcome of cancer at surgical excision. Studies were assessed for quality, and two reviewers extracted data. Random-effects meta-analysis was used to pool estimates. The impact of study-level characteristics was assessed by stratified meta-analysis and meta-regression.

Results

The inclusion criteria was met by 32 studies. A total of 1966 core needle biopsies showed pure FEA, and 1517 (77%) showed surgical excision. The proportions of patients with upgrade to cancer varied from 0 to 42%, with an overall pooled estimate of 11.1%. Heterogeneity was observed, with the greatest impact based on whether a study included cases of FEA diagnosed before 2003. With restriction of the investigation to 16 higher-quality studies, the cancer upgrade pooled estimate was 7.5% (95% confidence interval [CI], 5.4–10.4%), and the rate of invasive cancer was 3% (95% CI 1.9–4.5%). For upgrade to ADH, data from 22 studies including 937 patients were analyzed. The proportion of patients upgraded to ADH ranged from 0 to 60%, with a pooled estimate of 17.9% overall and 18.6% among high-quality studies.

Conclusions

With patient management change potential for approximately 25% of patients, this analysis supports a general recommendation for surgical excision of FEA diagnosed by core biopsy.

http://ift.tt/2gOMXnv

Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer

http://ift.tt/2yM067L

REMSA releases comprehensive white paper on its nationally acclaimed community health programs

RENO, Nev. — REMSA, the Regional Emergency Medical Services Authority based in northern Nevada, has released a new comprehensive White Paper that provides detailed information on its highly successful Community Health Programs. These nationally-acclaimed programs were launched in 2012 after REMSA received funding through a $9.1 million Health Care Innovation Award grant from the Center for Medicare ...

http://ift.tt/2liXxoi

Yeast phospholipase C is required for stability of casein kinase I Yck2p and expression of hexose transporters

Abstract

Phospholipase C (Plc1p) in Saccharomyces cerevisiae is required for normal degradation of repressor Mth1p and expression of the HXT genes encoding cell membrane transporters of glucose. Plc1p is also required for normal localization of glucose transporters to the cell membrane. Consequently, plc1Δ cells display histone hypoacetylation and transcriptional defects due to reduced uptake and metabolism of glucose to acetyl-CoA, a substrate for histone acetyltransferases. In the presence of glucose, Mth1p is phosphorylated by casein kinase I Yck1/2p, ubiquitinated by the SCF^Grr1 complex, and degraded by the proteasome. Here we show that while Plc1p does not affect the function of the SCF^Grr1 complex or the proteasome, it is required for normal protein level of Yck2p. Since stability of Yck1/2p is regulated by a glucose-dependent mechanism, PLC1 inactivation results in destabilization of Yck1/2p and defect in Mth1p degradation. Based on our results and published data, we propose a model in which plc1Δ mutation causes increased internalization of glucose transporters, decreased transport of glucose into the cells, and consequently decreased stability of Yck1/2p, increased stability of Mth1p and decreased expression of the HXT genes.

http://ift.tt/2zS5mVk

Regulatory role of XynR (YagI) in catabolism of xylonate in Escherichia coli K-12

Abstract

The genome of Escherichia coli K-12 contains ten cryptic phages, altogether constituting about 3.6% of the genome in sequence. Among more than 200 predicted genes in these cryptic phages, 14 putative transcription factor (TF) genes exist, but their regulatory functions remain unidentified. As an initial attempt to make a breakthrough for understanding the regulatory roles of cryptic phage-encoded TFs, we tried to identify the regulatory function of CP4–6 cryptic prophage-encoded YagI with unknown function. After SELEX screening, YagI was found to bind mainly at a single site within the spacer of bidirectional transcription units, yagA (encoding another uncharacterized TF) and yagEF (encoding 2-keto-3-deoxy gluconate aldolase, and dehydratase, respectively) within this prophage region. YagEF enzymes are involved in the catabolism of xylose downstream from xylonate. We then designated YagI as XynR (regulator of xylonate catabolism), one of the rare single-target TFs. In agreement with this predicted regulatory function, the activity of XynR was suggested to be controlled by xylonate. Even though low-affinity binding sites of XynR were identified in the E. coli K-12 genome, they all were inside open reading frames, implying that the regulation network of XynR is still fixed within the CR4–6 prophage without significant influence over the host E. coli K-12.

http://ift.tt/2xp3rpt

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery

Background: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity. Particular attention was placed on angiopoietins and their important effects on endothelial gap junctions. Furthermore, comparative measurements were undertaken in patients undergoing on- and off-pump cardiac surgery, the latter group presumably experiencing less ischemic stress. Methods: 30 patients undergoing elective coronary artery bypass surgery were assigned to the conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial (VE)-cadherin, and endocan at various time points. Results: There were significant increases in all measured parameters in both study groups versus the respective basal values. Maximal increases were as follows: Ang-1: CCAB +220%, OPCAB +166%, p #x3c; 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p #x3c; 0.05 each; VE-cadherin: CCAB +87%, OPCAB +66%, p #x3c; 0.05 each; endocan: CCAB +323%, OPCAB +72%, p #x3c; 0.05 each. Conclusion: The present study demonstrates the activation of endothelial cells, shedding of cell-cell contacts and a potential intrinsic counterregulation by Ang-1 and endocan in patients undergoing major cardiac surgery. Quantitatively greater deviations of parameters in the CCAB than in the OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and the extent of endothelial activation.
Eur Surg Res 2017;58:354–368

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Cardiac Mesenchymal Stem Cells Proliferate Early in the Ischemic Heart

Background/Purpose: Cardiac mesenchymal stem cells (MSCs) could stimulate cell-specific regenerative mechanisms after myocardial infarction (MI) depending on spatial origin, distribution, and niche regulation. We aimed at identifying and isolating tissue-specific cardiac MSCs that could contribute to regeneration. Methods: Following permanent ligation of the left anterior descending coronary artery in rats (n = 16), early cardiac tissues and cardiac mononuclear cells (MNCs) were analyzed by immunohistology, confocal laser scanning microscopy, and flow cytometry, respectively. Early postischemic specific MSCs were purified by fluorescence-activated cell sorting, cultivated under standardized culture conditions, and tested for multipotent differentiation in functional identification kits. Results: Cardiac MSC niches were detected intramyocardially in cell clusters after MI and characterized by positive expression for vimentin, CD29, CD44, CD90, CD105, PDGFRα, and DDR2. Following myocardial ischemia, proliferation was induced early and proliferation density was approximately 11% in intramyocardial MSC clusters of the peri-infarction border zone. Cluster sizes increased by 157 and 64% in the peri-infarction and noninfarcted areas of infarcted hearts compared with noninfarcted hearts 24 h following MI, respectively. Coincidentally, flow cytometry analyses illustrated postischemic moderate enrichments of CD45^–CD44⁺ and CD45^–DDR2⁺ cardiac MNCs. We enabled isolation of early postischemic culturable cardiac CD45^–CD44⁺DDR2⁺ MSCs that demonstrated typical clonogenicity with colony-forming unit-fibroblast formation as well as adipogenic, chondrogenic, and osteogenic differentiation. Conclusions: MI triggered early proliferation in specific cardiac MSC niches that were organized in intramyocardial clusters. Following targeted isolation, early postischemic cardiac CD45^–CD44⁺DDR2⁺ MSCs exhibited typical characteristics with multipotent differentiation capacity and clonogenic expansion.
Eur Surg Res 2017;58:341–353

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