Inequalities in healthcare access: how a man with exstrophy in rural India coped

We report a case of a 22-year-old man with adult exstrophy. The patient made a self-made urine collection device, which helped him to lead a normal life, carrying out his routine as well as occupational activities smoothly. This patient is a prime example of inequalities in healthcare distribution in low-income and middle-income countries. He was never taken to a proper medical centre to correct his condition nor was his mother ever given proper antenatal healthcare access. His background of being a poor person from rural India highlights the problems of inequalities in healthcare access.

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Posterior reversible encephalopathy syndrome in association with exacerbation of chronic obstructive pulmonary disease: a case report

Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical and neurological entity. There are varieties of comorbid conditions which are associated with PRES. Chronic obstructive pulmonary di...

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Antiviral Activities of Mulberry (Morus alba) Juice and Seed against Influenza Viruses

Antiviral activities of Morus alba (MA) juice and seed were examined using time-of-addition plaque assays against influenza viruses, A/Brisbane/59/2007 (H1N1) (BR59), pandemic A/Korea/01/2009(H1N1) (KR01), A/Brisbane/10/2007(H3N2) (BR10), and B/Florida/4/2006 (FL04). MA juice (MAJ) showed much higher antiviral activity than MA seed (MAS). In the pre- and cotreatment of virus, MAJ showed antiviral effects against BR59, KR01, and FL04 in a dose-dependent manner. In particular, MAJ at 4% concentration exhibited 1.3 log inhibition in the pre- and cotreatment of the virus against FL04, a type B virus. However, little or weak inhibition was observed in the posttreatment of MAJ. GSH levels in the virus-infected cells were also examined. The decreased levels by the viral infection were restored significantly by the addition of MAJ. MAJ also exhibited significant DPPH radical scavenging and ferric ion-reducing activities in a dose-dependent manner. Cyanidin-3-rutinoside, the most abundant polyphenol compound of MAJ identified by LC-MS in this study, showed weak inhibitory effects against FL04 in the pretreatment, whereas gallic acid, a minor compound of MAJ, revealed significant antiviral effect. These results suggest that MAJ can be developed as a novel plant-derived antiviral against influenza viruses.

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Development and Application of an UHPLC-MS/MS Method for Comparative Pharmacokinetic Study of Eight Major Bioactive Components from Yin Chen Hao Tang in Normal and Acute Liver Injured Rats

Yin Chen Hao Tang (YCHT) is one of the most famous hepatoprotective herbal formulas in China, but its pharmacokinetic investigation in model rats has been rarely conducted. In this study, the hepatic injury model was caused by intraperitoneal injections of carbon tetrachloride (CCl4), and YCHT was orally administered to the model and normal rats. An ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established to analyze the plasma pharmacokinetics of eight major bioactive ingredients from YCHT in both the normal and liver injured rats. The calibration curves presented good linearity (r > 0.9981) in the concentration range. The relative standard deviation (RSD%) of inter- and intraday precision was within 9.55%, and the accuracy (RE%) ranged from -10.72% to 2.46%. The extraction recovery, matrix effect, and stability were demonstrated to be within acceptable ranges. The lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were around 0.1 ng/mL and 0.5 ng/mL, respectively, which were much lower than those in other related researches. Results reveal that there are significant differences in the pharmacokinetics of scoparone, geniposide, rhein, aloe-emodin, physcion, and chrysophanol in hepatic injured rats as compared to those in control except for scopoletin and emodin. Our experimental results provide a meaningful reference for the clinical dosage of YCHT in treating liver disorders, and the improvement of LLOD and LLOQ can also broaden the range of our method's application, which is very suitable for quantitating these eight compounds with low levels.

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Vascular Protection by Ethanol Extract of Morus alba Root Bark: Endothelium-Dependent Relaxation of Rat Aorta and Decrease of Smooth Muscle Cell Migration and Proliferation

Morus alba (white mulberry) is native to the northern part of Korea and popularly used as a traditional medicine due to its numerous health benefits against human's disease. However, the possibility that M. alba may also affect the cardiovascular system remains unexplored. This study sought to investigate the vascular protective effects of the root bark extract of M. alba (MAE). Vascular reactivity was performed in organ baths using isolated rat thoracic aorta, while platelet derived growth factor (PDGF) induced proliferation and migration of vascular smooth muscle cells (VSMCs) were studied by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and wound healing assay, respectively. MAE evoked a concentration dependent vasorelaxation following endothelium-dependent pathway. However, vessel relaxations in response to MAE were markedly reduced after endothelium removal; treatment of endothelial nitric oxide synthase inhibitor, guanylyl cyclase inhibitor, and nonspecific potassium channel inhibitor, however, was not altered by cyclooxygenase inhibitor. Furthermore, MAE also significantly blunted contractile response to vasoconstrictor agent, phenylephrine. Taken together, the current evidence revealed that MAE is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, nitric oxide cyclic-guanosine monophosphate (NO-cGMP) pathway in combination with potassium (K+) channel activation. Moreover, MAE inhibited proliferation and migration of VSMCs induced by PDGF. Therefore, MAE could be a promising candidate of natural medicine for preventing and controlling cardiovascular diseases linked with endothelial dysfunction.

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Discovery of a diagnostic biomarker for colon cancer through proteomic profiling of small extracellular vesicles

Abstract

Background

Small extracellular vesicles (small-EVs) are membranous vesicles that contain unique information regarding the condition of cells and contribute to the recruitment and reprogramming of components associated with the tumor environment. Therefore, many researchers have suggested that small-EV proteins are potential biomarkers for diseases such as cancer. Colon cancer (CC) is one of the most common causes of cancer-related deaths worldwide. Biomarkers such as carcinoembryonic antigen (CEA) show low sensitivity (~ 40%), and thus the demand for novel biomarkers for CC diagnosis is increasing.

Methods

In this study, we identified biomarkers for diagnosing CC through proteomic analysis of small-EVs from CC cell lines. These small-EVs were characterized by western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy and analyzed using mass spectrometry.

Results

Five selected proteins were found to be upregulated in CC by western blot analysis. Among the candidate proteins, tetraspanin 1 (TSPAN1) was found to be upregulated in plasma EVs from CC patients compared to those from healthy controls (HCs) with 75.7% sensitivity.

Conclusions

These results suggest that TSPAN1 is a potent non-invasive biomarker for CC detection. Our experimental strategy provides useful insights into the identification of cancer-specific non-invasive biomarkers.

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Clinical significance and predictors of oncologic outcome after radical prostatectomy for invisible prostate cancer on multiparametric MRI

Abstract

Background

The objective of our study was to evaluate the clinical significance of invisible prostate cancer (iPCa) on multiparametric magnetic resonance imaging (mpMRI) by analyzing clinical parameters and oncologic outcomes.

Methods

We retrospectively reviewed the records of patients treated with radical prostatectomy (RP) from 2010 to 2015 at our institution. Before RP, all patients were confirmed to have prostate cancer based on prostate biopsy. We excluded patients who underwent neoadjuvant therapy. Additionally, we excluded patients who had incomplete mpMRI based on PI-RADS (Prostate Imaging Reporting and Data System). iPCa was defined as having no grade 3 or higher region of interests using a scoring system established by PI-RADS without limitations on interpretation from mpMRI by radiologists. We selected patients with iPCa using this protocol. We analyzed data using univariate and multivariate cox regression analysis, logistic analysis, Kaplan-Meier curves, and receiver operator characteristic curves to predict biochemical recurrence (BCR).

Results

A total of 213 patients with iPCa were selected according to the patient selection protocol. Among them, pathological findings showed that Gleason score (GS) G6, G7 and ≥ G8 were present in 115 cases (54.0%), 78 cases (36.6%), and 20 cases (9.4%), respectively. Further, extracapsular extension (ECE), positive surgical margins (PSM), and lymphovascular invasion (LVI) were present in 28 (13.1%), 18 (8.5%), and 3 cases (1.4%), respectively. Seminal vesicle invasion (SVI) was observed in one case (0.5%). During a median follow-up time of 51 months, BCR was observed 29 cases. Adverse pathology (AP) was defined as GS ≥8, ECE, SVI and LVI. AP and prostate specific antigen (PSA) were significantly associated with BCR. Moreover, PSA > 6.2 ng/ml was suggested as a cut-off value for predicting BCR.

Conclusions

In our results, cases of iPCa had clinically significant PCa, and AP and poor prognosis were also observed in some. Additionally, we found that PSA is the most clinically reliable predictor of oncologic outcome. We suggest that active treatment and diagnosis should be considered for patients with iPCa with PSA > 6.2 ng/ml.

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The small organic molecule C19 binds and strengthens the KRAS4b-PDEδ complex and inhibits growth of colorectal cancer cells in vitro and in vivo

Abstract

Background

Colorectal cancer is the third most common cancer worldwide; and in 40% of all cases, KRAS4b-activating mutations occur. KRAS4b is transported by phosphodiesterase-6δ (PDEδ) to the plasma membrane, where it gets activated. PDEδ downregulation prevents redistribution and activation of KRAS4b. Thus, targeting the KRAS4b-PDEδ complex is a treatment strategy for colorectal cancer.

Methods

Using docking and molecular dynamics simulations coupled to molecular mechanics, the generalized born model and solvent accessibility (MMGBSA) approach to explore protein-ligand stability, we found that the compound ((2S)-N-(2,5-diclorofenil)-2-[(3,4-dimetoxifenil)metilamino]-propanamida), termed C19, bound and stabilized the KRAS4b-PDEδ complex. We investigated whether C19 decreases the viability and proliferation of colorectal cancer cells, in addition to knowing the type of cell death that it causes and if C19 decreases the activation of KRAS4b and their effectors.

Results

C19 showed high cytotoxicity in the colorectal cancer cell lines HCT116 and LoVo, with a stronger effect in KRAS-dependent LoVo cells. Importantly, C19 significantly decreased tumor size in a xenograft mouse model and showed lower side effects than 5-fluorouracil that is currently used as colorectal cancer treatment.

Conclusions

Mechanistically, the cytotoxic effect was due to increased apoptosis of tumor cells and decreased phosphorylation of Erk and Akt. Therefore, our results suggest that C19 may serve as a promising new treatment for colorectal cancer.

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The role of cellular reactive oxygen species in cancer chemotherapy

Abstract

Most chemotherapeutics elevate intracellular levels of reactive oxygen species (ROS), and many can alter redox-homeostasis of cancer cells. It is widely accepted that the anticancer effect of these chemotherapeutics is due to the induction of oxidative stress and ROS-mediated cell injury in cancer. However, various new therapeutic approaches targeting intracellular ROS levels have yielded mixed results. Since it is impossible to quantitatively detect dynamic ROS levels in tumors during and after chemotherapy in clinical settings, it is of increasing interest to apply mathematical modeling techniques to predict ROS levels for understanding complex tumor biology during chemotherapy. This review outlines the current understanding of the role of ROS in cancer cells during carcinogenesis and during chemotherapy, provides a critical analysis of the methods used for quantitative ROS detection and discusses the application of mathematical modeling in predicting treatment responses. Finally, we provide insights on and perspectives for future development of effective therapeutic ROS-inducing anticancer agents or antioxidants for cancer treatment.

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Inhibition of MicroRNA-9-5p Protects Against Cardiac Remodeling Following Myocardial Infarction in Mice

Human Gene Therapy, Ahead of Print.


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Dosage Thresholds and Influence of Transgene Cassette in Adeno-Associated Virus–Related Toxicity

Human Gene Therapy, Ahead of Print.


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Pediatric Readiness in the Emergency Department

Note: This is a revision of the previous joint policy statement titled "Guidelines for Care of Children in the Emergency Department." Children have unique physical and psychosocial needs that are heightened in the setting of serious or life-threatening emergencies. The majority of ill and injured children are brought to community hospital emergency departments (EDs) by virtue of proximity. It is, therefore, imperative that all EDs have the appropriate resources (medications, equipment, policies, and education) and capable staff to provide effective emergency care for children.

https://ift.tt/2qkdrye

Monthly News Roundup - October 2018

FDA Approves Xofluza, a First-In-Class Flu Drug to Treat Symptoms It's been almost 20 years since a new influenza (flu) treatment was approved, and last year's flu season was one of the deadliest in decades. In response, the U.S. Food and...

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Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States

Abstract

Objectives

The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective.

Methods

A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness.

Results

In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY.

Conclusions

This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3-mutated AML, from a US third-party payer perspective.

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Copyright

ELSEVIER

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Ovarian Cancer

HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA

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Targeting Angiogenesis

Epithelial ovarian cancer remains the most lethal gynecologic cancers with a 5-year survival rate of less than 50%. Cytotoxic combinations are associated with incremental toxicity, leading to interest in evaluating cytotoxic/biologic combinations with improved therapeutic ratios. Angiogenesis is critical to the normal physiology of the gynecologic tract and a novel drug target. Current data suggests antiangiogenics should be considered a critical component of epithelial ovarian cancer treatment. Given the serious adverse event of gastrointestinal perforation/fistula in advanced disease, priority should be given to front-line treatment. Active investigation continues in the development of novel combinations with other biologics.

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Forthcoming Issues

Cutaneous Malignancy

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Management and Treatment of Recurrent Epithelial Ovarian Cancer

Most women with advanced epithelial ovarian cancer will experience many episodes of recurrent disease with progressively shorter disease-free intervals. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Enormous progress has been made in the management of this disease, and new targeted treatments such as antiangiogenic drugs, poly(adenosine diphosphate–ribose) polymerase inhibitors, and immune checkpoint inhibitors offer potential for improved survival. A variety of combination strategies are being evaluated to leverage these agents. The role of secondary cytoreduction remains a topic of active investigation.

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Mechanisms of Drug Resistance in High-Grade Serous Ovarian Cancer

Resistance in ovarian cancer is driven by a range of mechanisms, some of which are therapy specific whereas others confer multidrug resistance. This review outlines our current understanding of the heterogeneous mechanisms of both primary and acquired drug resistance in high-grade serous ovarian cancer with a focus on the most common therapeutics, including platinum and taxanes. Current therapeutic strategies for overcoming resistance, including the use of non–P- glycoprotein substrate therapies, are outlined, with an emphasis on the importance of developing resistance biomarkers to guide future therapy approaches and improve patient outcomes.

https://ift.tt/2P34WX9

Targeting DNA Damage Response and Repair as a Therapeutic Strategy for Ovarian Cancer

Large-scale genomic studies have demonstrated that ovarian cancer is characterized by frequent genetic and epigenetic alterations of gene members of the homologous recombination repair pathway. Homologous recombination repair deficiency induces genomic instability and hyperdependence on alternative DNA repair mechanisms, and is associated with enhanced sensitivity to double-strand break-inducing agents such as platinum analogues and poly(adenosine diphosphate)-ribose polymerase inhibitors. The authors review the DNA repair pathway alterations that are present in ovarian cancer, and discuss current and emerging therapeutic approaches that target the DNA damage response and repair focusing on chemotherapy and poly(adenosine diphosphate)-ribose polymerase inhibitors.

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Contents

Ursula A. Matulonis

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Contributors

GEORGE P. CANELLOS, MD

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Frontiers in the Pathology and Pathogenesis of Ovarian Cancer

This article summarizes the pathogenesis of ovarian carcinoma, focusing on the paradox of high-grade serous carcinogenesis. The fallopian tube is the prime site of origin in early serous cancers. Because a subset of serous cancers is associated with early serous proliferations absent intramucosal carcinomas, "precursor escape" is emerging, whereby some advanced cancers trace their roots to early serous proliferations. This has parallels in the endometriosis model and opens up a novel mechanism by which advanced malignancy could emerge without an obvious tubal carcinoma. The impact of this concept on classification of serous cancer and expectations from preventive strategies are discussed.

https://ift.tt/2P14GIu

Living Through Ovarian Cancer Treatment

Toxicities during chemotherapy for patients with ovarian cancer who present with advanced-stage disease are frequent and diverse. This review aims to describe common toxicities and management strategies for classic cytotoxic treatments and to briefly discuss the current understanding of toxicities associated with targeted therapies.

https://ift.tt/2CRpL0q

Diagnosis and Treatment of Ovarian Cancer

Epithelial ovarian cancer classically presents with vague persistent gastrointestinal, urologic, or nonacute abdominal/pelvic symptoms (bloating, early satiety, discomfort). Ultimately, a pelvic examination or imaging identifies an adnexal mass typically with accompanied advanced peritoneal dissemination. Management involves aggressive cytoreductive surgery in combination with platinum and taxane chemotherapy. Over the last 20 years, optimal resection and mode and timing of chemotherapy have evolved. The authors review the initial diagnosis and management and present the available data and recommendations to guide the decision tree of when to use neoadjuvant, intraperitoneal, HIPEC, dose-dense, and maintenance chemotherapy in the front-line treatment of epithelial ovarian cancer.

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Treatment of Rare Epithelial Ovarian Tumors

Traditionally, the management of epithelial ovarian cancer has been approached using a one-size-fits-all mentality. This strategy does not acknowledge the differences in epidemiology and clinical behavior of many of the histologic and molecular subgroups of ovarian cancer, specifically the rare histologies. While cytoreductive surgery followed by adjuvant platinum and taxane-based chemotherapy is the mainstay of primary treatment of epithelial ovarian cancer as a group, further investigation of novel therapeutics is critical for improving outcomes of these rare histologies. This article focuses on the management of non-high grade serous histologies of ovarian cancer.

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Palliative Care and Symptom Management for Women with Advanced Ovarian Cancer

The purpose of this article is to review data supporting the benefit of palliative care, specifically for women with advanced ovarian cancer. Authors discuss barriers to implementation of palliative care, including confusion with hospice and challenges of prognostication. Generalist-level palliative techniques for treatment of pain, shortness of breath, bowel obstruction, and ascites are described. A description of physician-assisted suicide in legalized states is provided. Resources for physicians regarding communication and end-of-life decision making support for patients and their families.

https://ift.tt/2P0QVt7

Total coliforms as an indicator of human enterovirus presence in surface water across Tianjin city, China

Enteric viruses in surface water pose considerable risk to morbidity in populations living around water catchments and promote outbreaks of waterborne diseases. However, due to poor understanding of the correl...

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The Effects of Radix Astragali Water Abstract on Energy Metabolism in Rat Yang-Deficiency Cold Syndrome Model through PPAR Signaling Pathway

Radix Astragali (RA) herb with warm property and significant "tonifying qi" effects is indicated for the syndrome of internal cold due to Yang deficiency. The purpose of this research was to explore effects of Radix Astragali (RA) through PPAR signaling pathway on gene expression profiles related to energy metabolism in rats with the Yang-deficiency cold (YDC) syndrome, for identifying the pathological mechanism of Yang-deficiency cold (YDC) syndrome and the effects mechanism of RA. The results indicated that RA could significantly increase body weight (BM), cold and heat tendency (CT), overall temperature (OT), rectum temperature (RT), toe temperature (TT), energy intake (EI), and V(O2)/V(CO2) ratio (which indicates basal metabolism, BM) (P

https://ift.tt/2qlSwuZ

Comparison of the Outcomes of Three Different Nutritional Supports in Patients with Oral and Maxillofacial Malignant Tumors following Surgery

Objective. This study aimed to compare the physical and mental states and the clinical effects of parenteral nutrition combined with enteral nutrition (PN+EN), total enteral nutrition (TEN), and total parenteral nutrition (TPN) after surgery in patients with maxillofacial malignant tumors. Methods. A total of 112 patients were divided into three groups, with 58, 33, and 21 patients in the PN+EN, TPN, and TEN groups, respectively. The psychological survey contained the Faces Pain Scale-Revised (FRS-R), visual analog scale (VAS), numerical rating scale (NRS), Hamilton anxiety rating scale (HAMA), and short-form 36 health survey questionnaire (SF-36). Spirit symptoms, length of hospital stay, nutritional assessments, and related biochemical indices were recorded and compared. Results. The traditional Chinese medicine (TCM) symptoms of anxiety and dysphoria were least frequently identified in the TPN group. The levels of lymphocytes, hemoglobin (HB), albumin (ALB), and prealbumin (PA) were significantly higher in the PE+EN group, whereas white blood cell count, neutrophil count, HB, PA, and ALB were significantly lower in the TPN group. Better psychological scores were observed in the TPN group. The PE+EN group had a shorter length of stay and higher SGA categories. Potassium, sodium, and chlorine levels were significantly lower in the TEN group (all P

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A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

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Dynamic Difficulty Adjustment (DDA) in Computer Games: A Review

Dynamic difficulty adjustment (DDA) is a method of automatically modifying a game's features, behaviors, and scenarios in real-time, depending on the player's skill, so that the player, when the game is very simple, does not feel bored or frustrated, when it is very difficult. The intent of the DDA is to keep the player engrossed till the end and to provide him/her with a challenging experience. In traditional games, difficulty levels increase linearly or stepwise during the course of the game. The features such as frequency, starting levels, or rates can be set only at the beginning of the game by choosing a level of difficulty. This can, however, result in a negative experience for players as they try to map a predecided learning curve. DDA attempts to solve this problem by presenting a customized solution for the gamers. This paper provides a review of the current approaches to DDA.

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The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous investigations on the role of immunomodulatory drugs as potential treatment options. Epigenetic modification via immune check point inhibition, while well established as a treatment method for advanced solid tumors, is a new approach being considered in hematologic malignancies including high risk MDS. Several trials are looking at the efficacy of these agents in MDS, as frontline therapy and in relapse, both as monotherapy and in combination with other drugs. In this review, we explore the utility of immune checkpoint inhibitors in MDS and current research evaluating their efficacy.

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Investigation of Antioxidant/Oxidant Status and Antimicrobial Activities of Lentinus tigrinus

In the present study, antioxidant and antimicrobial potential of the Lentinus tigrinus (Bull.) Fr. mushroom was determined. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) of the mushroom were measured with Rel Assay kits. Antimicrobial activities were tested on 9 standard bacterial and fungal strains (Staphylococcus aureus, Staphylococcus aureus MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida albicans, Candida krusei, and Candida glabrata) with a modified agar dilution method. It was determined that the TAS value of L. tigrinus was 1.748 ± 0.071, TOS value was 19.294 ± 0.237, and OSI was 1.106 ± 0.031. It was also found that mushroom extracts generally exhibited higher activity on Candida albicans, C. krusei, and C. glabrata. In conclusion, it was suggested that L. tigrinus can be used as a natural source due to its antioxidant and antimicrobial activities.

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Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation

Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation

Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation, Published online: 31 October 2018; doi:10.1038/s41419-018-1163-z

Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation

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YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma

YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma

YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma, Published online: 31 October 2018; doi:10.1038/s41419-018-1142-4

YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma

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Plau and Tgfbr3 are YAP-regulated genes that promote keratinocyte proliferation

Plau and Tgfbr3 are YAP-regulated genes that promote keratinocyte proliferation

<i>Plau</i> and <i>Tgfbr3</i> are YAP-regulated genes that promote keratinocyte proliferation, Published online: 31 October 2018; doi:10.1038/s41419-018-1141-5

Plau and Tgfbr3 are YAP-regulated genes that promote keratinocyte proliferation

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APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma

APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma

APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma, Published online: 31 October 2018; doi:10.1038/s41419-018-1162-0

APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma

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MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM, Published online: 31 October 2018; doi:10.1038/s41419-018-1153-1

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

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TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network

TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network

TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network, Published online: 31 October 2018; doi:10.1038/s41419-018-1150-4

TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network

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The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis Versus Respiration in Saccharomyces cerevisiae

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae. Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1-deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1-deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1-deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F₁-ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1. In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1. The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro. Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose towards respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1.

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Barriers to Prostate Cancer Research in Black Men Identified

WEDNESDAY, Oct. 31, 2018 -- A lack of understanding of terminology, health care system distrust, and a lack of prostate cancer knowledge are among the barriers to genomic testing for prostate cancer and prostate cancer research participation among...

https://ift.tt/2CSUvye

Opioid Use Often Persists in Workers' Compensation Claimants

WEDNESDAY, Oct. 31, 2018 -- Many patients in a workers' compensation cohort have persistent opioid use, according to a study published online Oct. 26 in JAMA Network Open. Nathan N. O'Hara, M.H.A., from the University of Maryland School of Medicine...

https://ift.tt/2P4lyxW

Some Weather Conditions Linked to Myocardial Infarction Risk

WEDNESDAY, Oct. 31, 2018 -- Certain weather conditions are associated with an increased risk for myocardial infarction (MI), according to a study published online Oct. 24 in JAMA Cardiology. Moman A. Mohammad, M.D., from Lund University in Sweden,...

https://ift.tt/2CV8Yd9

American College of Surgeons, Oct. 22-26

The 103rd Annual American College of Surgeons Clinical Congress The annual meeting of the American College of Surgeons was held from Oct. 22 to 26 in San Diego and attracted approximately 14,000 participants from around the world, including...

https://ift.tt/2P4lwWQ

Greater Weight Loss With Gastric Bypass Than Other Bariatric Sx

WEDNESDAY, Oct. 31, 2018 -- Roux-en-Y gastric bypass (RYGB) is associated with greater weight loss at one, three, and five years than sleeve gastrectomy (SG) or adjustable gastric banding (AGB), though it also has the highest rate of 30-day adverse...

https://ift.tt/2CTYACb

Corrigendum to “Investigation of the Antidiarrheal and Antimicrobial Activities of 80% Methanolic Leaf Extract of Discopodium penninervum (Hochst.)”

https://ift.tt/2PuxQ25

Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice

Abstract

Background

It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investigated whether dietary intervention could improve outcome from the most common pediatric cancer, ALL.

Methods

Diet-induced obese (DIO) mice raised on a 60% calories from fat diet and control mice were implanted with syngeneic ALL cells. Some DIO mice were switched to the low-fat control diet. Survival from ALL was assessed without or with chemotherapy treatment starting at the time of the diet switch. Cells from DIO mice before and after diet switch were assessed by FACS for BrdU incorporation and phosphorylation status of AKT, S6K, and EIF2a. Similar experiments were done with human ALL xenografts. Mouse and human ALL cells were cultured in media with 10% or 5% fetal bovine serum, and sensitivity to chemotherapies assessed.

Results

DIO mice had poorer survival (17%) after vincristine monotherapy than control mice on a 10% low fat diet (42%; n = 12/group; p = 0.09, log rank). However, switching obese mice to the low-fat diet prior to initiation of vincristine led to dramatically improved survival (92%, p < 0.01 vs both other groups). In vitro, FBS restriction made murine and human ALL cells more sensitive to vincristine. Interestingly, while serum restriction enhanced ALL sensitivity to dexamethasone and l-asparaginase, dietary switch did not improve survival of DIO mice treated with either drug in monotherapy. Thus, it appears that dietary intervention has a unique effect to improve ALL cell sensitivity to vincristine in vivo.

Conclusions

We report herein that a dietary intervention can improve ALL outcome in a preclinical model. Further work is needed to identify the mechanisms of this effect and investigate potential impact on human leukemia in patients.

https://ift.tt/2PuYRSY

Palliative Care Clinician Overestimation of Survival in Advanced Cancer: Disparities and Association with End-of-Life Care

Clinicians frequently overestimate survival time in serious illness.

https://ift.tt/2Svqslw

Provision of Palliative and Hospice Care to Children in the Community: A Population Study of Hospice Nurses

Approximately 500,000 children in the United States suffer from life-limiting illnesses each year, many of whom are hospice eligible each year. Few hospice agencies, however, offer formal pediatric programs.

https://ift.tt/2ziK8jX

Clinimetric Properties Of The Brief Fatigue Inventory Applied To Oncological Patients Hospitalized For Chemotherapy

The clinimetric properties of the Brief Fatigue Inventory (BFI) were not previously assessed in oncological patients hospitalized for chemotherapy.

https://ift.tt/2Sy8VJv

Did a goals-of-care discussion happen? Differences in the occurrence of goals-of-care discussions as reported by patients, clinicians, and in the electronic health record

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

https://ift.tt/2zhvgC9

Application of Ultrasound-Targeted Microbubble Destruction–Mediated Exogenous Gene Transfer in Treating Various Renal Diseases

Human Gene Therapy, Ahead of Print.


https://ift.tt/2JulsJQ

Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder

Abstract

The substantial difference between normal cells and cancer cells in terms of their energy metabolism in mitochondria provides an interesting basis for the development of novel therapeutic agents targeting energy machinery of tumour cells. TOMM34 is one of the Tom (translocase of the outer membrane of mitochondria) family that was found to be overexpressed in colorectal, hepatocellular, lung and early invasive breast carcinomas. The expression profile of mitochondrial translocases in bladder cancer compared to normal urinary bladder tissues has not been investigated yet. Therefore, the aim of the current study is to investigate the expression pattern of TOMM34 in bladder cancer tissues and explore its correlation with the clinico-pathological parameters of those cases. Sixty patients who underwent either transurethral resection or radical cystectomy for bladder cancer were included in this study with revision of all their clinicopathological data and tumor slides. Ten histologically normal urothelial biopsies were also included. Immunohistochemical staining for TOMM34 was done and semi-quantitatively scored using the modified H-score. All relations were analysed using established statistical methodologies. TOMM34 overexpression was significantly associated with high tumour stage, muscle invasion and high grade. Significant positive association was observed between TOMM34 expression and poor outcome in terms of shorter disease-specific survival. This study suggests TOMM34 as a biomarker of progression and poor prognosis in urothelial cell carcinoma patients. Furthermore, we suggest a role played by mitochondrial machinery in urothelial cell carcinoma progression, which is a potential target for the newly-discovered vaccine therapy for urothelial cell carcinoma.

https://ift.tt/2DfFQ0W

Transgenic Nicotiana tabacum seeds expressing the Mycobacterium tuberculosis Alanine- and Proline-rich antigen

The glycoprotein APA (Alanine- and Proline-rich Antigen, a 45/47 kDa antigen complex, Rv1860) is considered as a major immunodominant antigen secreted by M. tuberculosis. This antigen has proved to be highly immu...

https://ift.tt/2PuexG9

Do Mechanical Chest Compression Devices Compared With High-Quality Manual Chest Compressions Improve Neurologically Intact Survival of Patients Who Experience Cardiac Arrest?

Authors screened 2,554 studies, from which they included 11 randomized trials (12,944 patients) in the final meta-analysis. Trial publication dates ranged from 1978 to 2015. Authors added 5 trials not featured in the last iteration of this meta-analysis, including 3 large-scale randomized controlled trials accounting for greater than 90% of patients in this review.2-4 One added trial was a noninferiority randomized controlled trial.12 An initial shockable rhythm was present in 13% to 47% of included patients.

https://ift.tt/2F2R0Iq

Carcinosarcoma of Submandibular Salivary Gland with a Rare Sarcomatous Variant

https://ift.tt/2P22ujW

Wash. responders, civilians honored for saving life of retired fire chief

Retired Chehalis Fire Department Chief Bill Nacht went into cardiac arrest while waiting for a friend so they could go on a motorcycle trip

https://ift.tt/2Dfblby

Pictorial review of the pulmonary vasculature: from arteries to veins

Abstract

Pathology of the pulmonary vasculature involves an impressive array of both congenital and acquired conditions. While some of these disorders are benign, disruption of the pulmonary vasculature is often incompatible with life, making these conditions critical to identify on imaging. Many reviews of pulmonary vascular pathology approach the pulmonary arteries, pulmonary veins and bronchial arteries as individual topics. The goal of this review is to provide an integrated overview of the high-yield features of all major disorders of the pulmonary vasculature. This approach provides a more cohesive and comprehensive conceptualisation of respiratory pathology. In this review, we present both the salient clinical and imaging features of congenital and acquired disorders of the pulmonary vasculature, to assist the radiologist in identifying pathology and forming a robust differential diagnosis tailored to the presenting patient.

Teaching Points

• Abnormalities of the pulmonary vasculature are both congenital and acquired.

• Pathology of a single pulmonary vascular territory often affects the entire pulmonary vasculature.

• Anomalous pulmonary venous flow is named as a function of its location and severity.

• Bronchial arteries often undergo dilatation secondary to cardio-respiratory pathology.

https://ift.tt/2Q9jkJU

Emergence of Binocular Disparity Selectivity through Hebbian Learning

Neural selectivity in the early visual cortex strongly reflects the statistics of our environment (Barlow, 2001; Geisler, 2008). Although this has been described extensively in literature through various encoding hypotheses (Barlow and Földiák, 1989; Atick and Redlich, 1992; Olshausen and Field, 1996), an explanation as to how the cortex might develop the computational architecture to support these encoding schemes remains elusive. Here, using the more realistic example of binocular vision as opposed to monocular luminance-field images, we show how a simple Hebbian coincidence-detector is capable of accounting for the emergence of binocular, disparity selective, receptive fields. We propose a model based on spike timing-dependent plasticity, which not only converges to realistic single-cell and population characteristics, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Furthermore, we show that the receptive fields we obtain are closer in structure to electrophysiological data reported in macaques than those predicted by normative encoding schemes (Ringach, 2002). We also demonstrate the robustness of our model to the input dataset, noise at various processing stages, and internal parameter variation. Together, our modeling results suggest that Hebbian coincidence detection is an important computational principle and could provide a biologically plausible mechanism for the emergence of selectivity to natural statistics in the early sensory cortex.

SIGNIFICANCE STATEMENT Neural selectivity in the early visual cortex is often explained through encoding schemes that postulate that the computational aim of early sensory processing is to use the least possible resources (neurons, energy) to code the most informative features of the stimulus (information efficiency). In this article, using stereo images of natural scenes, we demonstrate how a simple Hebbian rule can lead to the emergence of a disparity-selective neural population that not only shows realistic single-cell and population tunings, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Our approach allows us to view early neural selectivity, not as an optimization problem, but as an emergent property driven by biological rules of plasticity.

https://ift.tt/2yR1DZl

EMCrit 236 – George Kovacs on EVLI Airway Incrementalization

Approach to steps of laryngoscopy/intubation

EMCrit Project by Scott Weingart.

https://ift.tt/2P4zPuz

Maintenance avelumab versus continuation of first-line chemotherapy in gastric cancer: JAVELIN Gastric 100 study design

Future Oncology, Ahead of Print.


https://ift.tt/2zmutQq

What to do to keep gums healthy

Practicing good oral hygiene can help a person keep their gums healthy and reduce the risk of gum disease. This involves regular brushing with fluoride toothpaste, flossing, and having frequent dental checkups. Learn more about these steps, the signs of gum disease, and how diet can improve gum health.

https://ift.tt/2CRGml0

Halloween: Is it the most dangerous day for kids?

Analysis of the 56 million ePCR records in the NEMSIS national dataset shows days with the most traumatic pediatric cardiac arrests in 2013 and 2014

https://ift.tt/2EVltIa

CoTCCC Chair Dr. Frank Butler Receives NAEMT’s Most Prestigious 2018 Rocco V. Morando Lifetime Achievement Award

CLINTON, Miss. — Captain Frank K. Butler, Jr., (USN ret), MD was presented with the 2018 Rocco V. Morando Lifetime Achievement Award, recognizing a lifetime of commitment, contributions and leadership to Emergency Medical Services (EMS). The award is NAEMT's most prestigious and is generously sponsored by the National Registry of Emergency Medical Technicians (NREMT). The presentation...

https://ift.tt/2zgAVZi

USPSTF: Evidence Lacking for Lead Screen in Kids, Pregnancy

WEDNESDAY, Oct. 31, 2018 -- The U.S. Preventive Services Task Force (USPSTF) has concluded that current evidence is insufficient for assessing the balance of harms and benefits of screening for elevated blood lead levels in asymptomatic children and...

https://ift.tt/2Rss3Hz

Genetic Risk Score IDs Breast CA Risk in Female Child CA Survivors

WEDNESDAY, Oct. 31, 2018 -- A polygenic risk score (PRS) can identify subsequent breast cancer risk among childhood survivors of cancer, according to a study published online Oct. 26 in Clinical Cancer Research. Zhaoming Wang, Ph.D., from St. Jude...

https://ift.tt/2RulyEd

Diagnoses, Treatment of Mental Health Conditions Up in College

WEDNESDAY, Oct. 31, 2018 -- Among college students, self-reported diagnoses and treatment of mental health conditions are increasing, according to a study published online Oct. 24 in the Journal of American College Health. Sara B. Oswalt, M.P.H.,...

https://ift.tt/2PA02R8

Oral Immunotherapy Beneficial in Patients With Wheat Allergy

WEDNESDAY, Oct. 31, 2018 -- Vital wheat gluten (VWG) oral immunotherapy (OIT) induces desensitization in about half of patients with wheat allergy after a year of treatment, according to a study published online Oct. 30 in the Journal of Allergy and...

https://ift.tt/2RujUm3

Link Between Statins, Non-CVD Outcomes Lacks Evidence

WEDNESDAY, Oct. 31, 2018 -- There is a lack of convincing evidence for an association between statin use and non-cardiovascular disease (CVD) outcomes, according to a review published in the Oct. 16 issue of the Annals of Internal Medicine. Yazhou...

https://ift.tt/2PstbxF

Sub-Concussive Hits May Not Be Tied to Neurocognitive Changes

WEDNESDAY, Oct. 31, 2018 -- Sub-concussive head impacts suffered over the course of a single season of youth tackle football may not be associated with neurocognitive functional outcomes, according to a study published Oct. 12 in the Journal of Head...

https://ift.tt/2RpMCo0

Black, Low-Income Women May Not Report Barriers to Care

WEDNESDAY, Oct. 31, 2018 -- Black women, women living in poverty, and those with higher levels of distrust are less likely to report barriers to timely screening mammography, according to a study published online Sept. 24 in Cancer. Sage J. Kim,...

https://ift.tt/2Pst9Wz

Antibiotics, Acid Suppressants in Infancy May Up Obesity Risk

WEDNESDAY, Oct. 31, 2018 -- Prescription of antibiotics and acid-suppressing medications in early childhood is associated with an increased risk for obesity, according to a study published online Oct. 30 in Gut. Christopher M. Stark, M.D., from the...

https://ift.tt/2Pst9px

Discharge Day Does Not Impact Readmission After Cardiac Sx

WEDNESDAY, Oct. 31, 2018 -- For cardiac surgical patients, the likelihood of readmission has no association with day of discharge, according to a study published online Oct. 11 in the Annals of Thoracic Surgery. Yas Sanaiha, M.D., from the...

https://ift.tt/2Rp2iry

50 Percent of Children Aged 2 to 5 Years Fear Doctor Visits

WEDNESDAY, Oct. 31, 2018 -- Half of parents report that their children aged 2 to 5 years are afraid of going to the doctor, according to survey results published in the Oct. 15 Mott Poll Report. For the C.S. Mott Children's Hospital National Poll on...

https://ift.tt/2PzqdY1

“Gardner and Sutherland’s chromosome abnormalities and genetic counseling” by R.J. McKinlay Gardner, David J. Amor. Oxford University Press

https://ift.tt/2QgxOYs

Neogenin in Amygdala for Neuronal Activity and Information Processing

Fear learning and memory are vital for livings to survive, dysfunctions in which have been implicated in various neuropsychiatric disorders. Appropriate neuronal activation in amygdala is critical for fear memory. However, the underlying regulatory mechanisms are not well understood. Here we report that Neogenin, a DCC (deleted in colorectal cancer) family receptor, which plays important roles in axon navigation and adult neurogenesis, is enriched in excitatory neurons in BLA (Basolateral amygdala). Fear memory is impaired in male Neogenin mutant mice. The number of cFos⁺ neurons in response to tone-cued fear training was reduced in mutant mice, indicating aberrant neuronal activation in the absence of Neogenin. Electrophysiological studies show that Neogenin mutation reduced the cortical afferent input to BLA pyramidal neurons and compromised both induction and maintenance of Long-Term Potentiation evoked by stimulating cortical afferent, suggesting a role of Neogenin in synaptic plasticity. Concomitantly, there was a reduction in spine density and in frequency of miniature excitatory postsynaptic currents (mEPSCs), but not miniature inhibitory postsynaptic currents, suggesting a role of Neogenin in forming excitatory synapses. Finally, ablating Neogenin in the BLA in adult male mice impaired fear memory likely by reducing mEPSC frequency in BLA excitatory neurons. These results reveal an unrecognized function of Neogenin in amygdala for information processing by promoting and maintaining neurotransmission and synaptic plasticity and provide insight into molecular mechanisms of neuronal activation in amygdala.

SIGNIFICANCE STATEMENT Appropriate neuronal activation in amygdala is critical for information processing. However, the underlying regulatory mechanisms are not well understood. Neogenin is known to regulate axon navigation and adult neurogenesis. Here we show that it is critical for neurotransmission and synaptic plasticity in the amygdala and thus fear memory by using a combination of genetic, electrophysiological, behavioral techniques. Our studies identify a novel function of Neogenin and provide insight into molecular mechanisms of neuronal activation in amygdala for fear processing.

https://ift.tt/2OftreJ

Halloween: Is it the most dangerous day for kids?

Analysis of the 56 million ePCR records in the NEMSIS national dataset shows days with the most traumatic pediatric cardiac arrests in 2013 and 2014

https://ift.tt/2EVltIa

EMS World Expo Quick Take: Assessing, treating and transporting patients with special needs

Be aware patients with special needs may have comorbidities, and their conditions fall on a spectrum

https://ift.tt/2Q8S9zb

Correlation of bio-optical properties with photosynthetic pigment and microorganism distribution in microbial mats from Hamelin Pool, Australia

Abstract

Microbial mats and stromatolites are widespread in Hamelin Pool, Shark Bay, however the phototrophic capacity of these systems is unknown. This study has determined the optical properties and light-harvesting potential of these mats with light microsensors. These characteristics were linked via a combination of 16S rDNA sequencing, pigment analyses, and hyperspectral imaging. Local scalar irradiance was elevated over the incident down-welling irradiance by 1.5-fold, suggesting light trapping and strong scattering by the mats. Visible light (400–700 nm) penetrated to a depth of 2 mm, whereas near infrared light (700–800 nm) penetrated to at least 6 mm. Chlorophyll a and bacteriochlorophyll a (Bchl a) were found to be the dominant photosynthetic pigments present, with BChl a peaking at the subsurface (2–4 mm). Detailed 16S rDNA analyses revealed the presence of putative Chl f-containing Halomicronema sp. and photosynthetic members primarily decreased from the mat surface down to a depth of 6 mm. Data indicated high abundances of some pigments and phototrophic organisms in deeper layers of the mats (6–16 mm). It is proposed that the photosynthetic bacteria present in this system undergo unique adaptations to lower light conditions below the mat surface, and that phototrophic metabolisms are major contributors to ecosystem function.

https://ift.tt/2ESMjk1

Cross-Reactivity between Major IgE Epitopes of Family 5 Allergens from Dermatophagoides pteronyssinus and Blomia tropicalis

Background: The aim of this work was to understand the molecular features that trigger the cross-reactivity observed between Der p 5 from Dermatophagoides pteronyssinus, Blo t 5 from Blomia tropicalis, and Der f 5 from D. farinae. Methods: We collected serum from 60 house dust mite (HDM)-allergic patients residing in the Dellys area of Boumerdès province in northern Algeria. The presence of specific IgE to Der p 5, Der f 5, and Blo t 5 was analyzed. We performed in silico analysis of the structure of the different allergens in order to identify epitopes that can elicit the cross-reactivity of the sera. Synthetic peptides corresponding to the linear epitope sequence of Der p 5, Der f 5, and Blo t 5 were used to evaluate its implication in the cross-reactivity between the allergens. We also modified the sequence of the conformational epitope of Der p 5 by site-directed mutagenesis to mimic Blo t 5. Results: Several sera of patients allergic to HDM contained specific IgE antibodies to Der p 5 and Blo t 5. We demonstrated that the linear epitope of Der p 5 and Blo t 5 is not involved in the cross-reactivity of the sera. Furthermore, mutations introduced in the sequence of Der p 5 to mimic Blo t 5 could not modulate the cross-reactivity between them. Conclusions: The major linear IgE epitopes of Der p 5 and Blo t 5 are involved in species-specific recognition. Our results may be useful for the development of a hypoallergenic vaccine against HDM group 5 allergens.
Int Arch Allergy Immunol

https://ift.tt/2PvXYcF

The optimal timing of radiotherapy in the combined modality therapy for limited-stage extranodal NK/T cell lymphoma (ENKTL): a systematic review and meta-analysis

Abstract

The optimal timing and sequencing of radiotherapy (RT) and chemotherapy (CT) in the treatment of limited-stage extranodal NK/T cell lymphoma (LS-ENKTL) has not been elucidated. The aim of this meta-analysis was to evaluate whether the timing of RT in relation to CT affects the survival of patients with LS-ENKTL. We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and relevant meeting abstract databases from inception through April 2018 without age or language restrictions. Studies comparing upfront RT plus CT with induction CT followed by RT in patients with LS-ENTKL were eligible for inclusion. Seven studies with 1593 patients were included, and all were retrospective cohort studies. Compared with induction CT followed by RT, upfront RT significantly improved OS of patients with LS-ENTKL (HR = 0.70, 95%CI 0.55–0.88, P = 0.002), with no evidence of heterogeneity across studies (I² = 0%). In subgroup analyses, the beneficial effect of upfront RT on survival did not differ significantly between subgroups of studies with different types of chemotherapy regimens (anthracycline-based or non-anthracycline-based), the administration of concurrent chemoradiotherapy or not, and different median doses of RT (≥ 45 or < 45 Gy). These results suggest that upfront RT plus CT confers survival advantage over induction CT followed by RT for the treatment of LS-ENTKL, and this survival advantage is not significantly affected by the types of CT regimens or timing of CT. Given the retrospective nature of included studies, these results should be interpreted with caution in clinical practice.

https://ift.tt/2qkL9Uv

Extending resectability of hilar cholangiocarcinomas: how can it be assessed and improved?

Future Oncology, Ahead of Print.


https://ift.tt/2qj5Qjs

Inflammatory breast cancer outcomes by breast cancer subtype: a population-based study

Future Oncology, Ahead of Print.


https://ift.tt/2Q79HeQ

Real-world use of bevacizumab in metastatic colorectal, metastatic breast, advanced ovarian and cervical cancer: a systematic literature review

Future Oncology, Ahead of Print.


https://ift.tt/2qmK6TU

Radiation therapy in indolent primary cutaneous B cell lymphoma: a single institute experience

Abstract

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p = 0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p = 0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.

https://ift.tt/2Qa7SOq

Prospective evaluation of metabolic syndrome and its features in a single-center series of hematopoietic stem cell transplantation recipients

Abstract

Available studies on metabolic syndrome (MS) after hematopoietic stem cell transplantation (HSCT) are retrospective with heterogeneous inclusion criteria, and little is known about the early post-transplant phase. In our prospective study, clinical and laboratory data were collected in 100 HSCT recipients, 48 allogeneic and 52 autologous, at baseline, at + 30, + 100 and + 360 days. At baseline, MS was observed in 24 patients, significantly associated with insulin resistance and leptin on multivariate analysis. At + 30, the diagnosis of MS was confirmed in 43 patients, significantly related to insulin resistance and allogeneic transplants. If the whole series was considered, patients with MS had significantly higher mortality from any cause. The baseline presence of any MS feature was a predictor of + 30 MS. Isolated occurrences of MS features were related to hyperleptinemia and hyperinsulinemia, except in the case of low HDL cholesterol, linked to adiponectin and resistin. Our data confirm that patients undergoing HSCT have a high prevalence of MS, with hyperleptinemia playing a major role. The early peak of new MS cases is primarily attributable to insulin resistance, notably but not exclusively immunosuppression-induced; the subsequent long-term increase in MS cases may be an effect of persistent adipokine imbalance.

https://ift.tt/2qkA1qD

Correction to: Multicenter phase 1/2 study of forodesine in patients with relapsed peripheral T cell lymphoma

The original version of this article contained a mistake in Fig. 4. The horizontal axis should be 36 instead of 60.

https://ift.tt/2Q9TJkn

A monocentric retrospective study of 138 therapy-related myeloid neoplasms

Abstract

As diagnosing therapy-related myeloid neoplasms (t-MN) is often challenging, we reviewed clinicopathological features of t-MN patients. Medical records of 138 patients, diagnosed with t-MN between 1995 and 2017, were reviewed. Of 138 patients, 80 had t-MDS, 53 t-AML, and 5 t-MDS/MPN (age, 22–88 years; median 64 years; male/female ratio, 0.8). The median latency time was 6 years and 5 months. Of 115 patients, 56 patients received cytotoxic-/radiotherapy for a solid tumor, 56 for hematological malignancy, and 3 for an auto-immune disorder, respectively. Another 21 patients had a combination of 2 disorders. Moreover, 2 patients had 3 previous malignancies. Breast cancer was the most prevalent tumor, followed by low-grade B non-Hodgkin lymphoma. Immunophenotyping and immunohistochemistry showed aberrant expression of B-, T-, or NK-cell markers in 21% and 6%, respectively. In 90% of the patients, dysplasia in ≥ 1 lineage was found. KMT2A fusion gene transcripts were seen in 5%. Cytogenetic analysis showed complex karyotypes (31%) and chromosome 5 and/or 7 abnormalities (40%). Almost 82% of the patients died and the median overall survival was about 1 year. Our study confirms that previous therapy for breast cancer is the most important cause of t-MN. KMT2A fusion genes are prevalent and complex karyotypes and/or chromosomes 5 and/or 7 abnormalities are common.

https://ift.tt/2qiXFUs

Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma

Abstract

The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, β2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n = 180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p = 0.02) and OS (p < 0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p < 0.05) in PFS and in addition, age> 65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM.

https://ift.tt/2QazQcM

Hairy cell leukemia presenting with progressive pericarditis and pleuritis

https://ift.tt/2qhswRo

Course of colonization by multidrug-resistant organisms after allogeneic hematopoietic cell transplantation

Abstract

Multidrug-resistant organisms (MDRO) have been developing as an emerging problem in allogeneic hematopoietic cell transplantation (HCT). Since no data are available on the course of MDRO colonization after HCT, we investigated in this retrospective, single-center study, persistence and clearance of MDRO after HCT. From June 2010 to December 2015, 121 consecutive HCT patients were included. Patients received a MDRO screening before conditioning as well as surveillance cultures after HCT. In MDRO-colonized patients, surveillance specimens were taken until MDRO were no longer detectable. Thirty-three patients (27%) were found to be colonized by at least one MDRO at any time point until day 100 post HCT. Day 100 (2-year) non-relapse mortality (NRM) and overall survival (OS) of MDRO-colonized (MDRO⁺) versus non-colonized (MDRO⁻) patients were essentially the same. NRM is 15% (21%) versus 15% (24%). Two-year OS is 60 versus 55% for MDRO⁺ versus MDRO⁻ patients. Out of the 33 MDRO⁺ patients, 21 cleared the MDRO. Median time to non-detectability of MDRO was 6 months. In 12 patients, the MDRO persisted. There was a significant (p < 0.0001) survival difference between patients who cleared the MDRO versus those with MDRO persistence (2-year OS 80 vs 40%). Except for the length of antibiotic therapy as a potential risk factor for MDRO persistence after HCT, no other conventional factors could be identified. (a) colonization by MDRO per se had no negative impact on the outcome, (b) MDRO can be cleared by the majority of patients after allogeneic HCT, and (c) to increase the probability to clear MDRO, the use of antibiotics in MDRO⁺ patients should be reviewed critically.

https://ift.tt/2Q79Eja

Correction to: Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia

The article Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia, written by Andreas Tiede and Andrew Worster, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 26 May 2018 without open access.

https://ift.tt/2Q9yhfc

Transient adrenal insufficiency in diffuse large B cell lymphoma patients after chemotherapy with short-course, high-dose corticosteroids

Abstract

Data on the rate of adrenal insufficiency (AI) in patients receiving short-course and high-dose corticosteroids are limited. In this study, we aimed to determine the incidence of AI in newly diagnosed, diffuse large B cell lymphoma (DLBCL) patients after receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [or prednisolone] (R-CHOP/CHOP) regimen. We enrolled newly diagnosed DLBCL patients who were scheduled to receive 6–8 cycles of R-CHOP/CHOP regimen. One-microgram adrenocorticotropic hormone (ACTH) stimulation tests were performed at the study entry and 3 weeks after each cycle of chemotherapy (CMT). AI was defined by a peak-stimulated serum cortisol of less than 18 μg/dL. For patients who had AI after completing a course of CMT, 1-μg ACTH stimulation tests were carried out at 60 and 90 days after the last CMT cycle to assess the duration of hypothalamic-pituitary-adrenal (HPA) axis recovery. Ten DLBCL patients were included in this study, with a total of 84 1-μg ACTH stimulation tests. Their mean age was 52 years. AI occurred in 3 out of the 10 patients (30%). The first occurrence of AI was after the third CMT cycle, and the incidence was highest after the fifth cycle. Adrenal function recovered completely 3 to 5 weeks after completing the course of CMT, except for 1 patient, whose HPA axis suppression persisted 90 days after the last CMT cycle. Receiver operating characteristic (ROC) analysis revealed that a basal cortisol level of < 8.7 μg/dL was predictive of AI, with a sensitivity and specificity of 80% and 72.2%, respectively. Transient HPA axis suppression can occur in DLBCL patients receiving R-CHOP/CHOP regimen. We strongly encourage careful observation and examination for potential adrenal insufficiency in such patients, particularly after the fifth cycle of chemotherapy.

https://ift.tt/2qmCvF8

Acknowledgement to referees

https://ift.tt/2Q8RjCe

Persistent peripheral blood EBV-DNA positive with high expression of PD-L1 and upregulation of CD4 + CD25 + T cell ratio in early stage NK/T cell lymphoma patients may predict worse outcome

Abstract

Although gemcitabine, oxaliplatin and L-asparaginase/pegylated asparaginase (P-GEMOX) treatment for early-stage extranodal natural killer/T cell lymphoma (ENKTL) is effective, some patients die within 1 year of diagnosis. We attempted to determine an optimal biomarker for identifying such patients. We enrolled 71 patients with ENKTL who received P-GEMOX between January 2011 and January 2014. We classified the patients according to the outcome into worse (died within 1 year) or better groups (survival time ≥ 3, 4 or 5 years). The area under the curve (AUC) was determined to identify the optimal biomarker for differentiating the groups. The AUC was highest in patients who were plasma Epstein–Barr virus (EBV) DNA-positive post-treatment. The AUC was 0.82, 0.86 and 0.86 when the worse group was compared to the better group, respectively. Among the post-treatment EBV DNA-positive patients, as compared to EBV DNA-negative patients, pre-treatment EBV DNA-positive patients had a higher proportion of CD4 + CD25 + T cells. There was higher programmed cell death protein ligand-1(PD-L1) expression in post-treatment EBV DNA-positive patients. Post-treatment positive EBV DNA status maybe a useful biomarker of worse outcomes in early stage ENKTL.

https://ift.tt/2qhstoG

Establishment of a flow cytometry assay for detecting paroxysmal nocturnal hemoglobinuria-type cells specific to patients with bone marrow failure

Abstract

Minor populations of glycosylphosphatidylinositol-anchored protein-deficient (GPI[−]) cells in the peripheral blood may have a prognostic value in bone marrow failure (BMF). Our objective is to establish the optimal flow cytometry (FCM) assay that can discriminate GPI(−) populations specific to BMF from those of healthy individuals. To identify a cut-off that discriminates GPI(−) rare cells from GPI(+) cells, we determined a position of the borderline that separates the GPI(−) from GPI(+) cells on a scattergram by testing more than 30 healthy individuals, such that no GPI(−) dot fell into the upper left quadrant where fluorescein-labeled aerolysin (FLAER)⁻CD11b⁺ granulocytes and CD55⁻CD59⁻ glycophorin A⁺ erythrocytes were positioned. This method allowed us to define ≥ 0.003% CD11b⁺FLAER⁻ granulocytes and ≥ 0.005% glycophorin A⁺CD55⁻CD59⁻ erythrocytes to be specific to BMF patients. Longitudinal cross-validation studies showed minimal (< 0.02%) inter-laboratory differences in the GPI(−) cell percentage. An analysis of 1210 patients with BMF revealed a GPI(−) cell population in 56.3% of patients with aplastic anemia and 18.5% of patients with myelodysplastic syndrome. The GPI(−) granulocyte percentages was 0.003–0.01% in 3.7% of patients. This FCM assay effectively identified an increase in the percentage of GPI(−) rare cells that are specific to BMF patients and allowed different laboratories to accurately detect 0.003–0.01% of pathological GPI(−) cells.

https://ift.tt/2qjO0wL

Characteristics of pulmonary complications in non-Hodgkin’s lymphoma patients treated with rituximab-containing chemotherapy and impact on survival

Abstract

Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555–1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75–580) days and 27 (14–163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60–4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.

https://ift.tt/2QeFLxG

Management of Dabigatran-associated bleeding in two elderly patients with acute renal failure

https://ift.tt/2QgpNCQ

Clinical value of abnormal findings on brain magnetic resonance imaging in patients with intravascular large B-cell lymphoma

Abstract

To investigate the prevalence and clinical value of abnormal findings detected via brain magnetic resonance imaging (MRI) in patients with intravascular large B-cell lymphoma (IVLBCL), we identified 33 patients with IVLBCL pathologically diagnosed and evaluated with pretreatment brain MRI. Abnormal findings on brain MRI were categorized into four patterns: (1) hyperintense lesion in the pons on T2-weighted imaging (T2WI), (2) nonspecific white matter lesions, (3) infarct-like lesions, and (4) meningeal thickening and/or enhancement. Abnormal cerebral findings were detected in 29 patients (87.9%). Hyperintense lesion in the pons was the most common finding (n = 19 (57.6%) patients), followed by nonspecific white matter lesions (n = 14 (42.4%) patients), infarct-like lesions (n = 8 (24.2%) patients), and meningeal thickening and/or enhancement (n = 4 (12.1%) patients). Impaired consciousness was seen in most of the patients with infarct-like lesions (87.5%) but less frequently in patients with hyperintense lesion in the pons (47.4%). We reviewed brain MRI findings in 39 patients with diffuse large B cell lymphoma with central nervous system (CNS) involvement and/or high-risk extranodal lesions for CNS involvement as a control group. In contrast to the patients with IVLBCL, no patient had hyperintense lesion in the pons in the control group (P < 0.001). Follow-up brain MRI revealed improvement of abnormal findings in most of the patients who responded to chemotherapy. This study highlighted the diagnostic implication of hyperintense lesion in the pons on T2WI and the clinical usefulness of pretreatment brain MRI in IVLBCL even in patients without impaired consciousness.

https://ift.tt/2qlS7sw

Novel synthetic 4-chlorobenzoyl berbamine inhibits c-Myc expression and induces apoptosis of diffuse large B cell lymphoma cells

Abstract

C-Myc expression is associated with poor prognosis and aggressive progression of diffuse large B cell lymphoma (DLBCL), and the development of drug-like c-Myc inhibitors remains challenging. In this study, we report a novel berbamine derivative termed 4-chlorobenzoyl berbamine (CBBM) that potently induced the apoptosis of c-Myc-overexpressing DLBCL cells but spared normal blood cells. The compound showed IC₅₀ values ranging from 1.93 to 3.89 μmol/L in DLCBL cells and exhibited a 4.75- to 9.64-fold increase in anti-tumor activity compared to berbamine. Additionally, CBBM inhibited the proliferation of the DLBCL line OCI-Ly3 cells through G0/G1 cell-cycle arrest and induced apoptosis. Further studies have shown that CBBM treatment leads to the proteasome-dependent degradation of c-Myc protein in OCI-Ly3 cells. Interestingly, we found that the inhibitory effect of CBBM was positively correlated with basal levels of CaMKIIγ, which is a key inducer of c-Myc expression in DLBCL cells. We also observed that CBBM inhibits the JAK2/STAT3 pathway, leading to reduced c-Myc transcription. Collectively, these findings suggest that CBBM could be a promising lead compound for treatment of c-Myc-driven DLBCL.

https://ift.tt/2Q79Cb2

Acute Liver Failure with Diffuse Liver Metastasis from Breast Cancer, Not Detected by Computed Tomography: 2 Case Reports

Diffuse liver metastasis is a rare pattern of liver metastasis that is associated with hepatic failure and poor prognosis. We experienced 2 cases of acute liver failure due to diffuse metastasis that could not be detected using computed tomography. In case 1, it was difficult to differentiate diffuse metastasis from alcoholic hepatitis. In case 2, it was difficult to diagnose diffuse liver metastasis because the patient had no history of malignancy. When liver enzyme levels are elevated, it is necessary to consider liver metastasis as a potential cause, regardless of computed tomography findings.
Case Rep Oncol 2018;11:699–704

https://www.karger.com/Article/FullText/493848

The Smallest Reported Malignant Struma Ovarii: A Case Report

Introduction: Malignant struma ovarii is a rare neoplasm. It is usually asymptomatic and not commonly diagnosed preoperatively. In addition, there is currently no established diagnostic and therapeutic approach for malignant struma ovarii. Case Report: A 66-year-old asymptomatic female was referred to our hospital. Computed tomography showed the presence of a well-defined mass with enhancement in the internal and peripheral areas. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Histopathology revealed the presence of a papillary thyroid carcinoma arising from a 2.5-cm-diameter struma ovarii (malignant struma ovarii). According to the criteria of the International Federation of Gynecology and Obstetrics, the patient had stage IA disease. Subsequently, she underwent a thyroid scan with normal findings. At the 3-month follow-up, the patient was alive, in good clinical condition, and disease free. Conclusion: In this report, we present the smallest malignant struma ovarii reported so far in the literature. Because of the rarity of these tumors and the lack of firm prognostic factors, the treatment decision should be customized for each patient according to the pathological and clinical parameters.
Case Rep Oncol 2018;11:693–698

https://www.karger.com/Article/FullText/493254

Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression

Thymic carcinoma is a relatively rare and aggressive thymic epithelial tumor. Herein, we report successful treatment of thymic carcinoma with pembrolizumab. A 68-year-old woman was admitted to our hospital for evaluation of chest pain. Chest computed tomography showed a mass in the anterior mediastinum and lymphadenopathy in the left cervical lymph node. Analysis of biopsy specimens detected squamous cell carcinoma in the left cervical lymph node, and immunohistochemical analysis showed 100% expression of programmed death-ligand 1 (PD-L1). Masaoka-Koga stage IVb thymic carcinoma was ultimately diagnosed. Since 3 cycles of first-line chemotherapy did not result in improvement, pembrolizumab was administered as second-line treatment every 3 weeks at a dosage of 200 mg. After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to be an effective therapy for thymic carcinoma with high PD-L1 expression.
Case Rep Oncol 2018;11:688–692

https://www.karger.com/Article/FullText/493187

Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case of Oral Cavity Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant epithelial neoplasm of the salivary glands. MECs of the mouth floor are rare, with only a few cases reported. Here we report a MEC of the mouth floor in a 55-year-old woman. Since several studies have shown that hydrogen sulfide (H₂S)-synthesizing enzymes are often increased in malignant tumors compared to benign counterpart tissues, we used western blotting to compare the protein levels of cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in a mouth floor MEC to adjacent benign oral mucosae. We also used high-performance liquid chromatography to quantify possible differences in tissue sulfur fraction concentrations between the two biopsy types. Last, we used western blotting to examine nicotinamide phosphoribosyl transferase (Nampt), mitoNEET, and phospho-ser727-Stat3 levels in the biopsies. We found that all the proteins and phospho-ser727-Stat3 are increased in the MEC compared to benign mucosae. Interestingly, free H₂S levels, acid-labile, and the sulfane sulfur factions were essentially the same between the MEC and benign tissue. Although limited to a single and unusual tumor type, to our knowledge this is only the third time H₂S concentrations were directly quantified inside a human tumor. Last, our results replicate those of two previous studies where the H₂S-synthesizing enzymes are increased in a malignant tumor, while free H₂S is either not increased or only slightly increased, suggesting that malignant tumors rapidly metabolize H₂S as part of tumor maintenance and growth.
Case Rep Oncol 2018;11:682–687

https://www.karger.com/Article/FullText/493008

Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.
Case Rep Oncol 2018;11:676–681

https://www.karger.com/Article/FullText/493255

Index of Mind Vol. 127 Nos 1–4, 2018

This index is intended as a complete bibliographical source for work published in MIND. Entries are divided into two sections: Articles, Symposia, Discussions, Critical Notices, Editorial Introductions, and Graduate Essay Prize 2017 and Book Reviews. Articles, symposia, discussions, and editorial introductions are listed by the title and by the author's name. Critical notices and book reviews are listed by the book title, by the author's name, and by the reviewer's name. The Yr/No column indicates first the year and then the issue number.

https://academic.oup.com/mind/article/127/508/1271/5151214?rss=1

Illocutionary Frustration

Abstract

This paper proposes a new category of linguistic harm: that of illocutionary frustration. I argue against Jennifer Hornsby and Rae Langton's notion of illocutionary silencing by challenging their claim that silencing occurs when there is a lack of uptake of the speaker's illocutionary act. I look at two scenarios that their view treats differently and argue that these scenarios warrant the same kind of analysis; Hornsby and Langton's notion of silencing can't capture the purported difference they want it to capture. I propose that we should look instead to standing to explain the phenomenon that illocutionary silencing intends to explain. I explicate the role of standing in terms of illocutionary frustration, then consider street harassment as an example of a linguistic interaction that is best explained by my proposed view.

https://academic.oup.com/mind/article/127/508/947/5127377?rss=1

EMS World Expo Quick Take: Active assailant preparation, response for EMS

20-60-90 minute rule underscores the importance of rapidly accessing trauma patients and transporting patients to definitive surgical care

https://ift.tt/2Q8wR4J

Cancers, Vol. 10, Pages 416: Scanning Electron Microscopy of Circulating Tumor Cells and Tumor-Derived Extracellular Vesicles

Cancers, Vol. 10, Pages 416: Scanning Electron Microscopy of Circulating Tumor Cells and Tumor-Derived Extracellular Vesicles

Cancers doi: 10.3390/cancers10110416

Authors: Afroditi Nanou Mateus Crespo Penny Flohr Johann S. De Bono Leon W. M. M. Terstappen

To explore morphological features of circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs), we developed a protocol for scanning electron microscopy (SEM) of CTCs and tdEVs. CTCs and tdEVs were isolated by immunomagnetic enrichment based on their Epithelial Cell Adhesion Molecule (EpCAM) expression or by physical separation through 5 &mu;m microsieves from 7.5 mL of blood from Castration-Resistant Prostate Cancer (CRPC) patients. Protocols were optimized using blood samples of healthy donors spiked with PC3 and LNCaP cell lines. CTCs and tdEVs were identified among the enriched cells by fluorescence microscopy. The positions of DNA+, CK+, CD45&minus; CTCs and DNA&minus;, CK+, CD45&minus; tdEVs on the CellSearch cartridges and microsieves were recorded. After gradual dehydration and chemical drying, the regions of interest were imaged by SEM. CellSearch CTCs retained their morphology revealing various shapes, some of which were clearly associated with CTCs undergoing apoptosis. The ferrofluid was clearly distinguishable, shielding major portions of all isolated objects. CTCs and leukocytes on microsieves were clearly visible, but revealed physical damage attributed to the physical forces that cells exhibit while entering one or multiple pores. tdEVs could not be identified on the microsieves as they passed through the pores. Insights on the underlying mechanism of each isolation technique could be obtained. Complete detailed morphological characteristics of CTCs are, however, masked by both techniques.

https://ift.tt/2ACtmxT

Arterial Stiffness in a Toddler with Neurofibromatosis Type 1 and Refractory Hypertension

Arterial hypertension is a common finding in patients with neurofibromatosis (NF) type 1. Renovascular hypertension due to renal artery stenosis or midaortic syndrome could be the underlying cause. We report the case of a 4-year-old girl with NF type 1 and midaortic syndrome whose changes in blood pressure and pulse wave velocity suggested the evolution of vasculopathy, diagnosis of renovascular hypertension, and provided insights of response to treatment. Hypertension persisted after percutaneous transluminal angioplasty in the abdominal aorta, requiring escalation of antihypertensive treatment, while arterial stiffness demonstrated a mild decrease. Regular assessment of blood pressure using ambulatory blood pressure monitoring and noninvasive assessment of arterial stiffness may enhance the medical care of patients with NF type 1.

https://ift.tt/2qmz8xI

IBCC chapter & cast: Anemia & transfusion targets

Most patients in the ICU will become anemic.  This chapter explores prevention, evaluation, and treatment of anemia in the ICU.  Causes of new-onset anemia in the ICU are distinct from the causes of anemia seen in the outpatient clinic, so the approach should be appropriately tailored to the critical care environment.   

EMCrit Project by Josh Farkas.

https://ift.tt/2EWzS6T

Osseous Metaplasia of the Cervix: A Rare Transformation Can Mimic a Tumor—Literature Review

Background. The transformation of nonosseous soft tissue into bone is known as osseous metaplasia (OM). This condition most commonly affects the musculoskeletal and central nervous systems and it is a well-known phenomenon in different soft tissue organs. Rarely, OM can affect the uterus, which can extend into the cervix. OM affecting the cervix alone is a more rare condition that has multiple different clinical presentations. The presentation can be similar to that of a tumor in extremely rare cases. Case Summary. A 23-year-old nulligravida was complaining of irregular vaginal bleeding for one-month duration. Speculum examination revealed a foul-smelling bloody purulent discharge, tender cervix, and a brownish growth located at the posterior cervical lip. A punch biopsy of the growth was performed. Histological examination of the tissue revealed multiple bone fragments with necrosis and an inflammatory exudate. Because of the unusual findings, a repeat biopsy was performed. The biopsy yielded the same findings, which confirmed the diagnosis of osseous metaplasia of the cervix. Conclusion. Although osseous metaplasia is a known phenomenon in different soft tissues, it is extremely rare in the uterine cervix and can mimic malignancy. Therefore, clinicians should be aware of it.

https://ift.tt/2DhsjG8

VISTA expressed in tumour cells regulates T cell function

VISTA expressed in tumour cells regulates T cell function

VISTA expressed in tumour cells regulates T cell function, Published online: 31 October 2018; doi:10.1038/s41416-018-0313-5

VISTA expressed in tumour cells regulates T cell function

https://ift.tt/2OeSkag

Statistically Significant

N/A.

https://ift.tt/2OXVlkB

Letter to the Editor about the Article: “Still Regarding Anxiety, Depression and Academic Performance: A Study Amongst Portuguese Medical Students Versus Non-Medical Students”, by João Moreira de Sousa, Cátia A. Moreira, Diogo Telles-Correia. Acta Med Port. 2018;31:454-62.

N/A.

https://ift.tt/2CSssig

How to Choose the Best Evidence?

N/A.

https://ift.tt/2OXVg0h

Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus

Introduction: Super-refractory status epilepticus is defined as status epilepticus that persists or recurs 24 hours after anaesthetic therapy onset or after its withdrawal. It is mostly found in intensive care units and carries high mortality but good long-term prognosis for those who survive. In contrast with the initial phases of status epilepticus, treatment lacks strong scientific evidence and is mostly derived from case reports or small case series.
Objective: To propose a protocol for the treatment of super-refractory status epilepticus in level III intensive care units, focusing on the treatment strategies to control clinical and/or electroencephalographic epileptic activity.
Material and Methods: Narrative review of the literature by PubMed search. Available evidence was discussed in consensus meetings by intensive care and neurology experts' from a level III intensive care unit and one of the Portuguese reference centres for the treatment of refractory epilepsy, respectively.
Results: Anaesthetics with the highest level of evidence are propofol, midazolam, thiopental and ketamine. These represent the basis of the treatment of super-refractory status epilepticus and should be used in combination with antiepileptic drugs. The level of evidence for the latter is lower, however, levetiracetam, topiramate, pregabalin, lacosamide, valproic acid, phenytoin and perampanel may be recommended. Alternative therapeutic strategies with very low level of evidence are recommended in cases of total absence of clinical response, such as magnesium sulphate, pyridoxine, ketogenic diet, therapeutic hypothermia and immunosupression.
Conclusion: We propose a treatment protocol based on a sequential combination of anaesthetics, anti-epileptic drugs and alternative therapies. Strategies to evaluate treatment response and to wean drugs based on clinical results are also proposed.

https://ift.tt/2CSNIok

Symptomatic Solitary Gastric Diverticulum: A Rare Endoscopic Finding

N/A.

https://ift.tt/2OXVbK1

Visceral Leishmaniasis Associated with Macrophage Activation Syndrome and Diffuse Alveolar Hemorrhage in a Lupus Patient

Systemic lupus erythematosus is a heterogeneous and unpredictable autoimmune disease which can be complicated to approach and treat. Hemophagocytic lymphohistiocytosis and diffuse alveolar hemorrhage are rare disease complications. The authors describe a clinical case of a 32-year-old woman with lupus and fever of unknown origin. From the investigations performed, the myelogram revealed hemophagocytosis and Leishmania parasites, therefore liposomal amphotericin B was then started. In addition to directed therapy, she maintained fever that evolved with diffuse alveolar hemorrhage. The myelogram was repeated and showed that she still had hemophagocytosis but now without parasites. Corticotherapy was increased and intravenous Immunoglobulin was started, with improvement. Rituximab was started as a result of macrophage activation syndrome and diffuse alveolar hemorrhage. Months after discharge, she began once again to have sustained fever and Leishmania parasites were found again, therefore liposomal amphotericin B was started once more associated with miltefosine. She continues being followed-up as she is asymptomatic and using steroids
in weaning scheme.

https://ift.tt/2COvsMR

Pulmonary Tuberculosis Reactivation: Triggered by the Descent in Altitude?

High altitudes are linked to decreased rates of pulmonary tuberculosis infection, disease and mortality. However, its relevance as a trigger for pulmonary tuberculosis reactivation in immunocompetent patients is not documented. A 28-year-old healthy Nepalese female was admitted in the emergency department with sudden left pleuritic back pain with shortness of breath, two weeks after arriving in Lisbon, having arrived from Kathmandu and undergone a change in altitude of 1400 metres. She also had evening low-grade fever and fatigue since she arrived. Her mother-in-law had died of tuberculosis two years before. Chest radiography and computed tomography scan showed a left upper lobe consolidation. Laboratory analyses were 79 mm/sec. Human immunodeficiency virus serology, blood cultures and urinary antigen testing were negative. Bronchial secretions' cultures became positive for Mycobacterium tuberculosis complex. The patient was started on anti-tuberculous treatment and made a steady recovery. This case reports a probable reactivation of pulmonary tuberculosis infection that could have been triggered by altitude differences.

https://ift.tt/2P2syLu

Overview of Drug Allergy: From Immunogenetic Basis to Practice

Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.

https://ift.tt/2CUdMiD

Ozone Therapy in Knee Osteoarthritis: A Systematic Review

Introduction: The aim of this study was to conduct a systematic review in order to examine the effectiveness of ozone therapy on knee osteoarthritis. The objectives were to evaluate the effect over time of ozone therapy in terms of knee pain, functional improvement and radiographic progression.
Material and Methods: A search was carried out on PubMed, Embase, Cochrane Library, Scopus and Web of Science databases to identify randomized and controlled studies focusing on this association. The following descriptors were used in English: ozone therapy, knee osteoarthritis. A descriptive summary and quality assessment was made of all studies included for analysis.
Results: Six randomized and controlled studies were identified. The risk of bias assessment demonstrated that one study was considered as having a moderate risk of bias and the remainder a high risk of bias. No quantitative analysis of the data was performed, as the studies included were not sufficiently homogeneous. The participants in the studies were generally elderly patients with mild to moderate knee osteoarthritis.
Discussion: The variability of ozone therapy and the comparators demonstrates that there is no standardized therapy. Few studies reported adverse effects, and where they occurred, they were mild and associated with the procedure.
Conclusion: Ozone therapy proved effective in the short-term in relation to placebo and when combined with hyaluronic acid, but it was not superior to other current treatments. More randomised and controlled studies are needed to evaluate the risks/benefits of ozone therapy, both in the short term and the medium/long term.

https://ift.tt/2P4msKZ

Epidemiological Trends of Proximal Femoral Fractures in the Elderly Population in Portugal

Introduction: Proximal femoral fractures are an important public health problem in industrialized societies. There are few studies that evaluate the incidence of this type of fracture in Portugal. The aim of this study was to analyze and interpret epidemiological trends of proximal femoral fractures in the elderly population in Portugal between 2005 and 2013.
Material and Methods: Cross-sectional study including all patients aged 65 years and older admitted due to proximal femoral fractures in Portuguese hospitals belonging to the National Health Service using data from the national registry of the health system central administration.
Results: 101,436 patients were included. There was a progressive increase in the number of hospitalizations per year over the period analyzed. The mean age at admission was 79.32 (± 12.33) years presenting a progressive and significant increase over the analyzed period (p < 0.001). 74.5% of the patients were female (p < 0.001). They had a significantly higher average age at admission, both globally and in each study year (p < 0.001). The age-adjusted incidence (≥ 65 years) was 597 fractures / year / 100,000 inhabitants. There was an increase in the incidence of proximal femoral fractures from 508.49 (2005) to 628.39 fractures per 100,000 person-years (2013). In the female sex the increase was from 616.78 to 762.88 and in the male sex from 339.95 to 419.06.
Discussion: This is the first study to evaluate and interpret the epidemiological trends of proximal femur fractures in patients admitted to the National Health Service in Portugal including only individuals aged 65 years or over.
Conclusion: The global number of proximal femoral fractures in Portugal showed a trend of increase between 2005 - 2013, affecting a significant percentage of the Portuguese population over 65 years of age, especially in females and progressively older individuals.

https://ift.tt/2CRZYFu

Rethinking Sciatica In View of a Bilateral Anatomical Variation of the Sciatic Nerve, with Low Origin and High Division: Historical, Anatomical and Clinical Approach

Introduction: The aim of the present study is to report an original, unusual, case of bilateral anatomical variation of the sciatic nerve, with low origin and high division.
Material and Methods: Anatomical dissection was performed on a 66 year-old female cadaver. The corpse was embalmed and conserved through our original embalming techniques.
Results: The particular anatomical variation was first detected during routine dissection classes for undergraduate students. The study was completed with contralateral dissection to unveil bilateral variation. In both hind limbs, the sciatic nerve had a low origin, deep below the mid-gluteal region, and suffered high division, near the lower margin of the gluteal region, after a short length of circa 8 cm, to divide into the common fibular and tibial nerves.
Discussion: We detect several cases of sciatic nerve high division, in the reports of the earliest anatomists, such as Leonardo da Vinci, Vesalius, Da Cortona, or Eustachius. Such ancestral interest for these anatomical variations demonstrates the importance of their knowledge for health professionals of different areas.
Conclusion: The accurate study of sciatic nerve anatomical variations bears evident surgical, anaesthesiology and clinical applications. As more meticulous as our anatomical studies may get, one will never reach the state of perfection to consider such studies as definitive.

https://ift.tt/2P5iRMI