Structure–Property Relations in Carbon Nanotube Fibers by Downscaling Solution Processing

Abstract

At the microscopic scale, carbon nanotubes (CNTs) combine impressive tensile strength and electrical conductivity; however, their macroscopic counterparts have not met expectations. The reasons are variously attributed to inherent CNT sample properties (diameter and helicity polydispersity, high defect density, insufficient length) and manufacturing shortcomings (inadequate ordering and packing), which can lead to poor transmission of stress and current. To efficiently investigate the disparity between microscopic and macroscopic properties, a new method is introduced for processing microgram quantities of CNTs into highly oriented and well-packed fibers. CNTs are dissolved into chlorosulfonic acid and processed into aligned films; each film can be peeled and twisted into multiple discrete fibers. Fibers fabricated by this method and solution-spinning are directly compared to determine the impact of alignment, twist, packing density, and length. Surprisingly, these discrete fibers can be twice as strong as their solution-spun counterparts despite a lower degree of alignment. Strength appears to be more sensitive to internal twist and packing density, while fiber conductivity is essentially equivalent among the two sets of samples. Importantly, this rapid fiber manufacturing method uses three orders of magnitude less material than solution spinning, expanding the experimental parameter space and enabling the exploration of unique CNT sources.

High-performance aligned films and fibers are processed from microgram quantities of carbon nanotubes dissolved in chlorosulfonic acid by a new method. The effect of alignment, twist, packing density, and aspect ratio on material properties is characterized. Compared to continuous solution spinning, discrete processing yields stronger fibers with comparable electrical conductivity.

http://ift.tt/2EtO5mU

Delivery of Tapasin-modified CTL epitope peptide via cytoplasmic transduction peptide induces CTLs by JAK/STAT signaling pathway in vivo

Abstract

Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role in viral control and clearance. Recent studies have elucidated that Tapasin, an endoplasmic reticulum chaperone, is a well-known molecule that appears to be essential in peptide-loading process. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in immune response regulation and cytokines secretion. We have previously verified that fusion protein CTP-HBcAg_18–27-Tapasin could facilitate the maturation of bone marrow derived dendritic cells and enhance specific CTLs responses in vitro, which might be associated with the activation of JAK/STAT signaling pathway. To further explore whether JAK/STAT signaling pathway participated in specific immune responses mediated by CTP-HBcAg_18–27-Tapasin, we suppressed the JAK/STAT pathway with pharmacological inhibitor (AG490) in vivo. Our studies showed that the number of IFN-γ⁺-CD8⁺ T cells was decreased significantly compared with other groups after being blocked by AG490. The percentage of IFN-γ⁺-CD4⁺ T cells and IL-2-CD4⁺ T cells was also decreased. Moreover, lower expression levels of Jak2, Tyk2, STAT1, and STAT4 were detected in AG490 group. In addition, the secretion levels of Th1-like cytokines were decreased and a weaker specific T-cell response was observed in AG490 group. Furthermore, the levels of HBV DNA and HBsAg in serum and expression levels of HBsAg and HBcAg in liver tissues were elevated after this pathway was inhibited in HBV transgenic mice. These results demonstrate that the JAK/STAT signaling pathway participates in Th1-oriented immune response induced by CTP-HBcAg_18–27-Tapasin and this might provide a theoretical basis for HBV immunotherapy.

http://ift.tt/2DhMCk2

Endometrial Adenocarcinoma With Pulmonary Recurrence

Description

We present the case of an 83-year-old woman with a history of grade 1 stage IB endometrial cancer (endometrial adenocarcinoma) (figure 1) involving the lower uterine segment. She underwent robotic hysterectomy with right salpingo-oophorectomy followed by brachytherapy. A year and a half later, she presented with difficulty in breathing. A chest X-ray showed 8 mm nodular density in the right lower lobe. The above finding was confirmed with CT. Given the concern for a malignant lesion, positron emission tomography/CT scan was performed, which revealed two metabolically active lung nodules, measuring 1.2 cm in the right middle lobe and other in the right lower lobe measuring 1.2 cm (figure 2). Video-assisted thoracoscopic wedge resection of the right lower lobe lung nodule was performed. The frozen section and histopathology revealed papillary adenocarcinoma (figures 3 and 4); nuclear staining was positive for oestrogen receptors and negative for thyroid...

http://ift.tt/2CQdR4i

Cervical ganglioneuroma: clinical and radiological features of a rare tumour

Description

Ganglioneuromas are rare benign tumours of neurogenic origin that most frequently develop in the cervical sympathetic chain,1 2 with genetic associations demonstrated with Neurofibromatosis type 1  (NF-1). We report the case of a 41-year-old woman with a history of cavum neoplasm at the age of 23. This tumour was classified after assessment of extension as T1N0M0 (tumour, node, metastases). Pathological examination of a biopsy concluded to a keratinising squamous cell carcinoma. The patient was then irradiated (2D Cobalt radiotherapy). The patient presented with gait trouble that appeared a few weeks ago. Clinical examination found a Brown-Séquard syndrome with paresis and loss of proprioception on the left side, and loss of pain and temperature sensation on the right side. Medullar MRI (figures 1 and 2) showed an intradural extramedullary well-circumscribed mass with an hourglass shape from C5 to C6 extending through the...

http://ift.tt/2DhvSJE

Rare cause of pulmonary cavitation in a 75-year-old man

A 75-year-old man of Asian descent presented to the acute medical unit with signs and symptoms suggestive of a community-acquired pneumonia. He had multiple comorbidities and was relatively immunocompromised as a result. Initial investigations supported the diagnosis of community-acquired pneumonia complicated by a cavitating lung lesion, and the patient was treated as per hospital guidelines. He continued to deteriorate despite appropriate therapy and developed a hydropneumothorax, requiring the insertion of a chest drain. A diagnosis of pulmonary mucormycosis (Rhizopus microsporus) was made based on microbiology results from pleural aspirate, and patient was treated with intravenous antifungals. The patient was referred to the thoracic team for consideration of surgical intervention but was not suitable due to his multiple comorbidities. This case highlighted the importance of early consideration of fungal infection in patients with multiple risk factors and the need for aggressive therapy to ensure the best outcome.

http://ift.tt/2CQGgac

Intradiploic cephalocele: a rare entity at a rare site

Description

A 52-year-old woman presented with complaints of non-specific headache. The patient had a history of head injury 1 year ago. Clinical neurological examination was nil significant. The skin over the occipital region is normal. No prior investigations were done immediately after the injury. MRI of the brain at present showed small intradiploic cerebrospinal fluid (CSF)-filled defect with herniation of foliae of the right cerebellar hemisphere (figure 1). The rest of the brain parenchyma revealed no abnormality and no skull fracture was seen. Features were suggestive of intradiploic cephalocele involving cerebellar foliae.

Figure 1

Axial Fluid attenuated inversion recovery (A), T2 (B), coronal T2 (C) and sagittal T1 (D) images at the level of the cerebellum showing small calvarial defect in the occipital bone on the right side with intradiploic herniation of the right cerebellar foliae (black arrows).

A cephalocele is...

http://ift.tt/2DiQSjm

Sternocleidomastoid tumour in neonate: fibromatosis colli

Description

We report a case of a 4-week-old female neonate who was admitted to the hospital for a anterior right lump of the neck, perceived by his mother the day before. The mother also noticed a preferential tilting of the head towards right. He was an otherwise full-term healthy baby, with a history of instrumented delivery. There was no fever, trauma or respiratory symptoms/signs. Family history was irrelevant. On examination, the neck swelling was a small firm, partially mobile, no warm on touch and apparently painless mass, with approximately 1.5–2 cm soft tissue mass, attached to the right sternocleidomastoid muscle. There was no restriction of neck movements. Ultrasonography (USG) revealed a 13 mm fusiform thickening of the right sternocleidomastoid muscle, with maintained structure of muscle fibres (figures 1 and 2). No cervical lymphadenopathy, signs of infiltration or other anomalies were found (figures 1 and...

http://ift.tt/2CThuXb

Ninety-year-old man with hypereosinophilia, lymphadenopathies and pruritus

We report a case of a 90-year-old man with hypereosinophilia, lymphadenopathies and skin lesions, namely lichenification and pruritus. An aetiological investigation was performed, and a bone marrow (BM) biopsy and aspirate showed a hypercellular marrow with hypereosinophilia without dysmorphia or abnormal elements, and the BM and inguinal node's immunophenotyping denied any presence of abnormal lymphoid cell population. The inguinal node biopsy revealed a multinodular proliferation of large cells S100 and CD1a⁺, and a diagnosis of Langerhans cell histiocytosis was made. The hypereosinophilia and skin lesions were managed with corticotherapy with substantial improvement of cutaneous lesions and lymphadenopathies and normalisation of eosinophil count. Finally, to define if it is a single or multisystem disease, a skin biopsy will be necessary.

http://ift.tt/2DiXy0W

Young adults perspectives on living with kidney failure: a systematic review and thematic synthesis of qualitative studies

Introduction

Young adults fare worse than younger adolescents or older adults on a broad range of health indicators. Those with a chronic illness such as renal failure are a particularly vulnerable group, who experience poor outcomes compared with both children and older adults. Understanding how being in receipt of renal replacement therapy (RRT) affects the lives of young adults might help us to better prepare and support these individuals for and on RRT, and improve outcomes. This study aimed to synthesise research describing young adults' experiences of the psychosocial impact of kidney failure and RRT.

Design

A systematic literature review identified qualitative research reporting the perspectives of people aged 16–30 years receiving RRT on the psychosocial impact of renal failure. Electronic databases (including Medline/EMBASE/PsycINFO/ASSIA) were searched to November 2017 for full-text papers. The transparency of reporting of each study was assessed using the Consolidated Criteria for Reporting Qualitative Health Research (COREQ) framework. Quality was assessed using the Critical Appraisal Skills Programme qualitative checklist. An inductive thematic synthesis was undertaken.

Participants

Seven studies from five different countries were included, comprising 123 young adults receiving RRT.

Results

Comprehensiveness of reporting was variable: studies reported 9–22 of the 32 COREQ-checklist items.

Three global themes about the impact of kidney failure on young adults were identified: (1) difference desiring normality, (2) thwarted or moderated dreams and ambitions, and (3) uncertainty and liminality. These reflected five organising themes: (1) physical appearance and body image, (2) activity and participation, (3) educational disruption and underachievement, (4) career ambitions and employment difficulties, and (5) social isolation and intimate relationships.

Conclusions

Across different countries and different healthcare settings, young adults on RRT experience difference and liminality, even after transplantation. Tailored social and psychological support is required to allow young adults to experience wellness while in receipt of RRT, and not have life on hold.

http://ift.tt/2CZtXwu

Establishing anchor-based minimally important differences (MID) with the EORTC quality-of-life measures: a meta-analysis protocol

Introduction

As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated.

Methods and analysis

Data will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30.

Ethics and dissemination

All patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID 'blue book' which will be made available online on the EORTC Quality of Life Group website as a free guideline document.

http://ift.tt/2AO2nfP

Variations in childbirth interventions in high-income countries: protocol for a multinational cross-sectional study

Introduction

There are growing concerns about the increase in rates of commonly used childbirth interventions. When indicated, childbirth interventions are crucial for preventing maternal and perinatal morbidity and mortality, but their routine use in healthy women and children leads to avoidable maternal and neonatal harm. Establishing ideal rates of interventions can be challenging. This study aims to describe the range of variations in the use of commonly used childbirth interventions in high-income countries around the world, and in outcomes in nulliparous and multiparous women.

Methods and analysis

This multinational cross-sectional study will use data from births in 2013 with national population data or representative samples of the population of pregnant women in high-income countries. Data from women who gave birth to a single child from 37 weeks gestation onwards will be included and the results will be presented for nulliparous and multiparous women separately. Anonymised individual level data will be analysed. Primary outcomes are rates of commonly used childbirth interventions, including induction and/or augmentation of labour, intrapartum antibiotics, epidural and pharmacological pain relief, episiotomy in vaginal births, instrument-assisted birth (vacuum or forceps), caesarean section and use of oxytocin postpartum. Secondary outcomes are maternal and perinatal mortality, Apgar score below 7 at 5 min, postpartum haemorrhage and obstetric anal sphincter injury. Univariable and multivariable logistic regression analyses will be conducted to investigate variations among countries, adjusted for maternal age, body mass index, gestational weight gain, ethnic background, socioeconomic status and infant birth weight. The overall mean rates will be considered as a reference category, weighted for the size of the study population per country.

Ethics and dissemination

The Medical Ethics Review Committee of VU University Medical Center Amsterdam confirmed that an official approval of this study was not required. Results will be disseminated at national and international conferences and published in peer-reviewed journals.

http://ift.tt/2D3SQaj

Period prevalence, risk factors and consequent injuries of falling among the Saudi elderly living in Riyadh, Saudi Arabia: a cross-sectional study

Objectives

Approximately 28% to 35% of people aged 65 and over fall each year. The consequent injuries of falls are considered a major public health problem. Falls account for more than half of injury-related hospitalisations among old people. The aim of this study was to measure a 1-year period prevalence of falling among old people in Riyadh, Saudi Arabia. In addition, this study described the most common risk factors and consequent injuries of falls.

Setting and participants

A cross-sectional survey was carried out in Riyadh, using a convenient sampling. The targeted population were Saudi citizens who were 60 years or above. Over a 6-month period, 1182 individuals were sampled (545 men and 637 women).

Results

The 1-year prevalence of falling among old Saudis (>=60 years) was 49.9%. Our results show that 74% of the participants who experienced falls had postfall injuries. Old participants who were uneducated and those with middle school certification were associated with falls (adjusted OR (aOR) 1.72; 95% CI 1.15 to 2.56, aOR 1.81; 95% CI 1.15 to 2.85, respectively). Those who live in rented houses had a higher risk of falls. Interestingly, having a caregiver was significantly associated with more falls (aOR 1.39; 95% CI 1.08 to 1.79). However, not using any medications was significantly related to fewer falls. In addition, old individuals using walking aids were more likely to fall than those who did not. Participants who mentioned 'not having stressors were associated with less frequent falls (aOR 0.62; 95% CI 0.39 to 0.97). Cerebrovascular accidents were strongly associated with falls with an estimated OR of 2.75 (95% CI 1.18 to 6.43). Moreover, osteoporosis, poor vision and back pain were found to be predictors for falls among the elderly.

Conclusion

49.9% of elderly Saudis had experienced one or more falls during a 12-month period. Several preventable risk factors could be addressed by routine geriatric assessment. Research on the impact of these risk factors is needed.

http://ift.tt/2AQ7VGx

Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) adnexectomy for benign pathology compared with laparoscopic excision (NOTABLE): a protocol for a randomised controlled trial

Introduction

Natural orifice transluminal endoscopic surgery (NOTES) uses natural orifices to access the cavities of the human body to perform surgical interventions. NOTES limits the magnitude of surgical trauma and potentially reduces postoperative pain. Our group published a protocol on a randomised study comparing transvaginal NOTES (vNOTES) versus laparoscopy for hysterectomy (HALON). We simultaneously designed a similar randomised controlled trial (RCT) comparing vNOTES with laparoscopy for adnexectomy. To the best of our knowledge, this is the first RCT comparing vNOTES with laparoscopy for adnexal surgery.

Methods and analysis

The methodology of the Notes Adnexectomy for Benign Indication versus Laparoscopic Excision (NOTABLE) study is similar to that of the HALON trial. Women aged 18–70 years with an indication for benign adnexal surgery will be eligible. We will use stratification according to adnexal size. Entrants will be randomised to the laparoscopic treatment (control) or vNOTES (intervention). Participants will be evaluated on days 0–7 and at 3 and 6 months. The primary outcome will be the proportion of women successfully treated by removing an adnexa by the allocated technique without conversion. We will collect the following data (secondary outcomes): proportion of women hospitalised on the day of surgery, postoperative pain scores measured two times per day from day 1 to 7, total dosage of pain killers used from day 1 to 7, hospital readmission during the first 6 weeks, dyspareunia and sexual well-being at baseline, 3 and 6 months using a validated questionnaire (Short Sexual Functioning Scale), health-related quality of life at baseline, 3 and 6 months after surgery using a validated questionnaire (EQ-5D-3L), duration of surgical intervention, infection or other surgical complications and direct costs up to 6 weeks following surgery. For the primary outcome measure, a one-sided 95% CI of the difference in the proportions of women with a successful removal of the uterus by the randomised technique will be estimated. Non-inferiority will be concluded when 15% lies above the upper limit of this 95% CI.

Ethics and dissemination

The study was approved on 1 December 2015 by the EthicsCommitteeof the Imelda Hospital (registration no: 689), Bonheiden, Belgium. We aim to present the final results of the NOTABLE trial in peer-reviewed journals and at scientific meetings within 4 years after the start of the recruitment.

Trial registration number

NCT02630329.

http://ift.tt/2D3SK2r

Association of erythrocyte parameters with metabolic syndrome in the Pearl River Delta region of China: a cross sectional study

Objective

Increasing studies have reported that erythrocyte parameters, including red blood cells (RBCs), haematocrit (HCT), haemoglobin (Hb) and red blood cell distribution width (RDW), are associated with metabolic syndrome (MetS) in adults worldwide. However, the association, stratified by sex, remains to be elucidated, particularly in the Pearl River Delta region of China. Therefore, our aim was to explore the association of erythrocyte parameters with MetS, stratified by sex, in the Pearl River Delta region of China.

Methods

In this cross sectional study, 2161 men and 2511 women were enrolled. MetS was diagnosed using a modified version of the Adult Treatment Panel III criteria. Logistic regression analyses were performed to calculate adjusted ORs of erythrocyte parameters associated with MetS stratified by sex.

Results

The prevalence of MetS was higher in women than in men (35.2%vs26.7%). RBC, HCT, Hb and RDW values increased linearly with the number of MetS components from 0 to 5 identified in both men and women. Among men, the ORs of MetS risk increased across the tertiles of Hb (Q2: OR=1.921, 95% CI=1.170 to 3.151; Q3: OR=1.992, 95%CI=1.198 to 3.312). Men in the highest tertiles of RDW had a 2.752-fold increased risk of suffering from MetS compared with those in the reference group. Among women, the ORs of MetS risk also increased across the tertiles of Hb (Q2: OR=1.538, 95%CI=1.008 to 2.348; Q3: OR=1.665, 95%CI=1.075 to 2.578). Women in the highest tertiles of RBC had a 1.718-fold increased risk of experiencing MetS compared with those in the reference group.

Conclusions

MetS was more prevalent in women than in men. The association between erythrocyte parameters and MetS differed between the sexes. RBC and Hb were identified as risk factors for MetS in women and Hb and RDW as risk factors in men.

http://ift.tt/2AQ7U5r

Assessing the effectiveness of a patient-centred computer-based clinic intervention, Health-E You/Salud iTu, to reduce health disparities in unintended pregnancies among Hispanic adolescents: study protocol for a cluster randomised control trial

Introduction

Teen pregnancy rates in the USA remain higher than any other industrialised nation, and pregnancies among Hispanic adolescents are disproportionately high. Computer-based interventions represent a promising approach to address sexual health and contraceptive use disparities. Preliminary findings have demonstrated that the Health-E You/Salud iTu, computer application (app) is feasible to implement, acceptable to Latina adolescents and improves sexual health knowledge and interest in selecting an effective contraceptive method when used in conjunction with a healthcare visit. The app is now ready for efficacy testing. The purpose of this manuscript is to describe patient-centred approaches used both in developing and testing the Health-E You app and to present the research methods used to evaluate its effectiveness in improving intentions to use an effective method of contraception as well as actual contraceptive use.

Methods and analysis

This study is designed to assess the effectiveness of a patient-centred computer-based clinic intervention, Health-E You/Salud iTu, on its ability to reduce health disparities in unintended pregnancies among Latina adolescent girls. This study uses a cluster randomised control trial design in which 18 school-based health centers from the Los Angeles Unified School District were randomly assigned, at equal chance, to either the intervention (Health-E You app) or control group. Analyses will examine differences between the control and intervention group's knowledge of and attitudes towards contraceptive use, receipt of contraception at the clinic visit and self-reported use of contraception at 3-month and 6-month follow-ups. The study began enrolling participants in August 2016, and a total of 1400 participants (700 per treatment group) are expected to be enrolled by March 2018.

Ethics and dissemination

Ethics approval was obtained through the University of California, San Francisco Institutional Review Board. Results of this trial will be submitted for publication in peer-reviewed journals. This study is registered with the US National Institutes of Health.

Trial registration number

NCT02847858.

http://ift.tt/2D2NwEo

Managing cognitive impairment following stroke: protocol for a systematic review of non-randomised controlled studies of psychological interventions

Introduction

Stroke is one of the primary causes of death and disability worldwide, leaving a considerable proportion of survivors with persistent cognitive and functional deficits. Despite the prevalence of poststroke cognitive impairment, there is no established treatment aimed at improving cognitive function following a stroke. Therefore, the aims of this systematic review are to identify psychological interventions intended to improve poststroke cognitive function and establish their efficacy.

Methods and analysis

A systematic review of non-randomised controlled studies that investigated the efficacy of psychological interventions aimed at improving cognitive function in stroke survivors will be conducted. Electronic searches will be performed in the PubMed, Embase and PsycINFO databases, the search dating from the beginning of the index to February 2017. Reference lists of all identified relevant articles will be reviewed to identify additional studies not previously identified by the electronic search. Potential grey literature will be reviewed using Google Scholar. Titles and abstracts will be assessed for eligibility by one reviewer, with a random sample of 50% independently double-screened by second reviewers. Any discrepancies will be resolved through discussion, with referral to a third reviewer where necessary. Risk of bias will be assessed with the Risk of Bias in Non-randomized Studies of Interventions tool. Meta-analyses will be performed if studies are sufficiently homogeneous. This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The quality of the evidence regarding cognitive function will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation.

Ethics and dissemination

This systematic review will collect secondary data only and as such ethical approval is not required. Findings will be disseminated through presentations and peer-reviewed publication. This review will provide information on the effectiveness of psychological interventions for poststroke cognitive impairment, identifying which psychological interventions are effective for improving poststroke cognitive function.

PROSPERO registration number

CRD42017069714.

http://ift.tt/2D1disB

Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals

Objectives

Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health outcomes in patients with IHDs.

Methods

We systematically searched PubMed and EMBASE for studies published between 1 January 2000 and 31 August 2017. We included original studies of interventions targeted at healthcare professionals to enhance prescribing guideline-recommended medications for IHDs. We only included randomised controlled trials (RCTs). Main outcomes were the proportion of eligible patients receiving guideline-recommended medications, the proportion of patients achieving target blood pressure and target low-density lipoprotein-cholesterol (LDL-C)/cholesterol level and mortality rate. Meta-analyses were performed using the inverse-variance method and the random effects model. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach.

Results

We included 13 studies, 4 RCTs (1869 patients) and 9 cluster RCTs (15 224 patients). 11 out of 13 studies were performed in North America and Europe. Interventions were of organisational or professional nature. The interventions significantly enhanced prescribing of statins/lipid-lowering agents (OR 1.23; 95% CI 1.07 to 1.42, P=0.004), but not other medications (aspirin/antiplatelet agents, beta-blockers, ACE inhibitors/angiotensin II receptor blockers and the composite of medications). There was no significant association between the interventions and improved health outcomes (target LDL-C and mortality) except for target blood pressure (OR 1.46; 95% CI 1.11 to 1.93; P=0.008). The evidence was of moderate or high quality for all outcomes.

Conclusions

Organisational and professional interventions improved prescribing of statins/lipid-lowering agents and target blood pressure in patients with IHDs but there was little evidence of change in other outcomes.

PROSPERO registration number

CRD42016039188.

http://ift.tt/2AOOEVO

A qualitative study of patients feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England: implications for service improvement

Objective

Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients' experiences of OPAT.

Design

In-depth, semistructured interviews.

Setting

Purposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or self-administration models.

Participants

We undertook 28 semistructured interviews and one focus group (n=4).

Results

Despite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information.

Conclusion

Services configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service.

http://ift.tt/2AOOAFy

Factors associated with neonatal pneumonia in India: protocol for a systematic review and planned meta-analysis

Introduction

India accounts for more neonatal deaths than any other country. There is a lack of consolidated evidence from India regarding the determining factors of pneumonia in neonates. This systematic review is aimed to consolidate and appraise the evidence on risk factors and determinants of pneumonia among neonates in India.

Methods and analysis

This protocol is part of a project consisting of three reviews (two systematic reviews and one scoping review) and a qualitative study on neonatal pneumonia in India. English language observational studies which report risk factors and determinants of neonatal pneumonia in India will be eligible for inclusion. Electronic searching of nine databases, and hand searching will be done. Two authors will independently conduct screening (title, abstract and full-text stages), extract data and assess risk of bias. A meta-analysis is planned to be performed with random-effects model. A narrative synthesis will be used to summarise the characteristics and findings of the review, if a meta-analysis cannot be performed. If there are more than 10 studies, publication bias will be assessed. Sensitivity and subgroup analysis will performed based on data availability. The quality of our review will be assessed by using 'Assessing the Methodological quality of Systematic Reviews' and 'Grades of Recommendation, Assessment, Development and Evaluation'.

Ethics and dissemination

The protocol of the entire project has been approved by the host institution's ethics body (Institutional Ethics Committee, Manipal University, Manipal, India), and the 'Health Ministry Screening Committee' under the Ministry of Health and Family Welfare, Government of India. The study findings will be disseminated among relevant stakeholders using knowledge dissemination workshops, policy briefs, publications, etc.

PROSPERO registration number

CRD42016044019.

http://ift.tt/2D2NpbW

Evidence for sample selection effect and Hawthorne effect in behavioural HIV prevention trial among young women in a rural South African community

Objectives

We examined the potential influence of both sample selection effects and Hawthorne effects in the behavioural HIV Prevention Trial Network 068 study, designed to examine whether cash transfers conditional on school attendance reduce HIV acquisition in young South African women. We explored whether school enrolment among study participants differed from the underlying population, and whether differences existed at baseline (sample selection effect) or arose during study participation (Hawthorne effect).

Methods

We constructed a cohort of 3889 young women aged 11–20 years using data from the Agincourt Health and socio-Demographic Surveillance System. We compared school enrolment in 2011 (trial start) and 2015 (trial end) between those who did (n=1720) and did not (n=2169) enrol in the trial. To isolate the Hawthorne effect, we restricted the cohort to those enrolled in school in 2011.

Results

In 2011, trial participants were already more likely to be enrolled in school (99%) compared with non-participants (93%). However, this association was attenuated with covariate adjustment (adjusted risk difference (aRD) (95% CI): 2.9 (– 0.7 to 6.5)). Restricting to those enrolled in school in 2011, trial participants were also more likely to be enrolled in school in 2015 (aRD (95% CI): 4.9 (1.5 to 8.3)). The strength of associations increased with age.

Conclusions

Trial participants across both study arms were more likely to be enrolled in school than non-participants. Our findings suggest that both sample selection and Hawthorne effects may have diminished the differences in school enrolment between study arms, a plausible explanation for the null trial findings. The Hawthorne-specific findings generate hypotheses for how to structure school retention interventions to prevent HIV.

http://ift.tt/2ANx9FL

Pilot study protocol to inform a future longitudinal study of ageing using linked administrative data: Healthy AGeing in Scotland (HAGIS)

Introduction

Population ageing is a welcome testament to improvements in the social, economic and health circumstances over the life course. However, these successes necessitate that we understand more about the pathways of ageing to plan and cost our health and social care services, to support our ageing population to live healthier for longer and to make adequate provisions for retirement. Longitudinal studies of ageing facilitate such understanding in many countries around the world. Scotland presently does not have a longitudinal study of ageing, despite dramatic increases to its ageing population and its poor health record. Healthy AGeing in Scotland (HAGIS) constitutes the launch of Scotland's first comprehensive longitudinal study of ageing.

Methods

A sample of 1000 people aged 50+ years will be invited to take part in a household social survey. The innovative sampling procedure used administrative data to identify eligible households. Anonymised survey responses will be linked to administrative data.

Ethics and dissemination

Ethics approval was obtained from the host institution for the study design and from the Public Benefits and Privacy Panel for administrative data linkage. Anonymised survey data will be deposited with the UK Data Service. A subset of survey data, harmonised with other global ageing studies, will be available via the Gateway to Global Aging platform. These data will enable powerful cross-country comparisons across the social, economic and health domains that will be relevant for national and international research.

Research publications from the HAGIS team will be disseminated through journal articles and national and international conferences. The findings will support current and future research and policy debate on ageing populations.

http://ift.tt/2D2Nhcs

Why do GPs leave direct patient care and what might help to retain them? A qualitative study of GPs in South West England

Objective

To identify factors influencing general practitioners' (GPs') decisions about whether or not to remain in direct patient care in general practice and what might help to retain them in that role.

Design

Qualitative, in-depth, individual interviews exploring factors related to GPs leaving, remaining in and returning to direct patient care.

Setting

South West England, UK.

Participants

41 GPs: 7 retired; 8 intending to take early retirement; 11 who were on or intending to take a career break; 9 aged under 50 years who had left or were intending to leave direct patient care and 6 who were not intending to leave or to take a career break. Plus 19 stakeholders from a range of primary care-related professional organisations and roles.

Results

Reasons for leaving direct patient care were complex and based on a range of job-related and individual factors. Three key themes underpinned the interviewed GPs' thinking and rationale: issues relating to their personal and professional identity and the perceived value of general practice-based care within the healthcare system; concerns regarding fear and risk, for example, in respect of medical litigation and managing administrative challenges within the context of increasingly complex care pathways and environments; and issues around choice and volition in respect of personal social, financial, domestic and professional considerations. These themes provide increased understanding of the lived experiences of working in today's National Health Service for this group of GPs.

Conclusion

Future policies and strategies aimed at retaining GPs in direct patient care should clarify the role and expectations of general practice and align with GPs' perception of their own roles and identity; demonstrate to GPs that they are valued and listened to in planning delivery of the UK healthcare; target GPs' concerns regarding fear and risk, seeking to reduce these to manageable levels and give GPs viable options to support them to remain in direct patient care.

http://ift.tt/2AOOpKo

PARENTS 2 study protocol: pilot of Parents Active Role and ENgagement in the review of Their Stillbirth/perinatal death

Background

The perinatal mortality review meeting that takes place within the hospital following a stillbirth or neonatal death enables clinicians to learn vital lessons to improve care for women and their families for the future. Recent evidence suggests that parents are unaware that a formal review following the death of their baby takes place. Many would welcome the opportunity to feedback into the meeting itself. Parental involvement in the perinatal mortality review meeting has the potential to improve patient satisfaction, drive improvements in patient safety and promote an open culture within healthcare. Yet evidence on the feasibility of involving bereaved parents in the review process is lacking. This paper describes the protocol for the Parents' Active Role and Engangement iN the review of their Stillbirth/perinatal death study (PARENTS 2) , whereby healthcare professionals' and stakeholders' perceptions of parental involvement will be investigated, and parental involvement in the perinatal mortality review will be piloted and evaluated at two hospitals.

Methods and analysis

We will investigate perceptions of parental involvement in the perinatal mortality review process by conducting four focus groups. A three-round modified Delphi technique will be employed to gain a consensus on principles of parental involvement in the perinatal mortality review process. We will use three sequential rounds, including a national consensus meeting workshop with experts in stillbirth, neonatal death and bereavement care, and a two-stage anonymous online questionnaire. We will pilot a new perinatal mortality review process with parental involvement over a 6-month study period. The impact of the new process will be evaluated by assessing parents' experiences of their care and parents' and staff perceptions of their involvement in the process by conducting further focus groups and using a Parent Generated Index questionnaire.

Ethics and dissemination

This study has ethical approval from the UK Health Research Authority. We will disseminate the findings through national and international conferences and international peer-reviewed journals.

http://ift.tt/2CZJD2I

Prevalence and burden of chronic kidney disease among the general population and high-risk groups in Africa: a systematic review

Objectives

While increasing attention is paid to the rising prevalence of chronic diseases in Africa, there is little focus on chronic kidney disease (CKD). This systematic review assesses CKD burden among the general population and high-risk groups on the entire African continent.

Design, setting and participants

We searched Medline and PubMed databases for articles published between 1 January 1995 and 7 April 2017 by sensitive search strategies focusing on CKD surveys at the community level and high-risk groups. In total, 7918 references were evaluated, of which 7766 articles were excluded because they did not meet the inclusion criteria. Thus, 152 studies were included in the final analysis.

Outcome measurement

The prevalence of CKD in each study group was expressed as a range and pooled prevalence rate of CKD was calculated as a point estimate and 95% CI. No meta-analysis was done. Data were presented for different populations.

Results

In the community-level studies, based on available medium-quality and high-quality studies, the prevalence of CKD ranged from 2% to 41% (pooled prevalence: 10.1%; 95% CI 9.8% to 10.5%). The prevalence of CKD in the high-risk groups ranged from 1% to 46% (pooled prevalence: 5.6%; 95% CI 5.4% to 5.8%) in patients with HIV (based on available medium-quality and high-quality studies), 11%–90% (pooled prevalence: 24.7%; 95% CI 23.6% to 25.7%) in patients with diabetes (based on all available studies which are of low quality except four of medium quality) and 13%–51% (pooled prevalence: 34.5%; 95 % CI 34.04% to 36%) in patients with hypertension (based on all available studies which are of low quality except two of medium quality).

Conclusion

In Africa, CKD is a public health problem, mainly attributed to high-risk conditions as hypertension and diabetes. The poor data quality restricts the validity of the findings and draws the attention to the importance of designing future robust studies.

http://ift.tt/2AOpkQ0

Correction to: Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors

Abstract

In the original publication, the values provided for the isoflavone and glucosinolate intake variables were incorrectly labeled in Table 1. The correct values of 6.3 mg/day for isoflavone intake, and 20.4 mg/day and 50.1 mg/day for glucosinolate intake are provided in this erratum.

http://ift.tt/2DhCnw6

Disparities in cancer outcomes across age, sex, and race/ethnicity among patients with pancreatic cancer

Abstract

Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early-stage and late-stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received. We used logistic regression to compare differences in treatment received across age, sex, and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian, and 2% Hispanic. Median age was 75; 56% were female and 53% had late-stage cancer. Among early-stage patients in the adjusted Cox model, older patient subgroups had worse survival compared with ages 66–69 (HR > 1.1, P < 0.01 for groups >69); no survival differences existed between sexes. Black (HR = 1.1, P = 0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with White. Among late-stage cancer patients, patients over age 84 had worse survival than those aged 66–69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had worse survival than females; there were no racial/ethnic differences. Older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC patients; these disparities persist after adjusting for differences in demographic and clinical characteristics.

Disparities in pancreatic cancer outcomes exists, but are not fully understood. Our research uses SEER–Medicare data to determine which factors contribute to the differences in treatment receipt and survival outcomes among age, sex, and racial/ethnic subgroups. Our conclusion that disparities continue to persist after adjusting for various covariates highlights the need for additional research in this area.

http://ift.tt/2AOPgLl

Clopidogrel Tablets USP, 75 mg by International Laboratories: Recall - Product Mislabeling

Audience: Pharmacy, Patient [Posted 01/10/2018] ISSUE: International Laboratories, LLC is voluntarily recalling Lot# 117099A of Clopidogrel Tablets, USP 75 mg, packaged in bottles of 30 tablets, to the consumer level due to mislabeling. The product...

http://ift.tt/2mqRAUg

Clopidogrel Tablets USP, 75 mg by International Laboratories: Recall - Product Mislabeling

Audience: Pharmacy, Patient [Posted 01/10/2018] ISSUE: International Laboratories, LLC is voluntarily recalling Lot# 117099A of Clopidogrel Tablets, USP 75 mg, packaged in bottles of 30 tablets, to the consumer level due to mislabeling. The product...

http://ift.tt/2mqRAUg

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients

Pharmacogenomics, Ahead of Print.


http://ift.tt/2EwsTwz

The pharmacogenetics of medications used in general anesthesia

Pharmacogenomics, Ahead of Print.


http://ift.tt/2FqckDu

Decoding oral cancer conundrums from ‘bad luck’ point of view

Future Oncology, Ahead of Print.


http://ift.tt/2AO53tS

Comparison of three prognostic models for predicting cancer-specific survival among patients with gastrointestinal stromal tumors

Future Oncology, Ahead of Print.


http://ift.tt/2D27Up5

Cardiovascular safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients: a prospective evaluation

Future Oncology, Ahead of Print.


http://ift.tt/2ANhZjv

Are redheads at an increased risk of melanoma?

Future Oncology, Ahead of Print.


http://ift.tt/2D27ZZV

Thymidylate synthase: a predictive biomarker in resected colorectal liver metastases receiving 5-FU treatment

Future Oncology, Ahead of Print.


http://ift.tt/2AO501a

What treatments should be skipped or intensified in localized rectal cancer?

Future Oncology, Ahead of Print.


http://ift.tt/2D1ZSfE

Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila melanogaster Macrophages and Surrounding Tissues

Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.

http://ift.tt/2CPfkrB

Construction of Designer Selectable Marker Deletions with CRISPR-Cas9 Toolbox in Schizosaccharomyces pombe and Optimized Design of Common Entry Vectors

Vectors encoding selectable markers have been widely used in yeast to maintain or express exogenous DNA fragments. In the fission yeast Schizosaccharomyces pombe, several engineered markers have been reported and widely used, such as ura4⁺ and ScLEU2 from Saccharomyces cerevisiae, which complement ura4 and leu1 mutations, respectively. These two auxotrophic markers share no homology with the Sch. pombe genome, however most others can recombine with the genomic due to sequence homology shared between the genomic and plasmid-born copies of the markers. Here, we describe a CRISPR-Cas9 toolbox that can be used to quickly introduce into host strains "designer" auxotrophic marker deletions, including leu1-0, his3-0 and lys9-0. Together with ura4-D18, this brings the total number of available designer deletion auxotrophic markers to four. The toolbox consists of a Cas9-gRNA expression vector and a donor DNA plasmid pair for each designer deletion. Using this toolbox, a set of auxotrophic Sch. pombe strains was constructed. Further, we reorganized essential components in the commonly used pREP series of plasmids and assembled the corresponding auxotrophic marker gene onto these plasmids. This toolbox for producing designer deletions, together with the newly developed strains and plasmids will benefit the whole yeast community.

http://ift.tt/2DjzzP1

Antitumor effects of blocking protein neddylation in T315I-BCR-ABL leukemia cells and leukemia stem cells

Imatinib (IM) revolutionized the treatment of chronic myeloid leukemia (CML) but drug resistance and disease recurrence remain a challenge. In this study, we suggest a novel strategy based on blocking protein neddylation to address BCR-ABL point mutations and leukemia stem cells (LSCs) that lie at the root of IM-resistant recurrences. Based on the finding that the NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, we hypothesized that the function of certain neddylation-dependent protein substrates might be targeted to therapeutic ends in IM-resistant CML cells and LSCs. In support of this hypothesis, we demonstrated that the NAE1 inhibitor MLN4924 induced G2/M-phase arrest and apoptosis in bulk CML cells with wild-type p53, regardless of their T315I mutation status in BCR-ABL. Moreover, MLN4924 inhibited the survival and self-renewal of primary human CML CD34+ cells and LSCs in CML-bearing mice via accumulation of p27kip1 in the nucleus. Notably, p27kip1 silencing attenuated the suppressive effect of MLN4924 on the maintenance of LSCs in CML-bearing mice. Taken together, our findings offer a preclinical proof of concept for targeting protein neddylation as a novel therapeutic strategy to override mutational and LSC-derived IM resistance in CML.

http://ift.tt/2mrpWGT

KRAS oncoprotein expression is regulated by a self-governing eIF5A-PEAK1 feed-forward regulatory loop

There remains intense interest in tractable approaches to target or silence the KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic adenocarcinoma (PDAC) and other cancers which overexpress it. Here we provide evidence that accumulation of the KRAS oncoprotein is controlled by a self-regulating feed-forward regulatory loop that utilizes a unique hypusinated isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1. Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which in turn facilitated increased KRAS protein synthesis. Mechanistic investigations shows that this feed-forward positive regulatory pathway was controlled by oncogenic KRAS-driven metabolic demands, operated independently of canonical mTOR signaling, and did not involve new KRas gene transcription. Perturbing eIF5A-PEAK1 signaling, by genetic or pharmacologic strategies or by blocking glutamine synthesis, was sufficient to inhibit expression of KRAS, eIF5A, and PEAK1, attenuate cancer cell growth and migration, and block tumor formation in established preclinical mouse models of PDAC. Levels of KRAS, eIF5A, and PEAK1 protein increased during cancer progression with the highest levels of expression observed in metastatic cell populations. Combinatorial targeting of eIF5A hypusination and the RAS-ERK signaling pathway cooperated to attenuate KRAS expression and its downstream signaling along with cell growth in vitro and tumor formation in vivo. Collectively, our findings highlight a new mechanistic strategy to attenuate KRAS expression as a therapeutic strategy to target PDAC and other human cancers driven by KRAS activation.

http://ift.tt/2qR6wA1

Rejuvenating Regenerative Medicine Regulation

The Food and Drug Administration (FDA) recently made long-awaited progress toward protecting patients from interventions involving human cell- and tissue-based products (HCT/P) of unknown safety and efficacy. By clarifying its position on the handling and therapeutic use of cells, the agency has…

http://ift.tt/2qPz2lr

Serum Copper Homeostasis in Hypertensive Intracerebral Hemorrhage and its Clinical Significance

Abstract

This study was to investigate the alterations of serum copper homeostasis after hypertensive intracerebral hemorrhage (ICH), which is not yet clear. We recruited 85 hypertensive ICH patients and determined their serum levels of total copper (TCu), small molecule copper (SMC), and ceruloplasmin (Cp). Sera from 32 healthy persons and 12 primary hypertension patients were collected and analyzed as well. Serum TCu levels in ICH patients were tested at three time points (on admission, day 3, and day 7) and found to be higher than that in hypertension patients (p < 0.05). The serum SMC levels in hypertension patients and ICH patients at three time points were higher than that in healthy controls (p < 0.05). Higher serum SMC levels on days 3 and 7 were associated with death in the hospital. Additionally, higher serum SMC levels on the seventh day were associated with poor outcome at discharge. High serum Cp levels on admission, as well as low serum Cp levels on the seventh day, were associated with death in the hospital (p = 0.002 and p = 0.034, respectively). Our findings indicated that declines in serum Cp and increases in serum SMC are correlated with lethal or poor outcome in hypertensive ICH patients, possibly as a result of contributions to secondary injury of brain after hemorrhage due to impairment of iron transport and enhanced oxidative stress.

http://ift.tt/2D2XrZs

Rejuvenating Regenerative Medicine Regulation

The Food and Drug Administration (FDA) recently made long-awaited progress toward protecting patients from interventions involving human cell- and tissue-based products (HCT/P) of unknown safety and efficacy. By clarifying its position on the handling and therapeutic use of cells, the agency has…

http://ift.tt/2qPz2lr

When the CHIPs Are Down — Health Coverage and Care at Risk for U.S. Children

Despite bipartisan agreement on a 5-year plan in both the Senate and the House of Representatives, Congress failed to reauthorize the Children's Health Insurance Program (CHIP) last fall, causing uncertainty and worry for families and state CHIP directors alike. Families in several states,…

http://ift.tt/2qSoOkc

Federal Right-to-Try Legislation — Threatening the FDA’s Public Health Mission

The Food and Drug Administration (FDA) is the gatekeeper of the country's drugs and medical devices. Originally created to prevent the misleading of patients, it was later tasked with ensuring the safety of medical products. In 1962, Congress expanded the FDA's mandate again, requiring it to…

http://ift.tt/2moU45D

PC-FACS January 3, 2018

Table of Contents

http://ift.tt/2D1DkuY

Electronic Nose in the Detection of Wound Infection Bacteria from Bacterial Cultures: A Proof-of-Principle Study

Background: Soft tissue infections, including postoperative wound infections, result in a significant burden for modern society. Rapid diagnosis of wound infections is based on bacterial stains, cultures, and polymerase chain reaction assays, and the results are available earliest after several hours, but more often not until days after. Therefore, antibiotic treatment is often administered empirically without a specific diagnosis. Methods: We employed our electronic nose (eNose) system for this proof-of-concept study, aiming to differentiate the most relevant bacteria causing wound infections utilizing a set of clinical bacterial cultures on identical blood culture dishes, and established bacterial lines from the gaseous headspace. Results: Our eNose system was capable of differentiating both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Clostridium perfringens with an accuracy of 78% within minutes without prior sample preparation. Most importantly, the system was capable of differentiating MRSA from MSSA with a sensitivity of 83%, a specificity of 100%, and an overall accuracy of 91%. Conclusions: Our results support the concept of rapid detection of the most relevant bacteria causing wound infections and ultimately differentiating MRSA from MSSA utilizing gaseous headspace sampling with an eNose.
Eur Surg Res 2018;59:1–11

http://ift.tt/2CPqZXo

Reply to “Movement-related neural processing in people with congenital mirror movements beyond the (cortical) surface”

Thank you for the invitation to respond, and for bringing to our attention the interesting research of Manara and colleagues on Kallmann syndrome (KS). We would first like to point out that our published research involving people with mirror movements has focused only on those with isolated congenital mirror movements, that is non-syndromic (referred to as 'CMM' in our papers and in this response). CMM involves mirroring of the hands/fingers in the homologous motor system(s) of intended unimanual movements, although a minority of cases also show evidence of mirroring in the upper arms or feet (Franz, 2003; Franz et al., 2015; Franz and Fu, 2017).

http://ift.tt/2Fp8UB2

High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2CZnIb9

Successful Endoscopic Transmural Drainage of Septate Walled off Necrosis by Fracturing the Septum under EUS guidance

http://ift.tt/2ExhjB1

Cross sectional study to assess the accuracy of electronic health record data to identify patients in need of lung cancer screening

Lung cancer is the leading cause of cancer death in the United States [Siegel et al. in CA Cancer J Clin 66:7–30, 1]. However, evidence from clinical trials indicates that annual low-dose computed tomography scre...

http://ift.tt/2Dlg1Kp

Intrarater reliability of the Humac NORM isokinetic dynamometer for strength measurements of the knee and shoulder muscles

To determine the intrarater reliability of the Humac NORM isokinetic dynamometer for concentric and eccentric strength tests of knee and shoulder muscles.

http://ift.tt/2CRiZVN

A quantitative CT imaging signature predicts survival and complements established prognosticators in stage I non-small cell lung cancer

We identified a CT imaging signature that predicts overall survival in stage I NSCLC. The imaging signature is associated with immune response and may serve as a noninvasive prognostic biomarker in stage I NSCLC.

http://ift.tt/2CYMEAq

Which risk understandings can be derived from the current disharmonized regulation of complementary and alternative medicine in Europe?

Many European citizens are seeking complementary and alternative medicine (CAM). These treatments are regulated very differently in the EU/EFTA countries. This may demonstrate differences in how risk associate...

http://ift.tt/2FonicU

The health impact of residential retreats: a systematic review

Unhealthy lifestyles are a major factor in the development and exacerbation of many chronic diseases. Improving lifestyles though immersive residential experiences that promote healthy behaviours is a focus of...

http://ift.tt/2EsN26D

Dual action of highbush blueberry proanthocyanidins on Aggregatibacter actinomycetemcomitans and the host inflammatory response

The highbush blueberry (Vaccinium corymbosum) has a beneficial effect on several aspects of human health. The present study investigated the effects of highbush blueberry proanthocyanidins (PACs) on the virulence...

http://ift.tt/2FlaIuS

The standardized Withania somnifera Dunal root extract alters basal and morphine-induced opioid receptor gene expression changes in neuroblastoma cells

Behavioral studies demonstrated that the administration of Withania somnifera Dunal roots extract (WSE), prolongs morphine-elicited analgesia and reduces the development of tolerance to the morphine's analgesic e...

http://ift.tt/2EvH9Fz

Factors Associated With Withdrawal From Maintenance Dialysis: A Case-Control Analysis

Little is known about differences in the clinical course between patients receiving maintenance dialysis who do and do not withdraw from dialysis therapy.

http://ift.tt/2EsLPw7

End-of-Life Care for Patients With Advanced Kidney Disease in the US Veterans Affairs Health Care System, 2000-2011

Little is known about patterns of end-of-life care for patients with advanced kidney disease not treated with maintenance dialysis.

http://ift.tt/2Fmwdvr

Atypical Presentation of Pregnancy-Related Hemolytic Uremic Syndrome

The cause of acute kidney injury during pregnancy and in the postpartum period can be particularly challenging to diagnose, especially when it is necessary to differentiate among preeclampsia; eclampsia; hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome; and thrombotic microangiopathies (TMAs). All these disease entities can present with kidney failure, microangiopathic hemolytic anemia, and thrombocytopenia. We present a teaching case of atypical hemolytic uremic syndrome in the postpartum period in a young woman who was found to have mutations of uncertain clinical significance in the complement cascade, including in C3, CFH, and CFI.

http://ift.tt/2Ew3N0J

Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells

Antibodies are critical responses to protect the host from dengue virus(DENV) infection. Antibodies target DENV by two pathologic mechanisms: virus neutralization and infection enhancement. In dengue patients,...

http://ift.tt/2mqhXtH

The impact of regular school closure on seasonal influenza epidemics: a data-driven spatial transmission model for Belgium

School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated...

http://ift.tt/2qQt3Nk

Active ingredients of a person-centred intervention for people on HIV treatment: analysis of mixed methods trial data

A new model of care is required to meet the changing needs of people living with HIV (PLWH), particularly in low and middle-income countries, where prevalence is highest. We evaluated a palliative care interve...

http://ift.tt/2mo0TEq

Prevalence and antibiotic susceptibility of Uropathogens from cases of urinary tract infections (UTI) in Shashemene referral hospital, Ethiopia

Urinary tract infection (UTI) remains to be one of the most common infectious diseases diagnosed in developing countries. And a widespread use of antibiotics against uropathogens has led to the emergence of an...

http://ift.tt/2qPHqBf

Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-naïve patients: a case-control study in a Han Chinese population

Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the huma...

http://ift.tt/2mo9vv3

Revealing Alzheimer’s disease genes spectrum in the whole-genome by machine learning

Alzheimer's disease (AD) is an important, progressive neurodegenerative disease, with a complex genetic architecture. A key goal of biomedical research is to seek out disease risk genes, and to elucidate the f...

http://ift.tt/2FlytTv

Predicting Extubation Outcomes—A Model Incorporating Heart Rate Characteristics Index

To test the hypothesis that in neonates on mechanical ventilation, heart rate characteristics index (HRCi) can be combined with a clinical model for predicting extubation outcomes in neonates.

http://ift.tt/2EwZnqb

Cryptorchidism in Sweden: A Nationwide Study of Prevalence, Operative Management, and Complications

To review the cumulative prevalence, operative management, and complications of treatment for cryptorchidism in Sweden.

http://ift.tt/2Eu80ls

Terra Firma-Forme Dermatosis

A 12-year-old girl with a history of alopecia areata and vitiligo presented with an asymptomatic brownish dirt-like lesion on the left postauricular skin of approximately 3 years of duration. The patient and her mother tried to clean the "dirt" with water and soap without success. There was no history of rapid weight gain. She had no history of an inflammatory dermatosis in the affected area. Physical examination revealed a dirt-like brownish plaque on the left postauricular skin (Figure 1). Rubbing of the lesion with a 70% isopropyl alcohol-soaked gauze pad and pressure resulted in complete disappearance of the lesion (Figure 2).

http://ift.tt/2FoaT8Q

Never Forget the Optic Fundi in Tuberculosis!

We evaluated a 5-year-old boy with high-grade, intermittent fever, weight loss, and episodic nonprojectile vomiting for the previous 2 months. There was no associated abdominal pain, jaundice, chronic cough, bleeding manifestations, altered sensorium, seizures, or focal motor or visual deficits. Perinatal period and development was normal. He was immunized for age. Family history was not contributory. On examination, he had pallor, cervical lymphadenopathy, failure to thrive, tachypnea, meningismus, and small, yellowish–white active choroiditis lesions (choroidal tubercles) as well as healed choroiditis scars in the left eye (Figure, A at presentation and Figure B at follow-up for comparison).

http://ift.tt/2FoaNOw

E-Health Care: Promise or Peril for Chronic Illness

Health disparities are commonly observed, systemic, and preventable.1 Individuals with chronic health problems are at highest risk for differential access to effective treatment.2-4 Most health disparities are potentiated by systemic barriers to health-services access, including explicit and implicit biases in care delivery, complex health information, and disparate access to health insurance, health plans, healthcare facilities, or other effective medical technology. In fact, the introduction of new medical technologies has often widened health disparities.

http://ift.tt/2EucwR4

Ohio ambulance manufacturer, Braun Industries, awarded contract for Detroit Fire Department

Braun Industries will deliver 49 new ambulances to the city of Detroit over the next 5 years. VAN WERT, Ohio — Braun Industries is pleased to announce that they will be manufacturing the new ambulance units for the Detroit Fire Department. The city of Detroit placed an order for 49 new Chief XL ambulances. Under the five-year contract, Braun Industries delivered 14 new units by the end of 2017 ...

http://ift.tt/2qPhgP3

Federal Right-to-Try Legislation — Threatening the FDA’s Public Health Mission

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2CS5LYV

ESO Solutions predicts key hospital trends to watch in 2018

Focus on Acute Care, Healthcare Financing, and Interoperability will be essential. You can download the free white paper here. AUSTIN — ESO Solutions, the leading data and software company serving emergency medical services, fire departments, and hospitals, today shared the trends it predicts will have the biggest impact on hospitals in 2018: A greater emphasis on evidence-based approaches to ...

http://ift.tt/2AE65IW

Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae

This method describes the cloning, expression, and purification of recombinant Nsa1 for structural determination by X-ray crystallography and small-angle X-ray scattering (SAXS), and is applicable for the hybrid structural analysis of other proteins containing both ordered and disordered domains.

http://ift.tt/2DhRPIN

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

An efficient screening protocol is presented for the identification of small molecules that promote astroglial differentiation in glioblastoma stem cells (GSCs). The assay is based on a stem cell differentiation reporter whereby the expression of the enhanced GFP (eGFP) is driven by the human GFAP promoter.

http://ift.tt/2DgoU7R

Cell therapy for severe hemophilia: study has come full circle

No abstract available

http://ift.tt/2ANrEqc

Necessity of interrupted time series analysis in evaluating the impact of PHS risk identification and introduction of direct-acting antiviral therapy and Share 35 implementation

No abstract available

http://ift.tt/2CYnrGi

Clinical and Pathological Features of Plasma Cell-Rich Acute Rejection after Kidney Transplantation

AbstractBackgroundPlasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general the prognosis of PCAR is poor, and its clinical and pathological features remain unclear.MethodsWe performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients.ResultsOf 1,956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs. 11.7%, P=0.0059), longer median total ischemia time (99 min, interquartile range: 71 – 144, vs. 77 min, interquartile range: 59 – 111, P=0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs. 22.5%, P=0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (Hazard Ratio=8.03, 95% Confidence Interval: 3.89 – 14.80, P

http://ift.tt/2ALH5zw

Preserving Treg function: beyond mTOR inhibitors

No abstract available

http://ift.tt/2D2MN60

Biomarkers and kidney transplant: Time for a new paradigm?

No abstract available

http://ift.tt/2ANylsv

Effect of Conversion to CTLA4Ig Treatment on Tacrolimus-Induced Diabetic Rats

ABSTRACTBackgroundThe effect of conversion to cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM) is still undetermined. In the present study, we tested the diabetogenicity of CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC-induced diabetic rats.MethodsWe tested diabetogenicity of CTLA4Ig by escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC-induced DM by intraperitoneal glucose tolerance test (IPGTT). Thereafter, TAC administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2 mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo and in vitro was evaluated by assessing pancreatic islet function, histopathology, oxidative stress, apoptosis, and macrophage infiltration.ResultsIPGTT in the CTLA4Ig groups did not differ from the control group. In addition, plasma insulin level, glucose-induced insulin secretion, and islet viability were not different between the CTLA4Ig and control groups. In the conversion study, TAC withdrawal ameliorated pancreatic islet dysfunction compared to the TAC group, and conversion to CTLA4Ig further improved pancreatic islet function compared to the TAC withdrawal group. TAC-induced oxidative stress, apoptotic cell death, and infiltration of macrophages decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet cell death and ROS production.ConclusionsCTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury. Background The effect of conversion to cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM) is still undetermined. In the present study, we tested the diabetogenicity of CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC-induced diabetic rats. Methods We tested diabetogenicity of CTLA4Ig by escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC-induced DM by intraperitoneal glucose tolerance test (IPGTT). Thereafter, TAC administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2 mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo and in vitro was evaluated by assessing pancreatic islet function, histopathology, oxidative stress, apoptosis, and macrophage infiltration. Results IPGTT in the CTLA4Ig groups did not differ from the control group. In addition, plasma insulin level, glucose-induced insulin secretion, and islet viability were not different between the CTLA4Ig and control groups. In the conversion study, TAC withdrawal ameliorated pancreatic islet dysfunction compared to the TAC group, and conversion to CTLA4Ig further improved pancreatic islet function compared to the TAC withdrawal group. TAC-induced oxidative stress, apoptotic cell death, and infiltration of macrophages decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet cell death and ROS production. Conclusions CTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury. *Corresponding author: Chul Woo Yang, MD, Department of Internal Medicine, Seoul St. Mary's Hospital, 505 Banpo-Dong, Seocho-Ku, 137-040, Seoul, Republic of Korea. Fax: +82-2-536-0323, Phone: +82-2-2258-6037, E-mail: yangch@catholic.ac.kr Author's contributions: LJ contributed to the experimental surgeries, analyzed the data, and co-drafted the manuscript; JJ and KL performed the experiments and analyzed the data; SWL, EJK, BHC, and HLL retrieved and analyzed the data; SWL and CWY designed the study and co-drafted the manuscript. All authors read and approved the final manuscript. Disclosure: The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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History of marijuana use does not affect outcomes on the liver transplant waitlist

AbstractBackgroundData are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use.MethodsRetrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period.Results884 adults were evaluated and 585 (66%) were listed for LT (median follow up 1.4 years, IQR 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (IRR=1.9) and hepatitis C (IRR=2.1) vs. hepatitis B, tobacco use (prior IRR=1.4; recent IRR=1.3 vs. never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs. social), and illicit drug use (prior IRR=2.3; recent =1.9 vs. never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior HR 0.9; recent HR=0.9 vs. never) or waitlist mortality/delisting (prior HR 1.0; recent HR 1.0 vs. never). However, recent illicit drug use was associated with higher risk of death or delisting (HR 1.8, p=0.004 vs. never).ConclusionsUnlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes. Background Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use. Methods Retrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period. Results 884 adults were evaluated and 585 (66%) were listed for LT (median follow up 1.4 years, IQR 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (IRR=1.9) and hepatitis C (IRR=2.1) vs. hepatitis B, tobacco use (prior IRR=1.4; recent IRR=1.3 vs. never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs. social), and illicit drug use (prior IRR=2.3; recent =1.9 vs. never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior HR 0.9; recent HR=0.9 vs. never) or waitlist mortality/delisting (prior HR 1.0; recent HR 1.0 vs. never). However, recent illicit drug use was associated with higher risk of death or delisting (HR 1.8, p=0.004 vs. never). Conclusions Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes. Corresponding Author: Prashant Kotwani, MD, Email – prashant.kotwani@ucsf.edu; prashant.kotwani@gmail.com, 505 Parnassus Avenue, Room 987, San Francisco, CA 94143, Phone: 415-476-1528, Fax: 415-502-1976 Authorship PK - contributed to research design, data collection, data analysis, manuscript preparation VS – contributed to research design, data analysis, manuscript preparation JLD – contributed to data analysis, manuscript preparation JR – contributed to research design, manuscript preparation FY – contributed to research design, manuscript preparation BH – contributed to research design, data analysis, manuscript preparation Conflict of Interest The authors declare no conflicts of interest Funding This work was supported, in part, by the Biostatistics Core of the UCSF Liver Center (P30 DK026743). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma

AbstractBackgroundLiver Transplant (LT) for Non-Alcoholic Steatohepatitis (NASH) related Hepatocellular Carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) vs. HCC from other liver diseases (non-NASH).MethodsUsing a two-centre retrospective design all patients from 2004-2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria.Results929 patients were transplanted for HCC. 60/929 (6.5%) had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96% and 80% in NASH vs. 95%, 84% and 78% in non-NASH (p=0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox Regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan, HR 0.21 (0.05-0.86), p=0.029.ConclusionAfter LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favourable outcomes after LT has been generated, but requires further study. Background Liver Transplant (LT) for Non-Alcoholic Steatohepatitis (NASH) related Hepatocellular Carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) vs. HCC from other liver diseases (non-NASH). Methods Using a two-centre retrospective design all patients from 2004-2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria. Results 929 patients were transplanted for HCC. 60/929 (6.5%) had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96% and 80% in NASH vs. 95%, 84% and 78% in non-NASH (p=0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox Regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan, HR 0.21 (0.05-0.86), p=0.029. Conclusion After LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favourable outcomes after LT has been generated, but requires further study. Corresponding Author: Dr. Gonzalo Sapisochin, Multi-Organ Transplant. Division of General Surgery, Department of Surgery, University of Toronto, 585 University Avenue, 11-PMB-184, Toronto, ON M5G 2N2, Canada. gonzalo.sapisochin@uhn.ca. T: +1 416 340 5230, F: +1 416 340 5242 Authorship E.M. Sadler - involved in study design, data collation, data analysis, manuscript preparation. N. Mehta – involved in study design, data collection, data analysis, and manuscript review. M. Bhat – involved in study design, manuscript preparation and review. A. Ghanekar – involved in data collection and manuscript review. P.D. Greig – involved in data collection and manuscript review. D.R. Grant – involved in data collection and manuscript review. F. Yao – involved in study design, data collection, and manuscript review. G. Sapisochin – involved in study design, data collection, data analysis, manuscript review. Disclosure The authors declare no conflict of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Selective CD28 inhibition modulates alloimmunity and cardiac allograft vasculopathy in anti-CD154-treated monkeys

AbstractBackgroundSelective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade.MethodsCynomolgus monkey heterotopic cardiac allograft recipients received sc28AT (10 mg/kg, d0-20, n=3), hu5C8 (10-30 mg/kg, d0-84, n=4), or combination (n=6). Graft survival was monitored by telemetry. Protocol biopsies and graft explants were graded according to ISHLT AR and CAV scores. Alloantibody, T cell phenotype and Tregs were analyzed by flow cytometry. Immunochemistry and gene expression (Nanostring) characterized intra-graft cellular infiltration.ResultsRelative to modest prolongation of median graft survival time with sc28AT alone (34 days), hu5C8 (133 days) and sc28AT+hu5C8 (141 days) prolonged survival to a similar extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the severity of acute rejection and cardiac allograft vasculopathy (CAV) during the first 3 months after transplantation relative to hu5C8 alone. These findings were associated with decreased proportions of circulating CD8+ and CD3+CD28- T cells, and modulation of inflammatory gene expression within allografts.ConclusionsInduction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants. Background Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade. Methods Cynomolgus monkey heterotopic cardiac allograft recipients received sc28AT (10 mg/kg, d0-20, n=3), hu5C8 (10-30 mg/kg, d0-84, n=4), or combination (n=6). Graft survival was monitored by telemetry. Protocol biopsies and graft explants were graded according to ISHLT AR and CAV scores. Alloantibody, T cell phenotype and Tregs were analyzed by flow cytometry. Immunochemistry and gene expression (Nanostring) characterized intra-graft cellular infiltration. Results Relative to modest prolongation of median graft survival time with sc28AT alone (34 days), hu5C8 (133 days) and sc28AT+hu5C8 (141 days) prolonged survival to a similar extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the severity of acute rejection and cardiac allograft vasculopathy (CAV) during the first 3 months after transplantation relative to hu5C8 alone. These findings were associated with decreased proportions of circulating CD8+ and CD3+CD28- T cells, and modulation of inflammatory gene expression within allografts. Conclusions Induction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants. * T.Z. and A.M.A. contributed equally to the first authorship of this study. #Correspondence: Richard N. Pierson III, MD, Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, 110 South Paca Street 7N-134, Baltimore, MD 21201. E-mail: rpierson@som.umaryland.edu. Phone: 410.328.5842, Fax: 410.328.2750 Authorship Contributions: T.Z., A.M.A., and R.N.P.III designed the experiments, analysed the data, and wrote the article. W.S., N.A.O., E.B., and G.B. performed experiments and analysed data. E.S., L.B., X.C., T.M., S.D., D.H., E.R., E.W., A.K., and C.A. conducted all experiments. Disclosure : The authors declare no conflict of interest. Funding: This work was supported by the NIH (UO1 AI 066719), an ASTS Mid-Career Award, a contract from the DOD ORD (N00014-04-1-0821), and an AHA Grant-in-Aid, all to RNP; by the Other Tobacco Related Diseases research grant from the Maryland Restitution Fund Program, to AA and RNP; and by the NIH Nonhuman Primate Reagent Resource (OD010976 and AI126683). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A high portal venous pressure gradient increases gut-related bacteremia and consequent early mortality after living donor liver transplantation

AbstractBackgroundPortal hypertension (PHT) is defined as a portal venous pressure gradient (PVPG) exceeding 5 mmHg, which results in severe clinical manifestations. However, the validity of intraoperative PVPG monitoring and the association between PHT and bacterial translocation (BT) after liver transplantation remain unclear.MethodsIn this retrospective study, 223 patients who underwent primary adult-to-adult living donor liver transplantation (ALDLT) from 2008 to 2015 were divided into 2 groups based on the PVPG at the end of the operation: high PVPG (>5 mmHg, n=69) and low PVPG (≤5 mmHg, n=154). The clinical factors were compared between the groups, and the association between a high PVPG and posttransplant bacteremia/bacterial infections was investigated.ResultsThe high PVPG group had a significantly higher incidence of bacteremia (46% vs. 24%, p<.001 higher mortality rate vs. p=".002)," and poorer survival the high pvpg group had a particularly incidence of bacteremia caused by bacteria including enterobacteriaceae bacteroides spp. enterococcus multivariate analysis showed that>5 mmHg (odds ratio, 2.55; 95% confidence interval, 1.18–5.55; p=.017) was an independent predictor of bacteremia due to gut bacteria.ConclusionsMonitoring of the PVPG is clinically meaningful for predicting patients' prognosis. In particular, a high PVPG with a threshold of 5 mmHg at the end of ALDLT may increase gut-related bacteremia through the mechanism of BT, resulting in early mortality. Background Portal hypertension (PHT) is defined as a portal venous pressure gradient (PVPG) exceeding 5 mmHg, which results in severe clinical manifestations. However, the validity of intraoperative PVPG monitoring and the association between PHT and bacterial translocation (BT) after liver transplantation remain unclear. Methods In this retrospective study, 223 patients who underwent primary adult-to-adult living donor liver transplantation (ALDLT) from 2008 to 2015 were divided into 2 groups based on the PVPG at the end of the operation: high PVPG (>5 mmHg, n=69) and low PVPG (≤5 mmHg, n=154). The clinical factors were compared between the groups, and the association between a high PVPG and posttransplant bacteremia/bacterial infections was investigated. Results The high PVPG group had a significantly higher incidence of bacteremia (46% vs. 24%, p<.001 higher mortality rate vs. p=".002)," and poorer survival the high pvpg group had a particularly incidence of bacteremia caused by bacteria including enterobacteriaceae bacteroides spp. enterococcus multivariate analysis showed that>5 mmHg (odds ratio, 2.55; 95% confidence interval, 1.18–5.55; p=.017) was an independent predictor of bacteremia due to gut bacteria. Conclusions Monitoring of the PVPG is clinically meaningful for predicting patients' prognosis. In particular, a high PVPG with a threshold of 5 mmHg at the end of ALDLT may increase gut-related bacteremia through the mechanism of BT, resulting in early mortality. Corresponding author: Shintaro Yagi, Ph.D., Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Telephone: +81-75-751-3242; FAX: +81-75-751-4263; E-mail: shintaro@kuhp.kyoto-u.ac.jp Authorship S.Yao and S.Yagi designed the study and wrote the draft. S.Yao, T.Iida, and Y.Okamura acquired the data. M.Nagao analyzed the data as a specialist of infection prevention. R.Uozumi analyzed the data as a specialist of medical statistician. S. Yagi, T. Iida, Y.Okamura, T.Anazawa, H.Okajima, T.Kaido and S.Uemoto performed living-donor liver transplantations, followed up the patients. M.Nagao, T.Anazawa, H.Okajima, T.Kaido, S.Uemoto contributed to editing the manuscript. S.Uemoto supervised the study design and revised the manuscript. Disclosures The authors have no conflicts of interest or financial ties to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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B Cells in Transplantation: of rat, mouse and man

No abstract available

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Long-term outcome of one-step kidney transplantation and bladder augmentation procedure in pediatric patients

ABSTRACTBackgroundGuidelines for bladder augmentation (BA) in kidney transplant (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure.MethodsA case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA.ResultsCompared to 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate (eGFR): 96.5±17.1 vs. 79.4±16.6 ml/min at 0-6 months (p=0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) vs. 13% (3/22); and asymptomatic bacteriuria was more common: 100% vs. 9% during the first 6 months (P

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Early Hospital Readmission: The Canary in the Coal Mine?

No abstract available

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Publication Rates of Oral Abstract Presentations at the 2014 International Congress of the Transplantation Society

No abstract available

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Opioid Prescription, Morbidity, and Mortality in US Transplant Recipients

ABSTRACTBackgroundCDC guidelines recommend caution in prescribing opioids for chronic pain. The characteristics of opioid prescription (OpRx) among kidney transplant (KTx) recipients has not been described in a national population.MethodsWe assessed OpRx prevalence among prevalent KTx recipients, and associated duration (chronic, defined as ≥90 days in a year) and dosing (in morphine milligram equivalents per day, MME, of

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Heart Transplantation in a Left Ventricular Assist Device Recipient Following Donor's Extracorporeal Membrane Oxygenation Support: Is it safe?

No abstract available

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Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria

AbstractBackgroundPatients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood.MethodsPatients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival.ResultsOf 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005).ConclusionsUnderestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Background Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. Methods Patients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. Results Of 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005). Conclusions Underestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Corresponding Author: Matthew H. Levine, MD, PhD, 3400 Spruce Street, 1 Founders, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Phone: 215.662.7367. E-mail: matthew.levine@uphs.upenn.edu. Author contributions: 1) conception and design (Ecker, Hoteit, Shaked, Olthoff, Levine), acquisition of data (Ecker), or analysis and interpretation of data (all authors); 2) drafting (Ecker, Levine) or revising (all authors) 3) final approval of the version to be published (all authors) Disclosures: The authors report no conflicts of interest Funding: none Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Mitigating Risk of Immunosuppression By Immune Monitoring: Are We There?

No abstract available

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Modulation of Ether-a-Go-Go Related Gene (ERG) Current Governs Intrinsic Persistent Activity in Rodent Neocortical Pyramidal Cells

While cholinergic receptor activation has long been known to dramatically enhance the excitability of cortical neurons, the cellular mechanisms responsible for this effect are not well understood. We used intracellular recordings in rat (both sexes) neocortical brain slices to assess the ionic mechanisms supporting persistent firing modes triggered by depolarizing stimuli following cholinergic receptor activation. We found multiple lines of evidence suggesting that a component of the underlying hyperexcitability associated with persistent firing reflects a reduction in the standing (leak) K⁺ current mediated by Ether-a-go-go-Related Gene (ERG) channels. Three chemically diverse ERG channel blockers (terfenadine, ErgToxin-1, and E-4031) abolished persistent firing and the underlying increase in input resistance in deep pyramidal cells in temporal and prefrontal association neocortex. Calcium accumulation during triggering stimuli appears to attenuate ERG currents, leading to membrane potential depolarization and increased input resistance, two critical elements generating persistent firing. Our results also suggest that ERG current normally governs cortical neuron responses to depolarizing stimuli by opposing prolonged discharges and by enhancing the poststimulus repolarization. The broad expression of ERG channels and the ability of ERG blocks to abolish persistent firing evoked by both synaptic and intracellular step stimuli suggest that modulation of ERG channels may underlie many forms of persistent activity observed in vivo.

SIGNIFICANCE STATEMENT Persistent activity, where spiking continues beyond the triggering stimulus, is a common phenomenon observed in many types of neurons. Identifying the mechanism underlying this elementary process of memory is a step forward in understanding higher cognitive function including short-term memory. Our results suggest that a reduction in the currents normally mediated by Ether-a-go-go-Related Gene (ERG) K⁺ channels contributes to persistent firing in neocortical pyramidal cells. ERG currents have been previously studied primarily in the heart; relatively little is known about ERG function in the brain, although mutations in ERG channels have recently been linked to schizophrenia. The present study is among the first to describe its role in neocortex in relation to biophysical correlates of memory function.

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