Exsanguinating Hemorrhage from an Anterior Abdominal Wall Metastasis of an Asymptomatic Renal Cell Carcinoma

Abstract

Renal cell carcinoma is the most frequently encountered urological malignancy and accounts for 3% of all adult malignancies. The classically described triad of hematuria, palpable mass, and flank pain is rarely encountered, and most patients are diagnosed by screening done for other reasons. It is notorious for unusual sites of metastatic spread. We present a case of an asymptomatic renal cell carcinoma that presented as an anterior abdominal wall swelling and its neglect led to ulceration, and torrential and exsanguinating hemorrhage to which the patient succumbed.

https://ift.tt/2QCErYD

The ethics of treating family members

Purpose of review Many medical professionals receive requests from family and friends asking for medical advice and treatment. But should medics treat their family? Ethically can we treat, or refuse to treat, family members? This is a common ethical challenge that most doctors face during their career and there is limited evidence available. By examining ethical principles, we aim to answer these questions and provide a framework that will guide decision making in this area. Recent findings There is a paucity of evidence available. Many ethical systems exist and have been discussed since ancient Greece but in recent years, bioethics has become more prominent in medical thinking and debate. Summary We examine ethical systems such as virtue ethics, utilitarianism, deontology and principlism and how they relate to treating family members. We then look at cases in different contexts and describe a system for approaching such cases, allowing doctors to conform to moral standards, and consider ethical arguments, prior to embarking upon any treatment course with a relative. Correspondence to Paul C. McConnell, MB, ChB (Hons), FRCA, EDIC, FFICM, Consultant Intensive Care Medicine, Royal Alexandra Hospital, Paisley PA2 9PJ, Scotland. Tel: +0141 314 6609; e-mail: paulmcconnell@nhs.net Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QDCb3j

Role of anesthesiologists in managing perioperative anemia

Purpose of review Anemia can contribute negatively to a patient's morbidity and mortality. Which treatment options do exist and what role do anesthesiologists play in management of perioperative anemia treatment? This review gives an overview about recent findings. Recent findings Patient Blood Management and standards for the management and treatment of anemia have been established worldwide. Various logistic settings and approaches are possible. With a special focus on cardiovascular anesthesia, intravenous iron is a therapeutic option in the preoperative setting. Autologous blood salvage is a standard procedure during surgery. Restrictive transfusion triggers in adult cardiac surgery have been shown to be beneficial in the majority of studies. Elderly patients and defined comorbidities might require higher transfusion triggers. Both, intravenous and oral iron increase hemoglobin values when given prior to surgery. Oral iron is effective when given several weeks prior to elective surgery. Erythropoietin is a treatment decision individualized to each patient. Summary Within the previous 18 months, important publications have demonstrated the established role of anesthesiologists in managing perioperative anemia. A substantial pillar for anemia treatment is the implementation of Patient Blood Management worldwide. Correspondence to Andrea U. Steinbicker, MD, MPH, Westfalische Wilhelms-Universitat Munster, Muenster; Muenster University Hospital, Albert-SChweitzer Campus 1, Building A1, 48149 Muenster, Germany. Tel: +0049 251 83 47898; e-mail: andrea.steinbicker@ukmuenster.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SwyUAg

Preoperative rehabilitation for thoracic surgery

Purpose of review Lung resection provides the best outcome for patients with early stage lung cancer. However, lung cancer surgery carries a significant risk of perioperative complications. Patient risk may be reduced by addressing modifiable risk factors in the preoperative period. We review how this can be achieved through preoperative rehabilitation pathways. Recent findings Cardiorespiratory fitness is an independent predictor of survival for nonsmall cell cancer. Preoperative exercise programmes may improve cardiorespiratory reserve and reduce perioperative complications. Additional benefits may be achieved through interventions such as smoking cessation programmes, correction of anaemia, improvement of nutritional status and improved oral hygiene. These interventions may also have the additional benefit of enabling high-risk patients previously deemed unsuitable for surgery to be optimized to such a degree that they can undergo surgery. These interventions will achieve maximal benefit when delivered early in lung cancer pathways; this requires close collaboration amongst multidisciplinary teams. Summary Lung cancer surgery carries significant risk of postoperative pulmonary complications. Through integrating prehabilitation interventions into lung cancer pathways, there are opportunities to improve long-term outcomes for patients. Correspondence to Richard Templeton, MB.ChB, FRCA, Wythenshawe Hospital, Manchester Foundation Trust, Southmoor Road, Manchester M23 9LT, UK. Tel: +441612914514; e-mail: rtempleton7@doctors.org.uk Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QJPBes

Sodium-glucose cotransporter-2 inhibitors: an overview and perioperative implications

Purpose of review Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a relatively new class of drugs used in the management of diabetes mellitus. This review will highlight key pharmacologic characteristics of this class of drugs; discuss their potential role in management of patients with cardiac disease; and raise several perioperative concerns for anesthesiologists caring for patients on SGLT-2 inhibitors. Recent findings Recent trials have shown a strong mortality benefit in diabetic patients on SGLT 2 inhibitors especially in patients with a high cardiovascular burden. In addition, there is a reduction in HbA1c levels, blood pressure, weight and readmissions secondary to heart failure in this patient population. However, these drugs have been also associated with an increased incidence of adverse events, such as euglycemic ketoacidosis, urinary tract infections, acute kidney injury and limb amputations. Summary SGLT 2 inhibitors are being increasingly prescribed secondary to their significant salutatory effect in patients with type II diabetes mellitus. Although there are no perioperative consensus guidelines for management of patients on SGLT2 inhibitors, they should be discontinued at least 24–48 h prior to major surgeries. Their overall management in the perioperative period should be carried out on a case-to-case basis using a multidisciplinary approach. Correspondence to Amit Bardia, MBBS, Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06515, USA. E-mail: amit.bardia@yale.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Sw3D0c

Ethical lessons learned and to be learned from mass casualty events by terrorism

Purpose of review The world has seen a major upturn in international terror awareness. Medicine has had to respond. In addition to the unique physical and mental injuries caused by terror which require special clinical attention, so too terror represents a challenge for medicine from an ethics perspective. Recent findings Several responses in the literature over the past few years have attempted to reflect where the battlefront of ethical dilemmas falls. These include issues of resource allocation, triage, bioterror, the therapeutic relationship with terrorists, dual loyalty, and challenges in the role in the promotion of virtuous behavior as a physician under difficult conditions. Summary Although many challenges exist, physicians need to be prepared for ethical response to terror. With their associated unique status, providing legitimacy and specialized ability in the management and approach to terror situations, physicians are held to a higher standard and need to rise to the occasion. This is required in order to promote ethical behavior under trying conditions and ethical sensitivity of the medical profession by means of being attuned to the reality around. Correspondence to Rael D. Strous, MD, MHA, Mayanei Hayeshua Medical Center, 17 HaRav Povarski Street, Bnei Brak, Israel. Tel: +972 73 3398015; fax: +972 73 3398003; e-mail: raels@post.tau.ac.il Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QCDXSj

Withholding or withdrawing life support versus physician-assisted death: a distinction with a difference?

Purpose of review Withholding or withdrawing life-sustaining therapy is generally differentiated from physician-assisted suicide or euthanasia based on the distinction between intention and foresight. We reviewed the literature surrounding the validity of this distinction. Recent findings Many physicians from different specialties express a perceived distinction between intention and foresight. The distinction between intention and foresight differs from the morally irrelevant distinction between doing and allowing. Intention and foresight may be distinguished by their opposing directions of fit between world and mind. Intention is held to be of greater moral significance than foresight because it guides and constrains our actions, determines the moral quality of our actions, and expresses the moral character of the agent. Opponents of the distinction argue that it undermines moral accountability for foreseen consequences of our actions and is overly concerned with the physician's state of mind rather than the patient's experience. They also argue that intentions may be vague and difficult to express or ascertain. Summary Several reasons may be given in favor of the distinction between intention and foresight. Given this distinction, the moral permissibility of withholding or withdrawing life-sustaining therapy does not necessarily entail the moral permissibility of physician-assisted suicide or euthanasia. Correspondence to Ewan C. Goligher, MD, PhD, Toronto General Hospital, 585 University Ave., Peter Munk Building, 11-192, Toronto, ON M5G 2N2, Canada. Tel: +1 416 340 4800 ext. 6810; e-mail: ewan.goligher@utoronto.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SxLM9f

Resource allocation in ICU: ethical considerations

Purpose of review Increasing scarcity of resources on the background of ever improving medical care and prolonged life expectancy has placed a burden on all aspects of health care. In this article we examine the current problems with resource allocation in intensive care and question whether we can find guidance on appropriate resource allocation through ethical models. Recent findings The problem of fair and ethical resource allocation has perpetually plagued health care. Recent work has looked at value for money, benefits of therapies and how we define futility, but these still fall victim to the same problems that classical schools of ethical thought have tried to tackle. Summary Many ethical principles provide a framework on which to allocate resources to certain cohorts of patients, however, most appear too rigid to be fully and primarily utilized for intensive care admission. We suggest a collaboration of principles be applied to achieve a moral, ethical and common sense approach to this issue. Over resourcing and under resourcing is also suggested to be problematic for patients and healthcare workers alike. Correspondence to Paul C. McConnell, MB ChB (Hons) FRCA EDIC FFICM, Royal Alexandra Hospital, Corsebar Road, Paisley PA2 9QF, UK. Tel: +0141 314 6609; e-mail: paulmcconnell@nhs.net Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SwRZlJ

Cheaper drugs and techniques to fulfill chief executive officer perspectives – any choices?

Purpose of review Against the background of increasing healthcare costs and diminishing budgets, this review aims to present clinicians with ethically viable options to overcome budgetary restraints when seeking to introduce novel products. Recent findings Healthcare administrators and primary healthcare providers are not unlikely to have different opinions when discussing the introduction of novel products. However, rather than taking a 'no' for an answer, doctors may be able to argue for a change – even if this may seem to come at a higher cost. The recent introduction of the reversal agent sugammadex may provide a timely example for the possibility of success 'against all financial odds'. Summary Health professionals have the responsibility to deliver high-quality care while acknowledging the financial budget constraints. However, evidence (vs. perception) for outcome benefits of novel drugs or devices should stimulate a robust desire for their timely introduction. Demonstrating actual benefits understandable to administrators, seeking alliances with other medical specialties or patient groups, as well as negotiations with the healthcare industry may all represent viable options. Simply waiting for patents to expire should remain a measure of last resort. Correspondence to Professor Thomas Ledowski, Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, 197 Wellington Street, Perth, Western Australia 6000, Australia. Tel: +61 8 92242244; e-mail: Thomas.ledowski@health.wa.gov.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QLERfD

Nonstandard do-not-resuscitate orders

Purpose of review Tattoos and medallions are examples of nonstandard do-not-resuscitate (DNR) orders that some people use to convey end-of-life wishes. These DNR orders are neither universally accepted nor understood for reasons discussed within this manuscript. Recent findings Studies show both providers and patients confuse the meaning and implication of DNR orders. In the United States, out-of-hospital DNR orders are legislated at the state level. Most states standardized out-of-hospital DNR orders so caregivers can immediately recognize and accept the order and act on its behalf. These out-of-hospital orders are complicated by the need to be printed on paper that does not always accompany the individual. Oregon created an online system whereby individuals recorded their end-of-life wishes that medical personnel can access with an Internet connection. This system improved communication of end-of-life wishes in patients who selected comfort care only. Summary To improve conveyance of an individual's wishes for end-of-life care, the authors discuss nationwide adoption of Oregon's online registry where a person's account could comprehensively document end-of-life wishes, be universally available in all healthcare institutions, and be searchable by common patient identifiers. Facial recognition software could identify unconscious patients who present without identification. Correspondence to Gregory E. Holt, MD, PhD, University of Miami School of Medicine, Miami, FL 33136, USA. E-mail: gholt@miami.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SwRW9x

Distribution of lymphomas in Mexico: a multicenter descriptive study

Abstract

Epidemiology of lymphoma is not well described in Mexico. We determined the frequencies and subtypes of the main non-Hodgkin's and Hodgkin's lymphomas in the Mexican population. Files for tissue samples for lymphomas stored in five different hospitals in Mexico City were retrieved for re-analysis and further immunostaining. The most common mature B cell, T cell/NK cell, Hodgkin's, and precursor lymphoid neoplasms were identified according to the 2008 WHO classification of tumors. All stains were performed in the same laboratory and interpreted by three pathologists. Five thousand seven hundred seventy-two neoplasms were included. Of these, 4213 were mature B cell neoplasms (73%; 95% CI 71.83–74.12), 888 Hodgkin's lymphomas (HLs) (15%; 95% CI 14.48–16.34), 496 mature T cell/NK neoplasms (9%; 95% CI 7.89–9.34), and 175 precursor lymphoid neoplasms (3%; 95% CI 2.62–3.5). Neoplasms had an even distribution between sexes. Main mature B cell lymphomas were diffuse large B cell lymphoma (DLBCL) (56%; 95% CI 54.39–57.39) and follicular lymphoma (FL) (20%; 95% CI 18.92–21.34). Hodgkin's lymphomas were also classified into five main subtypes, with nodular sclerosis (47%; 95% CI 44.14–50.7) and mixed cellularity (38%; 95% CI 34.49–40.85) being the most common. The most common mature T cell/NK neoplasm was peripheral T cell lymphoma NOS/anaplastic large cell lymphoma ALK negative (44%; 95% CI 39.85–48.84). This is the first descriptive study in Mexico with a large sample of lymphomas classified according to the 2008 WHO classification. The results obtained are in keeping with the numbers described in other populations.

https://ift.tt/2Pn66YV

Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2--a study protocol

Introduction

The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings.

Methods

STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks' gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).

The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks' gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.

We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups.

Analysis

Data will be analysed on the intention-to-treat principle.

Ethics

STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610.

Dissemination

Peer reviewed journals, presentations at national and international scientific meetings.

Trial registration number

ISRCTN98835694 and NCT02235181.

https://ift.tt/2BW8QJa

Development and evaluation of a WeChat-based life review programme for patients with cancer: protocol for a randomised controlled trial

Introduction

Patients with cancer often suffer from considerable distress. Life review is a process of recalling, evaluating and integrating life experiences to alleviate a sense of despair and achieve self-integrity. Empirical data have supported the fact that life review is an effective psychological intervention, but it is not always accessible to patients with cancer. There is little evidence of internet-based life review programmes tailored to patients with cancer. This study aims to develop a WeChat-based life review programme and evaluate its effectiveness on the psycho-spiritual well-being of patients with cancer undergoing chemotherapy.

Methods and analysis

A single-centre randomised parallel group superiority design will be used. Patients with cancer will be randomised, to either a control group, or to an experimental group receiving a 6-week WeChat-based life review programme. The programme, which was mainly developed based on Erikson's psycho-social development theory and Reed's self-transcendence theory, provides synchronous and asynchronous communication modes for patients to review their life. The former is real-time communication, providing an e-life review interview guided by a facilitator online. The latter is not simultaneously dialogic and is used to interact with patients before and after a life review interview through Memory Prompts, Review Extraction, Mind Space and E-legacy products. The primary outcomes include anxiety, depression and self-transcendence, and the secondary outcomes are meaning in life and hope. These will be measured at baseline, and immediately, at 3 months, and at 6 months after the programme's conclusion.

Ethics and dissemination

Ethics approval has been obtained from the Biological and Medical Research Ethics Committee of the corresponding author's university (IRB Ref No: 2016/00020). The trial results will be published in a peer-reviewed journal and presented at national and international conferences.

Trial registration number

ChiCTR-IOR-17011998.

https://ift.tt/2BVJFXj

Assessing health-related quality of life of patients with colorectal cancer using EQ-5D-5L: a cross-sectional study in Heilongjiang of China

Aim

This study aimed to assess the health-related quality of life (HRQoL) of patients with colorectal cancer (CRC) and its determinants.

Methods

A cross-sectional questionnaire survey was conducted on 300 newly diagnosed patients with CRC in China's Heilongjiang province, measuring HRQoL using the EuroQol five-dimension five-level (EQ-5D-5L). Kruskal-Wallis analyses were performed to identify the independent variables associated with the EQ-5D-5L utility scores. Predictors of the utility scores were confirmed using a Tobit regression model.

Results

The respondents had a mean EQ-5D-5L utility score of 0.617 (SD=0.371) and a median of 0.740 (range: –0.348 to 1.000). Pain/discomfort and anxiety/depression were major concerns of the respondents, with a prevalence of over 60% (all levels inclusive). The Kruskal-Wallis analyses found lower utility scores in those who were not married, worked as a farmer, enrolled with the new rural cooperative medical scheme and had lower household income (p<0.05). Those who were at a later stage of CRC, underwent surgical only therapy and had a stoma also had lower EQ-5D-5L scores than others (p<0.05). The Tobit regression model confirmed these predictors, except for occupation and marital status.

Conclusion

Patients with CRC have poor HRQoL, with pain/discomfort and depression/anxiety as the most frequently reported problems. The poor HRQoL is associated with the seriousness of the disease condition, as well as the low socioeconomic status of the patients.

https://ift.tt/2L0aI6I

Operationalising a conceptual framework for a contiguous hospitalisation episode to study associations between surgical timing and death after first hip fracture: a Canadian observational study

Objective

We describe steps to operationalise a published conceptual framework for a contiguous hospitalisation episode using acute care hospital discharge abstracts. We then quantified the degree of bias induced by a first abstract episode, which does not account for hospital transfers.

Design

Retrospective observational study.

Setting

All acute care hospitals in nine Canadian provinces.

Participants

We retrieved acute hospitalisation discharge abstracts for 189 448 patients aged 65 years and older admitted to acute care with hip fracture between 2003 and 2013.

Primary and secondary outcome measures

The percentage of patients treated surgically, delayed to surgery (defined as two or more days after admission) and dying, between contiguous hospitalisation episodes and the first abstract episodes of care.

Results

Using contiguous hospitalisation episodes, 91.6% underwent surgery, 35.7% were delayed two or more days after admission and 6.7% died postoperatively, whereas, using the first abstract only, these percentages were 83.7%, 32.5% and 6.5%, respectively.

Conclusion

We demonstrate that not accounting for hospital transfers when evaluating the association between surgical timing and death underestimates reporting of the percentage of patients treated surgically and delayed to surgery by 9%, and the percentage who die after surgery by 3%. Researchers must be aware of this potential and avoidable bias as, depending on the purpose of the study, erroneous inferences may be drawn.

https://ift.tt/2L0aMmY

Determining correct tracheal tube insertion depth by measuring distance between endotracheal tube cuff and vocal cords by ultrasound in Chinese adults: a prospective case-control study

Objectives

Unrecognised malposition of the endotracheal tube can lead to severe complications in patients under general anaesthesia. The purpose of this study was to verify the feasibility of using ultrasound to measure the distance between the upper edge of saline-inflated cuff and the vocal cords.

Design

Prospective case-control study.

Setting

A tertiary hospital in Beijing, China.

Methods

In this prospective study, 105 adult patients who required general anaesthesia were enrolled. Prior to induction, ultrasound was used to identify the position of the vocal cords. After intubation, the endotracheal tube (ETT) was fixed at a depth of 23 cm at the upper incisors in men and 21 cm in women. The depth of intubation was verified by video-assisted laryngoscopy. The distance between the upper edge of the saline-inflated cuff and the vocal cords was measured by ultrasound; the ideal distance was considered to be 1.9–4.1 cm.

Results

Among the 105 cases, two cuffs were too close to the vocal cords and one too far away from the vocal cords. These diagnoses were made by ultrasound and were in agreement with results from direct laryngoscopy. The overall accuracy of ultrasound in identifying malposition of the cuff was 100.0% (95% CI: 96.6% to 100%). The sensitivity, specificity, positive predictive value and negative predictive value of ultrasound were, respectively, 100% (95% CI: 96.5% to 100%), 100% (95% CI: 29.2% to 100%), 100% (95% CI: 96.5% to 100%) and 100% (95% CI: 29.2% to 100%).

Conclusion

Identification of the upper edge of the saline-inflated cuff and the vocal cords by ultrasound to assess the location of the ETT is a reliable method. It can be used to avoid malposition of the ETT cuff and reduce the incidence of vocal cords injury after intubation.

Trial registration number

ChiCTR-DDD-17011048.

https://ift.tt/2BX116p

Linkage to primary care after home-based blood pressure screening in rural KwaZulu-Natal, South Africa: a population-based cohort study

Objectives

The expanding burden of non-communicable diseases (NCDs) globally will require novel public health strategies. Community-based screening has been promoted to augment efficiency of diagnostic services, but few data are available on the downstream impact of such programmes. We sought to assess the impact of a home-based blood pressure screening programme on linkage to hypertension care in rural South Africa.

Setting

We conducted home-based blood pressure screening withinin a population cohort in rural KwaZulu-Natal, using the WHO Stepwise Approach to Surveillance (STEPS) protocol.

Participants

Individuals meeting criteria for raised blood pressure (≥140 systolic or ≥90 diastolic averaged over two readings) were referred to local health clinics and included in this analysis. We defined linkage to care based on self-report of presentation to clinic for hypertension during the next 2 years of cohort observation. We estimated the population proportion of successful linkage to care with inverse probability sampling weights, and fit multivariable logistic regression models to identify predictors of linkage following a positive hypertension screen.

Results

Of 11 694 individuals screened, 14.6% (n=1706) were newly diagnosed with elevated pressure. 26.9% (95% CI 24.5% to 29.4%) of those sought hypertension care in the following 2 years, and 38.1% (95% CI 35.6% to 40.7%) did so within 5 years. Women (adjusted OR (aOR) 2.41, 95% CI 1.68 to 3.45), those of older age (aOR 11.49, 95% CI 5.87 to 22.46, for 45–59 years vs <30) and those unemployed (aOR 1.71, 95% CI 1.10 to 2.65) were more likely to have linked to care.

Conclusions

Linkage to care after home-based identification of elevated blood pressure was rare in rural South Africa, particularly among younger individuals, men and the employed. Improved understanding of barriers and facilitators to NCD care is needed to enhance the effectiveness of blood pressure screening in the region.

https://ift.tt/2BX11mV

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis

Introduction

Fetal growth restriction (FGR) is a relevant research and clinical concern since it is related to higher risks of adverse outcomes at any period of life. Current predictive tools in pregnancy (clinical factors, ultrasound scan, placenta-related biomarkers) fail to identify the true growth-restricted fetus. However, technologies based on metabolomics have generated interesting findings and seem promising. In this systematic review, we will address diagnostic accuracy of metabolomics analyses in predicting FGR.

Methods and analysis

Our primary outcome is small for gestational age infant, as a surrogate for FGR, defined as birth weight below the 10th centile by customised or population-based curves for gestational age. A detailed systematic literature search will be carried in electronic databases and conference abstracts, using the keywords 'fetal growth retardation', 'metabolomics', 'pregnancy' and 'screening' (and their variations). We will include original peer-reviewed articles published from 1998 to 2018, involving pregnancies of fetuses without congenital malformations; sample collection must have been performed before clinical recognition of growth impairment. If additional information is required, authors will be contacted. Reviews, case reports, cross-sectional studies, non-human research and commentaries papers will be excluded. Sample characteristics and the diagnostic accuracy data will be retrieved and analysed. If data allows, we will perform a meta-analysis.

Ethics and dissemination

As this is a systematic review, no ethical approval is necessary. This protocol will be publicised in our institutional websites and results will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42018089985.

https://ift.tt/2L0az3a

Development and validation of a novel computer-aided score to predict the risk of in-hospital mortality for acutely ill medical admissions in two acute hospitals using their first electronically recorded blood test results and vital signs: a cross-sectional study

Objectives

There are no established mortality risk equations specifically for emergency medical patients who are admitted to a general hospital ward. Such risk equations may be useful in supporting the clinical decision-making process. We aim to develop and externally validate a computer-aided risk of mortality (CARM) score by combining the first electronically recorded vital signs and blood test results for emergency medical admissions.

Design

Logistic regression model development and external validation study.

Setting

Two acute hospitals (Northern Lincolnshire and Goole NHS Foundation Trust Hospital (NH)—model development data; York Hospital (YH)—external validation data).

Participants

Adult (aged ≥16 years) medical admissions discharged over a 24-month period with electronic National Early Warning Score(s) and blood test results recorded on admission.

Results

The risk of in-hospital mortality following emergency medical admission was 5.7% (NH: 1766/30 996) and 6.5% (YH: 1703/26 247). The C-statistic for the CARM score in NH was 0.87 (95% CI 0.86 to 0.88) and was similar in an external hospital setting YH (0.86, 95% CI 0.85 to 0.87) and the calibration slope included 1 (0.97, 95% CI 0.94 to 1.00).

Conclusions

We have developed a novel, externally validated CARM score with good performance characteristics for estimating the risk of in-hospital mortality following an emergency medical admission using the patient's first, electronically recorded, vital signs and blood test results. Since the CARM score places no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure.

https://ift.tt/2L2YytI

Cancers, Vol. 10, Pages 497: Developments in Stereotactic Body Radiotherapy

Cancers, Vol. 10, Pages 497: Developments in Stereotactic Body Radiotherapy

Cancers doi: 10.3390/cancers10120497

Authors: Anoop Haridass

Stereotactic body radiotherapy is the technique of accurately delivering high doses of radiotherapy to small volume targets in a single or small number of sessions. The high biological effective dose of this treatment is reflected in the high rates of local control achieved across multiple tumour sites. Toxicity of the treatment can be significant and ongoing prospective trials will help define the utility of this treatment as an alternative to surgery in treating primary tumours and oligometastatic disease. Longer follow-up and survival data from prospective trials will be essential in determining the value of this resource-intensive treatment. The opportunity to combine this treatment with systemic therapies and its potential synergy with immunotherapy opens up interesting avenues for research in the future.

https://ift.tt/2UoBz0t

Neuroendocrine Carcinoma of Duodenum—an Uncommon Tumour at an Unusual Site

Abstract

Neuroendocrine carcinoma rarely occurs in the duodenum, and most cases of neuroendocrine carcinoma in the duodenum show rapid progression of the disease. Such cases have poor prognosis even with radical surgery with or without chemotherapy with low 5-year survival rate. We present a case of a 52-year-old man who presented with abdominal pain of 1-month duration and one episode of vomiting. Upper gastrointestinal endoscopy revealed polypoidal lesions in the first and second part of the duodenum. Whipple's procedure was performed. Diagnosis of poorly differentiated neuroendocrine carcinoma was made with extension to pancreas with peripancreatic lymph node metastases. The patient expired on post operative day 17 following cardiac arrest.

https://ift.tt/2AWx0Sr

Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment

Abstract

With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole. Androgen receptor-axis-targeted therapies (ARAT) were previously only approved for patients with metastatic castration resistant prostate cancer (mCRPC). This has recently changed after reporting of results from the SPARTAN and PROSPER trials, which were conducted in nonmetastatic CRPC (nmCRPC) patients. These studies demonstrated improved metastasis-free survival with apalutamide and enzalutamide, each compared to placebo in a double blind randomized setting. In 2017, the LATITUDE and STAMPEDE studies demonstrated marked survival benefit with early abiraterone and prednisone in patients with metastatic hormone sensitive prostate cancer (mHSPC) in addition to ADT. Other second-generation AR antagonists are currently in phase 3 trials in mHSPC and nmCRPC. This article summarizes the key clinical trials that led to FDA approval of ARAT in the mHSPC and nmCRPC settings and highlights potential limitations, future directions, and treatment-algorithms when selecting patients for early therapy in mHSPC and NMPC.

https://ift.tt/2SDUuD9

The emerging role of liquid biopsy in diagnosis, prognosis and treatment monitoring of pancreatic cancer

Pharmacogenomics, Ahead of Print.


https://ift.tt/2G1CUY9

Integrated CYP2D6 interrogation for multiethnic copy number and tandem allele detection

Pharmacogenomics, Ahead of Print.


https://ift.tt/2rpcmG7

Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials

Pharmacogenomics, Ahead of Print.


https://ift.tt/2rqOjGO

Prolonged clonazepam-induced withdrawal symptoms in an NAT2 ultraslow acetylator

Pharmacogenomics, Ahead of Print.


https://ift.tt/2rlaDlc

Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure

Pharmacogenomics, Ahead of Print.


https://ift.tt/2rrePzT

Prediction of tacrolimus dosage in the early period after heart transplantation: a population pharmacokinetic approach

Pharmacogenomics, Ahead of Print.


https://ift.tt/2G1Arg8

Prevalence of pharmacogenomic variants affecting the efficacy of clopidogrel therapy in the Hispanic Community Health Study/Study of Latinos cohort

Pharmacogenomics, Ahead of Print.


https://ift.tt/2G1Aqc4

Is There Value in Molecular Profiling of Soft-Tissue Sarcoma?

Opinion statement

Soft-tissue sarcomas represent a heterogeneous group of diseases accounting for up to 1% of cancer in adults and 15% of cancer in children. Introduction of next-generation sequencing (NGS) technologies has allowed to gain additional insight into the genetic diversity and complexity of sarcomas, including the potential therapeutic implications of some genetic alterations.

Two large studies have investigated the role of targeted NGS to identify actionable mutations in patients with soft-tissue sarcomas. In these two studies, actionable alterations were identified in up to 50% of patients. Retrospective data suggest that genomically guided treatments may be associated with substantial clinical benefit in sarcoma patients with advanced disease. However, prospective data are lacking. The MULTISARC is a randomized phase 3 investigating the potential of NGS implementation to improve outcome of metastatic sarcoma patients.

Overall, a significant proportion of soft-tissue sarcoma bears potential targetable genomic alteration that can be identified through NGS. There is still a lack of evidence to support routine implementation of NGS for the management of sarcoma patient. The MULTISARC randomized trial which randomized patients to tumor genetic profiling or not might confirm the role of NGS to improve outcome of metastatic sarcoma patients through the identification of additional genomically guided lines of treatment.

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A systematic review of gut‐immune‐brain mechanisms in Autism Spectrum Disorder

Abstract

Despite decades of research, the etiological origins of Autism Spectrum Disorder (ASD) remain elusive. Recently, the mechanisms of ASD have encompassed emerging theories involving the gastrointestinal, immune, and nervous systems. While each of these perspectives presents its own set of supporting evidence, the field requires an integration of these modular concepts and an overarching view of how these subsystems intersect. In this systematic review, we have synthesized relevant evidences from the existing literature, evaluating them in an interdependent manner and in doing so, outlining their possible connections. Specifically, we first discussed gastrointestinal and immuno‐inflammation pathways in‐depth, exploring the relationships between microbial composition, bacterial metabolites, gut mucosa, and immune system constituents. Accounting for temporal differences in the mechanisms involved in neurodevelopment, prenatal and postnatal phases were further elucidated, where the former focused on maternal immune activation (MIA) and fetal development, while the latter addressed the role of immune dysregulation in contributing to atypical neurodevelopment. As autism remains, foremost, a neurodevelopmental disorder, this review presents an integration of disparate modules into a "Gut‐Immune‐Brain" paradigm. Existing gaps in the literature have been highlighted, and possible avenues for future research with an integrated physiological perspective underlying ASD have also been suggested.

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Since 1999, Uterine Cancer Incidence, Mortality Up

THURSDAY, Dec. 6, 2018 -- The incidence of uterine cancer and uterine cancer deaths has increased since 1999, according to research published in the Dec. 7 issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly...

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Smartphone App Uses Fingernail Bed Images to Detect Anemia

THURSDAY, Dec. 6, 2018 -- An app that detects color and metadata from fingernails can identify hemoglobin levels in the blood, according to research published online Dec. 4 in Nature Communications. Robert G. Mannino, Ph.D., from Emory University in...

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Many Americans Unaware of Promise of Personalized Medicine

THURSDAY, Dec. 6, 2018 -- Medical science has made tremendous advances in personalized medicine. However, the American public is still struggling to understand the implications of these targeted treatments, a new HealthDay/Harris Poll has...

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SABCS: Breast Cancer Outcomes Worse for Blacks Despite Similar Gene RS

THURSDAY, Dec. 6, 2018 -- Black women with breast cancer have worse clinical outcomes even when 21-gene recurrence scores (RS) are similar, according to a study presented at the annual San Antonio Breast Cancer Symposium, held from Dec. 4 to 8 in...

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Colonoscopy Receipt Varies After Advanced Adenoma Diagnosis

THURSDAY, Dec. 6, 2018 -- Many patients with three or more adenomas or any adenoma with villous/tubulovillous features do not receive a subsequent colonoscopy within 3.5 years, according to a study published online Nov. 20 in Cancer Epidemiology,...

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Firefly DE550/DE551 Is #1 in Best Otoscope Comparison

The Firefly DE550/DE551 Wireless Video Otoscope recently grabbed the top spot in wiki review's Top 9 Otoscopes of 2018! Jeff Newburgh has written a wonderful article detailing the history of otoscopes, various approaches to otoscopy, and a thorough comparison of the best otoscopes in 2018.

Click to see the Best Otoscopes of 2018

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Molecular subtype not immune response drives outcomes in endometrial carcinoma

Purpose: Tumors with high mutation load are thought to engender stronger immune responses which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TIL) and immunosuppressive factors across the four molecular subtypes of endometrial cancer (EC), which have characteristic mutation rates ranging from low to ultra-high. Experimental design: 460 ECs were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into four molecular subtypes: mismatch repair-deficient (MMRd), POLE mutant (POLE), p53 abnormal (p53abn), and p53 wildtype (p53wt). Immune markers (CD3, CD8, CD79a, CD138, PD-1, PD-L1, FoxP3, IDO-1) were quantified by multiplex immunohistochemistry and tested for associations with ProMisE subtype, survival, and other clinicopathological parameters. Results: Two major TIL patterns were observed. TIL high tumors harbored dense T- and B-lineage infiltrates and multiple immunosuppressive features and were common in molecular subtypes associated with high mutation load (MMRd and POLE); however, equally strong responses were seen in significant numbers of p53abn and p53wt tumors, which have characteristically low mutation loads. TIL low tumors were generally devoid of immunological features and more prevalent in p53abn and p53wt ECs, yet were also seen in MMRd and POLE subtypes. In multivariable models involving ProMisE subtype, T-cell markers, TIL clusters, only ProMisE showed independent prognostic significance. Conclusions: Immune response correlates with EC molecular subtype but does not carry independent prognostic significance. Profound variation in immune response is seen across and within EC molecular subtypes, suggesting that assessment of immune response rather than molecular subtype may better predict response to immunotherapy.

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NK cell infiltrates and HLA class I expression in primary HER2+ breast cancer predict and uncouple pathological response and disease-free survival

Purpose: We investigated the value of tumor-infiltrating NK cells (TI-NK) and HLA class I tumor expression as biomarkers of response to neoadjuvant anti-HER2 antibody-based treatment in breast cancer. Experimental Design: TI-NK cells and HLA-I were determined by immunohistochemistry in pre-treatment tumor biopsies from two cohorts of HER2-positive breast cancer patients [discovery cohort (n=42) and validation cohort (n=71)]. TIL were scored according to international guidelines. Biomarker association with pathological complete response (pCR) and disease-free survival (DFS) was adjusted for prognostic factors. Gene set variation analysis was used for determining immune-cell populations concomitant to NK cell enrichment in HER2-positive tumors from the TCGA (n=190). Results: TI-NK cells were significantly associated with pCR in the discovery cohort as well as in the validation cohort (p<0.0001), independently of clinicopathological factors. A ≥3 TI-NK cells/50xHPF cut off predicted pCR in the discovery and validation cohort [OR 188 (11-3154); OR 19.5 (5.3-71.8)]. Presence of TI-NK cells associated with prolonged DFS in both patient cohorts [HR 0.07 (0.01-0.6), p=0.01; HR 0.3 (0.08-1.3), p=0.1]. NK-, activated dendritic- and CD8 T-cell gene expression signatures positively correlated in HER2-positive tumors, supporting the value of NK cells as surrogates of effective anti-tumor immunity. Stratification of patients by tumor HLA-I expression identified patients with low and high relapse risk independently of pCR. Conclusions: This study identifies baseline TI-NK cells as an independent biomarker with great predictive value for pCR to anti-HER2 antibody-based treatment and points to the complementary value of tumor HLA-I status for defining patient prognosis independently of pCR.

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Keratinocyte Carcinomas: Current concepts and future research priorities

Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas (KC), the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in KC tumorigenesis and tumor characteristics which have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of KC continue to increase, strategies for prevention, including effective sun protective behavior, educational interventions and reduction of tanning bed access and usage are essential. Gaps in our knowledge requiring additional research in order to reduce the high morbidity and costs associated with KC include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.

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Personalized Medicine Applied to AML [News in Brief]

The Beat AML Master trial is using genomic information to rapidly match patients with first-line therapies.

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Augmenting CAR T Cells with PD-1 Blockade [News in Brief]

Addition of checkpoint inhibitors boosts persistence, function of engineered T cells.

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‘Cone Beam Computed Tomography in Endodontics’ Editors‐in‐Chief: Patel Shanon, Harvey Simon, Shemesh Hagay, Durack Conor Published by Quintessence Publishing (ISBN: 978‐1‐85097‐291‐4) provides up to date information on one of the most significant recent advances in Endodontics.

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Editor‐in‐Chief thanks the Associate Editors, Editorial Board and Referees

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Issue Information

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The Effect of Vitamin D Supplementation on Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials

Horm Metab Res
DOI: 10.1055/a-0774-8809

Vitamin D has received attention for its potential to disrupt cancer processes. However, its effect in the treatment of prostate cancer is controversial. This study aimed to assess the effect of vitamin D supplementation on patients with prostate cancer. In the present study, PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to September 2017 for trials that evaluated the effect of vitamin D supplementation on prostate specific antigen (PSA) response, mortality, and its possible side effects in participants with prostate cancer. The DerSimonian and Laird inverse-weighted random-effects model was used to pool the effect estimates. Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in the meta-analysis. The analysis of controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD)=–1.66 ng/ml, 95% CI: –0.69, 0.36, p=0.543)], PSA response proportion (RP=1.18, 95% CI: 0.97, 1.45, p=0.104) and mortality rate (risk ratio (RR)=1.05, 95% CI: 0.81–1.36; p=0.713) were not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had a modest effect on PSA response proportion: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Although before-after studies showed that vitamin D increases the PSA response proportion, it does not seem that patients with prostate cancer benefit from high dose vitamin D supplementation and it should not be recommended for the treatment.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Hypercortisolism in Newly Diagnosed Type 2 Diabetes: A Prospective Study of 384 Newly Diagnosed Patients

Horm Metab Res
DOI: 10.1055/a-0809-3647

Cross-sectional studies in small and selected populations report a high prevalence of hypercortisolism in patients with type 2 diabetes (T2D), which could have therapeutic implications, if confirmed. We therefore estimated the prevalence of hypercortisolism in a large and unselected cohort of recently diagnosed T2D patients. Consecutive patients with recently diagnosed T2D first underwent an overnight dexamethasone (1 mg) suppression test (OD). Patients not suppressing serum cortisol ≤50 nmol/l proceeded with a 48-h low dose dexamethasone suppression test (LDDST) and 24-h urinary free cortisol collection (UFC). Patients with elevated cortisol levels according to LDDST and/or UFC underwent imaging guided by plasma ACTH levels, and assessment of bone mineral density. A total of 384 T2D patients (232male/152 females) with a mean age of 60±10 years were included. Eighty-five (22%) patients suppressed incompletely to OD of whom 20 (5%) failed to suppress after LDDST and/or had elevated UFC (=hypercortisolism). Patients with hypercortisolism did not differ as regards age, BMI, HbA1c, T-score or blood pressure, but a higher proportion of them received antihypertensive treatment (100% vs. 64%, p=0.001). Imaging revealed adrenal adenoma(s) in 9 cases and a pituitary macroadenoma in 1 case. We found a 5% prevalence of hypercortisolism in unselected, recently diagnosed T2D, which was not associated with a persuasive cushingoid phenotype. The clinical implications are therefore uncertain.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Effect of Sodium Glucose Co-Transporter-2 Inhibition on the Aldosterone/Renin Ratio in Type 2 Diabetes Mellitus

Horm Metab Res
DOI: 10.1055/a-0794-7026

The aldosterone to renin ratio (ARR) is recommended for case detection of primary aldosteronism (PA). Several factors including medications can undermine its diagnostic accuracy. The objective was to explore the effect of Sodium Glucose Co-Transporter-2 Inhibition on the ARR in patients with type 2 diabetes mellitus (T2DM) who were prescribed a Sodium Glucose Co-Transporter-2 Inhibitor (SGLT-2i) as part of routine clinical care. The primary outcomes were intra-individual changes in aldosterone, renin and ARR. Participants were recruited at routine diabetes outpatient visits as part of a prospective longitudinal study. Eligible participants were prescribed standard doses of empagliflozin and sampled at baseline (pre-SGLT-2i) and at their next routine outpatient visit (post-SGLT-2i). After a mean of 198 (±87) days on SGLT-2i treatment (n=20), there was a significant reduction in HbA1c, BMI, eGFR and serum triglycerides and a significant increase in serum creatinine and sodium. Compared with baseline, there was a significant increase in median direct renin concentration (mIU/l) [40.3 (6.2–249.5) vs. 70.2 (7.0, 551.0) (p=0.005)] and no significant change in median plasma aldosterone concentration (pmol/l) [296 (101, 685) vs. 273 (101, 794) (p=0.541)] with a significant reduction in median ARR (pmol/mIU) [6.9 (0.6–70.7) vs. 5.3 (0.2–39.3) (p=0.007)]. The proportion of participants with a screen positive ARR decreased from 20% (pre-SGLT-2i) to 5% (post-SGLT-2i) (p=0.248). Although performed in a relatively small cohort of medically complex patients, the study indicates that SGLT-2i therapy has the potential to cause false-negative screening for PA in the setting of T2DM. Future confirmatory studies should include patients with confirmed PA.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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High renal DC‐SIGN+ cell density is associated with severe renal lesions and poor prognosis in patients with Immunoglobulin A Nephropathy

Abstract

Background and objectives

In this observational cohort study, we assessed the prognostic value of DC‐SIGN⁺ cells in pathogenesis and progression of IgA nephropathy (IgAN).

Design, setting, participants, & measurements

A total of 139 adult IgAN patients were enrolled in this study from June 2009 to June 2010. We characterized DC‐SIGN⁺ cells by immunohistochemistry or immunofluorescence in renal biopsy tissue. Correlations between the DC‐SIGN, ICAM‐3, CD4, and CD8 were evaluated. Patients were classified into the DC‐SIGN^high and DC‐SIGN^low group. Depending on a 100‐month follow‐up, the predictive value of DC‐SIGN⁺ cells in IgAN progression was analyzed.

Results

DC‐SIGN⁺ cells were found popular in IgAN kidneys while rarely observed in normal kidneys and almost all of DC‐SIGN⁺ cells expressed MHCII. We also found DC‐SIGN+ cells were adjacent to ICAM‐3 positive CD4⁺ and CD8⁺ lymphocytes. The density of DC‐SIGN⁺ cells was positively and linearly correlated with the density of ICAM‐3⁺ cells, CD4⁺ cells, CD8⁺ cells in renal biopsy tissues. In DC‐SIGN^high group, the degree of renal lesion and inflammatory cells infiltration were severer compared to DC‐SIGN^low group. Patients in DC‐SIGN^high group also had increased incidences of descending renal function over a 100‐month follow‐up compared to patients in DC‐SIGN^low group.

Conclusions

DC‐SIGN⁺ cells probably served as a potential contributor to exacerbate local inflammatory response. The density of DC‐SIGN⁺ cells was associated with severity of renal lesions of the patients. High renal DC‐SIGN+ cell density DC‐SIGN⁺ cells might be used as a predictor factor of poor prognosis in patients with IgAN.

This article is protected by copyright. All rights reserved.

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Does adult alcohol consumption combine with adverse childhood experiences to increase involvement in violence in men and women? A cross-sectional study in England and Wales

Objectives

To examine if, and to what extent, a history of adverse childhood experiences (ACEs) combines with adult alcohol consumption to predict recent violence perpetration and victimisation.

Design

Representative face-to-face survey (n=12 669) delivered using computer-assisted personal interviewing and self-interviewing.

Setting

Domiciles of individuals living in England and Wales.

Participants

Individuals aged 18–69 years resident within randomly selected locations. 12 669 surveys were completed with participants within our defined age range.

Main outcome measures

Alcohol consumption was measured using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and childhood adversity using the short ACEs tool. Violence was measured using questions on perpetration and victimisation in the last 12 months.

Results

Compliance was 55.7%. There were strong positive relationships between numbers of ACEs and recent violence perpetration and victimisation in both sexes. Recent violence was also strongly related to positive AUDIT-C (≥5) scores. In males, heavier drinking and ≥4ACEs had a strong multiplicative relationship with adjusted prevalence of recent violent perpetration rising from 1.3% (95% CIs 0.9% to 1.9%; 0 ACEs, negative AUDIT-C) to 3.6% (95% CIs 2.7% to 4.9%; 0 ACEs, positive AUDIT-C) and 8.5% (95% CI 5.6% to 12.7%; ≥4ACEs, negative AUDIT-C) to 28.3% (95% CI 22.5% to 34.8%; ≥4ACEs, positive AUDIT-C). In both sexes, violence perpetration and victimisation reduced with age independently of ACE count and AUDIT-C status. The combination of young age (18–29 years), ≥4ACEs and positive AUDIT-C resulted in the highest adjusted prevalence for both perpetration and victimisation in males (61.9%, 64.9%) and females (24.1%, 27.2%).

Conclusions

Those suffering multiple adverse experiences in childhood are also more likely to be heavier alcohol users. Especially for males, this combination results in substantially increased risks of violence. Addressing ACEs and heavy drinking together is rarely a feature of public health policy, but a combined approach may help reduce the vast costs associated with both.

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Angiogenic Signaling Pathways and Anti-angiogenic Therapies in Human Cancer

Abstract

Vascular endothelial growth factor (VEGF) is the principal regulator of tumor angiogenesis and is overexpressed in the majority of solid tumors. Therapeutic inhibition of VEGF and its main receptor (VEGFR2) has shown significant clinical efficacy in several human cancers. However, in unselected patient populations, often these agents have not offered sustainable clinical benefit. Some of the challenges with the clinical efficacy of anti-VEGF/VEGFR therapies may be explained by the heterogeneity of human tumor vessels and variation in their sensitivity to VEGF/VEGFR inhibition. However, the process of tumor angiogenesis is far more complex with frequent cross talk between VEGF/VEGFR and other signaling pathways. In addition to anti-angiogenic effects, anti-VEGF/VEGFR agents also cause "normalization" of tumor vessels and "pruning" of normal vessels. In order to achieve significant improvement in clinical efficacy of anti-VEGF/VEGFR therapies in the near future, it will be important to (1) better understand the complex biology of VEGF/VEGFR and non-VEGF/VEGFR signaling pathways in the context of pathologic (aberrant) angiogenesis in human cancer tissues, (2) translate such biologic concepts into a more comprehensive molecular profiling and pathologic disease state characterization, and (3) advance the much needed predictive biomarker science to drive rational patient-tailoring and combinatorial therapeutic strategies in next-generation clinical trials of anti-angiogenic therapies. It will also be critical to identify and address other clinical and scientific challenges, including various primary and acquired mechanisms of resistance to anti-angiogenic therapies.

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Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL)

To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers.

https://ift.tt/2rnfySz

Temporal Trends of Pediatric Hospitalizations with Acute Disseminated Encephalomyelitis in the United States: An Analysis from 2006 to 2014 using National Inpatient Sample

To determine the temporal trends in the epidemiology of acute disseminated encephalomyelitis (ADEM) and hospitalization outcomes in the US from 2006 through 2014.

https://ift.tt/2EknHzy

Exposure to Diabetes in Utero Is Associated with Earlier Pubertal Timing and Faster Pubertal Growth in the Offspring: The EPOCH Study

To examine the associations of in utero exposure to maternal diabetes with surrogate measures of offspring pubertal timing (age at peak height velocity [APHV]) and speed of pubertal growth (peak height velocity [PHV]).

https://ift.tt/2Eh3kU4

Future Research in the Immune System of Human Milk

Apart from a few discoveries in the 19th and early 20th centuries, little was known about the complex immune system in human milk and its many benefits to the recipient infant. Research during the latter part of the 20th century and this century demonstrated that the human milk immune system is significantly different from that produced by other mammals and that breastfeeding protects against many common infections, reduces inflammation, and lessens the likelihood of certain chronic diseases in later life.

https://ift.tt/2SvlB2U

Optimizing Discharge from Intensive Care and Follow-Up Strategies for Pediatric Patients

In this volume of The Journal, Berman et al use the voices of 15 families surrounding the discharge of 18 infants from the neonatal intensive care unit (NICU) to provide a framework to improve on our current practices surrounding NICU discharge.1 Owing to improving therapies in all aspects of pediatric critical illness, discharging a child after prolonged intensive care unit (ICU) hospitalization who has persistent healthcare needs is increasingly prevalent in the US. Survivorship has increased and so has resultant morbidity in both the neonatal and pediatric ICU (PICU) settings.

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A Comparison of Developmental Outcomes of Adolescent Neonatal Intensive Care Unit Survivors Born with a Congenital Heart Defect or Born Preterm

To compare cognitive, motor, behavioral, and functional outcomes of adolescents born with a congenital heart defect (CHD) and adolescents born preterm.

https://ift.tt/2EhVklE

Cerebrospinal Fluid Shunt Infection: Emerging Paradigms in Pathogenesis that Affect Prevention and Treatment

In this medical progress report, we outline the epidemiology and healthcare utilization associated with cerebrospinal fluid (CSF) shunt-associated infections in the US, the clinical features of CSF shunt infection, and our evolving understanding of the prevention and treatment of CSF shunt infection. We describe an emerging paradigm in CSF shunt infection under active investigation.

https://ift.tt/2Egm6eh

Beta-Hemolytic Nongroup A Streptococcal Pharyngitis in Children

To evaluate the epidemiology, clinical features, and antibiotic prescribing patterns for nongroup A streptococci (NGAS) in children.

https://ift.tt/2SyhyCW

Tris Pharma Issues Voluntary Nationwide Recall of Infants’ Ibuprofen Concentrated Oral Suspension, USP (NSAID) 50 mg per 1.25 mL, Due to Potential Higher Concentrations of Ibuprofen

Audience: Consumer, Health Professional, Pharmacy December 5, 2018 -- Tris Pharma, Inc. has voluntarily recalled three (3) lots of Infants' Ibuprofen Concentrated Oral Suspension, USP (NSAID) 50 mg per 1.25 mL, to the retail level. The recalled...

https://ift.tt/2AY7wEc

Particle Size and Gastrointestinal Absorption Influence Tiotropium Pharmacokinetics: A Pilot Bioequivalence Study of PUR0200 and Spiriva HandiHaler

Aims

Plasma pharmacokinetics permits the assessment of efficacy and safety of inhaled drugs, and possibly their bioequivalence to other inhaled products. Correlating drug product attributes to lung deposited dose is important to achieving equivalence. PUR0200 is a spray‐dried formulation of tiotropium that enables more efficient lung delivery than Spiriva® HandiHaler® (HH). The ratio of tiotropium lung‐to‐oral deposition in PUR0200 was varied to investigate the impact of particle size on tiotropium pharmacokinetics and the contribution of oral absorption to tiotropium exposure was assessed using charcoal block.

Methods

A seven‐period, single‐dose, cross‐over study was performed in healthy subjects. PUR0200 formulations differing in dose and aerodynamic particle size were administered in 5 periods and Spiriva HH in 2 periods. In one period, Spiriva HH gastrointestinal absorption was blocked with oral charcoal. Tiotropium plasma concentrations were assessed over 8h after inhalation.

Results

PUR0200 pharmacokinetics were influenced by aerodynamic particle size and the ratio of lung‐to‐oral deposition, with impactor sized mass (ISM) correlating most strongly with exposure. Formulation PUR0217a (3μg tiotropium) lung deposition was similar to Spiriva HH (18μg) with and without charcoal block, but total PUR0200 exposure was lower without charcoal. The C_max and AUC_0‐0.5h of Spiriva HH with and without charcoal block were bioequivalent, however Spiriva HH AUC_0‐8h was lower when gastrointestinal absorption was inhibited with oral charcoal administration.

Conclusions

Pharmacokinetic bioequivalence indicative of lung deposition and efficacy can be achieved by matching the reference product ISM. Due to reduced oral deposition and more efficient lung delivery, PUR0200 results in a lower AUC_0‐t than Spiriva HH due to reduced absorption of drug from the gastrointestinal tract.

https://ift.tt/2L0U7Qh

Antibiotic allergy labels in hospitalised and critically ill adults: a review of current impacts of inaccurate labelling

Abstract

Antibiotic Allergy Labels (AAL) are reported by approximately 20% of hospitalised patients, yet over 85% will be negative on formal allergy testing. Hospitalised patients with an AAL have inferior patient outcomes, increased colonization with multidrug resistant organisms and frequently receive inappropriate antimicrobials. Hospitalised populations have been well studied, yet to date the impact of AALs on patients with critical illness remain less well defined. We review the prevalence and impact of AALs on hospitalised patients, including those in in critical care.

https://ift.tt/2BTSr86

Tris Pharma Issues Voluntary Nationwide Recall of Infants’ Ibuprofen Concentrated Oral Suspension, USP (NSAID) 50 mg per 1.25 mL, Due to Potential Higher Concentrations of Ibuprofen

Audience: Consumer, Health Professional, Pharmacy December 5, 2018 -- Tris Pharma, Inc. has voluntarily recalled three (3) lots of Infants' Ibuprofen Concentrated Oral Suspension, USP (NSAID) 50 mg per 1.25 mL, to the retail level. The recalled...

https://ift.tt/2AY7wEc

Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high‐fat diet

Summary

Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH‐mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in the prevention for NASH‐related liver cirrhosis and HCC. In the present study, a steatohepatitis‐related HCC model, hepatocyte‐specific phosphatase and tensin homolog (Pten)‐deficient (Pten ^Δhep ) mice were fed a high‐fat (HF) diet with/without ezetimibe. In the standard‐diet group, ezetimibe did not reduce the development of liver tumors in Pten ^Δhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF‐positive cells and vascular endothelial cells in the tumors of Pten ^Δhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis, and tumor growth in Pten ^Δhep mice on the HF diet. Tumor cells were highly proliferative by HF‐diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in Pten ^Δhep mice with hypercholesterolemia.

This article is protected by copyright. All rights reserved.

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Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor that frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported exhibits anticancer activity against various types of tumors except human OS. The aims of this study were to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppresses the migration and invasion, decrease the colony forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum (ER) stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These evidences provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.

This article is protected by copyright. All rights reserved.

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circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

Summary

circular RNAs (circRNAs), a novel class of non‐coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumor is still a virgin soil to be upturned. Here we investigated the role of circLARP4 in cellular senescence and cell proliferation in hepatocellular carcinoma (HCC). Downregulated circLARP4 level was observed in HCC tissues and cell lines. Low expression level of circLARP4 independently predicted poor survival outcome. Gain‐of‐function and loss‐of‐function assays demonstrated that circLARP4 suppressed HCC cell proliferation, mediated cell cycle, and induced senescence in vitro. Levels of p53 and p21, two key regulatory molecules in cellular senescence, were increased in circLARP4‐overexpressed HCC cells and decreased in circLARP4‐silenced HCC cells. In vivo experiments further confirmed the tumor‐suppressing activities of circLARP4. Further mechanistic studies showed that circLARP4 dampened HCC progression via sponging miR‐761, thereby promoting the expression level of RUNX3 and activating the downstream p53/p21 signaling. Our study revealed the role of circLARP4/miR‐761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate in HCC.

This article is protected by copyright. All rights reserved.

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MiR-374a Activates Wnt/β-Catenin Signaling to Promote Osteosarcoma Cell Migration by Targeting WIF-1

Abstract

MiR-374a was proved to take part in the initiation and development of several cancers. However, the molecular mechanism of miR-374a in osteosarcoma (OS) cells remains unclear. The aim of our research was to investigate the role of miR-374a in OS cells migration and clarify the potential mechanisms. Quantitative real-time PCR (qRT-PCR) and western blot analysis were applied to evaluate the expression of miR-374a and Wnt inhibitory factor-1 (WIF-1). Bioinformatical methods and luciferase reporter assay were carried out to predict and confirm the combination of miR-374a and WIF-1. Transwell and wound healing assays were performed to detect the migration capacity of OS cells. Lithium chloride (LiCl) was used to investigate the role of LiCl-activated Wnt/β-catenin signaling pathway in regulating cell migration. Our studies revealed that miR-374a was up-regulated whereas WIF-1 was down-regulated in OS cells. Besides, WIF-1 was the target of miR-374a by performing luciferase reporter assay. By transfection of miR-374a inhibitor and/or WIF-1 siRNA to OS cells, we found that miR-374a promoted the migration of OS cells. In addition, the inhibition of WIF-1 abolished the miR-374a inhibitor-induced migration suppression of OS cells. LiCl experiment revealed that miR-374a promoted OS cells migration by regulating Wnt/β-catenin signaling. In conclusion, miR-374a promotes OS cells migration by activating Wnt/β-catenin signaling pathway via targeting WIF-1.

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New Guidance Addresses Early Dx of Dysmenorrhea in Adolescents

THURSDAY, Dec. 6, 2018 -- Early diagnosis of dysmenorrhea is key to ensuring that adolescents and women can maintain their quality of life, according to a Committee Opinion published in the December issue of Obstetrics & Gynecology. The American...

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Recommendations Developed for Psoriatic Arthritis Treatment

THURSDAY, Dec. 6, 2018 -- Recommendations have been developed for pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA); the evidence-based guideline was published online Nov. 30 in Arthritis & Rheumatology. Jasvinder A....

https://ift.tt/2QGBV3u

COPD Tied to Obesity in Male, Female Never-Smokers

THURSDAY, Dec. 6, 2018 -- Obesity is strongly associated with chronic obstructive pulmonary disease (COPD) in never-smokers, according to a study published online Nov. 20 in the Journal of Obesity. Esme Fuller-Thomson, Ph.D., from the University of...

https://ift.tt/2E99ghd

High Sensitivity, Specificity for Chlamydia Point-of-Care Test

THURSDAY, Dec. 6, 2018 -- A point-of-care (POC) polymerase chain reaction test (Atlas io) has high sensitivity and specificity for Chlamydia trachomatis (CT), according to a study published in the November issue of Sexually Transmitted Diseases. Lea...

https://ift.tt/2QCxIOj

Smoke Exposure High in Low-Income, Nonurban Infants

THURSDAY, Dec. 6, 2018 -- Infants from low-income, nonurban families have a high magnitude of environmental smoke exposure, according to a study published online Dec. 5 in Nicotine & Tobacco Research. Lisa M. Gatzke-Kopp, Ph.D., from...

https://ift.tt/2E2Gdf3

Pictorial Presentation of Silent Atherosclerosis Helps Cut CV Risk

THURSDAY, Dec. 6, 2018 -- Pictorial presentation of silent atherosclerosis contributes to the prevention of cardiovascular disease, according to a study published online Dec. 3 in The Lancet. Ulf Näslund, Ph.D., from the Umeå University in Sweden,...

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Projected Distribution of Common Ragweed Modeled in U.S.

THURSDAY, Dec. 6, 2018 -- Common ragweed is expected to expand at the northern margins of its current distribution, according to a study recently published in PLOS ONE. Michael J. Case, Ph.D., from Case Research LLC in Seattle, and Kristina A....

https://ift.tt/2E2G8Ih.

Functional Nasal Surgery Can Improve Headache Symptoms

THURSDAY, Dec. 6, 2018 -- For appropriately selected patients, functional nasal surgery is viable for improving headache symptoms, according to a review published in the December issue of Plastic and Reconstructive Surgery. Rebecca L. Farmer, M.D.,...

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Opioids Overprescribed After Arthroscopic Meniscectomy

THURSDAY, Dec. 6, 2018 -- Prescription opioid medications are overprescribed after simple arthroscopic meniscectomy, according to a study recently published in The Journal of Bone & Joint Surgery. Vance Gardner, M.D., from Hoag Orthopedics in...

https://ift.tt/2E2G77b

SABCS: Low-Dose Tamoxifen Cuts Risk for Breast Dz

THURSDAY, Dec. 6, 2018 -- Tamoxifen at a dose of 5 mg/day is associated with a reduced risk for recurrence for women with hormone-sensitive breast intraepithelial neoplasia, according to a study presented at the annual San Antonio Breast Cancer...

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Incidence and Risk Factors of Long-term Opioid Use in Elderly Trauma Patients

Objective: Evaluate the incidence and risk factors of opioid use 1 year after injury in elderly trauma patients. Background: The current epidemic of prescription opioid misuse and overdose observed in North America generally concerns young patients. Little is known on long-term opioid use among the elderly trauma population. Methods: In a retrospective observational multicenter cohort study conducted on registry data, all patients 65 years and older admitted (hospital stay >2 days) for injury in 57 adult trauma centers in the province of Quebec (Canada) between 2004 and 2014 were included. We searched for filled opioid prescriptions in the year preceding the injury, up to 3 months and 1 year after the injury. Results: In all, 39,833 patients were selected for analysis. Mean age was 79.3 years (±7.7), 69% were women, and 87% of the sample was opioid-naive. After the injury, 38% of the patients filled an opioid prescription within 3 months and 10.9% [95% confidence interval (CI) 10.6%–11.2%] filled an opioid prescription 1 year after trauma: 6.8% (95% CI 6.5%–7.1%) were opioid-naïve and 37.6% (95% CI 36.3%–38.9%) were opioid non-naive patients. Controlling for confounders, patients who filled 2 or more opioid prescriptions before the injury and those who filled an opioid prescription within 3 months after the injury were, respectively, 11.4 and 3 times more likely to use opioids 1 year after the injury compared with those who did not fill opioid prescriptions. Conclusions: These results highlight that elderly trauma patients are at risk of long-term opioid use, especially if they had preinjury or early postinjury opioid consumption.

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Estimating Sediment Denitrification Rates Using Cores and N2O Microsensors

This method estimates sediment denitrification rates in sediment cores using the acetylene inhibition technique and microsensor measurements of the accumulated N2O. The protocol describes procedures for collecting the cores, calibrating the sensors, performing the acetylene inhibition, measuring the N2O accumulation, and calculating the denitrification rate.

https://ift.tt/2Pq6uWy

Diffuse Tibiofemoral Cartilage Change Prior to the Development of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis Initiative

Introduction

We compared the spatial distribution of tibiofemoral cartilage change between individuals who will develop accelerated knee osteoarthritis (KOA) versus typical onset of KOA prior to the development of radiographic KOA.

Materials and Methods

We conducted a longitudinal case‐control analysis of 129 individuals from the Osteoarthritis Initiative. We assessed the percent change in tibiofemoral cartilage on magnetic resonance images at 36 informative locations from two to one year prior to the development of accelerated (n=44) versus typical KOA (n=40). We defined cartilage change in the accelerated and typical KOA groups at 36 informative locations based on thresholds of cartilage percent change in a no KOA group (n=45). We described the spatial patterns of cartilage change in the accelerated KOA and typical KOA groups and performed a logistic regression to determine if diffuse cartilage change (predictor; at least half of the tibiofemoral regions demonstrating change in multiple informative locations) was associated with KOA group (outcome).

Results

There was a non‐significant trend that individuals with diffuse tibiofemoral cartilage change were 2.2 times more likely to develop accelerated knee OA when compared to individuals who develop typical knee OA (OR [95% CI] = 2.2 [0.90,5.14]. Adults with accelerated or typical KOA demonstrate heterogeneity in spatial distribution of cartilage thinning and thickening.

Conclusions

These results provide preliminary evidence of a different spatial pattern of cartilage change between individuals that will develop accelerated versus typical KOA. These data suggest there may be different mechanisms driving the early structural disease progression between accelerated versus typical KOA.

This article is protected by copyright. All rights reserved.

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The Development of a Core Syllabus for Teaching Musculoskeletal Anatomy of the Vertebral Column and Limbs to Medical Students

Introduction

The study of human anatomy is fundamental to medical education globally. Knowledge of musculoskeletal anatomy is essential for safe and effective clinical practice, yet this topic often receives insufficient medical programme time and perceptions differ regarding which knowledge is core. Given the lack of syllabuses specific to musculoskeletal anatomy, this paper aims to provide a detailed syllabus for the vertebral column and limbs relevant to medical students.

Materials and Methods

A Delphi panel comprising anatomists and clinicians rated 2260 anatomical structures and concepts as "essential", "important", "acceptable" or "not required", with evaluations based around the core knowledge deemed acceptable for a competent medical student. Based on the percentage of panellist agreement for an item to be considered "essential", each item was then classified as core (≥60%), recommended (30%‐59%), not recommended (20%‐29%) or not core (<20%). Items not classified as core or recommended but rated important by >50% of the panel were highlighted for future consideration.

Results

A total of 252/389 musculoskeletal concept items were categorised as core or recommended. The number of core or recommended items for the vertebral column, upper limb and lower limb were 220/438, 322/663 and 318/770, respectively. Ninety‐six items were recommended for future consideration.

Conclusions

The results of this Delphi panel will be published on the International Federation of Associations of Anatomists website for continuing international consideration and deliberation by relevant stakeholders. The aim is to set an internationally recognized syllabus, that covers the minimum musculoskeletal content that is academically and clinically relevant.

This article is protected by copyright. All rights reserved.

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Medial elbow anatomy: A paradigm shift for UCL injury prevention and management

Introduction

To improve the management outcomes and diagnostic accuracy of the ulnar collateral ligament (UCL) injury, the anatomy of the medial side of the elbow joint is necessary to be understood in terms of the periarticular surroundings rather than the specific ligaments. The aim of this study was to anatomically clarify the medial side of the elbow joint in terms of the tendinous structures and joint capsule.

Materials and Methods

We conducted a descriptive anatomical study of 23 embalmed cadaveric elbows. We macroscopically analyzed the relationship between the flexor pronator muscles (FPMs) and the joint capsule in ten elbows, histologically analyzed in six elbows, and observed the bone morphology through micro computed tomography in seven elbows.

Results

The two tendinous septa (TS) were found: between the pronator teres (PT) and flexor digitorum superficial (FDS) muscles, and between the FDS and flexor carpi ulnaris (FCU) muscles. These two TS are connected to the medial part of the brachialis tendon, deep aponeurosis of the FDS, and FCU to form the tendinous complex, which linked the humeroulnar joint and could not be histologically separated from each other. Moreover, the capsule of the humeroulnar joint under the tendinous complex had attachment on the ST of 7 mm width.

Conclusions

The two TS, the brachialis tendon, the deep FDS and FCU aponeuroses, and the joint capsule linked the humeroulnar joint. These anatomical findings could lead to a paradigm shift in the prevention, diagnosis, and treatment of UCL injuries in baseball players.

This article is protected by copyright. All rights reserved.

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Cancers, Vol. 10, Pages 496: PHD3 Acts as Tumor Suppressor in Mouse Osteosarcoma and Influences Tumor Vascularization via PDGF-C Signaling

Cancers, Vol. 10, Pages 496: PHD3 Acts as Tumor Suppressor in Mouse Osteosarcoma and Influences Tumor Vascularization via PDGF-C Signaling

Cancers doi: 10.3390/cancers10120496

Authors: Antje Egners Maryam Rezaei Aleksandar Kuzmanov David M. Poitz Doreen Streichert Thomas Mueller-Reichert Ben Wielockx Georg Breier

Cancer cell proliferation and insufficient blood supply can lead to the development of hypoxic areas in the tumor tissue. The adaptation to the hypoxic environment is mediated by a transcriptional complex called hypoxia-inducible factor (HIF). HIF protein levels are tightly controlled by oxygen-dependent prolyl hydroxylase domain proteins (PHDs). However, the precise roles of these enzymes in tumor progression and their downstream signaling pathways are not fully characterized. Here, we study PHD3 function in murine experimental osteosarcoma. Unexpectedly, PHD3 silencing in LM8 cells affects neither HIF-1&alpha; protein levels, nor the expression of various HIF-1 target genes. Subcutaneous injection of PHD3-silenced tumor cells accelerated tumor progression and was accompanied by dramatic phenotypic changes in the tumor vasculature. Blood vessels in advanced PHD3-silenced tumors were enlarged whereas their density was greatly reduced. Examination of the molecular pathways underlying these alterations revealed that platelet-derived growth factor (PDGF)-C signaling is activated in the vasculature of PHD3-deficient tumors. Silencing of PDGF-C depleted tumor growth, increased vessel density and reduced vessel size. Our data show that PHD3 controls tumor growth and vessel architecture in LM8 osteosarcoma by regulating the PDGF-C pathway, and support the hypothesis that different members of the PHD family exert unique functions in tumors.

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Silodosin: An Update on Efficacy, Safety and Clinical Indications in Urology

Abstract

Introduction

Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Phase III trials have already demonstrated the efficacy and safety of silodosin in the treatment of patients bothered by lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

Objective

We aimed to describe the rationality for the use of silodosin and to summarize the current literature on the use of Silodosin for the treatment of LUTS.

Methods

PubMed and Web of Science were queried with the terms: 'silodosin' in combination (AND) with the terms 'lower urinary tract symptoms', 'LUTS', 'pathophysiology', 'symptoms' OR 'therapy'. Studies published in the last 10 years (2007–2017) in adults and core clinical journals in English were included.

Results

Silodosin 8 mg once-daily was superior to placebo in improving IPSS total score, voiding subscore, storage subscore and QoL score, and at least as effective as tamsulosin 0.4 mg once-daily in all the efficacy analyses. In addition, studies assessing the effect on urodynamic parameters showed that silodosin determined a higher improvement in the bladder outlet obstruction index compared to other alpha1 adrenergic receptor antagonists. Concerning the safety profile, long-term data (after 9 months of treatment) confirmed the limited effect of silodosin on the cardiovascular and gastrointestinal systems. Although ejaculatory disorders represented the main complaint of patients taking silodosin, the discontinuation rate due to this condition remained low even in a long-term follow-up study (7.5%). Encouraging findings showed that silodosin may be administered as a medical expulsive therapy for promoting spontaneous stone passage of distal ureteral stones < 10 mm, to relieve LUTS in patients who underwent prostate cancer brachytherapy and to increase the likelihood of successful trials without a catheter in patients experiencing acute urinary retention.

Conclusion

Silodosin is one of the drugs approved for the treatment of BPH, being highly effective in improving not only LUTS but also urodynamic parameter impairments secondary to BPH. Moreover, it has shown efficacy as medical expulsive therapy for distal ureteral stones in previous prospective randomized trials.

Funding

Sponsorship for this study and article processing charges were funded by Recordati.

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Silent night: A paramedic Christmas story

A paramedic's job is about helping people and doing the best he can for each patient

https://ift.tt/2SAsq3r

Randomized phase II trial of the prophylactic use of celecoxib for the prevention of oxaliplatin-related peripheral vascular pain in Capeox (YCOG1205)

Abstract

Purpose

Capeox is widely used as an adjuvant chemotherapy regimen of colorectal cancer that does not require central vein catheter insertion. However, oxaliplatin-related vascular pain with peripheral administration is a major adverse event. We assessed the preventive effect of Celecoxib on oxaliplatin-related vascular pain.

Methods

A multicenter study of the Yokohama Clinical Oncology Group (YCOG) in Japan. This study was an open label, randomized non-comparative phase II study between Capeox without Celecoxib (C+ Group) and with it (C− group). The primary endpoint was the appearance frequency of grade ≥ 2 vascular pain according to the Verbal Rating Scale (VRS).

Results

Between October 2012 and February 2014, 81 patients were recruited to this study and randomly divided into 2 groups: 38 patients in the C− group and 39 patients in the C+ group. Four cases were excluded at the analysis stage because they had not received the allocated intervention. The rate of grade ≥ 2 vascular pain was 55.3% in the C− group and 53.8% in the C+ group (p = 1.000).

Conclusions

Celecoxib was unable to prevent oxaliplatin-related vascular pain in this study. However, it may be able to decrease the vascular pain that patients already have.

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ASO Author Reflections: Can the Association Between Obesity and Colorectal Cancer Be Explained by an Unfavorable Tumor Immune Microenvironment?

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Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC.

Methods

A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998–2017 was reviewed. Perioperative variables and survival were analyzed.

Results

Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021).

Conclusions

The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.

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5 steps to make your EMS resolutions STICK

Every year starts with good intentions. Make this one filled with real world positive change

https://ift.tt/2KYmSwV

Silent night: A paramedic Christmas story

A paramedic's job is about helping people and doing the best he can for each patient

https://ift.tt/2Ehw5jy

Dispatcher honored for giving CPR instructions during call

Katie Porter was honored with the Lifesaving Award after guiding a woman through CPR to try and save her husband

https://ift.tt/2E2eQlk

Silent night: A paramedic Christmas story

A paramedic's job is about helping people and doing the best he can for each patient

https://ift.tt/2Ehw5jy

Nuclear compartmentalization, dynamics and function of regulatory DNA sequences

Abstract

Transcription regulatory elements (TREs) have been extensively studied on the biochemical level with respect to their interactions with transcription factors, other DNA segments and larger protein complexes. In this review we describe concepts and preliminary experimental evidence for positional changes of TREs within a dynamic, functional nuclear architecture. We suggest a multi‐layered shell‐like chromatin organization of chromatin domain clusters with increasing chromatin compaction levels from the periphery toward the interior with a decondensed transcriptionally active peripheral layer and compact repressed chromatin typically located in the interior. This model organization of nuclear architecture implies a differential accessibility of transcription factors to targets located in co‐aligned active and inactive nuclear compartments. It is based on evidence that active, easily accessible chromatin (perichromatin, PR) lines a network of channels (interchromatin compartment, IC) involved in nuclear import‐export functions. The IC and PR constitute the active nuclear compartment (ANC), whereas transcriptionally non‐competent chromatin with higher compactness is part of the likely less accessible inactive nuclear compartment (INC). Preliminary experimental evidence shows an enrichment of active TREs in the ANC and of inactive TREs in the INC suggesting positional changes of TREs between the ANC and INC depending on changes in their functional state.

This article is protected by copyright. All rights reserved.

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Duxbling Stem Cells Meet Tumorigenesis

Identification of tumor-initiating populations could provide insights into tumor heterogeneity and responses to treatments, but this has proven difficult in most cancers. Now in Cell Stem Cell, Preussner et al. (2018) provide direct evidence that regenerating muscle satellite cells can be transformed to initiate and propagate rhabdomyosarcoma tumors.

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Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition

Sato and colleagues develop a modified culture condition for human intestinal organoids that improves the culture efficiency and maintains their long-term multi-differentiation capacity. scRNA-seq of human small intestinal crypts and organoids demonstrates that in vivo cellular diversity can be preserved in organoids cultured with the refined condition.

https://ift.tt/2BUkrIJ

Restoring Fertility with Human Induced Pluripotent Stem Cells: Are We There Yet?

Overcoming infertility with assisted reproduction requires high-quality eggs and sperm. For those young women who no longer make functional eggs, the hope of conceiving a biological child just got one step closer with a recent publication in Science from Yamashiro et al. (2018).

https://ift.tt/2L0wlnx

Inhibition of Inflammatory Signaling in Tet2 Mutant Preleukemic Cells Mitigates Stress-Induced Abnormalities and Clonal Hematopoiesis

Cai et al. report that Tet2-deficient hematopoietic stem and progenitor cells manifest a hyperactive IL-6/Shp2/Stat3/Morrbid pathway, which promotes cell survival under basal conditions and in response to inflammatory stress. Blocking this pathway using anti-inflammatory drugs (E3330 and SHP099) or by genetic loss of Morrbid mitigates this response.

https://ift.tt/2BUzodV

Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency

(Cell Stem Cell 23, 266–275.e1–e6; August 2, 2018)

https://ift.tt/2BUCZbW

Karyopherin-Centric Control of Nuclear Pores Based on Molecular Occupancy and Kinetic Analysis of Multivalent Binding with FG Nucleoporins

(Biophysical Journal 106, 1751–1762; April 15, 2014)

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Considerations for Assessing the Extent of Hippocampal Neurogenesis in the Adult and Aging Human Brain

Adult hippocampal neurogenesis (AHN) is implicated in brain adaptations and disease pathogenesis. A seminal study showed adult-born neurons in the subgranular zone (SGZ) of the dentate gyrus (DG) in cancer patients 58–72 years of age, detecting bromodeoxyuridine co-localization with neuronal markers (Eriksson et al., 1998). Subsequently, human AHN was reported using immunohistochemistry targeting markers expressed by neuronal cells at different maturational stages, in situ hybridization (ISH), and 14C decay-defined neuronal age (Spalding et al., 2013).

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Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram Cell Fate

(Cell Stem Cell 23, 727–741.e1–e9, November 1, 2018)

https://ift.tt/2L0wpnh

Histone Demethylases KDM4B and KDM6B Promote Osteogenic Differentiation of Human MSCs

(Cell Stem Cell 11, 50–61; July 6, 2012)

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Does Adult Neurogenesis Persist in the Human Hippocampus?

Whether new neurons are added to the human brain in childhood or adulthood is of widespread interest. Our recent observations suggest that newborn neurons in the adult human hippocampus (HP) are absent or very rare (Sorrells et al., 2018). A subsequent study proposes that large numbers of new neurons continue to be produced in the adult human HP (Boldrini et al., 2018). This has stimulated discussion and re-appraisal of this topic. Human studies have intractable caveats, making it important to interpret both positive and negative observations, including our own work, with a critical lens.

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Mentoring the Next Generation: Hans Clevers

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Hans Clevers about his views.

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Getting Past HSC Security: Cyclosporine H Gives Lentiviruses an Entry Pass

In this issue of Cell Stem Cell, Petrillo et al. (2018) improve lentiviral transduction of hematopoietic stem cells (HSCs) by using cyclosporine H to relieve viral entry restriction by interferon-induced transmembrane protein 3 (IFITM3). This finding promises to enhance the efficiency of ex vivo therapeutic gene transfer and gene editing of HSCs.

https://ift.tt/2KYvKTf

New CRISPR-Cas9 vectors for genetic modifications of Bacillus species

Abstract

Genetic manipulation is a fundamental procedure for the study of gene and operon functions and new characteristics acquisition. Modern CRISPR-Cas technology allows genome editing more precise and increases the efficiency of transferring mutations in a variety of hard to manipulate organisms. Here, we describe new CRISPR-Cas vectors for genetic modifications in bacillary species. Our plasmids are single CRISPR-Cas plasmids comprising all components for genome editing and should be functional in a broad host range. They are highly efficient (up to 97%) and precise. The employment and delivery of these plasmids to bacillary strains can be easily achieved by conjugation from E. coli. During our research we also demonstrated the absence of compatibility between CRISPR-Cas system and NHEJ in B. subtilis.

https://ift.tt/2RFazrO

Human Embryonic Stem Cells: Distinct Molecular Personalities and Applications in Regenerative Medicine

The field of stem cell biology is exciting because it provides researchers and clinicians with seemingly unlimited applications for treating many human diseases. Stem cells are a renewable source of pluripotent cells that can differentiate into nearly all human cell types. In this article we focus particularly on human embryonic stem (hES) cells, derived from the inner cell mass of the blastocyst and cultured for expansion while remaining undifferentiated, to explore their unique molecular personalities and clinical applications. The aim of this literature review is to reflect the interest in hES cells and to provide a resource for researchers and clinicians interested in the molecular characteristics of such cells.

This article is protected by copyright. All rights reserved.

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