The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

Abstract

Breast cancer (BC) is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer (TNBC) still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signaling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μM) that would not be compatible with further drug development against invasive breast cancer driven by FAK signaling. In this study, molecular modeling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesised and their anti-proliferative activity was evaluated against three human breast cancer lines (MDA-MB-231, BT474 and T47D). Compound 5c was identified to display an average activity of IC₅₀ = 23.5- 31.3 μM, which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series.

This article is protected by copyright. All rights reserved.

• 17 New chloropyramine (C4) analogues were designed and synthesised.

• All new compounds were evaluated for their activity in three different breast cancer cell lines.

• For the most active compound 5c, in vitro pharmacokinetic studies were performed.

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Comparative in vitro study on cytotoxicity of recombinant β-hairpin peptides

Abstract

Natural antimicrobial peptides (AMPs) are important components of the innate immune system with a wide spectrum of biological activity. In this study, we investigated the cytotoxic effect of three recombinant β-hairpin cationic AMPs: arenicin-1 from the polychaeta Arenicola marina, tachyplesin I from the horseshoe crab Tachypleus tridentatus, and gomesin from the spider Acanthoscurria gomesiana. All the three β-hairpin AMPs were overexpressed in E. coli. Different cell lines were incubated with various concentrations of the investigated AMPs in order to evaluate their cytotoxic activity. Double staining with subsequent flow cytometric analysis was used to determine the predominant way of cell death mediated by each AMP. Hemolytic activity of the peptides was tested against fresh human red blood cells. Our results indicated that all the three AMPs exhibited significant cytotoxic effect against cancer cells that varied depending on the cell line type and, in most cases, on the presence of serum components. Flow cytometric analysis implicitly indicated that tachyplesin I mostly promoted late apoptosis/necrosis, while arenicin-1 and gomesin induced early apoptosis under the same conditions. Tachyplesin I proved to be the most promising therapeutic candidate as it displayed the highest specific cytotoxicity against cancer cell lines, independent of the serum presence.

This article is protected by copyright. All rights reserved.

Natural antimicrobial peptides (AMPs) are important components of the innate immune system with a wide spectrum of biological activity. In this study, we investigated the cytotoxic effect of three recombinant β-hairpin cationic AMPs: arenicin-1 from the polychaeta Arenicola marina, tachyplesin I from the horseshoe crab Tachypleus tridentatus, and gomesin from the spider Acanthoscurria gomesiana. Tachyplesin I proved to be the most promising therapeutic candidate as it displayed the highest specific cytotoxicity against cancer cell lines, independent of the serum presence.

http://ift.tt/2wdkJbp

MicroRNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole miRNome profiling of human hippocampus

Summary

Objective

Mesial temporal lobe epilepsy (mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis (HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+HS complicates its therapy. The pathological mechanism underlying mTLE+HS may involve abnormal gene expression regulation, including posttranscriptional networks involving microRNAs (miRNAs). miRNA expression deregulation has been reported in various disorders, including epilepsy. However, the miRNA profile of mTLE+HS is not completely known and needs to be addressed.

Methods

Here, we have focused on hippocampal miRNA profiling in 33 mTLE+HS patients and nine postmortem controls to reveal abnormally expressed miRNAs. In this study, we significantly reduced technology-related bias (the most common source of false positivity in miRNA profiling data) by combining two different miRNA profiling methods, namely next generation sequencing and miRNA-specific quantitative real-time polymerase chain reaction.

Results

These methods combined have identified and validated 20 miRNAs with altered expression in the human epileptic hippocampus; 19 miRNAs were up-regulated and one down-regulated in mTLE+HS patients. Nine of these miRNAs have not been previously associated with epilepsy, and 19 aberrantly expressed miRNAs potentially regulate the targets and pathways linked with epilepsy (such as potassium channels, γ-aminobutyric acid, neurotrophin signaling, and axon guidance).

Significance

This study extends current knowledge of miRNA-mediated gene expression regulation in mTLE+HS by identifying miRNAs with altered expression in mTLE+HS, including nine novel abnormally expressed miRNAs and their putative targets. These observations further encourage the potential of microRNA-based biomarkers or therapies.

http://ift.tt/2uHbAIE

Can ad hoc analyses of clinical trials help personalize treatment decisions?

http://ift.tt/2wPnE7V

Biophysical processes supporting the diversity of microbial life in soil

Abstract

Soil, the living terrestrial skin of the Earth, plays a central role in supporting life and is home to an unimaginable diversity of microorganisms. This review explores key drivers for microbial life in soils under different climates and land-use practices at scales ranging from soil pores to landscapes. We delineate special features of soil as a microbial habitat (focusing on bacteria) and the consequences for microbial communities. This review covers recent modeling advances that link soil physical processes with microbial life (termed biophysical processes). Readers are introduced to concepts governing water organization in soil pores and associated transport properties and microbial dispersion ranges often determined by the spatial organization of a highly dynamic soil aqueous phase. The narrow hydrological windows of wetting and aqueous phase connectedness are crucial for resource distribution and longer range transport of microorganisms. Feedbacks between microbial activity and their immediate environment are responsible for emergence and stabilization of soil structure—the scaffolding for soil ecological functioning. We synthesize insights from historical and contemporary studies to provide an outlook for the challenges and opportunities for developing a quantitative ecological framework to delineate and predict the microbial component of soil functioning.

http://ift.tt/2vDbSz7

Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer

Abstract

In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort (n = 277, treatment between 2006 and 2009) and Recent cohort (n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high- and low-risk groups. Relative to the low-risk group, the high-risk patients had a shorter disease free survival (DFS) and overall survival (OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high- and low-risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high-risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery.

Daxx NCR can be used as a prognosis factor in GC patients, and may provide an alternative view on adjuvant chemotherapy in patients with gastric cancer.

http://ift.tt/2i4fkOh

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania

Sickle Cell Trait (SCT) has been shown to be protective against malaria. A growing literature suggests that malaria exposure can reduce educational attainment. This study assessed the relationship and interact...

http://ift.tt/2vGXep2

Examining self-reported and biological stress and near misses among Emergency Medicine residents: a single-centre cross-sectional assessment in the USA

Objectives

To examine the relationship between perceived and biological stress and near misses among Emergency Medicine residents.

Design

Self-rated stress and stress biomarkers were assessed in residents in Emergency Medicine before and after a day shift. The supervising physicians and residents reported numbers of near misses.

Setting

The study took place in the Emergency Department of a large trauma 1 centre, located in Detroit, USA.

Participants

Residents in Emergency Medicine volunteered to participate. The sample consisted of 32 residents, with complete data on 28 subjects. Residents' supervising physicians assessed the clinical performance of each resident.

Primary and secondary outcome measures

Participants' preshift and postshift stress, biological stress (salivary cortisol, plasma interleukin-6, tumour necrosis factor-alpha (TNF-α) and high-sensitivity C-reactive protein), residents' and supervisors' reports of near misses, number of critically ill and patients with trauma seen during the shift.

Results

Residents' self-reported stress increased from an average preshift level of 2.79 of 10 (SD 1.81) to a postshift level of 5.82 (2.13) (p<0.001). Residents cared for an average of 2.32 (1.52) critically ill patients and 0.68 (1.06) patients with trauma. Residents reported a total of 7 near misses, compared with 11 reported by the supervising physicians. After controlling for baseline work-related exhaustion, residents that cared for more patients with trauma and had higher levels of TNF-α reported a higher frequency of near misses (R²=0.72; p=0.001). Residents' preshift ratings of how stressful they expected the shift to be were related to the supervising physicians' ratings of residents' near misses during the shift.

Conclusion

Residents' own ratings of near misses were associated with residents' TNF-α, a biomarker of systemic inflammation and the number of patients with trauma seen during the shift. In contrast, supervisor reports on residents' near misses were related only to the residents' preshift expectations of how stressful the shift would be.

http://ift.tt/2w0t56G

An electronic trigger tool to optimise intravenous to oral antibiotic switch: a controlled, interrupted time series study

Timely switch from intravenous (iv) antibiotics to oral therapy is a key component of antimicrobial stewardship programs in order to improve patient safety, promote early discharge and reduce costs. We have in...

http://ift.tt/2w8TzD9

Epithelial-to-Mesenchymal and Mesenchymal-to-Epithelial Transition in Mesenchymal Tumors: A Paradox in Sarcomas?

The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described in several carcinomas, which are cancers of epithelial origin, and is crucial to metastatic tumor cell dissemination and drug resistance. In contrast, the precise role of EMT-related processes in tumors originating from mesenchymal tissues, such as bone and soft-tissues sarcomas, is still largely unclear. In fact, although the existence of the EMT in sarcomas appears paradoxical because these cancers are, by definition, mesenchymal ab initio, accumulating evidence suggests that many sarcomas can undergo EMT-related processes, which may be associated with aggressive clinical behavior. These processes may be especially operative in certain sarcoma subtypes, such as carcinosarcomas displaying a biphenotypic morphology with characteristics of both mesenchymal and epithelial tumors. In this review, we discuss findings regarding the potential existence of EMT-related processes in sarcomas and propose that sarcomas can reside in a metastable state, enabling them to become either more mesenchymal or epithelial under specific conditions, which likely has important clinical implications. Cancer Res; 77(17); 1–6. ©2017 AACR.

http://ift.tt/2fJoiQn

Transglutaminase 2 Is a Direct Target Gene of YAP-TAZ—Response

http://ift.tt/2i3iiTl

Transglutaminase 2 Is a Direct Target Gene of YAP/TAZ—Letter

http://ift.tt/2fJohvN

De Novo Lipid Synthesis facilitates Gemcitabine Resistance Through Endoplasmic Reticulum Stress In Pancreatic Cancer

Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients. Furthermore, we investigated the relationship between alterations in lipogenesis pathway and gemcitabine resistance by utilizing tissues from the genetically engineered mouse model and human pancreatic cancer patients. We observed a significant increase in fatty acid synthase (FASN) expression with increasing disease progression in a spontaneous pancreatic cancer mouse model, and a correlation of high FASN expression with poor survival in patients and poor gemcitabine responsiveness in cell lines. We observed a synergistic effect of FASN inhibitors with gemcitabine in pancreatic cancer cells in culture and orthotopic implantation models. Combination of gemcitabine and the FASN inhibitor orlistat significantly diminished stemness, in part due to induction of ER stress that resulted in apoptosis. Moreover, direct induction of ER stress with thapsigargin caused a similar decrease in stemness and showed synergistic activity with gemcitabine. Our in vivo studies with orthotopic implantation models demonstrated a robust increase in gemcitabine responsiveness upon inhibition of fatty acid biosynthesis with orlistat. Altogether, we demonstrate that fatty acid biosynthesis pathway manipulation can help overcome the gemcitabine resistance in pancreatic cancer by regulating ER stress and stemness.

http://ift.tt/2i4VBhN

Targeting a single alternative polyadenylation site coordinately blocks expression of androgen receptor mRNA splice variants in prostate cancer

Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3. Blocking this signal with morpholino technology or silencing of the polyadenylation factor CPSF1 caused a splice switch that inhibited expression of AR variants and blocked androgen-independent growth of CRPC cells. Our findings support the development of new therapies targeting the polyadenylation signal in AR intron 3 as a strategy to prevent expression of a broad array of AR variants in CRPC.

http://ift.tt/2fJnfzP

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature

Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first ...

http://ift.tt/2vGLti3

Synergistic Antioxidant and Anti-Inflammatory Effects between Modified Citrus Pectin and Honokiol

Inflammation is a normal physiological process; however, dysregulation of this process may contribute to inflammatory-based chronic disorders and diseases in animals and humans. Therefore, the antioxidant and anti-inflammatory properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled inflammatory processes which in turn potentially ameliorate or prevent sequelae of inflammatory-based symptoms of chronic diseases. We have investigated the antioxidant and anti-inflammatory effects of honokiol (HNK) and modified citrus pectin (MCP) in vitro and examined whether the MCP : HNK combination has synergistic effects on antioxidant and anti-inflammatory properties. Although both HNK and MCP induced a dose-dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. The MCP : HNK (9 : 1) combination induced a synergistic effect on antioxidant activity suggesting that the combination is significantly more efficacious than individual compounds. In mouse monocytes, the lipopolysaccharide- (LPS-) induced tumor necrosis- (TNF-) synthesis was significantly inhibited by HNK and the MCP : HNK combination in a dose-dependent manner and synergistic effects were clearly demonstrated with the combination on TNF- inhibition. This combination effect was also evident on inhibition of nuclear factor-kappa B activity, cyclooxygenase-II activity, and lipid peroxidation in mouse monocytes. Further research into the combination is warranted.

http://ift.tt/2x2n06r

Immunotherapy-Resistance Genes Identified [News in Brief]

CRISPR screen identifies top 100 genes that tumors must have for T cell–mediated destruction to work.

http://ift.tt/2vGNb30

$10M Gift Supports "Data Recycling" at UCSF [News in Brief]

The approach involves mining existing data to uncover potential uses for existing drugs, improve care.

http://ift.tt/2vZOKvF

Variable forgetting factor mechanisms for diffusion recursive least squares algorithm in sensor networks

In this work, we present low-complexity variable forgetting factor (VFF) techniques for diffusion recursive least squares (DRLS) algorithms. Particularly, we propose low-complexity VFF-DRLS algorithms for dist...

http://ift.tt/2w8yoRG

The association between tuberculosis and the development of insulin resistance in adults with pulmonary tuberculosis in the Western sub-district of the Cape Metropole region, South Africa: a combined cross-sectional, cohort study

The existence of a bi-directional relationship between tuberculosis (TB) and insulin resistance (IR)/diabetes has been alluded to in literature. Although diabetes has been linked to increased tuberculosis risk...

http://ift.tt/2vZMnJh

Predictors of delayed care seeking for tuberculosis in southern India: an observational study

Reducing delay to accessing care is necessary to reduce the Tuberculosis (TB) burden in high incidence countries such as India. This study aimed to identify factors associated with delays in seeking care for T...

http://ift.tt/2vGB7yF

Secondary organizing pneumonia following viral pneumonia caused by severe influenza B: a case report and literature reviews

Some reported that organizing pneumonia (OP) may occur after influenza A infections including swine-origin influenza A (H1N1). However, OP associated with influenza B infection has never been reported. We repo...

http://ift.tt/2vZvVIN

Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study

Objective. This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD) assisted sonolysis in both the in vitro and in vivo clots. Methods. Therapeutic ultrasound (TUS) and lipid microbubbles (MBs) were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI) and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT) in rabbits. FAT were dyed with H&E. Results. The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both ). Clots had different pathological changes. Recanalization rates and flow scores in TUS + MB group were significantly higher than the control and TUS group. Flow scores and recanalization ratios were grade 0 in 0% of the control group, grade I in 25% of TUS group, and grade II or higher in 87.5% of TUS + MB group after 30 min sonolysis. Conclusions. Both the in vitro and in vivo sonolysis can be significantly augmented by the introduction of MBs without thrombolytic agents, which might be induced by the enhanced cavitation via UMMD.

http://ift.tt/2vBrXVQ

Emotion Recognition from EEG Signals Using Multidimensional Information in EMD Domain

This paper introduces a method for feature extraction and emotion recognition based on empirical mode decomposition (EMD). By using EMD, EEG signals are decomposed into Intrinsic Mode Functions (IMFs) automatically. Multidimensional information of IMF is utilized as features, the first difference of time series, the first difference of phase, and the normalized energy. The performance of the proposed method is verified on a publicly available emotional database. The results show that the three features are effective for emotion recognition. The role of each IMF is inquired and we find that high frequency component IMF1 has significant effect on different emotional states detection. The informative electrodes based on EMD strategy are analyzed. In addition, the classification accuracy of the proposed method is compared with several classical techniques, including fractal dimension (FD), sample entropy, differential entropy, and discrete wavelet transform (DWT). Experiment results on DEAP datasets demonstrate that our method can improve emotion recognition performance.

http://ift.tt/2wNVaeN

Can Mixed Parasite Infections Thwart Targeted Malaria Elimination Program in India?

India is highly endemic to malaria with prevalence of all five species of human malaria parasites of Plasmodium genus. India is set for malaria elimination by 2030. Since cases of mixed Plasmodium species infections remain usually undetected but cause huge disease burden, in order to understand the distributional prevalence of both monospecies infections and mixed species infections in India, we collated published data on the differential infection incidences of the five different malaria parasites based on PCR diagnostic assay. About 11% of total cases were due to mixed species infection. Among several interesting observations on both single and mixed parasitic infections, incidences of Plasmodium falciparum monoinfection were found to be significantly higher than P. vivax monoinfection. Also, P. malariae seems to be emerging as a potential malaria threat in India. Putting all the facts together, it appears that the dream of achieving malaria elimination in India will not be completely successful without dealing with mixed species infection.

http://ift.tt/2vCGOQ1

Predictors of Hypertension among Nonpregnant Females Attending Health Promotion Clinic with Special Emphasis on Smokeless Tobacco: A Cross-Sectional Study

Aim. To determine the predictors of hypertension among nonpregnant females attending a health promotion clinic. Design and Setting. A cross-sectional study was conducted during March to June 2016, at the National Institute of Cancer Prevention and Research, India. Methods. The study included 319 nonpregnant females of age 20–70 years. Demographics such as age, literacy, and income were noted. History regarding use, frequency, and quantity of smokeless tobacco was taken. Height, weight, and blood pressure were measured and body mass index was calculated. Statistical Analysis. Pearson's product-moment correlation coefficient was calculated between each of the variables of age, smokeless tobacco consumption, and body mass index versus systolic and diastolic blood pressure, respectively. The linear as well as multiple linear regression analysis was employed to identify the risk factors for hypertension. Results. A univariate linear regression analysis showed that age, smokeless tobacco consumption, and body mass index were associated with systolic blood pressure ( value

http://ift.tt/2wO22ZC

Impact of Thyroid Hormone Levels on Functional Outcome in Neurological and Neurosurgical Early Rehabilitation Patients

Background. Neurological and neurosurgical early rehabilitation (NNER) is a specialized treatment option for patients with severe neurological disorders. The present study investigated whether thyroid hormone levels on admission have an impact on the outcome of NNER patients. Method. The study included 500 NNER patients who were admitted to the BDH-Clinic Hessisch Oldendorf between 2009 and 2010. Data such as age, sex, diagnoses, comorbidities, Glasgow Coma Scale score, length of stay, and thyroid hormone levels (obtained as part of clinical routine care) were analyzed retrospectively. Improvement in the Early Rehabilitation Barthel Index (ERBI) at the end of the NNER treatment was defined as outcome parameter. Results. Most patients made functional progress during treatment, as reflected in significant enhancements of the ERBI. Approximately half of the patients were transferred to further rehabilitation treatment. Young age, early onset of NNER treatment, low functional impairment on admission, and, in particular, low total T3 levels were independently associated with a good outcome. Conclusion. Age, severity of disease, and time between injury and admission are known to predict outcome. The present study confirms the influence of these general factors. In addition, an association between thyroid hormones and functional outcome was demonstrated for NNER patients.

http://ift.tt/2vC9qsN

Combination of celecoxib (Celebrex(®)) and CD19 CAR-redirected CTL immunotherapy for the treatment of B-cell non-Hodgkin's lymphomas.

Related Articles

Combination of celecoxib (Celebrex(®)) and CD19 CAR-redirected CTL immunotherapy for the treatment of B-cell non-Hodgkin's lymphomas.

Am J Clin Exp Immunol. 2017;6(3):27-42

Authors: Dinh TN, Onea AS, Jazirehi AR

Abstract
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family. CD19-redirected chimeric antigen-receptor (CD19 CAR) T cell therapy has shown promise in the treatment of B cell malignancies. Considering its regulatory effect on apoptotic gene products in various tumor types, Celecoxib is a promising drug to be used in combination with CD19 CAR T cell therapy to optimize immunotherapy of NHL.

PMID: 28804691 [PubMed]

http://ift.tt/2fHORW8

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

Abstract

Background

Several of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood.

Methods

LncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation. The role of HOXD-AS1 in HCC cells was assessed both in vitro and in vivo. ceRNA function of HOXD-AS1 was evaluated by RNA immunoprecipitation and biotin-coupled miRNA pull down assays.

Results

In this study, we found that HOXD-AS1 was significantly upregulated in HCC tissues. Clinical investigation demonstrated high expression level of HOXD-AS1 was associated with poor prognosis and high tumor node metastasis stage of HCC patients, and was an independent risk factor for survival. Moreover, our results revealed that STAT3 could specifically interact with the promoter of HOXD-AS1 and activate HOXD-AS1 transcription. Knockdown of HOXD-AS1 significantly inhibited migration and invasion of HCC cells in vitro and distant lung metastasis in vivo. Additionally, HOXD-AS1 was enriched in the cytoplasm, and shared miRNA response elements with SOX4. Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA-mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis.

Conclusions

In summary, HOXD-AS1 is a prognostic marker for HCC patients and it may play a pro-metastatic role in hepatocarcinogenesis.

http://ift.tt/2uZXai5

In vitro antiplasmodial activity and prophylactic potentials of extract and fractions of Trema orientalis (Linn.) stem bark

Trema orientalis (T. orientalis Linn) has been used in the management of malaria in the western part of Nigeria and despite its application in ethnomedicine, there is dearth of scienti...

http://ift.tt/2fJUEuh

Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: comparison in terms of melphalan pharmacokinetic pelvic bio-availability

Isolated pelvic perfusion (IPP) can be used to treat unresectable melanoma metastases of the pelvis. IPP can be performed either by surgical or percutaneous approaches, using different balloon catheters. The a...

http://ift.tt/2vZwiDi

Chikungunya: an emerging viral infection with varied clinical presentations in Bangladesh: Reports of seven cases

Chikungunya is an emerging and rapidly spreading viral infection in many parts of the world including Bangladesh. It shares many epidemiological and clinical characteristics with dengue. So, a sound knowledge ...

http://ift.tt/2vH4Mbk

Strength of Occipital Hair as an Explanation for Pilonidal Sinus Disease Caused by Intruding Hair

BACKGROUND: Pilonidal sinus disease is thought to be caused by intrusion of hair into healthy skin; loose hair in the intergluteal fold is thought to promote disease. However, compelling evidence to support these postulates is lacking; the cause of pilonidal sinus disease remains uncertain. OBJECTIVE: To determine whether particular properties of hair are associated with susceptibility to pilonidal sinus disease, we compared physical properties of hairs of patients with pilonidal sinus disease with hairs from control subjects who were matched for sex, BMI, and age. DESIGN: This was an experimental study with establishment of a mechanical strength test for single hairs to quantify the maximum vertical force that a hair could exert, following tests of strength of occipital, lumbar, and intergluteal hair. SETTINGS: Hair from patients with pilonidal sinus disease and matched control subjects were harvested from patients of the St. Marienhospital Vechta Department of Procto-Surgery. PATIENTS: A total of 17 adult patients with pilonidal sinus disease and 217 control subjects were included. MAIN OUTCOME MEASURES: ANOVA and intraclass and interclass variations of data gained from mechanical strength tests of occipital, lumbar, and intergluteal hair were included. RESULTS: Vertical hair strength was significantly greater in patients with pilonidal sinus disease. Occipital hair exhibited 20% greater, glabella sacralis 1.1 times greater, and intergluteal hair 2 times greater strength in patients with pilonidal sinus disease than in matched control subjects (all p = 0.0001). In addition, patients with pilonidal sinus disease presented with significantly more hair at the glabella sacralis and in the intergluteal fold. LIMITATIONS: The study was limited by its relatively small number of patients from a specific cohort of European patients. CONCLUSIONS: Occipital hair exhibited considerable vertical strength. Because occipital hair exerted the greatest force and cut hair fragments were found in the pilonidal nest in large quantities, these data suggest that pilonidal sinus disease is promoted by occipital hair. See Video Abstract at http://ift.tt/2w81gtm .

http://ift.tt/2w8nFa7

Residency Programs in Colon and Rectal Surgery

No abstract available

http://ift.tt/2x1Z7vZ

What Every Colorectal Surgeon Should Know About the Medicare Access and Children’s Health Insurance Program Reauthorization Act of 2015

No abstract available

http://ift.tt/2w8qR5k

Is the Failure of Laparoscopic Peritoneal Lavage Predictable in Hinchey III Diverticulitis Management?

BACKGROUND: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in Hinchey III diverticulitis (generalized purulent peritonitis). The main limitation of laparoscopic peritoneal lavage is the higher rate of reoperation for persistent sepsis in comparison with sigmoid resection. OBJECTIVE: The purpose of the current study was to identify risk factors for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. DESIGN: This was a retrospective multicenter study. SETTINGS: The study was conducted in 3 clinical sites in France. PATIENTS: From 2006 to 2015, all consecutive patients undergoing emergent surgery for diverticulitis were reviewed. All patients operated on with laparoscopic peritoneal lavage for laparoscopically confirmed Hinchey III diverticulitis were included. MAIN OUTCOME MEASURES: The main outcome was laparoscopic peritoneal lavage failure, defined as reoperation or death at 30 postoperative days. RESULTS: A series of 71 patients (43 men, mean age 58 ± 15 years) were operated on with laparoscopic peritoneal lavage for Hinchey III diverticulitis. Laparoscopic peritoneal lavage failed in 14 (20%) of them: 1 died and 13 underwent reoperations. No major complication (Dindo-Clavien score ≥3) occurred after reoperation. Immunosuppressive drugs (p = 0.01) and ASA grade ≥3 (p = 0.02) were associated with laparoscopic peritoneal lavage failure after univariate analysis. Multivariate analysis identified only immunosuppressive drug intake (steroids or chemotherapy for cancer) as an independent predictive factor. Mean length of stay was 14.9 days (5–67). At the end of the 30 first postoperative days, 12 (17%) patients had a stoma. LIMITATIONS: The study was limited by its retrospective nature and the small size of the cohort. CONCLUSION: Our results highlight immunosuppressive drug intake as a major risk factor for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. Immunosuppression and severe comorbidities (ASA ≥3) should be considered when selecting a surgical option in patients with Hinchey III diverticulitis. See Video Abstract at http://ift.tt/2fIqc3X .

http://ift.tt/2w8qPdI

The Authors Reply

No abstract available

http://ift.tt/2x23W8b

Patient, Hospital, and Geographic Disparities in Laparoscopic Surgery Use Among Surveillance, Epidemiology, and End Results–Medicare Patients With Colon Cancer

BACKGROUND: Surgical resection is the primary treatment for colon cancer, but use of laparoscopic approaches varies widely despite demonstrated short- and long-term benefits. OBJECTIVE: The purpose of this study was to identify characteristics associated with laparoscopic colon cancer resection and to quantify variation based on patient, hospital, and geographic characteristics. DESIGN: Bayesian cross-classified, multilevel logistic models calculated adjusted ORs and CIs for patient, surgeon, hospital, and geographic characteristics and unexplained variability (predicted vs. observed values) using adjusted median odds ratios for hospitals and counties. SETTINGS: The Surveillance, Epidemiology, and End Results–Medicare claims database (2008–2011) supplemented with county-level American Community Survey (2008–2012) demographic data was used. PATIENTS: A total of 10,618 patients ≥66 years old who underwent colon cancer resection were included. MAIN OUTCOME MEASURES: Nonurgent/nonemergent resections for colon cancer patients ≥66 years old were classified as laparoscopic or open procedures. RESULTS: Patients resided in 579 counties and used 950 hospitals; 47% of patients underwent laparoscopic surgery. Medicare/Medicaid dual enrollment, age ≥85 years, and higher tumor stage and grade were negatively associated with laparoscopic surgery receipt; proximal tumors and increasing hospital size and surgeon caseload were positively associated. Significant unexplained variability at the hospital (adjusted median OR = 3.31; p

http://ift.tt/2x27U0H

Postoperative Chemoradiotherapy After Local Resection for High-Risk T1 to T2 Low Rectal Cancer: Results of a Single-Arm, Multi-Institutional, Phase II Clinical Trial

BACKGROUND: After treatment with local excision for TNM stage I low rectal cancer, the risk of local recurrence is not only high for T2 lesions but also for T1 lesions with features of massive invasion to the submucosal layer and/or lymphovascular invasion. OBJECTIVE: The purpose of this study was to determine the efficacy of chemoradiotherapy combined with local excision in the treatment of T1 to T2 low rectal cancer. DESIGN: We conducted a prospective, single-arm, phase II trial. SETTINGS: This was a multicenter study. PATIENTS: From April 2003 to October 2010, 57 patients were treated with local excision after additional external beam irradiation (45 Gy) plus continuous 5-week intravenous injection of 5-fluorouracil (250 mg/m2 per day) at 10 domestic hospitals. Fifty-three patients had clinical T1N0 lesions, and 4 had T2N0 lesions in the low rectum, located below the peritoneal reflection. MAIN OUTCOMES MEASURES: The primary end point was disease-free survival at 5 years. RESULTS: The completion rate for full-dose chemoradiotherapy was 86% (49/57). Serious, nontransient treatment-related complications were not reported. With a median follow-up of 7.3 years after local excision, the 5-year disease-free survival rate was 94% for the 53 patients with T1 lesions and 75% for the 4 patients with T2 lesions. There were 2 local recurrences during the entire observation period. Anal function after local excision and chemoradiation were kept at almost the same levels as observed before treatment. LIMITATIONS: The study was limited by the small number of registered T2 rectal cancers, retrospective evaluations of quality of life, and the exclusion of poorly differentiated adenocarcinoma (a high-risk feature of T1 lesions). CONCLUSIONS: The addition of chemoradiotherapy to local excision of T1 rectal adenocarcinomas with poor prognostic features including deep submucosal invasion and lymphovascular invasion could improve on less favorable historic oncologic outcomes of local excision alone in this high-risk group for lymph node metastasis. See Video Abstract at http://ift.tt/2i2zXuo .

http://ift.tt/2w8ixTs

Surgical Site Infection in Colorectal Surgery: A Study in Antibiotic Duration

BACKGROUND: Despite distant historical studies that demonstrated the adequacy of preoperative antibiotic prophylaxis, current surgical practice continues to use antibiotics for postoperative coverage up to 24 hours. OBJECTIVE: The aim of this study was to evaluate a change in antibiotic prophylaxis duration and its effect on surgical site infection in a high-volume modern colorectal practice. DESIGN: A case-controlled series retrospectively reviewed outcomes through a prospective validated data base. SETTING: The study was conducted at Mayo Clinic, Rochester, Minnesota. PATIENTS: A total of 965 patients were evaluated. Our study analyzed patient outcomes related to surgical site infection comparing cohort 1 (2012–2013), which had the same antibiotic coverage preoperatively up to 24 hours postoperatively, and cohort 2 (2014–2015), which eliminated postoperative doses and relied solely on pre- and intraoperative dosing duration. MAIN OUTCOME MEASURES: The primary outcomes of this study are superficial and deep surgical site infection. RESULTS: There were no differences identified for superficial or deep surgical site infection rates between cohorts. Before the change in antibiotic dosing duration (2012–2013), 28 of 493 patients (5.7%) vs after the practice change (2014–2015), 25 of 472 patients (5.3%) were reported to have superficial or deep surgical site infection (p = 0.794). LIMITATIONS: This study is limited by its retrospective design within a single institution. CONCLUSION: These equivalent results present an opportunity for surgeons to reconsider optimal antibiotic duration and minimize unnecessary antibiotic dosing. See Video Abstract at http://ift.tt/2x27TtF .

http://ift.tt/2x23TJx

Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus

BACKGROUND: Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. OBJECTIVE: The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at Commission on Cancer designated hospitals. PATIENTS: Patients (2006–2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. MAIN OUTCOME MEASURES: Overall survival and the need for salvage surgery were measured. RESULTS: Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p

http://ift.tt/2x2ke0V

Measurement Bias of Polyp Size at Colonoscopy

BACKGROUND: The success of current and proposed strategies to reduce colorectal cancer (CRC) incidence and mortality rates are fundamentally based on measurement accuracy. OBJECTIVE: The aim of this study was to evaluate the densities of colorectal polyps individually measured at colonoscopy and whether measurement bias is a systemic phenomenon among colonoscopists. DESIGN: A population-wide, observational study. SETTING: All hospitals of the government-funded health system in Brisbane, Australia. PATIENTS: Our study investigated measurement bias at colonoscopy through systematic analysis of 8,591 individual polyp measurements recorded from 12,597 colonoscopies. All colonoscopies performed over a 12-month period between December 1, 2014, and November 30, 2015, were included. RESULTS: A total of 12,597 electronic colonoscopy reports were individually reviewed, hospital-by-hospital, and 8,591 individual size measurements from 18,276 detected polyps (47%) were obtained. LIMITATIONS: Our study is limited because the true size of unresected polyps was unknown. We chose not to compare pathologic and histologic sizes as resection specimens sent to pathologists are morphologically different and are measured differently to the pre-resection polyp images seen by endoscopists. CONCLUSIONS: Colonoscopists may be inaccurate in the measurement of polyp size and appear biased towards and against certain size measurements. These findings cast doubt over the validity of international post-polypectomy surveillance guidelines and the safety of optical diagnosis as a potential management paradigm for diminutive colorectal polyps. They also question the historical accuracy of polyp size data and risk estimates upon which these strategies were based.

http://ift.tt/2x2lWPM

Quality of Local Excision for Rectal Neoplasms Using Transanal Endoscopic Microsurgery Versus Transanal Minimally Invasive Surgery: A Multi-institutional Matched Analysis

BACKGROUND: There are no data comparing the quality of local excision of rectal neoplasms using transanal endoscopic microsurgery and transanal minimally invasive surgery. OBJECTIVE: The purpose of this study was to compare the incidence of tumor fragmentation and positive margins for patients undergoing local excision of benign and malignant rectal neoplasms using transanal endoscopic microsurgery versus transanal minimally invasive surgery. DESIGN: This was a multi-institutional cohort study using coarsened exact matching. SETTINGS: The study was conducted at high-volume tertiary institutions with specialist colorectal surgeons. PATIENTS: Patients undergoing full-thickness local excision for benign and malignant rectal neoplasms were included. INTERVENTIONS: Transanal endoscopic microsurgery and transanal minimally invasive surgery were the included interventions. MAIN OUTCOME MEASURES: The incidence of poor quality excision (composite measure including tumor fragmentation and/or positive resection margin) was measured. RESULTS: The matched cohort consisted of 428 patients (247 with transanal endoscopic microsurgery and 181 with transanal minimally invasive surgery). Transanal minimally invasive surgery was associated with shorter operative time and length of stay. Poor quality excision was similar (8% vs 11%; p = 0.233). There were also no differences in peritoneal violation (3% vs 3%; p = 0.965) and postoperative complications (11% vs 9%; p = 0.477). Cumulative 5-year disease-free survival for patients undergoing transanal endoscopic microsurgery was 80% compared with 78% for patients undergoing transanal minimally invasive surgery (log rank p = 0.824). The incidence of local recurrence for patients with malignancy who did not undergo immediate salvage surgery was 7% (8/117) for transanal endoscopic microsurgery and 7% (7/94) for transanal minimally invasive surgery (p = 0.864). LIMITATIONS: All of the procedures were also performed at high-volume referral centers by specialist colorectal surgeons with slightly differing perioperative practices and different time periods. CONCLUSIONS: High-quality local excision for benign and rectal neoplasms can be equally achieved using transanal endoscopic microsurgery or transanal minimally invasive surgery. The choice of operating platform for local excisions of rectal neoplasms should be based on surgeon preference, availability, and cost. See Video Abstract at http://ift.tt/2fHjdrR .

http://ift.tt/2fJoy1O

Serum Albumin: A Promising Biomarker to Anticipate Postoperative Complications

No abstract available

http://ift.tt/2i3P46V

Is MRI of the Liver Needed During Routine Preoperative Workup for Colorectal Cancer?

BACKGROUND: The clinical efficacy of gadoxetic acid–enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer remains unclear. OBJECTIVE: The purpose of this study was to evaluate the efficacy of preoperative gadoxetic acid–enhanced liver MRI for the diagnosis of liver metastasis in patients with colorectal cancer. DESIGN: This was a retrospective analysis from a prospective cohort database. SETTINGS: All of the patients were from a subspecialty practice at a tertiary referral hospital. PATIENTS: Patients who received preoperative gadoxetic acid–enhanced liver MRI after CT and attempted curative surgery for colorectal cancer were included. MAIN OUTCOME MEASURES: The number of equivocal hepatic lesions based on CT and gadoxetic acid–enhanced liver MRI and diagnostic use of the gadoxetic acid–enhanced liver MRI were measured. RESULTS: We reviewed the records of 690 patients with colorectal cancer. Equivocal hepatic lesions were present in 17.2% of patients based on CT and in 4.5% based on gadoxetic acid–enhanced liver MRI. Among 496 patients with no liver metastasis based on CT, gadoxetic acid–enhanced liver MRI detected equivocal lesions in 15 patients and metastasis in 3 patients. Among 119 patients who had equivocal liver lesions on CT, gadoxetic acid–enhanced liver MRI indicated hepatic lesions in 103 patients (86.6%), including 90 with no metastasis and 13 with metastasis. Among 75 patients who had liver metastasis on CT, gadoxetic acid–enhanced liver MRI indicated that the hepatic lesions in 2 patients were benign, in contrast to CT findings. The initial surgical plans for hepatic lesions according to CT were changed in 17 patients (3%) after gadoxetic acid–enhanced liver MRI. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The clinical efficacy of gadoxetic acid–enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer is low, in spite of its high diagnostic value for detecting liver metastasis. However, this study showed gadoxetic acid–enhanced liver MRI was helpful in characterizing equivocal hepatic lesions identified in CT and could lead to change in treatment plans for some patients. See Video Abstract at http://ift.tt/2fHxSU3 .

http://ift.tt/2i3OV3n

Metronidazole for Posthemorrhoidectomy Pain: Does No Statistical Significance Mean Insignificant Effect on Pain Relief?

No abstract available

http://ift.tt/2fIAwsC

The Sexting Phenomenon in Spanish Nursing Students

One of the adverse effects arising among young people who engage in various social practices is the phenomenon of sexting. Sexting involves the production and delivery of sexual content voluntarily and freely and, in many cases, without the consent of the recipient. The aim of this study was to describe the presence of sexting in undergraduate students at the College of Nursing of the University of Almeria in Spain. It is a descriptive cross-sectional quantitative study. A total of 105 undergraduate nursing students completed the sexuality and technology questionnaire. The questionnaire consists of seven dimensions with 59 items. Depending on size, statistically significant differences between the use of social networks and the dimension "sexting actions completed" and the dimension "position on statements about sexting" were found. No statistically significant differences between gender and the practice of sexting were found. The three main reasons for sexting match in both genders, these being "to draw attention," "as a sexy gift," and "to feel sexy." Nursing students associated behaviors to show sexting, being a standard practice, common in both genders. Future research should consider the possible influence of this behavior on future professionals and on the field of nursing.

http://ift.tt/2uZIvDx

Member Highlights at the NENIC 2017 Annual Symposium

No abstract available

http://ift.tt/2uZq6GM

Establishing a Classification System for High Fall-Risk Among Inpatients Using Support Vector Machines

We constructed a model using a support vector machine to determine whether an inpatient will suffer a fall on a given day, depending on patient status on the previous day. Using fall report data from our own facility and intensity-of-nursing-care-needs data accumulated through hospital information systems, a dataset comprising approximately 1.2 million patient-days was created. Approximately 50% of the dataset was used as training and testing data. A multistep grid search was conducted using the semicomprehensive combination of three parameters. A discriminant model for the testing data was created for each parameter to identify which parameter had the highest score by calculating the sensitivity and specificity. The score of the model with the highest score had a sensitivity of 64.9% and a specificity of 69.6%. By adopting a method that relies on daily data recorded in the electronic medical record system and accurately predicts unknown data, we were able to overcome issues described in previous studies while simultaneously constructing a discriminant model for patients' fall risk that does not burden nurses and patients with information gathering.

http://ift.tt/2uZZHZt

The Relationship Between Magnet Designation, Electronic Health Record Adoption, and Medicare Meaningful Use Payments

The objective of this study was to examine the relationship between nursing excellence and electronic health record adoption. Of 6582 US hospitals, 4939 were eligible for the Medicare Electronic Health Record Incentive Program, and 6419 were eligible for evaluation on the HIMSS Analytics Electronic Medical Record Adoption Model. Of 399 Magnet hospitals, 330 were eligible for the Medicare Electronic Health Record Incentive Program, and 393 were eligible for evaluation in the HIMSS Analytics Electronic Medical Record Adoption Model. Meaningful use attestation was defined as receipt of a Medicare Electronic Health Record Incentive Program payment. The adoption electronic health record was defined as Level 6 and/or 7 on the HIMSS Analytics Electronic Medical Record Adoption Model. Logistic regression showed that Magnet-designated hospitals were more likely attest to Meaningful Use than non-Magnet hospitals (odds ratio = 3.58, P

http://ift.tt/2uZvpX2

Can Mobile Technology Enhance Learning and Change Educational Practice?

No abstract available

http://ift.tt/2uZq6qg

e-Prescribing in the Acute Care Setting: Determining the Educational and Motivational Needs of Healthcare Providers

The study sought to determine the barriers to e-prescribing particular to the acute care setting, the educational and motivational needs of acute care providers, and the optimal process for incentive, education, and implementation of e-prescribing. A theoretically based survey instrument was adapted from previous work. Four domains were assessed: finesse, intent to use, perceived usefulness, and perceived ease of use. The survey was offered to a group of acute care providers. The educational and motivational needs of acute care providers are different from those in primary care. Perceived barriers centered on uncertain pharmacy hours, unconfirmed transmittal, and accidental transmission to wrong pharmacy. Healthcare providers with more self-assessed knowledge of e-prescribing are more likely to use e-prescribing. Providers with fewer years in practice seem to have greater knowledge of e-prescribing. Providing education and exposure to e-prescribing has the potential to decrease perception of barriers and increase perceived usefulness for acute care providers. Software redesign may be needed to remove barriers associated with uncertain pharmacy hours, controlled substance prescribing, transmittal confirmation, and bidirectional communication needs, thereby improving motivation to e-prescribe.

http://ift.tt/2uZc3kL

Implementation of Electronic Health Records in US Nursing Homes

While electronic health records have emerged as promising tools to help improve quality of care, nursing homes have lagged behind in implementation. This study assessed electronic health records implementation, associated facility characteristics, and potential impact on quality indicators in nursing homes. Using national Centers for Medicare & Medicaid Services and survey data for nursing homes, a cross-sectional analysis was conducted to identify variations between nursing homes that had and had not implemented electronic health records. A difference-in-differences analysis was used to estimate the longitudinal effect of electronic health records on commonly used quality indicators. Data from 927 nursing homes were examined, 49.1% of which had implemented electronic health records. Nursing homes with electronic health records were more likely to be nonprofit/government owned (P = .04) and had a lower percentage of Medicaid residents (P = .02) and higher certified nursing assistant and registered nurse staffing levels (P = .002 and .02, respectively). Difference-in-differences analysis showed greater quality improvements after implementation for five long-stay and two short-stay quality measures (P = .001 and .01, respectively) compared with those who did not implement electronic health records. Implementation rates in nursing homes are low compared with other settings, and better-resourced facilities are more likely to have implemented electronic health records. Consistent with other settings, electronic health records implementation improves quality in nursing homes, but further research is needed to better understand the mechanism for improvement and how it can best be supported.

http://ift.tt/2uZFHX7

Using an iPad for Basic Communication Between Spanish-Speaking Families and Nurses in Pediatric Acute Care: A Feasibility Pilot Study

The growing number of Spanish speakers in the United States poses communication challenges for healthcare providers. Language barriers in pediatric acute care have been associated with an increased risk for adverse events, longer hospital stays, and decreased quality of care. In addition, clinicians' usage of interpreter services is inconsistent. In fact, nurses often lack interpreter support during daily bedside care. Nursing staff at a pediatric children's hospital in the southeastern United States identified bedside communication with Spanish-speaking patients and families as a clinical challenge. To address this challenge, a basic communication interface, UTalk version 1.0 (the author is the owner and proprietor), supported by an Apple iPad, was developed by the researcher with input from nursing staff, a certified medical interpreter, and Spanish-speaking community members. A feasibility pilot study of the interface's usability and engagement was conducted on the hospital's pediatric medical-surgical unit through qualitative interviews with nurse-family dyads. Three themes emerged from the data: UTalk-facilitated communication, UTalk needs improvement, and interpreter miscommunication. These findings indicate that a mobile digital device interface is a feasible method for augmenting bedside communication with Spanish-speaking patients and families. These results also may serve as a reference for the development of similar mobile device interfaces. Further research with a larger sample size is needed.

http://ift.tt/2uZi3Km

e-Prescribing in the Acute Care Setting: Determining the Educational and Motivational Needs of Healthcare Providers

No abstract available

http://ift.tt/2uGRwGa

DNA degrades during storage in formalin-fixed and paraffin-embedded tissue blocks

Abstract

Formalin-fixed paraffin-embedded (FFPE) tissue blocks are widely used to identify clinically actionable molecular alterations or perform retrospective molecular studies. Our goal was to quantify degradation of DNA occurring during mid to long-term storage of samples in usual conditions. We selected 46 FFPE samples of surgically resected carcinomas of lung, colon, and urothelial tract, of which DNA had been previously extracted. We performed a second DNA extraction on the same blocks under identical conditions after a median period of storage of 5.5 years. Quantitation of DNA by fluorimetry showed a 53% decrease in DNA quantity after storage. Quantitative PCR (qPCR) targeting KRAS exon 2 showed delayed amplification of DNA extracted after storage in all samples but one. The qPCR/fluorimetry quantification ratio decreased from 56 to 15% after storage (p < 0.001). Overall, remaining proportion of DNA analyzable by qPCR represented only 11% of the amount obtained at first extraction. Maximal length of amplifiable DNA fragments assessed with a multiplex PCR was reduced in DNA extracted from stored tissue, indicating that DNA fragmentation had increased in the paraffin blocks during storage. Next-generation sequencing was performed on 12 samples and showed a mean 3.3-fold decrease in library yield and a mean 4.5-fold increase in the number of single-nucleotide variants detected after storage. In conclusion, we observed significant degradation of DNA extracted from the same FFPE block after 4 to 6 years of storage. Better preservation strategies should be considered for storage of FFPE biopsy specimens.

http://ift.tt/2x1U92j

SAXS versus FRET: A Matter of Heterogeneity?

Determining how conformational properties of unfolded proteins vary as a function of denaturant concentration has important implications for understanding the early stages of protein folding, and for our understanding of protein-solvent interactions. Upon dilution from a high concentration of denaturant into native conditions, does an unfolded protein undergo collapse first followed by folding, or does the chain remain expanded before folding and collapse occur concomitantly? The global dimensions of a protein are captured by its radius of gyration (Rg), meaning that, in principle, this question should be simple to answer by measuring Rg as a function of denaturant concentration.

http://ift.tt/2uMyni0

SAXS versus FRET: A Matter of Heterogeneity?

Determining how conformational properties of unfolded proteins vary as a function of denaturant concentration has important implications for understanding the early stages of protein folding, and for our understanding of protein-solvent interactions. Upon dilution from a high concentration of denaturant into native conditions, does an unfolded protein undergo collapse first followed by folding, or does the chain remain expanded before folding and collapse occur concomitantly? The global dimensions of a protein are captured by its radius of gyration (Rg), meaning that, in principle, this question should be simple to answer by measuring Rg as a function of denaturant concentration.

http://ift.tt/2uMyni0

Predicting response to radical (chemo)radiotherapy with circulating HPV DNA locally advanced head and neck squamous carcinoma

http://ift.tt/2vZtgz3

GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

http://ift.tt/2vGptE0

Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer

http://ift.tt/2vZcUGD

Study Uncovers Previously Unrecognized Effect of Chemotherapy

A new study conducted primarily in mice suggests that chemotherapy given before surgery for breast cancer can cause changes in cells in and around the tumor that are tied to an increased risk of the cancer spreading to other areas of the body.

http://ift.tt/2wNzboq

Real-time In Vivo Recording of Arabidopsis Calcium Signals During Insect Feeding Using a Fluorescent Biosensor

This protocol outlines a simple method for analyzing calcium signals in plants generated by feeding hemipteran insects, such as aphids. Arabidopsis thaliana transformed with the GFP calcium biosensor GCaMP3 allow for the real-time in vivo imaging of calcium dynamics with a high temporal and spatial resolution.

http://ift.tt/2fJAKQl

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

Electroconvulsive seizure (ECS) is an experimental animal model of electroconvulsive therapy for severe depression. ECS globally stimulates activity in the hippocampus, leading to synaptogenesis and synaptic plasticity. Here, we describe methods for ECS induction in rats and for subcellular fractionation of their hippocampi to examine seizure-induced changes in synaptic proteins.

http://ift.tt/2vZnqOd

Imaging the Root Hair Morphology of Arabidopsis Seedlings in a Two-layer Microfluidic Platform

This article demonstrates how to culture Arabidopsis thaliana seedlings in a two-layer microfluidic platform that confines the main root and root hairs to a single optical plane. This platform can be used for real-time optical imaging of fine root morphology as well as for high-resolution imaging by other means.

http://ift.tt/2vZ8waA

Identification of Plasmodesmal Localization Sequences in Proteins In Planta

Plant intercellular connections, the plasmodesmata (Pd), play central roles in plant physiology and plant-virus interactions. Critical to Pd transport are sorting signals that direct proteins to Pd. However, our knowledge about these sequences is still in its infancy. We describe a strategy to identify Pd localization signals in Pd-targeted proteins.

http://ift.tt/2vZ5G5D

Molecular determination of antimicrobial resistance in Escherichia coli isolated from raw meat in Addis Ababa and Bishoftu, Ethiopia

Consumption of meat contaminated by E. coli causes a serious illness and even death to affected individuals. Recently the emerging of antibiotic resistant foodborne E. coli poses serious public health risks world...

http://ift.tt/2vBmKxl

Single-dose pharmacokinetics of Co-Crystal of Tramadol-Celecoxib: results of a 4-way randomized open-label Phase I clinical trial in healthy subjects

Abstract

Aim

Co-Crystal of Tramadol-Celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients (APIs) under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products (immediate-release [IR] tramadol and celecoxib) alone and in open combination.

Methods

Healthy adults aged 18–55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment-1); 100 mg IR tramadol (Treatment-2); 100 mg celecoxib (Treatment-3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment-4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg).

Results

Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml^-1 (mean maximum plasma concentration [C_max]); 3039, 2979 and 3119 ng h ml^-1 (mean cumulative area under the plasma concentration–time curve [AUC_τ]); and 2.7, 1.8 and 1.8 h (median time to C_max [T_max]). For Treatments-1, -3 and -4, celecoxib PK parameters were 313, 449 and 284 ng ml^-1; 2183, 3093 and 2856 ng h ml^-1; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported.

Conclusion

PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination.

http://ift.tt/2w71gK8

Efficacy and safety of endoscopic submucosal tunnel dissection for superficial esophageal squamous cell carcinoma: a propensity score matching analysis: methodologic issues

We read the valuable article by Huang and colleagues1 published in Gastrointestinal Endoscopy in 2017 with great interest. The authors' purpose was to assess the efficacy of the tunnel technique in endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma. They found that the ESD procedure time was significantly shorter in the tunnel ESD group than in the conventional ESD group. Also, they found that specimen size smaller than 40 mm was significantly and strongly associated with shorter procedure times both in the univariate model (odds ratio [OR], 19.25; 95% confidence interval [CI], 2.18-169.78) and the multivariate model (OR, 8.74; 95% CI, 1.30-58.5).

http://ift.tt/2vG5S74

Does short-term morbidity and stoma reduction outweigh a potential long-term risk of colonic stent placement?

The management of malignant colonic obstruction remains a major challenge in clinical practice. Even while more and more countries introduce a colorectal cancer screening program,1 8% of patients still present with an advanced tumor that causes acute large bowel obstruction.2 These patients usually come to the emergency department because of nausea, vomiting, bloating, constipation, and abdominal distention, often combined with poor intake of food for several days. Emergency resection of the obstructed colonic segment has resulted in high rates of postoperative morbidity (54%) and mortality (12%),3 which could be attributed to the poor clinical condition and nutritional status of the patient, the invasiveness of the surgical intervention, and the surgical team available in the emergency setting.

http://ift.tt/2vYGwUH

Society Leadership and Diversity: Hail to the Women!

A landmark event occurred in Chicago at Digestive Disease Week (DDW) in May 2017. For the first time in history, all four gastroenterology and hepatology societies in the United States have women presidents: the American Association for the Study of Liver Diseases (AASLD), the American College of Gastroenterology (ACG), the American Gastroenterological Association (AGA), and the American Society for Gastrointestinal Endoscopy (ASGE). This occurrence was not the result of careful coordination, but a timing coincidence and a significant signal that the GI societies recognize the importance of diversity and inclusion for all our members.

http://ift.tt/2vFGNJu

Should performance status impact stent decision-making in patients with long-term survival from advanced esophageal cancer?

We read with interest the article concerning adverse events (AEs) of self-expandable esophageal metallic stents (SEMSs) in patients with long-term survival from advanced esophageal cancer by Medeiros et al1 in Gastrointestinal Endoscopy. AEs occurred in 63.5% of the 63 patients; however, they were not related to higher mortality rate, and 84.5% could be successfully managed endoscopically. Only performance status was a risk factor for AEs. The authors hypothesized that poor performance status could be associated with more aggressive biological behavior, which could explain a higher rate of AEs.

http://ift.tt/2vY0Q8y

A new aim for targeted biopsies in Barrett’s esophagus

Patients with Barrett's esophagus (BE) are at an increased risk for the development of esophageal adenocarcinoma. This risk is relatively low in patients with nondysplastic BE (∼0.1%-0.3% per year) but much higher in patients with BE and high-grade dysplasia (∼6% per year). Several gastroenterology societies recommend interval surveillance for patients with nondysplastic BE, whereas endoscopic eradication therapy is reserved for patients with BE and associated dysplasia or early neoplasia.1-3 The accurate detection of dysplasia associated with BE is therefore instrumental to the management of this disease.

http://ift.tt/2vFgdjH

Etomidate: Coming to an endoscopy unit near you?

In this issue of Gastrointestinal Endoscopy, Kim et al1 present a double-blinded, randomized controlled trial of etomidate versus propofol for patients undergoing EUS. Etomidate bears some similarities to propofol. It is rapidly acting (although not quite as nimble as its more controversial "milk of anesthesia" comparator), is highly protein bound, works by facilitating γ-aminobutyric acid neurotransmission, and has no analgesic qualities.2,3 The penchant of etomidate for not eroding hemodynamic and respiratory function makes it particularly attractive for patients with shock or significant cardiopulmonary disease.

http://ift.tt/2vFCKgn

Retention rate in small-bowel capsule endoscopy

We read the recent article by Rezapour et al1 with great interest. The authors reported a video capsule endoscopy (VCE) retention rate of 3.6% in suspected inflammatory bowel disease (IBD) and 8.2% in established IBD. However, it appears that the study design precluded the inclusion of several recent publications, which may have shifted the pooled ratios for VCE retention downward. We note that Rezapour et al1 excluded from the main analysis studies in which the patency capsule or cross-sectional imaging was used.

http://ift.tt/2vYGgFd

Response:

We read with interest the correspondence from van de Bruaene et al1 in response to our meta-analysis2 on rebleeding rates after negative results of small-bowel capsule endoscopy (SBCE) for small-bowel bleeding (SBB; previously OGIB). We would like to thank them for the information they provided.3,4 The authors mention that in the long term (>2 years), their patients had a high rate of rebleeding of 34%; however, it is interesting to note that most of those patients had a bleeding source outside the small bowel.

http://ift.tt/2vFCDBc

Response:

We have reviewed the comments by Drs Kopylov et al1 regarding our recently published meta-analysis.2 The authors raised important points about the use of patency capsules, which are now recommended in current guidelines for patients with inflammatory bowel disease (IBD) before they undergo video capsule endoscopy because of the increased risk of retention in this patient cohort.3 The use of CT enterography (CTE), MR enterography (MRE), or both has also shown similar sensitivity and specificity for small-bowel strictures when compared with the use of the patency capsule.

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Focus on...

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Continuing Medical Education Exam: September 2017

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Contents

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ASGE update

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Response:

We thank Drs Ayubi and Safiri1 for their interest in the statistics of our study on the efficacy and safety of endoscopic submucosal tunnel (ESD) dissection for superficial esophageal squamous cell carcinoma. In regression analysis, specimen size did show a large confidence interval, possibly because of the small sample size of the study. We agree that there is potential doubt about the significance of this factor.

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In upcoming issues...

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Information for readers

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Oncologic and Cosmetic Outcomes of Oncoplastic Breast Surgery in Locally Advanced Breast Cancer After Neoadjuvant Chemotherapy, Experience from a Developing Country

Abstract

Oncoplastic surgery (OPS) has emerged as a new approach for extending breast conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision rates, while avoiding breast deformities. OPS is based upon the integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer. This is a prospective feasibility cohort study of oncoplastic breast surgery after neoadjuvant chemotherapy that was carried at the National Cancer Institute, Cairo University and included 70 patients. The primary outcome was the local recurrence rate. Secondary outcomes included survival and margins obtained as well as cosmetic outcomes. Survival analysis was performed. Oncoplastic breast surgery did not compromise oncologic safety in the patients included in the study. It even allowed wider margins of resection which could be associated with better oncologic outcomes. At the same time, it gave a better cosmetic outcome and therefore higher patient satisfaction. Oncoplastic breast surgery includes a wide spectrum of surgical techniques, ranging from the basic level I techniques in breast conserving surgery to the more complex procedures of level II which are broadly classified into volume replacement (therapeutic mammoplasty) and volume displacement procedures. We suggest that oncoplastic breast surgery techniques should be the standard of care in breast surgery. They are the basis for breast conserving surgery techniques in early breast cancer. In our experience, oncoplastic surgery is feasible in locally advanced tumours after downstaging with neoadjuvant chemotherapy without compromising the oncologic safety.

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Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors

Abstract

Background

Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors.

Methods

In this bicentric phase I trial with a 3 + 3 + 3 dose-escalation design, patients received oral pazopanib once daily plus intravenous infusion of bevacizumab every 2 weeks from D15, at one of the four dose levels (DL) planned according to the occurrence of dose limiting toxicities (DLT). 400 and 600 mg pazopanib were respectively combined with 7.5 mg/kg bevacizumab in DL1 and DL2, and 600 and 800 mg pazopanib with 10 mg/kg bevacizumab in DL3 and DL4. Tumor response was evaluated every 8 weeks. Blood samples were assayed to investigate pazopanib pharmacokinetics.

Results

Twenty five patients including seven mRCC were enrolled. Nine patients received the DL1, ten received the DL2. No DLT were observed at DL1, five DLT at DL2, and 3 DLT in the six additional patients who received the DL1. A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response. The mean (range) plasmatic concentrations of 400 and 600 pazopanib were respectively 283 (139–427) and 494 (227–761) μg.h/mL at Day 1, and 738 (487–989) and 1071 (678–1464) μg.h/mL at Day 15 i.e. higher than those previously reported with pazopanib, and were not directly influenced by bevacizumab infusion.

Conclusions

The combination of pazopanib and bevacizumab induces angiogenic toxicity in patients without any pre-existing renal or vascular damage. Even if a marginal efficacy was reported with five (22%) patients in partial response in different tumor types, the toxicity profile compromises the development of this combination.

Trial registration

The study was retrospectively registered on ClinicalTrials.gov (number NCT01202032) on 2010, Sept 14th.

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The Host Response in Patients with Sepsis Developing Intensive Care Unit–acquired Secondary Infections

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 458-470, August 15, 2017.


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Radiation-induced Angiosarcoma as a Cause of Pleural Effusion

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page e10-e11, August 15, 2017.


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Application of a Natural Language Processing Algorithm to Asthma Ascertainment. An Automated Chart Review

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 430-437, August 15, 2017.


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Reply: Direct Detection of Circulating MicroRNAs Unveiled the Absence of MicroRNA-218-5p in Smoker Subjects

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 533-533, August 15, 2017.


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What’s New in Noninvasive Ventilation: Factors Associated with Failure, Patterns of Use in Acute Asthma, and the Role of New Interfaces

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 520-522, August 15, 2017.


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Simultaneously Mounted Pro- and Anti-inflammatory Host Response Relates to the Development of Secondary Infections in Patients with Sepsis

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 406-407, August 15, 2017.


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Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 512-519, August 15, 2017.


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FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 438-446, August 15, 2017.


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A Biosignature Predicting Complicated Course in Children Presenting with Septic Shock. Why PERSEVERE?

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 411-413, August 15, 2017.


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Individualization of Positive End-Expiratory Pressure Setting in Patients with Acute Respiratory Distress Syndrome under Extracorporeal Membrane Oxygenation. Inputs from Electrical Impedance Tomography

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 404-406, August 15, 2017.


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Gender Parity in Critical Care Medicine

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 425-429, August 15, 2017.


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Early Lung Function Decline in Cystic Fibrosis. Can Registry Data Explain Divergent Phenotypes?

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 407-409, August 15, 2017.


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Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 494-501, August 15, 2017.


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Vascular Endothelial Growth Factor in Idiopathic Pulmonary Fibrosis. An Imbalancing Act

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 409-411, August 15, 2017.


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N-Terminal Pro–Brain Natriuretic Peptide Trial Design

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 530-530, August 15, 2017.


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Direct Detection of Circulating MicroRNAs Unveiled the Absence of MicroRNA-218-5p in Smoker Subjects

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 532-532, August 15, 2017.


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Triple Therapy for Chronic Obstructive Pulmonary Disease Management. Are Our Expectations Fulfilled?

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 402-404, August 15, 2017.


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Phenotypes of Rapid Cystic Fibrosis Lung Disease Progression during Adolescence and Young Adulthood

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 4, Page 471-478, August 15, 2017.


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Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Abstract

Objective

Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging,NODDI), to demonstrate the strong potential of the new marker.

Methods

We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion.

Results

We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.

Interpretation

Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

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Ultra-early Detection of Microcirculatory Injury as Predictor of Developing Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Abstract

Purpose

Delayed cerebral ischemia (DCI) still remains a major complication after subarachnoid hemorrhage (SAH). The aim of our study was to evaluate whether flow analysis of admission digital subtraction angiography (DSA) using parametric color coding (PCC), a postprocessing algorithm, allows ultra-early identification of SAH patients at risk for developing subsequent symptomatic vasospasm.

Methods

In this study 52 patients who suffered SAH from aneurysm rupture, were retrospectively enrolled. Of the patients 26 developed DCI and angiographically proven cerebral vasospasm and 26 age, gender-and clinical status-matched SAH patients without DCI served as controls. Using PCC, the following flow parameters were calculated: cerebral circulation time (CirT), cortical relative time to peak (rTTP) and microvascular transit time (TT).

Results

Mean cerebral CirT and cortical rTTP were longer in the DCI group (6.42 s ± 1.54 and 3.16 s ± 0.86, respectively) than in the non-DCI group (5.77 s ± 1.86 and 3.11 s ± 1.41, respectively), but without statistical significance. The mean microvascular TT was statistically significantly (p = 0.04) longer in the DCI group (3.19 s ± 0.78) than in the non-DCI group (2.67 s ± 0.73).

Conclusion

Angiographic flow analysis might be suitable for ultra-early detection and quantitative assessment of microcirculatory injury in SAH patients, predictive of developing subsequent DCI. Prolonged microvascular TT seems to be a significant independent factor positively associated with DCI development. Identifying SAH patients at risk for DCI ultra-early after ictus might contribute to initiate prophylactic therapies before clinical deterioration.

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The association between patient attitudes and values and the strength of consideration for contralateral prophylactic mastectomy in a population-based sample of breast cancer patients

BACKGROUND

Little is known about how the individual decision styles and values of breast cancer patients at the time of treatment decision making are associated with the consideration of different treatment options and specifically with the consideration of contralateral prophylactic mastectomy (CPM).

METHODS

Newly diagnosed patients with early-stage breast cancer who were treated in 2013-2014 were identified through the Surveillance, Epidemiology, and End Results registries of Los Angeles and Georgia and were surveyed approximately 7 months after surgery (n = 2578; response rate, 71%). The primary outcome was the consideration of CPM (strong vs less strong). The association between patients' values and decision styles and strong consideration was assessed with multivariate logistic regression.

RESULTS

Approximately one-quarter of women (25%) reported strong/very strong consideration of CPM, and another 29% considered it moderately/weakly. Decision styles, including a rational-intuitive approach to decision making, varied. The factors most valued by women at the time of treatment decision making were as follows: avoiding worry about recurrence (82%) and reducing the need for more surgery (73%). In a multivariate analysis, patients who preferred to make their own decisions, those who valued avoiding worry about recurrence, and those who valued avoiding radiation significantly more often strongly considered CPM (P < .05), whereas those who reported being more logical and those who valued keeping their breast did so less often.

CONCLUSIONS

Many patients considered CPM, and the consideration was associated with both decision styles and values. The variability in decision styles and values observed in this study suggests that formally evaluating these characteristics at or before the initial treatment encounter could provide an opportunity for improving patient clinician discussions. Cancer 2017. © 2017 American Cancer Society.

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Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism

Abstract

Background

Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear.

Methods

A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo.

Results

shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis.

Conclusion

Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

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Outcome of hearing preservation related to tumor morphologic analysis in acoustic neuromas treated by gamma knife radiosurgery

Abstract

Background

Gamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been rigorously studied. In this cohort, we evaluated the morphological features of the tumor in the tumor response and neurological outcomes after GKRS.

Material and methods

From July 2003 to December 2008, there were 93 cases of acoustic neuromas treated upfront with GKRS with 64 cases with serviceable hearing and 29 cases without serviceable hearing to fulfill the margin dose of 12Gy with at least follow up 5 years.

Results

The duration of symptom before GKRS in serviceable /no serviceable hearing was 7.9 ± 1.2 and 15.3 ± 3.1 months (p < 0.001) and associated no-hearing symptom was 70% and 35%, respectively (p < 0.001). There was 81.2% of hearing preservation after GKRS in serviceable hearing group including 27 cases of pear type (84%), 14 of linear type (70%), and 9 cases of sphere type (90%) (p < 0.01); however, there was no case of hearing improvement in the no-serviceable hearing group (0 of 29). There were 85% of patients with decreased tinnitus in serviceable hearing groups as compared to 61.5% of patients in no serviceable hearing group (p < 0.05). In multivariate analysis, the tumor morphology was highly correlated to hearing preservation rate (p < 0.01).

Conclusion

In the limited case of this cohort, we found that the tumor morphology and timing of treatment was highly correlated to the rate of hearing preservation. The sphere type of tumor morphology was associated with the best chance of hearing preservation.

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Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study

Abstract

Background

Concurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, transarterial chemoembolization (TACE) is not preferred in this setting. The aim of this study was to assess the factors affecting survival after CCRT, including additional TACE during repeated HAIC.

Methods

Thirty-eight patients who underwent CCRT as the initial treatment for Barcelona Clinic Liver Cancer stage C HCC with vascular invasion between 2009 and 2016 were reviewed retrospectively. During CCRT, 5-fluorouracil (5-FU) was infused via chemoport during the first and last five days of five weeks of external beam radiation therapy. After CCRT, repeated HAIC with cisplatin and 5-FU was performed monthly. Nineteen patients (50%) underwent additional TACE between repeated HAICs. Factors related to overall survival and progression free survival (PFS) were analyzed.

Results

The mean age of patients was 55 years (male:female, 33:5). Underlying liver diseases were hepatitis B, hepatitis C and non-B/C in 29, 1 and 8 patients, respectively. The median radiation dose was 4500 cGy. The objective response (OR) rate at one months after CCRT was 36.8%. The median PFS was 7.4 (range, 1.8 − 32.1) months. The median overall survival was 11.6 (range 2.8-65.7) months. Achieving an OR after CCRT (hazard ratio [HR], 0.028; P < 0.001), additional TACE (HR, 0.134, P < 0.001), and further rounds of HAIC (HR, 0.742, P = 0.001) were independent significant factors related to overall survival. The overall survival duration of patients with an OR after CCRT (median 44.2 vs. 6.6 months, P < 0.001) and additional TACE (median 19.8 vs. 9.1 months, P = 0.001) were significantly greater than those without an OR after CCRT or additional TACE.

Conclusion

Patients who achieved an OR after CCRT, underwent additional TACE, and were subjected to repeated rounds of HAIC following CCRT showed better survival after CCRT for advanced stage of HCC with vascular invasion. A further prospective study is needed to confirm the positive effect of additional TACE after CCRT.

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Classification of chronic radiation-induced ulcers in the chest wall after surgery in breast cancers

Abstract

Background and purpose

To explore the methods of clinical classification in chronic radiation-induced ulcers in the chest wall (CRUCWs).

Materials and methods

A total of 64 patients with CRUCWs were treated. We divided the cases into 3 types (mild, moderate, or severe) according to their clinical manifestations. Conservative treatments, axial-pattern myocutaneous or local flaps, or filleted flaps were applied correspondingly.

Results

The cases were divided as follows: mild (n = 11), moderate (n = 45), and severe (n = 8). Eight cases were cured by conservative surgical therapy. One case had a recurrence 6 months after conservative therapy and was cured by a latissimus dorsi myocutaneous flap. The transferred flaps all survived, including 26 transverse rectus abdominis myocutaneous flaps, 8 longitudinal rectus abdominis myocutaneous flaps, 6 latissimus dorsi myocutaneous flaps, 3 contralateral breast flaps, 5 lateral thoracic rotation flaps, and 7 filleted flaps. In 2 transverse rectus abdominis myocutaneous flaps and 2 latissimus dorsi myocutaneous flaps, distal necrosis appeared in small areas. The resulting wounds were salvaged with skin graft and full healing was achieved.

Conclusion

CRUCWs can be divided into three types. Surgical methods should vary with distinguished classifications. The effective classification of CRUCWs has definite instructive significance on the selection of surgical approaches.

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Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy

Abstract

Purpose

The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy.

Methods and materials

Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared.

Results

There were no significant differences in target volume dose coverage or dose conformity, except improved D₉₅ was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D_1cc and D_5cc for major blood vessels, as compared with IMPT (p = 0.01).

Conclusion

Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.

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Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity

Abstract

Background

Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts.

Methods

We retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients.

Results

Mean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 – 0.916, p = 0.004). Factors clearly affecting survival were not observed.

Conclusions

When comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

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Effect of different inner core diameters on structural strength of cannulated pedicle screws under various lumbar spine movements

Currently, cannulated pedicle screws have been widely used in minimal invasive or navigation techniques. However, the stress distribution and the strength of different core diameters of cannulated screw are no...

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Society Leadership and Diversity: Hail to the Women!

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A meta-analysis: microRNAs’ prognostic function in patients with nonsmall cell lung cancer

Abstract

Accumulating papers have demonstrated that microRNAs play an important role in the progression of lung cancer, mainly as oncogenic and tumor suppressive. Therefore, microRNAs may influence the survival of lung cancer patients. In this meta-analysis, we evaluated the role of microRNAs in affecting the overall survival in nonsmall cell lung cancer (NSCLC) patients, which may provide valuable information for the treatment of nonsmall cell lung cancer. We used keywords to retrieve literatures from online databases PUBMED, EMBASE and Web of Science and included 12 studies into our investigation according to pre-set criteria. Then, we analyzed the data with stata13.1 to evaluate the microRNAs role on the prognosis of NSCLC patients. NSCLC patients with higher microRNAs expression levels tend to show lower overall survival. HR (hazard ratio): 2.49, 95% CI (confidence interval): 1.84–3.37. Besides, both oncogenic and tumor suppressive microRNAs have an evident influence on prognosis with HR values of 2.60 (95% CI: 2.12–3.19) and 0.41 (95% CI: 0.05–0.34), respectively. microRNAs, especially from tissue, have an influence on overall survival of NSCLC patients, which indicates that microRNAs could serve as potential prognostic markers for NSCLC and may provide a treatment strategy for advanced NSCLC patients.

The article is different from other researches about miRNAs' function in cancer patients, which considered much miRNAs to evaluate its comprehensive influence as there were kinds of miRNAs existed in human body instead of only one or several kinds of them. So there was a new idea in it.

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