Normal and altered pre-mRNA processing in the DMD gene

Abstract

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression controlled by multiple post- and co-transcriptional mechanisms. The large Duchenne muscular dystrophy gene encoding the protein dystrophin provides a striking example of the complexity of human pre-mRNAs. In this review, we summarize the current state of knowledge about canonical and non-canonical splicing in the DMD pre-mRNA, with a focus on mechanisms that take place in the full-length transcript isoform expressed in human skeletal muscle. In particular, we highlight recent work demonstrating that multi-step events are required for long DMD intron removal. The role of temporary intron retention in the occurrence of alternative splicing events is also discussed. Even though the proportion of splicing mutations is lower than reported in other genes, a great diversity of splicing defects linked to point mutations, but also large genomic rearrangements are observed in the DMD gene. We provide an overview of the molecular mechanisms underlying aberrant splicing in patients with Duchenne or Becker muscular dystrophy, and we also detail how alternative splicing can serve as a disease modifier in patients by changing the outcome of the primary defect.

http://ift.tt/2t0xdhS

A Case Report Demonstrating the Potential Clinical Benefit of Exhaustive Molecular Profiling in an Aggressive Muscle-Invasive High-Grade Metastatic Urothelial Carcinoma

We present a muscle-invasive high-grade metastatic urothelial carcinoma patient, aged 71 years, with rapid progression from the diagnosis and a poor prognosis after 3 lines of treatment. A clinical exhaustive genomic profile was performed with the goal of finding potential actionable molecular alterations. The patient showed significant symptomatic and laboratory improvement with a nonstandard chemotherapy combination treatment identified by the molecular profiling, which would otherwise not have been considered. This approach illustrates the clinical benefit of a comprehensive genomic analysis in an aggressive and refractory urothelial carcinoma.
Case Rep Oncol 2017;10:493–500

http://ift.tt/2r8pMII

Small Cell Cancer of the Genitourinary Tract: A Case Report and Review of the Literature

Small cell carcinoma of the urinary tract is an extremely rare disease with very few cases reported in the literature. Its clinical course is aggressive, and the prognosis is poor. Here, we present a case of metastatic extrapulmonary small cell carcinoma of the upper urinary tract in a 74-year-old African-American male. He initially presented with gross hematuria, 20-pound weight loss, and abdominal pain for 2 months. CT imaging showed a 14.0 × 7.0 × 16.0 cm retroperitoneal mass within the left renal fossa; biopsy revealed a carcinoma which was positive for synaptophysin and chromogranin. The patient also had detectable neuroendocrine cells in his urine cytology, confirming the diagnosis of small cell carcinoma. He was treated with carboplatin and etoposide as extrapolated from the treatment of its pulmonary counterpart. Due to the rarity of urinary tract small cell carcinoma, no randomized studies exist to guide therapy or management.
Case Rep Oncol 2017;10:489–492

http://ift.tt/2rSzTPg

Radiation Therapy in Elderly Persons: An Old Issue With New Approaches

Aging is not "lost youth" but a new stage of opportunity and strength.Betty Friedan (1921-2006)

http://ift.tt/2s2sgHQ

Improving Consistency and Quality of Care for Older Adults With Cancer: The Challenges of Developing Consensus Guidelines for Radiation Therapy

The demographics of cancer patients are changing. For decades, epidemiologists and clinicians have predicted rising numbers of older patients with cancer (1, 2). Although aging is a heterogeneous process, older patients often present with challenges that can significantly affect their ability to tolerate antineoplastic therapy. Older age is associated with higher rates of comorbidities, polypharmacy, organ dysfunction, and immune cell senescence (3). Many of these changes with aging are silent until the patients are introduced to stressors (eg, surgery, chemotherapy, or radiation therapy) that unmask the aging process and manifest as an increased risk of toxicity or functional decline.

http://ift.tt/2s2zWd5

Breaking Up Is Hard to Do: Omission of Radiation Therapy for Select Women Aged >70 Years With Breast Cancer

The goal of treatment for early-stage breast cancer is cure. Consecutive advances in local and systemic therapy have steadily improved cancer outcomes for patients with surgically resectable disease. When there is evidence that we can improve care by doing more, adoption of new interventions is relatively rapid. For example, within 3 years of the drug's US Food and Drug Administration approval, more than 92% of eligible locally advanced HER2-positive breast cancer patients had received adjuvant trastuzumab (1).

http://ift.tt/2s2vqLR

Frailty is our Destiny: An Introduction to the Red Journal's Special Edition on Radiation Therapy in the Elderly

Simple systems function well until one critical piece fails, then the whole system stops and will not work again. Complex systems have a series of backups and built-in redundancy. They are thus capable of absorbing damage and do not fail until truly overwhelmed, although some functions may be lost along the way.

http://ift.tt/2t0rRTN

Evaluation of Treatment Candidacy in Older Adults With Cancer

Older adults (aged ≥65 years) are the fasting growing demographic of the population. Because age is an independent risk factor for most cancers, the care of geriatric oncology patients will pose ever-increasing challenges for healthcare providers and systems of care. In elderly patients for whom radiation therapy is a potential modality for curative or palliative treatment with or without systemic therapy, understanding the patient's priorities and goals of care is key to the shared decision-making process (Fig. 1).

http://ift.tt/2t0Arln

Toward Personalized Cancer Care for Elderly Head and Neck Cancer Patients

To the Editor: Approximately 50% of the head and neck cancer (HNC) population are elderly patients (aged ≥65 years), and this rate is inevitably projected to increase over time, especially in developed countries (1).

http://ift.tt/2s2JpRH

Meetings

September 11-13, 2017

http://ift.tt/2t0tfFU

“But We Are Already Geriatric Oncologists”—Why Older Patients Need a Special Approach (A View from a United Kingdom Cancer Center)

To the Editor: Cancer incidence increases in the elderly, with more than half of cancers in the United Kingdom (UK) diagnosed in patients aged >70 years. Over the last decade the number of people aged >85 years has increased by one-third to 1.5 million (1). In our center, 46% of patients undergoing radiation therapy last year were more than 68 years old, with 10% over the age of 80 years. Older patients are a heterogeneous group, ranging from very fit to frail.

http://ift.tt/2t0Ceqq

The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment

Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults.

http://ift.tt/2s2sfUi

The Association Between Normal Range TSH and Lipid Profile

Horm Metab Res 2017; 49: 424-429
DOI: 10.1055/s-0043-110142

Dyslipidemia in thyroid dysfunction is mostly attributed to thyrotropin (TSH) levels, especially in subclinical disorders, but the exact role of TSH in dyslipidemia has not been explained. A total of 3 020 subjects who remained euthyroid in 3 phases of the Tehran Thyroid study were enrolled and divided according to quartiles of TSH as: Q1 (0.32–1.02), Q2 (1.02–1.53), Q3 (1.53–2.27), and Q4 (2.27–5.06). General Linear model was used to determine whether there was a significant correlation between subjects' lipid profile and quartiles of TSH from 1st to 2nd and from 1st to 3rd phase. Mean TC, LDL-C level and median TG were significantly higher for Q1 in all study phases. All lipid parameters of participants after 6 years (3rd phase study) except LDL-C were significantly varied in different TSH groups. Highest levels of TC, TG and HDL-C were observed in Q4. Thus, irrespective of TC and LDL-C in Q1 and Q4 (participants with the lowest and highest limit of TSH within the normal range), the difference in lipid parameters in middle of normal TSH range was not significant. Normal range TSH levels have a statistically significant effect on lipid profile, but the effect size is not clinically significant.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2rHjI8Q

Impact of the Triglyceride/High-Density Lipoprotein Cholesterol Ratio and the Hypertriglyceremic-Waist Phenotype to Predict the Metabolic Syndrome and Insulin Resistance

Horm Metab Res
DOI: 10.1055/s-0043-107782

Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n=1 333) or impaired fasting glucose (n=599), also for the impact of gender. Within the lipid ratios, triglyceride/HDL-C had the strongest associations with insulin resistance/sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80% sensitivity, 71% specificity) and 1.9 for women (80% sensitivity, 75% specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2rceaj9

Dermoscopic images of malignant and benign skin lesions

http://sfaki.blogspot.com/2017/06/using-watson-to-diagnose-skin-cancer.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tilt-induced cardio-inhibitory reflex syncope (BIOSync trial) : 12-item questionnaire to distinguish between complete transient loss of consciousness (i.e., syncope) and pre-syncope or other minor symptoms and, additionally, to provide a standardized categorical description of the clinical presentation of syncope including duration, reproducibility with previous episodes, presence of prodromes, presence of witnesses, context, and consequences of the episode.

http://sfaki.blogspot.com/2017/06/12-item-questionnaire-to-distinguish.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, benralizumab), IL-13 (lebrikizumab, tralokinumab), IL-4 receptor alpha (dupilumab), Immune globuline E (IgE) (omalizumab), anti-Thymic Stromal Lymphopoitin (TSLP) (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant, timapiprant). New Anti-Eosinophil Drugs for asthma and COPD

http://sfaki.blogspot.com/2017/06/monoclonal-antibodies-against-il-5-or.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Substituting physicians with nurse practitioners, physician assistants or nurses in nursing homes: protocol for a realist evaluation case study

Introduction

In developed countries, substituting physicians with nurse practitioners, physician assistants and nurses (physician substitution) occurs in nursing homes as an answer to the challenges related to the ageing population and the shortage of staff, as well as to guarantee the quality of nursing home care. However, there is great diversity in how physician substitution in nursing homes is modelled and it is unknown how it can best contribute to the quality of healthcare. This study aims to gain insight into how physician substitution is modelled and whether it contributes to perceived quality of healthcare. Second, this study aims to provide insight into the elements of physician substitution that contribute to quality of healthcare.

Methods and analysis

This study will use a multiple-case study design that draws upon realist evaluation principles. The realist evaluation is based on four concepts for explaining and understanding interventions: context, mechanism, outcome and context–mechanism–outcome configuration. The following steps will be taken: (1) developing a theory, (2) conducting seven case studies, (3) analysing outcome patterns after each case and a cross-case analysis at the end and (4) revising the initial theory.

Ethics and dissemination

The research ethics committee of the region Arnhem Nijmegen in the Netherlands concluded that this study does not fall within the scope of the Dutch Medical Research Involving Human Subjects Act (WMO) (registration number 2015/1914). Before the start of the study, the Board of Directors of the nursing home organisations will be informed verbally and by letter and will also be asked for informed consent. In addition, all participants will be informed verbally and by letter and will be asked for informed consent. Findings will be disseminated by publication in a peer-reviewed journal, international and national conferences, national professional associations and policy partners in national government.

http://ift.tt/2rbOK5k

Cohort profile: the Nordic Antireflux Surgery Cohort (NordASCo)

Purpose

To describe a newly created all-Nordic cohort of patients with gastro-oesophageal reflux disease (GORD), entitled the Nordic Antireflux Surgery Cohort (NordASCo), which will be used to compare participants having undergone antireflux surgery with those who have not regarding risk of cancers, other diseases and mortality.

Participants

Included were individuals with a GORD diagnosis recorded in any of the nationwide patient registries in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) in 1964–2014 (with various start and end years in different countries). Data regarding cancer, other diseases and mortality were retrieved from the nationwide registries for cancer, patients and causes of death, respectively.

Findings to date

The NordASCo includes 945 153 individuals with a diagnosis of GORD. Of these, 48 433 (5.1%) have undergone primary antireflux surgery. Median age at primary antireflux surgery ranged from 47 to 52 years in the different countries. The coding practices of GORD seem to have differed between the Nordic countries.

Future plans

The NordASCo will initially be used to analyse the risk of developing known or potential GORD-related cancers, that is, tumours of the oesophagus, stomach, larynx, pharynx and lung, and to evaluate the mortality in the short-term and long-term perspectives. Additionally, the cohort will be used to evaluate the risk of non-malignant respiratory conditions that might be caused by aspiration of gastric contents.

http://ift.tt/2rc6cGT

Timing of two versus three doses of quadrivalent HPV vaccine and associated effectiveness against condyloma in Sweden: a nationwide cohort study

Objective

To assess incidence of condyloma after two doses of quadrivalent human papillomavirus (qHPV) vaccine, by time since first vaccine dose, in girls and women initiating vaccination before age 20 years.

Design

Register-based nationwide open cohort study.

Setting

Sweden.

Participants

Girls and women initiating qHPV vaccination before age 20 years between 2006 and 2012. The study cohort included 264 498 girls, of whom 72 042 had received two doses of qHPV vaccine and 185 456 had received all three doses.

Main outcome measure

Incidence rate ratios (IRRs) of condyloma estimated by time between first and second doses of qHPV in months (m) and age at vaccination, adjusted for attained age.

Results

For girls first vaccinated with two doses before the age of 17 years, the IRR of condyloma for 0–3 months between the first and second doses was 1.96 (95% CI 1.43 to 2.68) as compared with the standard three-dose schedule. The IRRs were 1.27 (95% CI 0.63 to 2.58) and 4.36 (95% CI 2.05 to 9.28) after receipt of two doses with 4–7 months and 8+ months between doses, respectively. For women first vaccinated after the age of 17 years, vaccination with two doses of qHPV vaccine and 0–3 months between doses was associated with an IRR of 2.12 (95% CI 1.62 to 2.77). For an interval of 4–7 months between doses, the IRR did not statistically significantly differ to the standard three-dose schedule (IRR=0.81, 95% CI 0.36 to 1.84). For women with 8+ months between dose 1 and dose 2 the IRR was 3.16 (95% CI 1.40 to 7.14).

Conclusion

A two-dose schedule for qHPV vaccine with 4–7 months between the first and second doses may be as effective against condyloma in girls and women initiating vaccination under 20 years as a three-dose schedule. Results from this nationwide study support immunogenicity data from clinical trials.

http://ift.tt/2rHmwmg

Erratum

http://ift.tt/2rHmTx9

Issue Information

No abstract is available for this article.

http://ift.tt/2rc5tFr

Issue highlights

http://ift.tt/2rHtR5n

Editorial Board: Eur. J. Immunol. 6'17

http://ift.tt/2rbQaMY

Cover Picture: Eur. J. Immunol. 6'17

Our inside cover features Ly6C^low monocytes (green), patroling along the endothelial wall (black) in the steady state, while neutrophils (red) are transported by the blood flow. The image is taken from Imhof et al. (pp. 1002–1008), where the authors visualized tracks of patrolling cells along the blood vessel wall, which appear like stripes whereas cells transported in the blood circulation appear like isolated dots.

http://ift.tt/2rHn8bw

Journal roundup

http://ift.tt/2rHu2Oh

In this issue

http://ift.tt/2rc0yV7

BTN3A1-antibodies and phosphoantigens: TCRVγ9Vδ2 “see” the difference

Human blood γδ T lymphocytes express TCRVγ9Vδ2 and respond to nonpeptide phosphoantigens (PAgs) by a mysterious mechanism involving the BTN3A1 (CD277) molecule . BTN3A1 is a butyrophilin-like protein related to CD80, PD-L1, and MHC, and is either a presenting or a co-stimulatory molecule for PAgs. Although the precise roles and molecular interactions with the TCRVγ9Vδ2 are currently not determined, it is commonly thought that all TCRVγ9Vδ2 lymphocytes 'see' PAg and BTN3A1 together, presumably in a single molecular recognition event. But whether this recognition event could be reproduced in a simplified model was not addressed in previous studies. In this issue, Starick et al. (Eur. J. Immunol. 2017. 47: 982–992) compared the response of three TCRVγ9Vδ2 pairs of murine and human cell transfectants to PAg and anti-BTN3A1 antibodies using IL-2 release as a readout. The authors found that although the two murine transfectants responded similarly to either stimuli, one murine TCRVγ9Vδ2 transfectant reacted to PAgs but not to anti-BTN3A1 (mAb 20.1). Human transductants behave in a similar fashion, demonstrating that TCRVγ9Vδ2 lymphocytes differentiate PAg and BTN3A1 signals, while species of the transductants unmask this differential sensitivity. Indeed, understanding the puzzling mode of antigen recognition by γδ T lymphocytes will be essential for developing γδ T-cell-based immunotherapies, and the authors of this study now demonstrate that TCRVγ9Vδ2 lymphocytes are able to differentiate the PAg and BTN3A1 stimuli.

How the TCRVγ9Vδ2 expressed by most human blood γδ T lymphocytes confer specificity for phosphoantigens (PAg) and BTN3A1+ target cells was unclear. Here, Franchini et al. comment novel insights from the report by Starick et al., who carefully dissected these responses using human and murine transfectants for various TCRVγ9Vδ2.

http://ift.tt/2rHsQKF

March for Science Germany — A short impression of the scene in Bonn

http://ift.tt/2rcbSAp

Contents: Eur. J. Immunol. 6'17

http://ift.tt/2rHuxHO

Cover Picture: Eur. J. Immunol. 6'17

Our back cover shows a clonal colony-forming unit that emerges from dedicated cortical thymic epithelial cells of the murine thymus, as captured by high-content fluorescent microscope. The staining represents cytokeratin 8 (K8) (red), K5 (green) and DAPI (blue). The image was retrieved from Meireles et al. (pp. 958–969), who studied how the rules underlying the establishment of functionally competent cortical and medullary thymic epithelial cell (TEC) micro environments are regulated. Meireles and colleagues provide evidence that the postnatal cortex harbors cortical and medullary TEC progenitors and their abundance drops with age as result of continual thymic crosstalk.

http://ift.tt/2rc9gm7

Impressum

http://ift.tt/2rHxVCT

Cover Picture: Eur. J. Immunol. 6'17

Our front cover represents a transmission electron microscopy image with a detail of the threatening situation of a newborn infection, represented by in-vitro infection of a granulocytic myeloid derived suppressor cell (GR-MDSC) from cord blood challenged by Escherichia coli.The image is taken from Leiber et al. (pp. 1009–1021) andartificially coloured with bacteria marked in green. GR-MDSCs are hardly distinguishable from mature polymorphonuclear neutrophils (PMN), besides the less segmented nucleus.

http://ift.tt/2rcilLV

Efficacy and Safety of Rituximab in the Management of Pediatric Systemic Lupus Erythematosus: A Systematic Review

To evaluate the efficacy and safety of rituximab for treating pediatric systemic lupus erythematosus (pSLE).

http://ift.tt/2r7ocqR

Variability of Care in Infants with Severe Bronchiolitis: Less-Invasive Respiratory Management Leads to Similar Outcomes

To compare the management of children with severe bronchiolitis requiring intensive care (based on duration of ventilatory support and duration of pediatric intensive care unit [PICU] stay) in 2 countries with differing pediatric transport and PICU organizations.

http://ift.tt/2r7Uge7

Sleep Duration and Telomere Length in Children

To test the association between sleep duration and telomere length in a pediatric population.

http://ift.tt/2rS5pNg

Complementary and conventional providers in cancer care: experience of communication with patients and steps to improve communication with other providers

Effective interdisciplinary communication is important to achieve better quality in health care. The aims of this study were to compare conventional and complementary providers' experience of communication abo...

http://ift.tt/2skQqOk

Antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from Punjab, Pakistan

The plant species Aristolochia indica (AI), Melilotus indicus (MI), Tribulus terrestris (TT) and Cuscuta pedicellata (CP) are widely used in folk medicine in the villages around Chowk Azam, South Punjab, Pakistan...

http://ift.tt/2skQgH3

The SHIVA01 trial: what have we learned?

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS9Qro

Availability of CYP2D6 genotyping results in general practitioner and community pharmacy medical records

Pharmacogenomics Ahead of Print.


http://ift.tt/2r7T0r7

Should CYP2D6 be genotyped when treating with tamoxifen?

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS9S2u

The experience of physicians in pharmacogenomic clinical decision support within eight German university hospitals

Pharmacogenomics Ahead of Print.


http://ift.tt/2r81Buf

Don't think twice it's all right: tamoxifen and CYP2D6 genotyping in the treatment of breast cancer patients

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS9RLY

Is a polygenic predictor of antidepressant response a possibility?

Pharmacogenomics Ahead of Print.


http://ift.tt/2r7Vs13

Influence of two variants of CYP450 oxidoreductase on the stable dose of acenocoumarol in a Spanish population

Pharmacogenomics Ahead of Print.


http://ift.tt/2rSkgqS

Genetic variants associated with warfarin dosage in Kuwaiti population

Pharmacogenomics Ahead of Print.


http://ift.tt/2r7t7rP

The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS821o

Pharmacogenetics and aromatase inhibitor induced side effects in breast cancer patients

Pharmacogenomics Ahead of Print.


http://ift.tt/2r8diRA

Pharmacological factors affecting accumulation of gemcitabine’s active metabolite, gemcitabine triphosphate

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS82yq

Role of vitamin D pathway gene polymorphisms on rifampicin plasma and intracellular pharmacokinetics

Pharmacogenomics Ahead of Print.


http://ift.tt/2r8kay9

Clinical and educational impact of pharmacogenomics testing: a case series from the INGENIOUS trial

Pharmacogenomics Ahead of Print.


http://ift.tt/2rS61SZ

Rapid and reliable screening of HLA-B*15:02 in four Chinese populations using single-tube multiplex real-time PCR assay

Pharmacogenomics Ahead of Print.


http://ift.tt/2r86zXB

Tailoring of recommendations to reduce serious cutaneous adverse drug reactions: a pharmacogenomics approach

Pharmacogenomics Ahead of Print.


http://ift.tt/2rSy70w

Pharmacogenomics in Asia: a systematic review on current trends and novel discoveries

Pharmacogenomics Ahead of Print.


http://ift.tt/2r7T1LH

Intermittent Obstructive Symptoms in a Patient with Diphyllobothriasis

http://ift.tt/2sa1mip

Kidney Function, Proteinuria, and Cancer Incidence: The Korean Heart Study

Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort.

http://ift.tt/2sJd8xf

Multiplex detection in tonsillar tissue of all known human polyomaviruses

In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections wit...

http://ift.tt/2rHemdC

Prevalence and risk factors for latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique

Healthcare workers in high tuberculosis burdened countries are occupationally exposed to the tuberculosis disease with uncomplicated and complicated tuberculosis on the increase among them. Most of them acquire M...

http://ift.tt/2rbNjnk

Night work and prostate cancer in men: a Swedish prospective cohort study

Objectives

Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men.

Design

Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men.

Setting

Individuals in the Swedish Twin Registry.

Participants

12 322 male twins.

Outcome measures

Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454.

Results

Multiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer.

Conclusions

The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer.

http://ift.tt/2rHkT8s

Serious gaming during multidisciplinary rehabilitation for patients with complex chronic pain or fatigue complaints: study protocol for a controlled trial and process evaluation

Introduction

Many individuals suffer from chronic pain or functional somatic syndromes and face boundaries for diminishing functional limitations by means of biopsychosocial interventions. Serious gaming could complement multidisciplinary interventions through enjoyment and independent accessibility. A study protocol is presented for studying whether, how, for which patients and under what circumstances, serious gaming improves patient health outcomes during regular multidisciplinary rehabilitation.

Methods and analysis

A mixed-methods design is described that prioritises a two-armed naturalistic quasi-experiment. An experimental group is composed of patients who follow serious gaming during an outpatient multidisciplinary programme at two sites of a Dutch rehabilitation centre. Control group patients follow the same programme without serious gaming in two similar sites. Multivariate mixed-modelling analysis is planned for assessing how much variance in 250 patient records of routinely monitored pain intensity, pain coping and cognition, fatigue and psychopathology outcomes is attributable to serious gaming. Embedded qualitative methods include unobtrusive collection and analyses of stakeholder focus group interviews, participant feedback and semistructured patient interviews. Process analyses are carried out by a systematic approach of mixing qualitative and quantitative methods at various stages of the research.

Ethics and dissemination

The Ethics Committee of the Tilburg School of Social and Behavioural Sciences approved the research after reviewing the protocol for the protection of patients' interests in conformity to the letter and rationale of the applicable laws and research practice (EC 2016.25t). Findings will be presented in research articles and international scientific conferences.

Trial registration number

A prospective research protocol for the naturalistic quasi-experimental outcome evaluation was entered in the Dutch trial register (registration number: NTR6020; Pre-results).

http://ift.tt/2rHbs8W

Systematic review and meta-analysis of prevalence of, and risk factors for, pelvic floor disorders in community-dwelling women in low and middle-income countries: a protocol study

Introduction

Pelvic floor disorders (PFDs) including urinary incontinence, faecal incontinence and pelvic organ prolapse are common debilitating conditions among women in high-income countries. However, PFDs in women in low/middle-income countries (LMICs) have not been studied extensively. We aim to conduct a systematic review and meta-analysis of the available literature to determine the prevalence of, and/or risk factors for, PFDs in women in LMIC.

Methods and analysis

We will search electronic databases including MEDLINE, EMBASE, PsycINFO, CINAHL, Maternity & Infant Care and Google Scholar for eligible studies. Inclusion criteria will be observational studies of healthy women, which have collected data using validated or non-validated tools, are published in English and were conducted in community women in LMICs, defined by the World Bank. A standardised data extraction form will be developed and piloted, based on the template of the Cochrane good practice data extraction form. All included studies will be assessed based on a risk-of-bias tool specifically developed for prevalence studies. Pooled prevalence estimates of PFDs will be generated using RevMan V.5.2.1 software. Forest plots will be generated to display the overall random-effects pooled estimates with CIs. A metaregression will be conducted to identify sources of between-study heterogeneity in the pooled prevalence estimates. We will quantify heterogeneity using the I² measure and its CI. We will use funnel plots to detect potential reporting biases and small-study effects. We will also conduct a sensitivity analysis to verify the robustness of the study conclusions, assessing the impact of methodological quality, study design, sample size and the effect of missing data.

Ethics and dissemination

Our review is entirely based on published data. Thus, an ethics committee approval or written informed consent will not be required for this study as primary data will not be collected. The results will be disseminated by publication of the manuscript in a peer-reviewed journal and/or will be presented at relevant conferences.

PROSPERO registration number

CRD42016043881.

http://ift.tt/2rbRTlp

Performance-based functional impairment and readmission and death: a prospective study

Objectives

Readmission and death are frequent after a hospitalisation and difficult to predict. While many predictors have been identified, few studies have focused on functional status. We assessed whether performance-based functional impairment at discharge is associated with readmission and death after an acute medical hospitalisation.

Design, setting and participants

We prospectively included patients aged ≥50 years admitted to the Department of General Internal Medicine of a large community hospital. Functional status was assessed shortly before discharge using the Timed Up and Go test performed twice in a standard way by trained physiotherapists and was defined as a test duration ≥15 s. Sensitivity analyses using a cut-off at >10 and >20 s were performed.

Primary and secondary outcome measures

The primary and secondary outcome measures were unplanned readmission and death, respectively, within 6 months after discharge.

Results

Within 6 months after discharge, 107/338 (31.7%) patients had an unplanned readmission and 31/338 (9.2%) died. Functional impairment was associated with higher risk of death (OR 2.44, 95% CI 1.15 to 5.18), but not with unplanned readmission (OR 1.34, 95% CI 0.84 to 2.15). No significant association was found between functional impairment and the total number of unplanned readmissions (adjusted OR 1.59, 95% CI 0.95 to 2.67).

Conclusions

Functional impairment at discharge of an acute medical hospitalisation was associated with higher risk of death, but not of unplanned readmission within 6 months after discharge. Simple performance-based assessment may represent a better prognostic measure for mortality than for readmission.

http://ift.tt/2rHdyFH

Association between preoperative anaemia with length of hospital stay among patients undergoing primary total knee arthroplasty in Singapore: a single-centre retrospective study

Objectives

Studies in western healthcare settings suggest that preoperative anaemia is associated with poor outcomes after elective orthopaedic surgery. We investigated the prevalence of preoperative anaemia among patients with primary unilateral total knee arthroplasty (TKA) in Singapore and its association with length of hospital stay (LOS), perioperative blood transfusion and hospital readmission rates.

Methods

Retrospective cohort study performed in a tertiary academic medical centre in Singapore, involving patients who underwent primary unilateral TKA between January 2013 and June 2014. Demographics, comorbidities, preoperative haemoglobin (Hb) level, LOS and 30-day readmission data were collected. Anaemia was classified according to WHO definition. Prolonged LOS was defined as more than 6 days, which corresponds to >75th centile LOS of the data.

Results

We analysed 2394 patients. The prevalence of anaemia was 23.7%. 403 patients (16.8%) had mild anaemia and 164 patients (6.8%) had moderate to severe anaemia. Overall mean LOS was 5.4±4.8 days. Based on multivariate logistic regression, preoperative anaemia significantly increased LOS (mild anaemia, adjusted OR (aOR) 1.71, p<0.001; moderate/severe anaemia, aOR 2.29, p<0.001). Similar effects were seen when preoperative anaemia was defined by Hb level below 13 g/dL, regardless of gender. Transfusion proportionately increased prolonged LOS (1 unit: aOR 2.12, p=0.006; 2 or more units: aOR 6.71, p<0.001). Repeat operation during hospital stay, previous cerebrovascular accidents, general anaesthesia and age >70 years were associated with prolonged LOS. Our 30-day related readmission rate was 1.7% (42) cases.

Conclusion

Anaemia is common among patients undergoing elective TKA in Singapore and is independently associated with prolonged LOS and increased perioperative blood transfusion. We suggest measures to correct anaemia prior to surgery, including the use of non-gender-based Hb cut-off for establishing diagnosis.

http://ift.tt/2rHlTsV

A mixed-methods evaluation of the Educational Supervision Agreement for Wales

Objectives

In a bid to promote high-quality postgraduate education and training and support the General Medical Council's (GMC) implementation plan for trainer recognition, the Wales Deanery developed the Educational Supervision Agreement (EdSA). This is a three-way agreement between Educational Supervisors, Local Education Providers and the Wales Deanery which clarifies roles, responsibilities and expectations for all. This paper reports on the formative evaluation of the EdSA after 1 year.

Design

Evaluation of pan-Wales EdSA roll-out (2013–2015) employed a mixed-methods approach: questionnaires (n=191), interviews (n=11) with educational supervisors and discussion with key stakeholders (GMC, All-Wales Trainer Recognition Group, Clinical Directors). Numerical data were analysed in SPSS V.20; open comments underwent thematic content analysis.

Participants

The study involved Educational Supervisors working in different specialties across Wales, UK.

Results

At the point of data collection, survey respondents represented 14% of signed agreements. Respondents believed the Agreement professionalises the Educational Supervisor role (85%, n=159 agreed), increases the accountability of Educational Supervisors (87%; n=160) and health boards (72%, n=131), provides leverage to negotiate supporting professional activities' (SPA) time (76%, n=142) and continuing professional development (CPD) activities (71%, n=131). Factor analysis identified three principal factors: professionalisation of the educational supervisor role, supporting practice through training and feedback and implementation of the Agreement.

Conclusions

Our evidence suggests that respondents believed the Agreement would professionalise and support their Educational Supervisor role. Respondents showed enthusiasm for the Agreement and its role in maintaining high standards of training.

http://ift.tt/2rbO28f

Cross-sectional study of factors associated with community health centre use in a recently urbanised community in Chengdu, China

Objectives

Public investment in community health centres (CHCs) has been increasing as a response to rapid urbanisation in China. The objectives of this study were: (1) to examine factors associated with CHC use among residents from a recently urbanised community in western China and (2) to describe satisfaction with CHC among users.

Design

Cross-sectional design.

Setting

A community recently converted to urban status with a newly constructed CHC in Southwest China.

Participants

A random sample of 2259 adults in the Hezuo community in Chengdu, China, completed the survey in 2013.

Outcome measures

Trained staff interviewed study participants in their homes using structured questionnaires. The survey included questions regarding sociodemographics, health status, access to and usage of healthcare, health behaviours and CHC use. The Andersen's behavioural model of health service use was used to guide multivariable logistic regression modelling in identifying predisposing, enabling and need factors associated with the likelihood of using CHC. Descriptive statistics were used to describe residents' satisfaction with the CHC.

Results

A total of 71.8% of the respondents reported using the CHC during the past year. Factors influencing adults' CHC use included: gender, marital status, education level and knowledge of one's blood pressure (predisposing factors); annual household per capita income and walking time to the CHC (enabling factors) and self-rated health as well as physical activities (need factors). CHC users reported modest satisfaction across various aspects of the CHC.

Conclusions

Neighbourhood CHC in urban areas provides important services to these residents living in a recently urbanised community. All three categories of factors in the Andersen model help explain the likelihood of CHC use. There is much room for improvement in CHC to enhance customer satisfaction. Future research is needed to improve access to CHCs and promote their use in urbanised populations with low to modest education.

http://ift.tt/2rH7FZc

Optimal timing for elective caesarean delivery in a Chinese population: a large hospital-based retrospective cohort study in Shanghai

Objective

To assess the relationship between the timing of antepartum elective caesarean delivery (CD) at term and perinatal outcomes in a Chinese population.

Methods

We conducted a retrospective cohort study of mode of delivery at a large obstetric centre in Shanghai, China between 2007 and 2014. Eligibility criteria included: term nulliparous women with a singleton gestation undergoing antepartum elective CD.

Results

There were 19 939 women delivered by antepartum CD without indications, with 5.9% performed at 37–37 6/7 weeks, 36.2% at 38–38 6/7 weeks, 38.4% at 39–39 6/7 weeks, 15.4% at 40–40 6/7 weeks, 4.0% at ≥41 weeks. As compared with births at 39–39 6/7 weeks, births at 37 weeks were associated with an increased odds of neonatal respiratory disease (adjusted odds ratian(aOR): 4.82; 95% CI 3.35 to 6.94), neonatal infection (aOR: 3.68; 95% CI 1.80 to 7.52), hypoglycaemia (aOR: 3.85; 95%CI 2.29 to 6.48), hyperbilirubinaemia (aOR: 3.50; 95%CI 2.12 to 5.68), neonatal intensive care admission (aOR: 3.73; 95% CI 2.84 to 4.89) and prolonged hospitalisation (aOR: 7.51; 95% CI 5.10 to 11.07). Births at 38 weeks, 40 weeks or ≥41 weeks were also associated with an increased odds of neonatal respiratory disease with corresponding aORs (95% CI) of 2.26 (1.71 to 3.00), 1.97 (1.33 to 2.94) and 2.91 (1.80 to 4.70), respectively.

Conclusion

For women undergoing elective CD, neonatal outcome data suggest that delivery at 39–39 6/7 complete weeks is optimal timing in a Chinese population.

http://ift.tt/2rHl1Vg

Assessing the diagnostic accuracy of PCR-based detection of Streptococcus pneumoniae from nasopharyngeal swabs collected for viral studies in Canadian adults hospitalised with community-acquired pneumonia: a Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research (CIRN) study

Study design

Detection and serotyping of Streptococcus pneumoniae are important to assess the impact of pneumococcal vaccines. This study describes the diagnostic accuracy of PCR-based detection of S. pneumoniae directly from nasopharyngeal (NP) swabs collected for respiratory virus studies.

Methods

Active surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed from December 2010 to 2013. Detection of pneumococcal CAP (CAP_Spn) was performed by urine antigen detection (UAD), identification of S. pneumoniae in sputum or blood cultures. S. pneumoniae was detected in NP swabs using lytA and cpsA real-time PCR, and serotyping was performed using conventional and real-time multiplex PCRs. For serotyping, the Quellung reaction, PCR-based serotyping or a serotype-specific UAD was used.

Results

NP swab results were compared against CAP cases where all pneumococcal tests were performed (n=434), or where at least one test was performed (n=1616). CAP_Spn was identified in 22.1% (96/434) and 14.9% (240/1616), respectively. The sensitivity of NP swab PCR for the detection of S. pneumoniae was poor for CAP_Spn (35.4% (34/96) and 34.17% (82/240)), but high specificity was observed (99.4% (336/338) and 97.89% (1347/1376)). Of the positive NP swabs, a serotype could be deduced by PCR in 88.2% (30/34) and 93.9% (77/82), respectively.

Conclusions

While further optimisation may be needed to increase the sensitivity of PCR-based detection, its high specificity suggests there is a value for pneumococcal surveillance. With many laboratories archiving specimens for influenza virus surveillance, this specimen type could provide a non-culture-based method for pneumococcal surveillance.

http://ift.tt/2rHwMLt

A self-efficacy education programme on foot self-care behaviour among older patients with diabetes in a public long-term care institution, Malaysia: a Quasi-experimental Pilot Study

Objective

A pilot self-efficacy education programme was conducted to assess the feasibility, acceptability and potential impact of the self-efficacy education programme on improving foot self-care behaviour among older patients with diabetes in a public long-term care institution.

Method

A prequasi-experimental and postquasi-experimental study was conducted in a public long-term care institution in Selangor, Malaysia. Patients with diabetes aged 60 years and above who fulfilled the selection criteria were invited to participate in this programme. Four self-efficacy information sources; performance accomplishments, vicarious experience, verbal persuasion and physiological information were translated into programme interventions. The programme consisted of four visits over a 12-week period. The first visit included screening and baseline assessment and the second visit involved 30 min of group seminar presentation. The third and fourth visits entailed a 20-min one-to-one follow-up discussion and evaluation. A series of visits to the respondents was conducted throughout the programme. The primary outcome was foot self-care behaviour. Foot self-efficacy (efficacy-expectation), foot care outcome expectation, knowledge of foot care, quality of life, fasting blood glucose and foot condition were secondary outcomes. Data were analysed with descriptive and inferential statistics (McNemar's test and Wilcoxon signed-rank test) using the Statistical Package for the Social Sciences V.20.0.

Results

Fifty-two residents were recruited but only 31 met the inclusion criteria and were included in the analysis at baseline and at 12 weeks postintervention. The acceptability rate was moderately high. At postintervention, foot self-care behaviour (p<0.001), foot self-efficacy (efficacy-expectation), (p<0.001), foot care outcome expectation (p<0.001), knowledge of foot care (p<0.001), quality of life (physical symptoms) (p=0.003), fasting blood glucose (p=0.010), foot hygiene (p=0.030) and anhydrosis (p=0.020) showed significant improvements.

Conclusion

Findings from this pilot study would facilitate the planning of a larger study among the older population with diabetes living in long-term care institutions.

Trial registration number

ACTRN12616000210471; Pre-results.

http://ift.tt/2rHf62k

Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis

Background

Despite the clinical recommendation of exercise and diet for people with knee osteoarthritis (OA), there are no systematic reviews synthesising the effectiveness of combining physical activity and dietary restriction interventions on the musculoskeletal function of overweight and obese older adults with knee OA.

Objective

To evaluate the effectiveness of combined physical activity and dietary restriction programmes on body weight, body mass index (BMI) and the musculoskeletal function of overweight and obese older adults with knee OA.

Information sources

A detailed search strategy was applied to key electronic databases (Ovid, Embase, Web of Science andCumulative Index to Nursing and Allied Health Literature (CINAHL)) for randomised controlled trials (RCTs) published in English prior to 15 January 2017.

Participants

Participants with BMI ≥25 kg/m², aged ≥55 years of age and with radiographic evidence of knee OA.

Interventions

Physical activity plus dietary restriction programmes with usual care or exercise as the comparators.

Outcome measures

Primary outcome measures were body weight, BMI or musculoskeletal function. Secondary outcome measures were pain and quality of life.

Results

One pilot and two definitive trials with n=794 participants were included. Two articles reporting additional data and outcome measures for one of the RCTs were identified. All included RCTs had an unclear risk of bias. Meta-analysis was only possible to evaluate mobility (6 min walk test) at 6 months and the pooled random effect 15.05 (95% CI –11.77 to 41.87) across two trials with n=155 participants did not support the combined intervention programme. Narrative synthesis showed clear differences in favour of a reduced body weight and an increased 6 min walk in the intervention group compared with control groups.

Conclusion

The quality of evidence of benefit of combining exercise and dietary interventions in older overweight/obese adults with knee OA is unclear.

Trail registration number

CRD42015019088 and ISRCTN, ISRCTN12906938.

http://ift.tt/2rbNvCZ

Are self-reported unhealthy food choices associated with an increased risk of breast cancer? Prospective cohort study using the British Food Standards Agency nutrient profiling system

Objectives

French authorities are considering the implementation of a simplified nutrition labelling system on food products to help consumers make healthier food choices. One of the most documented candidates (Five-Colour Nutrition Label/Nutri-score) is based on the British Food Standards Agency Nutrient Profiling System (FSA-NPS), a score calculated for each food/beverage using the 100 g amount of energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits and vegetables. To assess its potential public health relevance, studies were conducted on the association between the nutritional quality of the diet, measured at the individual level by an energy-weighted mean of all FSA-NPS scores of foods usually consumed (FSA-NPS dietary index (FSA-NPS DI)), and the risk of chronic diseases. The present study aimed at investigating the relationship between the FSA-NPS DI and breast cancer risk.

Design

Prospective study.

Setting

Population based, NutriNet-Santé cohort, France.

Participants

46 864 women aged ≥35 years who completed ≥3 24-hour dietary records during their first 2 year of follow-up.

Primary outcome measure

Associations between FSA-NPS DI and breast cancer risk (555 incident breast cancers diagnosed between 2009 and 2015) were characterised by multivariable-adjusted Cox proportional hazard models.

Results

A higher FSA-NPS DI (lower nutritional quality of the diet) was associated with an increased breast cancer risk (HR_{1-point increment}=1.06 (1.02–1.11), p=0.005; HR_Q5vs.Q1=1.52 (1.11–2.08), p trend=0.002). Similar trends were observed in premenopausal and postmenopausal women (HR_{1-point increment}=1.09 (1.01–1.18) and 1.05 (1.00–1.11), respectively).

This study was based on an observational cohort using self-reported dietary data, thus residual confounding cannot be entirely ruled out. Finally, this holistic approach does not allow investigating which factors in the diet most specifically influence breast cancer risk.

Conclusions

These results suggested that unhealthy food choices, as characterised by the FSA-NPS, may be associated with an increase in breast cancer risk, supporting the potential public health relevance of using this profiling system in the framework of public health nutritional measures.

http://ift.tt/2rbFVIQ

Development and validation of a risk stratification model for prediction of disability and hospitalisation in patients with heart failure: a study protocol

Background

Chronic heart failure (CHF) reduces quality of life and causes hospitalisation and death. Identifying predictive factors of such events may help change the natural history of this condition.

Aim

To develop and validate a stratification system for classifying patients with CHF, according to their degree of disability and need for hospitalisation due to any unscheduled cause, over a period of 1 year.

Methods and analysis

Prospective, concurrent, cohort-type study in two towns in the Madrid autonomous region having a combined population of 1 32 851. The study will include patients aged over 18 years who meet the following diagnostic criteria: symptoms and typical signs of CHF (Framingham criteria) and left ventricular ejection fraction (EF)<50% or structural cardiac lesion and/or diastolic dysfunction in the presence of preserved EF (EF>50%).

Outcome variables will be(a) Disability, as measured by the WHO Disability Assessment Schedule V.2.0 Questionnaire, and (b) unscheduled hospitalisations. The estimated sample size is 557 patients, 371 for predictive model development (development cohort) and 186 for validation purposes (validation cohort). Predictive models of disability or hospitalisation will be constructed using logistic regression techniques. The resulting model(s) will be validated by estimating the probability of outcomes of interest for each individual included in the validation cohort.

Ethics and dissemination

The study protocol has been approved by the Clinical Research Ethics Committee of La Princesa University Teaching Hospital (PI-705). All results will be published in a peer-reviewed journal and shared with the medical community at conferences and scientific meetings.

http://ift.tt/2rbRIGL

Social epidemiology of hypertension in Buffalo City Metropolitan Municipality (BCMM): cross-sectional study of determinants of prevalence, awareness, treatment and control among South African adults

Objectives

This study examined hypertension prevalence, awareness, treatment and control and their determinants among adults attending health facilities in Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape.

Design

A cross-sectional analytical study.

Settings

The three largest outpatient clinics in BCMM.

Participants

Ambulatory adults (aged 18 years and over) attending the study settings during the study period (n=998).

Primary outcome measure

The prevalence of hypertension (systolic blood pressure (BP) of ≥140 mm Hg and/or a diastolic BP of ≥90 mm Hg or current medication for hypertension), the awareness of it (prior diagnosis of it) and its treatment and control (Eighth Joint National Committee Criteria of BP <140/90/90 mm Hg).

Secondary outcome measure

Associated factors of hypertension, hypertension unawareness and uncontrolled hypertension.

Results

Of the 998 participants included, the prevalence of hypertension was 49.2%. Hypertension unawareness was reported by 152 participants (23.1%) with significant gender difference (p=0.005). Male sex, age <45 years, higher level of education, single status, current employment, higher monthly income, current smoking, alcohol usage, absence of diabetes and non-obese were significantly associated (p<0.05) with hypertension unawareness.

Of the participants who were aware of having hypertension (n=339), nearly all (91.7%, n=311) were on antihypertensive medication and only 121 participants (38.9%) achieved the BP treatment target. In the multivariate logistic regression model analysis, ageing (95% CI 1.9 to 4.4), being married (95% CI 1.0 to 2.0), male sex (95% CI 1.2 to 2.3), concomitant diabetes (95% CI 1.9 to 3.9), lower monthly income (95% CI 1.2 to 2.2), being unemployed (95% CI 1.0 to 1.9) and central obesity (95% CI 1.5 to 2.8) were the significant and independent determinants of prevalent hypertension.

Conclusion

The prevalence and awareness of hypertension was high in the study population. In addition, the suboptimal control of BP among treated individuals, as well as the significant cardiovascular risk factors, warrant the attention of health authorities of BCMM and the country.

http://ift.tt/2rH6zwn

The Optimal Screening for Prediction of Referral and Outcome (OSPRO) in patients with musculoskeletal pain conditions: a longitudinal validation cohort from the USA

Purpose

There is an increased need for determining which patients with musculoskeletal pain benefit from additional diagnostic testing or psychologically informed intervention. The Optimal Screening for Prediction of Referral and Outcome (OSPRO) cohort studies were designed to develop and validate standard assessment tools for review of systems and yellow flags. This cohort profile paper provides a description of and future plans for the validation cohort.

Participants

Patients (n=440) with primary complaint of spine, shoulder or knee pain were recruited into the OSPRO validation cohort via a national Orthopaedic Physical Therapy-Investigative Network. Patients were followed up at 4 weeks, 6 months and 12 months for pain, functional status and quality of life outcomes. Healthcare utilisation outcomes were also collected at 6 and 12 months.

Findings to date

There are no longitudinal findings reported to date from the ongoing OSPRO validation cohort. The previously completed cross-sectional OSPRO development cohort yielded two assessment tools that were investigated in the validation cohort.

Future plans

Follow-up data collection was completed in January 2017. Primary analyses will investigate how accurately the OSPRO review of systems and yellow flag tools predict 12-month pain, functional status, quality of life and healthcare utilisation outcomes. Planned secondary analyses include prediction of pain interference and/or development of chronic pain, investigation of treatment expectation on patient outcomes and analysis of patient satisfaction following an episode of physical therapy.

Trial registration number

The OSPRO validation cohort was not registered.

http://ift.tt/2rc0GE7

A novel rhamnolipid-producing Pseudomonas aeruginosa ZS1 isolate derived from petroleum sludge suitable for bioremediation

Petroleum pollutants emulsified by biosurfactants facilitate uptake and biodegradation by environmental microbes. In this report, we show the characterization of an indigenous surfactant-producing crude-oil-ea...

http://ift.tt/2t0gTO3

High expression of COX5B is associated with poor prognosis in breast cancer

Future Oncology Ahead of Print.


http://ift.tt/2rHhDKd

Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation

To the Editor:

http://ift.tt/2rbQb3H

Some pathological and clinical factors are important to describe association between Ki67 expression and recurrences in breast cancer patients receiving neoadjuvant chemotherapy

To the Editor,

http://ift.tt/2rHfrlJ

Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation—reply

To the Editor:

http://ift.tt/2rc1OaZ

Ethnicity influences Phenotype and Outcomes in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Population-Based Studies

Inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC)) are global diseases. Similarities and differences in disease presentation and outcomes across different geographic regions and ethnic groups have not been compared previously.

http://ift.tt/2rbTbNh

Colonic Diverticula Are Not Associated with Mucosal Inflammation or Chronic Gastrointestinal Symptoms

Colonic diverticulosis has been reported to be associated with low-grade mucosal inflammation possibly leading to chronic gastrointestinal symptoms. However, there is poor evidence for this association. We aimed to determine whether colonic diverticula are associated with mucosal inflammation and whether diverticula are associated with chronic gastrointestinal symptoms. We explored whether inflammation was present among symptomatic participants with and without diverticula.

http://ift.tt/2rHeUAh

Comparable Long-term Outcomes of 1-minute vs 5-minute Endoscopic Papillary Balloon Dilation for Bile Duct Stones

Endoscopic papillary balloon dilation (EPBD) is an alternative to endoscopic sphincterotomy (EST) for choledocholithiasis. Unlike EST, EPBD preserves biliary sphincter function, reducing long-term risk of recurrent choledocholithiasis by 50%. Guidelines recommend that duration of EPBD exceeds 2 minutes, to adequately loosen the sphincter and reduce risks of failed stone extraction and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, it is unclear whether this long duration of EPBD impairs sphincter function and negates the long-term benefit of EPBD.

http://ift.tt/2rbQThh

Improved outcomes with proactive versus reactive therapeutic drug monitoring of infliximab in IBD

http://ift.tt/2rHdYfd

Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017

Although eosinophilic esophagitis (EoE) has been extensively studied, there have been few epidemiology studies of other eosinophilic gastrointestinal disorders (EGIDs). Using a large, population-based database, we investigated epidemiologic features of eosinophilic gastroenteritis (EoGE), and colitis (EoC) in the United States (US).

http://ift.tt/2rbOTWp

An uncommon gastric submucosal tumor with mucosal erosion

http://ift.tt/2rH8RLX

Efficacy of a 4-Food Elimination Diet for Children With Eosinophilic Esophagitis

A 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE.

http://ift.tt/2rbGS3C

Workplace accommodation for persons with IBD: What is needed and what is accessed

People with inflammatory bowel disease (IBD) often experience periods of illness that interfere with their ability to work. We aimed to understand the need for workplace accommodation during periods of acute illness among persons IBD.

http://ift.tt/2rHmtXI

Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients with Autoimmune Hepatitis

Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.

http://ift.tt/2rceTks

Optimizing Fecal Immunochemical Testing for Colorectal Cancer Screening

http://ift.tt/2rH4kJK

CMV-specific T Cell Monitoring Offers Superior Risk Stratification of CMV-seronegative Kidney Transplant Recipients of a CMV-seropositive Donor.

Background: Detectable CMV-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV-sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV-replication. Methods: 326 KTRs were studied and classified with respect to CMV-serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-[gamma] Elispot assay. Results: 19/67 D+R- KTRs (28%) showed pretransplant CMV-specific T cells. Although no differences were observed for CMV-replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV-loads (p

http://ift.tt/2t0bZ3o

Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera from Subjects Dosed with the Anti-C1s Monoclonal Antibody TNT009 - Results from a Randomized First-in-Human Phase 1 Trial.

Background: Complement may play a key role in antibody-mediated rejection (ABMR). A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. Methods: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n=48; 7 consecutive cohorts: 0.3-100 mg/kg) or 4 weekly infusions (n=16; 2 consecutive cohorts: 30 and 60 mg/kg per infusion) of TNT009 or placebo. To assess the effect of treatment on complement activity, sera from dosed subjects were analysed in a CP activation assay evaluating C3d deposition on HLA-coated microbeads spiked with alloantibodies. Results: Single doses of TNT009 at 3-100 mg/kg uniformly and profoundly inhibited HLA antibody-mediated C3d deposition (>=86% after 60 min), whereby the duration of CP inhibition (2-14 days) was dose-dependent. Four weekly doses persistently blocked complement for 5-6 weeks. Ex vivo serum CP activity was profoundly inhibited when TNT009 concentrations exceeded 20 [mu]g/mL. Infusions were well tolerated without serious or severe adverse events. Conclusions: Treatment with TNT009 was safe and potently inhibited CP activity. Future studies in patients are required to assess the potential of TNT009 for preventing or treating ABMR. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s2feub

DHRS9 is a Stable Marker of Human Regulatory Macrophages.

Background: The human regulatory macrophage (Mreg) has emerged as a promising cell type for use as a cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. In this brief report, dehydrogenase/reductase 9 (DHRS9) is identified as a robust marker of human Mregs. Materials and Methods: The cognate antigen of a mouse monoclonal antibody raised against human Mregs was identified as DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression of DHRS9 within a panel of monocyte-derived macrophages was investigated by quantitative PCR, immunoblotting and flow cytometry. Results: DHRS9 expression discriminated human Mregs from a panel of in vitro derived macrophages in other polarisation states. Likewise, DHRS9 expression distinguished Mregs from a variety of human monocyte-derived tolerogenic antigen-presenting cells in current development as cell-based immunotherapies, including Tol-DC, Rapa-DC, DC-10 and PGE2-induced MDSC. A subpopulation of DHRS9-expressing human splenic macrophages was identified by immunohistochemistry. Expression of DHRS9 was acquired gradually during in vitro development of human Mregs from CD14+ monocytes and was further enhanced by IFN-[gamma] treatment on day 6 of culture. Stimulating Mregs with 100 ng/ml lipopolysaccharide for 24-hours did not extinguish DHRS9 expression. Dhrs9 was not an informative marker of mouse Mregs. Conclusion: DHRS9 is a specific and stable marker of human Mregs. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2t0iLq0

Inhibition of spleen tyrosine kinase reduces renal allograft injury in a rat model of acute antibody-mediated rejection in sensitized recipients.

Background: Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signalling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. Methods: Recipient Lewis rats (RT1l) were immunized with donor (Dark Agouti, RT1av1) spleen cells (day -5). Recipients underwent bilateral nephrectomy and orthotopic renal transplantation (day 0). Cellular rejection was minimized by tacrolimus treatment from day -1. Groups received GS-492429 (30mg/kg/bid) (n=11) or vehicle (n=12) from 1hr before transplantation until being killed on day 3. Results: Vehicle treated recipients developed graft dysfunction on day 1 which rapidly worsened by day 3. Histology showed severe damage (thrombosis, acute tubular injury, capillaritis) and infiltration of many Syk+ leukocytes. GS-492429 did not affect graft dysfunction on day 1, but treatment reduced allograft damage and prevented the rapid deterioration of graft function on day 3. GS-492429 reduced the prominent macrophage infiltrate and reduced the M1 proinflammatory response. Neutrophil and NK cell infiltration and capillary thrombosis were also significantly reduced by GS-492429 treatment. Serum DSA levels and the deposition of IgG and C4d in the allograft were equivalent in the 2 groups. Conclusion: Treatment with a Syk inhibitor significantly reduced renal allograft injury in a model of severe antibody-mediated damage in highly sensitized recipients. Further studies are warranted to determine whether Syk inhibition is a potential adjunctive treatment in clinical AMR. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s210cE

Correction

http://ift.tt/2sZPn2X

Specialty preferences among medical students in Botswana

With the establishment of a new medical college in Botswana to train generalist-doctors and specialists, we set out to explore the career preferences of medical students, factors that influence their choices a...

http://ift.tt/2rbKLWe

Correction

http://ift.tt/2rbhH1g

Advances in Aging Research Vol.6,No.3 (May 2017)

Ontogenetic Approach to the Study of Mechanisms of Copper-Induced Liver Fibrosis
Lipid Hydroperoxides, Glutathione Peroxidase, Aconitase, Liver Fibrosis, Ontogenesis
Paper Information Full Paper: PDF (Size:2368KB)
DOI: 10.4236/aar.2017.63005

http://ift.tt/11MQ3FG

General practitioners views of clinically led commissioning: cross-sectional survey in England

Objectives

Involving general practitioners (GPs) in the commissioning/purchasing of services has been an important element in English health policy for many years. The Health and Social Care Act 2012 handed responsibility for commissioning of the majority of care for local populations to GP-led Clinical Commissioning Groups (CCGs). In this paper, we explore GP attitudes to involvement in commissioning and future intentions for engagement.

Design and setting

Survey of a random sample of GPs across England in 2015.

Method

The Eighth National GP Worklife Survey was distributed to GPs in spring 2015. Responses were received from 2611 respondents (response rate = 46%). We compared responses across different GP characteristics and conducted two sample tests of proportions to identify statistically significant differences in responses across groups. We also used multivariate logistic regression to identify the characteristics associated with wanting a formal CCG role in the future.

Results

While GPs generally agree that they can add value to aspects of commissioning, only a minority feel that this is an important part of their role. Many current leaders intend to quit in the next 5 years, and there is limited appetite among those not currently in a formal role to take up such a role in the future. CCGs were set up as 'membership organisations' but only a minority of respondents reported feeling that they had 'ownership' of their local CCG and these were often GPs with formal CCG roles. However, respondents generally agree that the CCG has a legitimate role in influencing the work that they do.

Conclusion

CCGs need to engage in active succession planning to find the next generation of GP leaders. GPs believe that CCGs have a legitimate role in influencing their work, suggesting that there may be scope for CCGs to involve GPs more fully in roles short of formal leadership.

http://ift.tt/2sknSVi

45 Frontiers of performance: using a mathematical model to discover unobservable performance limits in a pre-hospital and retrieval service

Aim

We aimed to establish if a validated computer model could derive otherwise unobservable performance limits for a physician-led pre-hospital and retrieval service.

Methods

Using our previously validated model for the ?ScotSTAR Emergency Medical Retrieval Service (EMRS), we randomly simulated varying numbers of primary pre-hospital and secondary retrieval missions using the MATLAB software suite Simulink program. The parameters of simultaneous retrieval rate and number of missed primary missions were calculated and plotted. The 45o tangent of the corresponding exponential curve was identified and used as the performance frontier.

Results

Based on the current system demand, the number of missed primaries rose exponentially above a performance frontier of 400 missed primaries per year on a total of 1550 completed primary missions per year (corresponding to 15% absolute service utilisation). However, the simultaneous retrieval rate for both primary and secondary retrieval rose exponentially above 12% at 810 primary missions per year (corresponding to 13% utilisation).

Conclusion

These results provide a useful insight into potential system performance, and its limitations. When combined with forecasting of service growth and demand, they provide useful guidance on what a service may be able to achieve. By knowing the limits of achievable performance, we can also work to derive an absolute number of missions as a specification limit. Furthermore, they illustrate the importance of maintaining relatively low service utilisation in order to achieve rapid response to critically ill or injured patients.

Conflict of interest

None declared.

Funding

Scottish Ambulance Service ScotSTAR

http://ift.tt/2sIOblr

46 Forecasting the demand profile for a physician-led pre-hospital care service using a mathematical model

Aim

We aimed to investigate if a queueing-theory derived, stochastic, computerised mathematical model could accurately predict the number and seasonal pattern of primary pre-hospital missions undertaken by a physician-led pre-hospital and retrieval service in 2016.

Methods

We used queueing theory to derive parameters for a computer model built using the MATLAB software suite Simulink program. The model was primed with retrospective data, validated with contemporaneous data and then used to forecast 1 year ahead. A total of 100 iterations of the model were studied. The model output was compared to the real-world data with regard to total number of missions and seasonal pattern using standard statistical tests.

Results

Our model forecast 547 missions (95% CI 516–586) during the prospective study period, compared to 565 real-world missions. (t-test p=0.21). The seasonal patterns were adequately matched to generate a non-significant result under the Kolmogorov-Smirnov test (p=0.14).

Conclusion

Our model was able to correctly predict the number of pre-hospital primary retrieval missions undertaken by the ScotSTAR Emergency Medical Retrieval Service (EMRS) by demonstrating no statistically significant differences to the real-world mission numbers or distribution. This suggests that a queueing theory derived model is able to accurately replicate, and forecast, the real-world performance of ScotSTAR EMRS operations. This finding presents useful implications for resource utilisation, asset allocation and investigating system capability.

Reference

Kendall DG. Stochastic Processes Occurring in the Theory of Queues and their Analysis by the Method of the Imbedded Markov Chain. The Annals of Mathematical Statistics 24(3):1953.

Conflict of interest

None declared.

Funding

Scottish Ambulance Service ScotSTAR

http://ift.tt/2s9cZGm

44 Point-of-care analysis of lactate from intraosseous samples during resuscitation

Aim

Intraosseous (IO) access with power-driven devices has become a commonly used method of vascular access during cardiopulmonary resuscitation (CPR). Blood aspirated to confirm correct IO needle position could readily be available for point-of-care (POC) testing. The aim was to investigate how POC lactate levels of intraosseous blood reflect the lactate values in systemic circulation during VF and resuscitation in order to see whether POC IO samples could be used for clinical decision-making during CPR.

Methods

We conducted an experimental study comparing POC results of lactate from intraosseous, arterial and venous blood of 23 piglets undergoing induced cardiac arrest (VF) and CPR. All blood samples were analysed with i-STAT POC device and the results were compared using Bland-Altman method (ref 1).

Results

Prior to VF the IO lactate levels were similar to arterial and venous samples (bias [95% CI] between IO and arterial samples was 0.11 mmol/L [–0.02–0.24] and between IO and venous samples 0.03 mmol/L [–0.25–0.31]). Five minutes after onset of VF, intraosseous lactate levels had increased more than arterial and venous values (bias 3.76 mmol/L [1.93–5.59] and 3.52 mmol/L [1.41–5.64] respectively). Five minutes after initiation of CPR with an automatic CPR device (LucasTM) the difference diminished (bias 0.81 mmol/L, [–0.31–1.93] and 1.50 mmol/L [0.07–2.92]).

Conclusion

Intraosseous lactate values showed good agreement with arterial and venous values before cardiac arrest, but IO values were clearly higher during VF and CPR. During resuscitation IO lactate values seem to represent better the metabolic state at tissue level than arterial or venous lactate.

Reference

Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet1986;1:307–10

Conflict of interest

None declared.

Funding

None declared.

http://ift.tt/2sIE1kV

FDA Requests Removal of Opana ER for Risks Related to Abuse

June 8, 2017 -- Today, the U.S. Food and Drug Administration requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market. After careful consideration, the agency is...

http://ift.tt/2r6Ijp7

KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

http://ift.tt/2r7tHFR

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

http://ift.tt/2rRcEEV

NPR: Music to Ease Hearing Loss

NPR featured a piece on  "All Things Considered," considering how to improve speech understanding in noisy environments. The segment focused on an ongoing study by Frank Russo, the director of the Science of Music, Auditory Research, and Technology Lab (SMART Lab) at Ryerson University in Toronto.

Tweet

http://ift.tt/2rbhJ99

Preclinical models for translational sarcoma research

Purpose of review: Sarcoma is a basket term for mesenchymal tumors for which more than 75 genetically and histologically distinct subtypes are recognized. Therapeutic progress has largely been achieved with classical chemotherapeutic drugs that were tested in empirical clinical trials. However, outcome in metastatic patients remains poor and with few exceptions numerous trials have failed or only provided limited improvement in recent years. Recent findings: Given the genomic heterogeneity, preclinical model systems will be indispensable to identify new molecular targets and to prioritize drugs and drug combinations. Cell culture is still widely used in preclinical sarcoma research to identify potential novel therapeutic approaches and resistance mechanisms. New and improved techniques in genome-wide and proteome-wide screens enable a better characterization. In addition to cell line xenograft mouse models, patient-derived xenografts crucially broadened and improved preclinical studies using primary human samples. Finally, novel strategies for genome editing, like CRISPR/Cas and sleeping beauty transposon, lead to development of novel genetically engineered cell lines and mouse models. Summary: The present review gives a non-comprehensive overview on current model systems used in sarcoma research and discusses their translational relevance. Those include cell lines, subtype-specific patient-derived cell lines and xenografts as well as developments in genome editing and genetically engineered cell lines and mouse models.

http://ift.tt/2sIwwu2

Long-term survival after cancer: at what cost?

No abstract available

http://ift.tt/2sICjzU

Treatment of retroperitoneal sarcoma: current standards and new developments

Purpose of review: Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give an overview of current standards in treatment of this disease and discuss new developments. Recent findings: Surgery with complete resection of the primary tumor is still the only curative modality. The role of preoperative radiotherapy is not clear and is currently being investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard of care but can be considered occasionally when complete resection is uncertain. Local and distant recurrent disease carries a dismal prognosis, although long-term survival can be achieved. Liposarcomas tend to recur locally, whereas distant recurrences are more often seen in leiomyosarcoma and other subtypes. Outcome improves when patients are treated in high volume sarcoma centers. In the metastatic setting, newer systemic agents have recently been approved. Summary: Treatment of retroperitoneal sarcomas is complex and all patients should be treated in a multidisciplinary sarcoma centers. Increasing international collaboration of expert centers in sharing expertise and performing clinical trials might lead to better treatment and improved survival.

http://ift.tt/2s95oY4

Advances in management of hepatocellular carcinoma

Purpose of review: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. Recent findings: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging. Extension of criteria for liver transplantation, but also for liver resection and percutaneous ablation, aims to increase the number of patients being treated in a curative attempt. Moreover, radioembolization is a competitor for transarterial chemoembolization in Barcelona clinic liver cancer B patients, and sorafenib in Barcelona clinic liver cancer C with tumor portal thrombosis. In advanced HCC, sorafenib is the standard of first-line care and regorafenib as a second line. Summary: New concepts on liver resection, percutaneous ablation or liver transplantation aim to extend the numbers of patients treated for HCC in curative attempts. Moreover, immunotherapy (anti death protein 1) and biotherapy adapted to tumor biology seem promising and are currently being tested in advanced stages.

http://ift.tt/2s9rZ79

Physical long-term side-effects in young adult cancer survivors: germ cell tumors model

Purpose of review: After the important advances in the treatment of germ cell tumors (GCTs) leading to high cure rates, physical long-term side-effects represent an important cause of death in these young adult survivors. Highlighting these physical long-term side-effects, their monitoring and their prevention modalities is necessary for a better management of these cancer survivors. Recent findings: Impaired fertility, increased risk of developing a second cancer, cardiac, pulmonary, renal and neural toxicity, hearing and vision impairment are the major physical side-effects in young adult cancer survivors. Long-term cardiac toxicity, next to second malignancies, represents life-threatening conditions in testicular cancer survivors. The long-term nephrotoxity in testicular GCTs survivors is most frequently associated to the treatment either in those treated with cisplatin-based chemotherapy, mainly Bleomycine, Etoposide, Cisplatin, or those receiving infradiaphragmatic radiation therapy, whereas pulmonary toxicity is mainly attributed to bleomycin related toxicities. Summary: There are no clear and comprehensive data concerning the monitoring and prevention of long-term side-effects in testicular cancer survivors. Physical activity and interventions in modifiable cardiovascular risk factors and lifestyles may reduce the incidence of long-term side-effects in these cancer survivors.

http://ift.tt/2sICXNC

Editorial introductions

No abstract available

http://ift.tt/2sIP2CE

Integrative medicine in cancer survivors

Purpose of review: Due to medical advances and an aging population, the number of cancer survivors continues to rise. Survivors often experience late and long-term sequelae of cancer and its treatment (e.g., fatigue, pain, fear of recurrence, and stress). As a result, some patients have utilized or expressed interest in integrative medicine (IM) modalities for prevention of recurrence, optimizing health, enhancing quality of life, and managing symptoms. The purpose of this review is to focus on research published during the past year that informs our understanding of the utility of IM for cancer survivors. Recent findings: Physical activity, diet, dietary supplements, mind–body modalities, acupuncture, and massage therapy all may play a role in the management of the physical (e.g., fatigue and pain) and emotional (e.g., anxiety and fear) issues faced by cancer survivors. Summary: IM therapies are appealing to and utilized by many cancer survivors and may reduce symptom burden. Clinicians who provide cancer survivorship care may improve patient care by understanding the evidence for and against their use.

http://ift.tt/2sIzcYy

Adult desmoid tumors: biology, management and ongoing trials

Purpose of review: To summarize the current knowledge about the biology and clinical management of adult desmoid tumors. Recent findings: In the past decade, we have learned that desmoid tumors are driven by alterations of the Wnt/APC/β-catenin pathway, sporadic desmoid tumors are associated with somatic mutations of CTNNB1, and germline mutations of APC and somatic mutations of CTNNB1 are probably mutually exclusive. One-third of desmoid tumors are misdiagnosed; a second pathological opinion is therefore of major importance for desmoid tumor. Surgery is no longer regarded as the cornerstone of desmoid tumors; several retrospective studies have demonstrated the safety of a 'wait and see' policy in sporadic abdominal wall desmoid tumor. Desmoid tumors is no longer regarded as an absolute contraindication for pregnancy. At least two new investigational drugs targeting the Wnt/APC/β-catenin pathway are currently being developed. Summary: The management of desmoid tumors requires multidisciplinary expertise by an experienced team. We must fully understand the physiopathology of the disease (factors influencing the natural history of the disease) and learn how to avoid desmoid tumors occurrence in patients with APC germline mutations, identify reliable prognostic/predictive factors and better assess the efficacy of systemic treatment.

http://ift.tt/2sIllBN

Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art

Purpose of review: For trying to help physicians in counseling their young patients with breast cancer interested in fertility preservation and future reproductive plans, this manuscript aims to perform an overview of the main available data on 10 controversies in this field. Recent findings: Thanks to the improvement in patients' prognosis, a growing attention towards fertility and pregnancy issues has been given over the past years and is currently provided to young breast cancer patients. However, several grey zones persist in many domains of this field and some physicians are still uncomfortable to deal with these issues. Summary: Despite the great number of breast cancer patients experiencing fertility and pregnancy concerns at the time of diagnosis, the pursuit of fertility preserving strategies is realized only for a small proportion of them. The lack of adequate oncofertility counseling at the time of anticancer treatment decisions and the high costs of fertility preserving procedures can be considered the main explanations for these findings. The several ongoing registries and prospective studies investigating fertility and pregnancy issues in young breast cancer patients are crucial to acquire more robust data and try to address and solve the still unmet controversies in this field.

http://ift.tt/2sICX04

The meaningness of colon cancer sidedness

No abstract available

http://ift.tt/2s9dvEf

Neoadjuvant treatment: a novel standard?

Purpose of review: The aim of this study was to summarize developments in the adjuvant/neoadjuvant chemotherapy of high-risk adult-type soft tissue sarcomas (STS). Recent findings: The role of adjuvant/neaodjuvant chemotherapy in these patients is controversial, with a meta-analysis suggesting a 10% survival benefit. Recently, a randomized controlled trial in high-risk STS of extremities and trunk wall showed a 20% improvement in progression-free and overall survival after three preoperative cycles of epirubicin along with ifosfamide compared with a histology-tailored chemotherapy. This study has major strengths, including the selected high-risk population and the full-dose chemotherapy regimen. However, this was an interim analysis with a short follow-up in a trial originally planned to test the superiority of a histology-driven chemotherapy. As to high-risk patient selection, the new AJCC TNM staging system adds primary tumour site as a stratifying factor, while available prognostic nomograms account for additional criteria. Summary: A recent trial strengthens perioperative chemotherapy as an option for high-risk STS patients within a shared decision-making process. If the final analysis of this trial confirms the currently observed progression-free and overall survival benefits, perioperative chemotherapy may become a standard. Also, new staging tools may refine our ability to select patients with a risk high enough as to deserve chemotherapy.

http://ift.tt/2s9aK5P

Tackling immunomonitoring in gastrointestinal cancer

Purpose of review: The growing awareness that the immune system is a key player in the antitumoral response and the excellent clinical results achieved in some settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the rise of immunotherapy as a supplement or an alternative to conventional cancer treatment. The high costs associated with these therapies, their significant toxicity and the need to understand and circumvent immune escape mechanisms raise the urgent need for immunological assessment of therapy response. The study of the immunological parameters before, during and after treatment is referred to as immunomonitoring. This review discusses the current knowledge of immunomonitoring markers in gastrointestinal cancers. Recent findings: The last decade has seen a collaborative effort to standardize the assays performed in clinical trials to assess response to immunotherapy. Since then, multiple studies have been conducted on blood samples, biopsies and surgical specimens to determine their immunological profiles leading to the identification of several immunological markers possessing a predictive value of response to treatment. Summary: Future research will focus on detangling the predictive value of immune markers in different therapeutic models, and also to develop new noninvasive means to monitor the immune response of patients. Video abstract: http://ift.tt/2rlA6sx .

http://ift.tt/2sIoph7

Committees

http://ift.tt/2rboHei

Biology of extreme ages - Pediatric and Geriatric laboratory medicine - Prenatal and postnatal testing

http://ift.tt/2rGGmyc

Education and Training in Laboratory Medicine

http://ift.tt/2rbdrP5

Pharmacogenetics - Personalized Medicine

http://ift.tt/2rGtvMe

Laboratory and Sports medicine

http://ift.tt/2rbbfqY

Inherited disorders - Metabolic disorders

http://ift.tt/2rGA4yt

Evidence based medicine - Guidelines

http://ift.tt/2rboEiC

Contents

http://ift.tt/2rGu2ho

Bone metabolism - Osteoporosis

http://ift.tt/2rb4eXj

Atherosclerosis - Lipids and Lipoproteins

http://ift.tt/2rGxqJd

Bioinformatics - Information technology applications

http://ift.tt/2rbbaUc

Rare Diseases

http://ift.tt/2rGp0l6

Frontmatter

http://ift.tt/2rb1RDS

Plenary Lecture Abstracts

http://ift.tt/2rGIea1

Biomarkers of acute kidney injury: a step forward

Authors: Plebani, Mario


http://ift.tt/2qOKs8b

Long-term prognostic implications of myocardial perfusion imaging in octogenarians: an all-comer, cohort study

Abstract

Purpose

Evaluation of the long-term prognostic value of myocardial perfusion imaging (MPI) in octogenarians.

Methods

Six hundred and twenty-nine octogenarians [51% previous myocardial infarction (MI) or revascularization] who underwent single-isotope MPI (78% ²⁰¹Tl, 22% ^99mTc-tetrofosmin) with exercise (38% Bruce, 2% leg ergometry) or pharmacologic (58% adenosine, 2% dobutamine) stress were studied. All patients had LVEF determined by echocardiography within 1 month from MPI. Myocardial perfusion scoring was performed on a 17-segment LV-model with a 5-point grading system and three summed stress score (SSS)-based risk categories were formed [high-(SSS > 12), low-(SSS < 4), medium]. Prospective follow-up was performed to document all-cause (ACD), cardiac death (CD), MI, and revascularization. Revascularization was used to censor follow-up in survival analysis regarding ACD, CD, and CD/MI. For analysis of the CD, MI, or late revascularization (LR) composite, only revascularizations within 3 months from MPI (early revascularizations) were used for censoring.

Results

After 9.3 years there were 187 ACDs, 86 CDs, 28 MIs, and 77 revascularizations, including 28 early revascularizations. Adjusting for LVEF and stress-modality type, SSS was identified as an independent predictor of ACD [HR 1.03 (1.01–1.05)], CD [HR 1.05 (1.03–1.08)], CD,MI [HR 1.05 (1.02–1.07)], and CD,MI or LR [HR 1.05 (1.03–1.07)] (p ≤ 0.001 in all cases). Increased lung uptake had independent prognostic value only for the CD, MI, or LR end-point [HR 3 (1.2–7.7), p = 0.02]. Survival modeling demonstrated that LVEF and SSS, but not non-perfusion scintigraphic data provided incremental prognostic value over pre-test available clinical and historical information for all end-points. Differences between Kaplan-Meier survival curves of SSS-based risk groups were significant for all end-points (p < 0.001 in all cases).

Conclusions

In octogenarians, MPI provides effective long-term risk stratification, regardless of stress type used or underlying cardiac function.

http://ift.tt/2s16yEm

Cutaneous Squamous Cell Carcinoma: Review of the Eighth Edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants

Cutaneous squamous cell carcinoma is the second most common form of nonmelanoma skin cancer after basal cell carcinoma and accounts for the majority of nonmelanoma skin cancer–related deaths. In 2017, the American Joint Committee on Cancer revised the staging guidelines of cutaneous squamous cell carcinoma to reflect recent evidence concerning high-risk clinicopathologic features. This update reviews the literature on prognostic features and staging, including the eighth edition of the American Joint Committee on Cancer Staging Manual. A wide range of histopathologic variants of cutaneous squamous cell carcinoma exists, several of which are associated with aggressive behavior. A review of cutaneous squamous cell carcinoma variants, emphasizing diagnostic pitfalls, immuhistochemical findings and prognostic significance, is included. Of note, the eighth edition of the American Joint Committee on Cancer Staging Manual refers to squamous cell carcinoma of the head and neck only.

http://ift.tt/2sZkpZ1

Current Valuation of Pathology Service

Health care reform has accelerated as the existing health care system undergoes continuing financial stress. Medicare's new value-based payment system, commonly referred to as MACRA, provides opportunities for physicians to participate in this new system in a variety of ways. However, many of the value-based adjustments are based on existing valuations of services through traditional mechanisms. To achieve appropriate valuation of pathologist's services in the new payment models, it is imperative that we continue to achieve proper valuation of services through the traditional mechanisms.

http://ift.tt/2sZfjfg

Perspectives on Low-grade Sarcomas: The Extraordinary Contributions of Sharon W. Weiss, MD

Soft-tissue pathology encompasses a wide spectrum of neoplasms that represent some of the most challenging and problematic tumors in surgical pathology. Owing to the intensive work of dedicated pathologists, this once esoteric field has become increasingly well defined. In this review, Dr Sharon Weiss' monumental contributions to low-grade sarcomas, including low-grade fibromyxoid sarcoma/so-called hyalinizing spindle cell tumor, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and dermatofibrosarcoma protuberans with fibrosarcomatous transformation will be discussed.

http://ift.tt/2sZf7ge

Clinical Applications of Whole-slide Imaging in Anatomic Pathology

The development of whole-slide imaging has paved the way for digitizing of glass slides that are the basis for surgical pathology. This transformative technology has changed the landscape in research applications and education but despite its tremendous potential, its adoption for clinical use has been slow. We review the various niche applications that initiated awareness of this technology, provide examples of clinical use cases, and discuss the requirements and challenges for full adoption in clinical diagnosis. The opportunities for applications of image analysis tools in a workflow will be changed by integration of whole-slide imaging into routine diagnosis.

http://ift.tt/2sZfirI

Role of Human Papillomavirus in Vulvar Cancer

Human papillomavirus (HPV) is involved in one of the at least 2 pathways leading to vulvar squamous cell carcinoma (VSCC). Inactivation of p53 and retinoblastoma by the viral products E6 and E7 is involved in malignant transformation. The percentage of HPV-positive VSCCs ranges from 18% to 75%, depending on the geographical area. HPV-associated tumors affect relatively young women and arise from high-grade intraepithelial lesions, identical to other HPV-associated premalignant lesions of the anogenital tract. HPV-independent tumors tend to affect older women and usually arise in a background of inflammatory skin disorders and a subtle variant of in situ lesion called differentiated vulvar intraepithelial neoplasia. HPV-positive tumors tend to be of basaloid or warty types, whereas HPV-independent tumors tend to be of keratinizing type, but there is frequent overlap between histologic types. There is no conclusive evidence yet on the best strategy in terms of determining HPV attribution. HPV DNA detection is generally considered the gold standard although there is some concern about misclassification when using this technique alone. p16 immunostaining has shown to be an excellent surrogate marker of HPV infection. Positive results for both techniques are considered the best evidence for HPV-association. The prognostic role of HPV in VSCC is still contradictory, but increasing evidence suggests that HPV-associated tumors are less aggressive. Currently, there are no differences in treatment between HPV-associated and HPV-independent VSCC, but novel immunological strategies based on anti-HPV antigens are being evaluated in clinical trials.

http://ift.tt/2sZsJb3

Pathophysiology of ANCA-associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules. The propensity to develop these antibodies depends on a variety of predisposing factors such as microbial infection, genetic factors, environmental agents, and therapeutic drugs among others. These factors are usually associated with production of proinflammatory cytokines with capacity to prime the neutrophils. As a result a high proportion of neutrophils in circulation may be primed resulting in exposure of cytoplasmic proteins including myeloperoxidase and proteinase 3 on the surface of the neutrophils. Primed neutrophils are activated by interaction with ANCA in circulation. Activated neutrophils attach to and transmigrate through endothelium and accumulate within the vessel wall. These neutrophils degranulate and produce reactive oxygen radicals and ultimately die, causing tissue injury. Endothelial injury results in leakage of serum proteins and coagulation factors causing fibrinoid necrosis. B cells produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes with excess of Th17, which perpetuate the inflammatory process.

http://ift.tt/2sZ0ZTV

Antimicrobial susceptibility of Clostridium difficile isolated in Thailand

Exposure to antimicrobials is the major risk factor associated with Clostridium difficile infection (CDI). Paradoxically, treatment of CDI with antimicrobials remains the preferred option. To date, only three stu...

http://ift.tt/2s1mRB3