Bilateral Spontaneous Hyphemas in a Patient with Aplastic Anemia

Bilateral spontaneous hyphemas are a rare ophthalmic event. Aplastic anemia is a hematologic condition with well-documented manifestations in the posterior segment but not the anterior segment. We present a patient with aplastic anemia without obvious risk factors for hyphema who developed bilateral spontaneous hyphemas. To our knowledge, this is the first reported case of bilateral spontaneous hyphemas in a patient with aplastic anemia.
Case Rep Ophthalmol 2018;9:444–448

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Detection of Candida Endophthalmitis in a Newborn Using Handheld Spectral-Domain Optical Coherence Tomography

In a newborn with candidemia, two retinal lesions were seen without external inflammatory signs or reaction in the anterior chamber or vitreous. However, handheld spectral domain-optical coherence tomography (HH SD-OCT) images show that one of the retinal lesions had a "firework display" projecting to the vitreous that was not identified in indirect ophthalmoscopy. This finding suggested a Candida endophthalmitis. HH SD-OCT findings allowed us to make an accurate diagnosis and, therefore, modified the decision-making process in the treatment of the pathology.
Case Rep Ophthalmol 2018;9:439–443

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Chemotherapy in localized Soft Tissue Sarcoma: will we soon have to treat grade 1 tumours? Update on CINSARC performances

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Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response – final results from GeparSixto

Abstract

Background

In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD).

Patients and Methods

Patients were randomized to paclitaxel plus non-pegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study endpoints disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in FFPE tumor samples of 193/315 (61.3%) participants with TNBC. HR deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA).

Results

A significantly better DFS (hazard ratio 0.56, 95%CI 0.34-0.93; P=0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors.HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) (odds ratio (OR) 2.60, 95%CI 1.26-5.37, P=0.008). Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P=0.001), but only marginally in HR non-deficient tumors (from 20.0% to 29.6%, P=0.540; test for interaction P=0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P=0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR non-deficient (hazard ratio 0.44, 0.17–1.17, P=0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P=0.059).

Conclusions

The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.

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Interpretation of Time-to-event Outcomes in Randomized Trials: an online randomized experiment

Abstract

Background

Multiple features in the presentation of randomized controlled trial (RCT) results are known to influence comprehension and interpretation. We aimed to compare interpretation of cancer RCTs with time-to-event outcomes when the reported treatment effect measure is the hazard ratio (HR), difference in restricted mean survival times (RMSTD), or both (HR+RMSTD). We also assessed the prevalence of misinterpretation of the HR.

Patients and methods

We performed a randomized experiment. We selected 15 cancer RCTs with statistically significant treatment effects for the primary outcome. We masked each abstract and created 3 versions reporting either the HR, RMSTD, or HR+RMSTD. We randomized corresponding authors of RCTs and medical residents and fellows to one of 15 abstracts and one of 3 versions. We asked how beneficial the experimental treatment was (0 to 10 Likert scale). All participants answered a multiple-choice question about interpretation of the HR. Participants were unaware of the study purpose.

Results

We randomly allocated 160 participants to evaluate an abstract reporting the HR, 154 to the RMSTD, and 155 to both HR+RMSTD. The mean Likert score was statistically significantly lower in the RMSTD group as compared with the HR group (mean difference -0.8, 95% confidence interval, -1.3 to -0.4, p < 0.01) and as compared with the HR+RMSTD group (difference -0.6, -1.1 to -0.1, p = 0.05). In all, 47.2% (42.7% to 51.8%) of participants misinterpreted the HR, with 40% equating it with a reduction in absolute risk.

Conclusion

Misinterpretation of the HR is common. Participants judged experimental treatments to be less beneficial when presented with RMSTD as compared with HR. We recommend that authors present RMST-based measures alongside the HR in reports of RCT results.

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Statistical challenges posed by uncontrolled master protocols: sensitivity analysis of the Vemurafenib study

Abstract

Within the evidentiary hierarchy of experimental inquiry, randomized trials are the gold standard. Oncology patients enter clinical studies with diverse lifestyles, treatment pathways, host tissue environments, and competing co-morbidities. Randomization attempts to balance prognostic characteristics among study arms, thereby enabling statistical inference of "average benefit" and attribution to the studied therapies. In contrast, interpretations of uncontrolled trials require additional scrutiny to attempt to place the findings in the context of external evidence. Counter-factual reasoning and speculation across trials may be obscured by the disproportionate enrollment of prognostic subpopulations which may be unknown from publications of trial reports. Recent modifications to the regulatory environment (Food and Drug Administration Safety and Innovation Act) have elevated the importance of non-comparative trials. Moreover, the emergence of recent innovations in precision medicine have yielded trial designs that partition potentially heterogeneous subpopulations into "statistically exchangeable" cohorts by histologies, or genetic alterations, further elevating the importance of single-cohort analyses. As patient cohorts become ever more refined into smaller targeted subsets, consumers of reports of uncontrolled trials should be further empowered with improvements in reporting practices that better describe the enrolled prognostic subpopulations and importantly their association with study endpoints. This article demonstrates the issue with a sensitivity analysis of the findings reported in a recent trial which was devised to evaluate the preliminary clinical efficacy of vemurafenib in BRAFV⁶⁰⁰ mutation–positive nonmelanoma cancers.

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Endoscopic resection of a huge orbital ethmoidal mucocele masquerading as dacryocystocele

Paranasal mucoceles are cystic masses lined with epithelium thought to result from chronic obstruction of an impaired sinus ostia. If sufficiency large, they can cause ophthalmological sequelae including diplopia, visual acuity, globe displacement as well as the rhinological symptoms of facial pain and headache. We present the case of a 57-year-old man who presented with a 1-year history of epiphora and right globe prominence with associated diplopia. Imaging demonstrated a mass located within the medial aspect of the orbit, closely associated to the lamina papyracea and nasolacrimal duct consistent with a dacryocystocele. An alternate diagnosis of an ethmoidal mucocele was considered preoperatively following rhinologist opinion. Complete endoscopic resection of the cyst was undertaken. Histopathology confirmed diagnosis of an ethmoidal mucocele. Our report highlights mucocele should be considered in patients with chronic symptoms secondary to a mass situated in the nasolacrimal duct without radiological orbital bone destruction.

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Thrombus straddling a patent foramen ovale, pulmonary embolism and paradoxical embolism: a rare trifecta

Description 

A 55-year-old male presented to the emergency room after awakening with left facial droop, left-sided weakness and garbled speech. Vitals were significant for hypotension (73/43 mm Hg) and hypothermia (35.3°C). Physical examination was significant for left facial droop, dysarthria, bilateral upper extremity strength 4/5, bilateral lower extremity strength 3/5. Laboratory tests were significant for leucocytosis of 16.9x10⁹/L thou/mcL, lactic acid 2.5 mmol/L, creatinine 3.07 mg/dL and troponin 0.07 ng/mL.

Chest X-ray revealed no acute process. Head CT revealed no acute process with old right basal ganglia and right frontal lobe infarcts. Head and neck magnetic resonance angiography (MRA) revealed no blockages or aneurysmal dilatations. Brain MRI revealed three areas of diffusion restriction in left temporal occipital lobe, compatible with acute infarcts. Tissue plasminogen activator was not given since he was outside the window. Stroke work-up was ordered, pancultures were sent, broad-spectrum antibiotics were started, and he was sent to the intensive care unit.

Transthoracic...

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Pelvic hydatid: the great masquerader

Description 

A 52-year-old man presented with urinary frequency and occasional lower abdominal pain for 4 months. His uroflow study and postvoid residual urine were normal and his digital rectal examination had grade 2 prostatic enlargement. His urinary symptoms were attributed to benign prostatic hyperplasia, and he was prescribed tamsulosin (0.4 mg) and solifenacin (5 mg) for his symptoms. One week later he only had partial relief of symptoms, thus an ultrasound was done that showed a cystic lesion abutting the urinary bladder in the region of right iliac fossa (figure 1). A contrast-enhanced CT (CECT) scan was then done, which showed a cystic lesion (3.8x4 cm) with enhancing internal septa and peripheral wall enhancement abutting the urinary bladder (figure 2). There was no other cyst in the abdomen so a provisional diagnosis of primary pelvic peritoneal hydatid cyst was made. We then carried out a cystoscopy to...

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Development of acquired haemophilia A in a patient treated with alemtuzumab for multiple sclerosis

This case illustrates a 36-year-old man who presented with a factor VIII (FVIII) inhibitor (acquired haemophilia A) with cutaneous bleeding and a significant thigh haematoma. No traditional risk factors for the development of a FVIII inhibitor were identified. However, previous treatment with alemtuzumab for multiple sclerosis was noted in the patient's history. Alemtuzumab is an anti-CD52 monoclonal antibody and is known to be associated with the development of a number of autoimmune conditions, with a delay in onset of these conditions as long as 5 years after the cessation of treatment. To our knowledge, there have only been three previously documented cases of a FVIII inhibitor in the setting of alemtuzumab therapy. This case adds further evidence to the current body of literature suggesting alemtuzumab as a causative agent for the development of an FVIII inhibitor.

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Meningococcemia: rare but life-threatening

Description 

A previously healthy 5-month old girl, presented at the emergency department with high fever (40°C), vomiting and nasal congestion. She had no abnormalities on physical exam and was discharged home with diagnosis of a probable viral infection, after excluding urinary infection.

Ten hours later, the infant was readmitted with purpuric lesions and prostration (figure 1), rapidly presenting with labial cyanosis, capillary refill of 6 s, tachycardia, hypotension and anuria (cold shock). The patient was empirically treated with ceftriaxone and vancomycin, started inotropic and ventilator support, having been transferred to a hospital with a paediatric intensive care unit with a refractory shock, purpuric rash and disseminated intravascular coagulation (figure 2).

Figure 1

Petechiae and purpuric lesions only on the thoracoabdominal region.

Figure 2

Purpura fulminans with necrosis of extremities.

Blood workout revealed leucopenia (2.600/mm³) with neutropenia (2.00/mm³),...

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Influenza A: another cause of SIADH?

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a frequent cause of hyponatraemia. It is a dilutional hyponatraemia secondary to impaired urinary dilution in the absence of renal disease or any identifiable non-osmotic stimulus known to induce antidiuretic hormone secretion. SIADH can arise secondary to various respiratory tract infections; however, the association between SIADH and influenza A infection is described in only a few cases in the literature. The authors present a case report of influenza A that may have caused a profound SIADH-related hyponatraemia.

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Verruciform xanthoma overlying inflammatory linear verrucous epidermal nevus and in broad segmental distribution

A 17-year-old woman presented with moderately itchy, non-progressive, linearly arranged verrucous plaques over dorsum of left foot since early childhood. Two years ago, she developed slowly increasing, verrucous exophytic growth in posterior most aspect of linear verrucous plaque. One year ago, she also developed multiple, linearly arranged, fleshy plaques with surface crusting over lateral aspect of right leg extending to thigh. Biopsy from both verrucous lesion on left foot and fleshy plaque on right leg showed an exophytic growth with significant papillomatosis, neutrophils in stratum corneum, acanthosis and infiltration of papillary dermis with foamy macrophages that were CD 68 positive, features compatible with verruciform xanthoma (VX). Biopsy from linear verrucous plaque over left foot was consistent with inflammatory linear verrucous epidermal nevus (ILVEN). A diagnosis of segmental VX and VX overlying ILVEN was made.

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Churg-Strauss vasculitis presenting with steroid-responsive left ventricular cardiac mass

A 35-year-old black Saudi man, with a known case of bronchial asthma and allergic rhinitis since childhood, presented with joint pain and swelling, orthopnoea, paroxysmal nocturnal dyspnoea and lower extremity oedema. On examination, we found jugular venous distension, bilateral basal crepitation, wheezing and diffuse synovitis. Investigations were notable for peripheral blood eosinophilia, pericardial effusion and elongated structure in the left ventricular outflow tract on echocardiography, mediastinal and hilar lymphadenopathy and right upper lobe infiltrate on high-resolution CT scan. Pulmonary infiltrate biopsy confirmed eosinophilic vasculitis. Intracardiac mass resolved shortly after pulse steroids indicating an inflammatory mass.

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Correction: Vacuum-assisted right atrial infected clot extraction due to persistent bacteraemia: a percutaneous approach for the management of right-sided endocarditis

Ahmed M, Montford JH, Lau E. Vacuum-assisted right atrial infected clot extraction due to persistent bacteraemia: a percutaneous approach for the management of rightsided endocarditis. BMJ. doi:10.1136/bcr-2018-226493.

The previous version of this manuscript contains an error in author's surname namely Jaime Hernandez Montford. It should read as:

Jaime Hernandez Montfort

instead of

Jaime Hernandez Montford

Also, the location of Baystate Medical Center should read as:

Baystate Medical Center, Springfield, MA, USA

Instead of

Baystate Medical Center, Springfield, Illinois, USA

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Resolved heart tamponade and controlled exophthalmos, facial pain and diabetes insipidus due to Erdheim-Chester disease

A 69-year-old woman suffering from exophthalmos and facial pain came to us referred for aetiological diagnosis of exophthalmos. Orbital MRI showed thinned extrinsic ocular musculature, intraconal fat infiltration, retro-ocular compression and thickening of maxillary and sphenoid sinus walls. She had been suffering from diabetes insipidus for the last 7 years. During our diagnosis process, she presented signs of cardiac tamponade. Transthoracic heart ultrasound revealed large pericardial effusion and a heterogeneous mass that compressed the right ventricle. No osteosclerotic lesions on appendicular bones were present. Pericardiocentesis temporarily controlled tamponade and corticoid therapy temporarily abated exophthalmos. Pericardiectomy definitively resolved tamponade. Histological examination of pericardial tissue was conclusive of Erdheim-Chester disease. Exophthalmos responded to pegylated interferon-alpha-2a. Facial bone pain disappeared after zoledronic acid and interferon treatment. During interferon therapy, the patient suffered from a severe generalised desquamative exanthema that slowly resolved after discontinuing interferon. Diabetes insipidus remains controlled with desmopressin.

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Nurse-led clinic for patients with liver cirrhosis--effects on health-related quality of life: study protocol of a pragmatic multicentre randomised controlled trial

Introduction

Liver cirrhosis affects health-related quality of life (HRQoL) even in its early stages. Morbidity is especially high when the disease decompensates and self-care actions become essential. Nurse involvement in secondary prevention in other chronic diseases has contributed to better symptom control, less need of inpatient care and improved HRQoL. In order to evaluate the impact of nurse involvement in the follow-up of patients with liver cirrhosis, we decided to compare structured nurse-led clinics, inspired by Dorothea Orem's nursing theory and motivational strategies, with a group of patients receiving standard care. The primary outcome is HRQoL and the secondary outcomes are quality of care, visits to outpatient clinics or hospitals, disease progress and health literacy.

Methods and analysis

This is a pragmatic, multicentre randomised controlled study conducted at six Swedish hepatology departments. Eligible patients are adults with diagnosed cirrhosis of the liver (n=500). Participants are randomised into either an intervention with nurse-led follow-up group or into a standard of care group. Recruitment started in November 2016 and is expected to proceed until 2020. Primary outcomes are physical and mental HRQoL measured by RAND-36 at enrolment, after 1 and 2 years.

Ethics and dissemination

The study is ethically approved by the Regional Ethical Review Board in Uppsala. The results shall be disseminated in international conferences and peer-reviewed articles.

Trial registration number

NCT02957253; Pre-results.

https://ift.tt/2NNjXHk

Short-term and long-term cost-effectiveness of a pedometer-based exercise intervention in primary care: a within-trial analysis and beyond-trial modelling

Objectives

A short-term and long-term cost-effectiveness analysis (CEA) of two pedometer-based walking interventions compared with usual care.

Design

(A) Short-term CEA: parallel three-arm cluster randomised trial randomised by household. (B) Long-term CEA: Markov decision model.

Setting

Seven primary care practices in South London, UK.

Participants

(A) Short-term CEA: 1023 people (922 households) aged 45–75 years without physical activity (PA) contraindications. (b) Long-term CEA: a cohort of 100 000 people aged 59–88 years.

Interventions

Pedometers, 12-week walking programmes and PA diaries delivered by post or through three PA consultations with practice nurses.

Primary and secondary outcome measures

Accelerometer-measured change (baseline to 12 months) in average daily step count and time in 10 min bouts of moderate to vigorous PA (MVPA), and EQ-5D-5L quality-adjusted life-years (QALY).

Methods

Resource use costs (£2013/2014) from a National Health Service perspective, presented as incremental cost-effectiveness ratios for each outcome over a 1-year and lifetime horizon, with cost-effectiveness acceptability curves and willingness to pay per QALY. Deterministic and probabilistic sensitivity analyses evaluate uncertainty.

Results

(A) Short-term CEA: At 12 months, incremental cost was £3.61 (£109)/min in ≥10 min MVPA bouts for nurse support compared with control (postal group). At £20 000/QALY, the postal group had a 50% chance of being cost saving compared with control. (B) Long-term CEA: The postal group had more QALYs (+759 QALYs, 95% CI 400 to 1247) and lower costs (–£11 million, 95% CI –12 to –10) than control and nurse groups, resulting in an incremental net monetary benefit of £26 million per 100 000 population. Results were sensitive to reporting serious adverse events, excluding health service use, and including all participant costs.

Conclusions

Postal delivery of a pedometer intervention in primary care is cost-effective long term and has a 50% chance of being cost-effective, through resource savings, within 1 year. Further research should ascertain maintenance of the higher levels of PA, and its impact on quality of life and health service use.

Trial registration number

ISRCTN98538934; Pre-results.

https://ift.tt/2pXGMyz

Cohort study of workers at a New Zealand agrochemical plant to assess the effect of dioxin exposure on mortality

Objectives

To describe how the exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) influenced mortality in a cohort of workers who were exposed more recently, and at lower levels, than other cohorts of trichlorophenol process workers.

Design

A cohort study.

Setting

An agrochemical plant in New Zealand

Participants

1,599 men and women working between 1 January 1969 and 1 November 1988 at a plant producing the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) with TCDD as a contaminant. Cumulative TCDD exposure was estimated for each individual in the study by a toxicokinetic model.

Primary outcome measures

Calculation of cause-specific standardised mortality ratios (SMRs) and 95% confidence intervals (95% CI's) compared those never and ever exposed to TCDD. Dose–response trends were assessed firstly through SMRs stratified in quartiles of cumulative TCCD exposure, and secondly with a proportional hazards model.

Results

The model intercept of 5.1 ppt of TCDD was consistent with background TCDD concentrations in New Zealand among older members of the population. Exposed workers had non-significant increases in all-cancer deaths (SMR=1.08, 95% CI 0.86 to 1.34), non-Hodgkin lymphoma (SMR=1.57, 95% CI: 0.32 to 4.59), soft tissue sarcoma (one death) (SMR=2.38, 95% CI: 0.06 to 13.26), diabetes (SMR=1.27, 95% CI: 0.55 to 2.50) and ischaemic heart disease (SMR=1.21, 95% CI: 0.96 to 1.50). Lung cancer deaths (SMR=0.95, 95% CI: 0.56 to 1.53) were fewer than expected. Neither the stratified SMR nor the proportional hazard analysis showed a dose–response relationship.

Conclusion

There was no evidence of an increase in risk for 'all cancers', any specific cancer and no systematic trend in cancer risk with TCDD exposure. This argues against the carcinogenicity of TCDD at lower levels of exposure.

https://ift.tt/2NMwLxn

Effectiveness and safety of herbal medicines for induction of labour: a systematic review and meta-analysis

Objective

The use of herbal medicines for induction of labour (IOL) is common globally and yet its effects are not well understood. We assessed the efficacy and safety of herbal medicines for IOL.

Design

Systematic review and meta-analysis of published literature.

Data sources

We searched in MEDLINE, AMED and CINAHL in April 2017, updated in June 2018.

Eligibility criteria

We considered experimental and non-experimental studies that compared relevant pregnancy outcomes between users and non-user of herbal medicines for IOL.

Data extraction and synthesis

Data were extracted by two reviewers using a standardised form. A random-effects model was used to synthesise effects sizes and heterogeneity was explored through I² statistic. The risk of bias was assessed using 'John Hopkins Nursing School Critical Appraisal Tool' and 'Cochrane Risk of Bias Tool'.

Results

A total of 1421 papers were identified through the searches, but only 10 were retained after eligibility and risk of bias assessments. The users of herbal medicine for IOL were significantly more likely to give birth within 24 hours than non-users (Risk Ratio (RR) 4.48; 95% CI 1.75 to 11.44). No significant difference in the incidence of caesarean section (RR 1.19; 95% CI 0.76 to 1.86), assisted vaginal delivery (RR 0.73; 95% CI 0.47 to 1.14), haemorrhage (RR 0.84; 95% CI 0.44 to 1.60), meconium-stained liquor (RR 1.20; 95% CI 0.65 to 2.23) and admission to nursery (RR 1.08; 95% CI 0.49 to 2.38) was found between users and non-users of herbal medicines for IOL.

Conclusions

The findings suggest that herbal medicines for IOL are effective, but there is inconclusive evidence of safety due to lack of good quality data. Thus, the use of herbal medicines for IOL should be avoided until safety issues are clarified. More studies are recommended to establish the safety of herbal medicines.

https://ift.tt/2pYYlhO

Is body mass index associated with symptom severity and health-related quality of life in irritable bowel syndrome? A cross-sectional study

Objective

The aim of this study was to describe the body mass index (BMI) distribution in patients with irritable bowel syndrome (IBS) based on the Rome III criteria and to evaluate the association of BMI with symptom severity and quality of life (QOL).

Methods

A cross-sectional study was carried out in patients visiting our outpatient functional gastrointestinal disorders specialty clinic. IBS diagnosis was made based on Rome III criteria. IBS symptom severity was investigated using the IBS severity score system. QOL was assessed using the Short Form 36 Health Survey, which consists of physical health and mental health.

Results

366 patients (252 women) who fulfilled Rome III criteria and provided complete BMI data (23.90±5.22 kg/m²) were included. Overall, 59.0% of patients with IBS were in the normal weight range, 30.3% were overweight or obese, and 10.7% were underweight. Both physical and mental health decreased significantly with the severity of symptoms (all p<0.01), while controlling for several covariates (age, gender, family status, education status and IBS subtypes). Obesity and symptom severity (β=–0.177,R²=0.037, p<0.01; β=–0.387,R²=0.147, p<0.01) were significant negative factors that influencing physical health. Symptom severity (β=–0.301,R²=0.084, p<0.01) was significant negative factor that influencing mental health. However, BMI didn't account for additional variance in mental health (p>0.05).

Conclusion

Being overweight is a common phenomenon in patients with IBS regardless of IBS subtype. The association between QOL and symptom severity followed a negative dose-response pattern. Patients with higher BMI, especially obese patients, were more frequently in poor physical health. However, this kind of relationship was not found in BMI and mental health.

https://ift.tt/2NMwMkV

Parental attitudes and willingness to donate childrens biospecimens for congenital heart disease research: a cross-sectional study in Shanghai, China

Objectives

To assess attitudes and willingness of parents of children with congenital heart disease (CHD) regarding donating biospecimens for future CHD research, and to identify factors associated with biospecimen donation.

Design

Face-to-face cross-sectional survey data were analysed using logistic regression.

Setting

Cardiothoracic Surgery Inpatient Department, Shanghai Children's Medical Centre.

Participants

Parents of children attending the cardiothoracic surgery inpatient department at Shanghai Children's Medical Center, 1 March–31 December 2016.

Primary and secondary outcome measures

Willingness and motivation regarding donating children's biospecimens, and ethical and legal considerations concerning children's future willingness to donate.

Results

Of 550 parents, 508 completed the questionnaire (response rate=92.4%). Overall, 69.1% (n=351) were willing to donate their children's biospecimens for medical research. Multivariate analysis indicated higher education level (college/graduate degree: OR 2.435, 95% CI 1.221 to 4.857, p=0.012; high school: OR 1.827, 95% CI 1.190 to 2.804, p=0.006) and children's hospitalisation history (OR 1.581; 95% CI 1.069 to 2.338, p=0.022) were positively associated with willingness to donate. The most common motivation for donation was potential benefit to other children with CHD (81.2%, n=285). The main barriers to donation were physical discomfort to their children (52.3%, n=54) and concerns about personal privacy (47.1%, n=48). Most parents (86.0%, n=302) wanted to be informed of research results using their children's donated biospecimens, and 34.8% (n=177) believed that children aged 10–18 years had the right to consent independently to research participation.

Conclusions

Nearly 70% of the parents in this study were willing to donate their children's biospecimens for future CHD research. Parents' education level and children's hospitalisation history influenced willingness to donate. Most parents wanted to receive the research results related to their children's biospecimens.

https://ift.tt/2pY4wm1

Environmental exposure to triclosan and polycystic ovary syndrome: a cross-sectional study in China

Objectives

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women at reproductive age. Although the aetiology of PCOS remains unclear, potential effects of environmental endocrine-disrupting compounds on the development of PCOS have drawn increasing attention. The aim of the current study was to examine the association between triclosan (TCS) and PCOS, and explore possible mechanisms on how TCS may contribute to the development of clinical manifestations of PCOS.

Design

Cross-sectional study.

Setting

This study was conducted in one tertiary-level hospital located in Zhejiang, China.

Participants

A total of 674 infertile women at 18–45 years of age were recruited in 2014–2015. Participants with (n=84) and without (n=212) PCOS with urinary TCS concentration available were included in the analyses.

Methods

Urinary TCS concentration was measured using a high-performance liquid chromatography–electrospray ionisation tandem mass spectrometry. Logistic regression model was used to examine the association between TCS and PCOS. Fractional polynomial regression models were built to fit the potential non-linear relationship between TCS concentrations and luteinising hormone (LH) and LH/follicle stimulate hormone (FSH).

Results

The PCOS group had significantly higher level of TCS concentration than the non-PCOS group (the median of TCS (IQR), μg/g creatinine: 1.49 (0.68–3.80) vs 1.06 (0.52–3.02), p=0.0407). Compared with the lowest tertile, the highest tertile of TCS concentration was associated with an increased odd of PCOS (OR 2.12, 95% CI 1.12 to 3.99). After adjusting for potential confounders, the significant association remained (OR 1.99, 95% CI 1.05 to 3.79). Positive relationships were found between TCS levels and LH and LH/FSH ratio in non-PCOS participants.

Conclusions

TCS exposure at a relatively low level is associated with PCOS in Chinese women. Further epidemiological studies are needed to confirm our finding, which may have important public health implications.

https://ift.tt/2NMvTsA

Protocol for a gender-sensitised weight loss and healthy living programme for overweight and obese men delivered in Australian football league settings (Aussie-FIT): A feasibility and pilot randomised controlled trial

Introduction

Overweight and obesity are highly prevalent among Australian men. Professional sports settings can act as a powerful 'hook' to engage men in weight loss programmes; the Football Fans in Training programme delivered in professional UK soccer clubs was successful and cost-effective in helping men lose weight. The Australian Football League (AFL) is a potentially attractive setting to engage men in a weight loss programme. We aim to develop, pilot and evaluate the feasibility of a weight loss intervention for overweight/obese middle-aged men, delivered in AFL settings, to promote weight loss and healthier lifestyles and determine its suitability for a future randomised control trial.

Methods and analysis

120 overweight/obese male fans will complete baseline physical and psychological health measures and objective measures of physical activity (PA), weight, waist size and blood pressure prior to randomisation into the intervention or waitlist comparison group. The intervention group will receive 12 weekly 90 min workshops incorporating PA, nutrition education, behaviour change techniques and principles of effective motivation. Four community coaches will be trained to deliver Aussie-FIT at two AFL clubs in Western Australia. Measurements will be repeated in both groups at 3 months (post-intervention) and 6 months (follow-up). Outcomes will include programme uptake, attendance, changes in lifestyle and weight variables to inform power calculations for a future definitive trial, fidelity of programme delivery, acceptability, satisfaction with the programme and perceptions of effectiveness. We will also determine trial feasibility and potential to gather cost-effectiveness data.

Ethics and dissemination

Ethics approval was granted by Curtin University's Human Research Ethics Committee (HREC2017-0458). Results will be disseminated via peer-reviewed publications, conference presentations and reports. A multicomponent dissemination strategy will include targeted translation and stakeholder engagement events to establish strategies for sustainability and policy change.

Trial registration number

ACTRN12617000515392; Pre-results.

https://ift.tt/2q11Y6x

Relationship between leisure time physical activity, sedentary behaviour and symptoms of depression and anxiety: evidence from a population-based sample of Canadian adolescents

Background

Physical and sedentary activities have been identified as potentially modifiable risk factors for many diseases, including mental illness, and may be effective targets for public health policy and intervention. However, the relative contribution of physical activity versus sedentary behaviour to mental health is less clear. This study investigated the cross-sectional association between physical activity, sedentary activity and symptoms of depression and anxiety at age 14–15 in the National Longitudinal Survey of Children and Youth (NLSCY).

Methods

Respondents aged 14–15 years between 1996 and 2009 who reported on symptoms of depression in the NLSCY were included (n=9702). Multinomial logistic regression was used to assess the relationship between physical and sedentary activity and symptoms of depression and anxiety. Joint models including both physical and sedentary activity were also explored. Models were adjusted for sex, ethnicity, immigration status, family income, parental education, recent major stressful life events and chronic health conditions.

Results

The odds of having moderate and severe symptoms of depression and anxiety compared with no symptoms was 1.43 (1.11 to 1.84) and 1.88 (1.45 to 2.45) times higher, respectively, in physically inactive youth relative to physically active youth. The odds of having moderate and severe symptoms of depression and anxiety compared with no symptoms was 1.38 (1.13 to 1.69) and 1.31 (1.02 to 1.69) times higher, respectively, in sedentary youth relative to non-sedentary youth. In joint models including both physical and sedentary activity, sedentary activity was not consistently associated with symptoms of depression and anxiety.

Conclusions

Both physical inactivity and sedentary activity appear to be significantly related to symptoms of depression and anxiety. The importance of distinguishing these two behaviours has relevance for research as well as policies targeting physical activity and mental health in youth.

https://ift.tt/2NNtHkW

Patient engagement, treatment preferences and shared decision-making in the treatment of opioid use disorder in adults: a scoping review protocol

Introduction

Opioid use disorder (OUD) is characterised by the fifth Edition of the Diagnostic and Statistics Manual as a problematic pattern of opioid use (eg, fentanyl, heroin, oxycodone) that leads to clinically significant impairment. OUD diagnoses have risen substantially over the last decade, and treatment services have struggled to meet the demand. Evidence suggests when patients with chronic illnesses are matched with their treatment preferences and engaged in shared decision-making (SDM), health outcomes may improve. However, it is not known whether SDM could impact outcomes in specific substance use disorders such as OUD.

Methods and analysis

A scoping review will be conducted according to Arksey and O'Malley's framework and by recommendations from Levac et al. The search strategy was developed to retrieve relevant publications from database inception and June 2017. MEDLINE, EMBASE, PsycINFO, Cochrane Database for Controlled Trials, Cochrane Database for Systematic Reviews and reference lists of relevant articles and Google Scholar will be searched. Included studies must be composed of adults with a diagnosis of OUD, and investigate SDM or its constituent components. Experimental, quasi-experimental, qualitative, case–control, cohort studies and cross-sectional surveys will be included. Articles will be screened for final eligibility according to title and abstract, and then by full text. Two independent reviewers will screen excluded articles at each stage. A consultation phase with expert clinicians and policy-makers will be added to set the scope of the work, refine research questions, review the search strategy and identify additional relevant literature. Results will summarise whether SDM impacts health and patient-centred outcomes in OUD.

Ethics and dissemination

Scoping review methodology is considered secondary analysis and does not require ethics approval. The final review will be submitted to a peer-reviewed journal, disseminated at relevant academic conferences and will be shared with policy-makers, patients and clinicians.

https://ift.tt/2pXGDv1

Reporting of outcomes in gastric cancer surgery trials: a systematic review

Background

The development of clinical guidelines for the surgical management of gastric cancer should be based on robust evidence from well-designed trials. Being able to reliably compare and combine the outcomes of these trials is a key factor in this process.

Objectives

To examine variation in outcome reporting by surgical trials for gastric cancer and to identify outcomes for prioritisation in an international consensus study to develop a core outcome set in this field.

Data sources

Systematic literature searches (Evidence Based Medicine, MEDLINE, EMBASE, CINAHL, ClinicalTrials.gov and WHO ICTRP) and a review of study protocols of randomised controlled trials, published between 1996 and 2016.

Intervention

Therapeutic surgical interventions for gastric cancer. Outcomes were listed verbatim, categorised into groups (outcome themes) and examined for definitions and measurement instruments.

Results

Of 1919 abstracts screened, 32 trials (9073 participants) were identified. A total of 749 outcomes were reported of which 96 (13%) were accompanied by an attempted definition. No single outcome was reported by all trials. 'Adverse events' was the most frequently reported 'outcome theme' in which 240 unique terms were described. 12 trials (38%) classified complications according to severity, with 5 (16%) using a formal classification system (Clavien-Dindo or Accordion scale). Of 27 trials which described 'short-term' mortality, 15 (47%) used one of five different definitions. 6 out of the 32 trials (19%) described 'patient-reported outcomes'.

Conclusion

Reporting of outcomes in gastric cancer surgery trials is inconsistent. A consensus approach to develop a minimum set of well-defined, standardised outcomes to be used by all future trials examining therapeutic surgical interventions for gastric cancer is needed. This should consider the views of all key stakeholders, including patients.

https://ift.tt/2NMOwwT

CELEB trial: Comparative Effectiveness of Lung volume reduction surgery for Emphysema and Bronchoscopic lung volume reduction with valve placement: a protocol for a randomised controlled trial

Introduction

Although lung volume reduction surgery and bronchoscopic lung volume reduction with endobronchial valves have both been shown to improve lung function, exercise capacity and quality of life in appropriately selected patients with emphysema, there are no direct comparison data between the two procedures to inform clinical decision-making.

Methods and analysis

We describe the protocol of the CELEB study, a randomised controlled trial which will compare outcomes at 1 year between the two procedures, using a composite disease severity measure, the iBODE score, which includes body mass index, airflow obstruction, dyspnoeaand exercise capacity (incremental shuttle walk test).

Ethics and dissemination

Ethical approval to conduct the study has been obtained from the Fulham Research Ethics Committee, London (16/LO/0286). The outcome of this trial will provide information to guide treatment choices in this population and will be presented at national and international meetings and published in peer-reviewed journals. We will also disseminate the main results to all participants in a letter.

Trial registration number

ISRCTN19684749; Pre-results.

https://ift.tt/2NM6NKI

Cross-sectional analysis of UK research studies in 2015: results from a scoping project with the UK Health Research Authority

Objectives

To determine whether data on research studies held by the UK Health Research Authority (HRA) could be summarised automatically with minimal manual intervention. There are numerous initiatives to reduce research waste by improving the design, conduct, analysis and reporting of clinical studies. However, quantitative data on the characteristics of clinical studies and the impact of the various initiatives are limited.

Design

Feasibility study, using 1 year of data.

Setting

We worked with the HRA on a pilot study using research applications submitted for UK-wide ethical review. We extracted into a single dataset, information held in anonymised XML files by the Integrated Research Application System (IRAS) and the HRA Assessment Review Portal (HARP). Research applications from 2014 to 2016 were provided. We used standard text extraction methods to assess information held in free-text fields. We use simple, descriptive methods to summarise the research activities that we extracted.

Participants

Not applicable—records-based study

Interventions

Not applicable.

Primary and secondary outcome measures

Feasibility of extraction and processing.

Results

We successfully imported 1775 non-duplicate research applications from the XML files into a single database. Of these, 963 were randomised controlled trials and 812 were other studies. Most studies received a favourable opinion. There was limited patient and public involvement in the studies. Most, but not all, studies were planned for publication of results. Novel study designs (eg, adaptive and Bayesian designs) were infrequently reported.

Conclusions

We have demonstrated that the data submitted from IRAS to the HRA and its HARP system are accessible and can be queried for information. We strongly encourage the development of fully resourced collaborative projects to further this work. This would aid understanding of how study characteristics change over time and across therapeutic areas, as well as the progress of initiatives to improve the quality and relevance of research studies.

https://ift.tt/2q0rxF2

B-type natriuretic peptide reference interval of newborns from healthy and pre-eclamptic women: a prospective, multicentre, cross-sectional study

Objective

To define and compare the reference interval of B-type natriuretic peptide (BNP) in healthy newborns (HN) from healthy mothers and with severe pre-eclampsia.

Design

Prospective, multicentre, cross-sectional study.

Setting

Four obstetric wards of second-level academic hospitals.

Participants

167 HN, from 146 healthy and 21 severe pre-eclamptic women. We included newborns from healthy mothers with full-term pregnancies (38 to 42 gestational weeks), who received adequate prenatal care and who had Apgar scores ≥7 at 0 and 5 min. Newborns with chromosomopathies identified during prenatal consultations, those with respiratory distress and those with cardiac or pulmonary disease detected in the first paediatric evaluation were excluded from this study. In the group of pre-eclamptic women, we considered the same inclusion criteria, but the patients also had to meet the diagnostic criteria for pre-eclampsia with severity features, according to the American College of Obstetricians and Gynaecologists guidelines. The same exclusion criteria used for the healthy group were applied to the pre-eclampsia-associated newborn.

Interventions

A single blood sample from the umbilical cord artery after delivery (vaginal or caesarean section).

Primary outcome

Reference level of BNP in HN.

Results

In the HN group, the median BNP was 12.15 pg/mL (IQR 7.7–16.8 pg/mL) and in the pre-eclamptic group 20.8 pg/mL (IQR 5.8–46.5 pg/mL). The reference interval for BNP in HN was 5pg/mL (95% CI 5 to 5) to 34 pg/mL (95% CI 28.4 to 38.8). We identified higher expression of BNP in newborns from pre-eclamptic women overall (p=0.037, r=0.16) and in newborns exposed to stress conditions, such as complications during labour and delivery (p=0.004, r=0.33).

Conclusions

In HN, BNP concentrations at birth were lower than reported in other similar populations. In neonates with stress conditions, the higher expression of this biomarker establishes another possible link between stress and the cardiovascular response.

Trial registration number

NCT02574806; Pre-results.

https://ift.tt/2pXG5Ft

Public, medical professionals and patients preferences for the allocation of donor organs for transplantation: study protocol for discrete choice experiments

Introduction

Organ transplantation is the treatment of choice for patients with severe organ failure. Nevertheless, donor organs are a scarce resource resulting in a large mismatch between supply and demand. Therefore, priority-setting leads to the dilemma of how these scarce organs should be allocated and who should be considered eligible to receive a suitable organ. In order to improve the supply–demand mismatch in transplantation medicine, this study explores preferences of different stakeholders (general public, medical professionals and patients) for the allocation of donor organs for transplantation in Germany. The aims are (1) to determine criteria and preferences, which are relevant for the allocation of scarce donor organs and (2) to compare the results between the three target groups to derive strategies for health policy.

Methods and analysis

We outline the study protocol for discrete choice experiments, where respondents are presented with different choices including attributes with varied attribute levels. They were asked to choose between these choice sets. First, systematic reviews will be conducted to identify the state of art. Subsequently, focus group discussions with the public and patients as well as expert interviews with medical professionals will follow to establish the attributes that are going to be included in the experiments and to verify the results of the systematic reviews. Using this qualitative exploratory work, discrete choice studies will be designed to quantitatively assess preferences. We will use a D-efficient fractional factorial design to survey a total sample of 600 respondents according to the public, medical professionals and patients each. Multinomial conditional logit model and latent class model will be analysed to estimate the final results.

Ethics and dissemination

This study has received Ethics Approval from the Hannover Medical School Human Ethics Committee (Vote number: 7921_BO_K_2018). Findings will be disseminated through conference presentations, workshops with stakeholders and peer-reviewed journal articles.

https://ift.tt/2q03FkS

Using internet search data to predict new HIV diagnoses in China: a modelling study

Objectives

Internet data are important sources of abundant information regarding HIV epidemics and risk factors. A number of case studies found an association between internet searches and outbreaks of infectious diseases, including HIV. In this research, we examined the feasibility of using search query data to predict the number of new HIV diagnoses in China.

Design

We identified a set of search queries that are associated with new HIV diagnoses in China. We developed statistical models (negative binomial generalised linear model and its Bayesian variants) to estimate the number of new HIV diagnoses by using data of search queries (Baidu) and official statistics (for the entire country and for Guangdong province) for 7 years (2010 to 2016).

Results

Search query data were positively associated with the number of new HIV diagnoses in China and in Guangdong province. Experiments demonstrated that incorporating search query data could improve the prediction performance in nowcasting and forecasting tasks.

Conclusions

Baidu data can be used to predict the number of new HIV diagnoses in China up to the province level. This study demonstrates the feasibility of using search query data to predict new HIV diagnoses. Results could potentially facilitate timely evidence-based decision making and complement conventional programmes for HIV prevention.

https://ift.tt/2NOPjgR

The management of common recurrent headaches by chiropractors: a descriptive analysis of a nationally representative survey

Headache management is common within chiropractic clinical settings; however, little is yet known about how this provider group manage headache sufferers. The aim of this study is to report on the prevalence o...

https://ift.tt/2P0pAqn

Validation of the brief international cognitive assessment for multiple sclerosis (BICAMS) in the Portuguese population with multiple sclerosis

The validation of international cognitive batteries in different multiple sclerosis (MS) populations is essential. Our objective was to obtain normative data for the Portuguese population of the Brief Internat...

https://ift.tt/2PGKmrR

A rare case of Aerococcus urinae infective endocarditis in an atypically young male: case report and review of the literature

Aerococcus urinae is a gram-positive, alpha-hemolytic coccus bacterium primarily implicated in less than 1 % of all symptomatic urinary tract infections. Risk factors for disease include male gender, advanced age...

https://ift.tt/2Pbdta4

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Human norovirus is the leading cause of viral gastroenteritis globally, and the GII.4 has been the most predominant genotype for decades. This genotype has numerous variants that have caused repeated epidemics...

https://ift.tt/2PG37vF

Deciphering Hybrid Larch Reaction Norms Using Random Regression

The link between phenotypic plasticity and heterosis is a broad fundamental question, with stakes in breeding. We report a case-study evaluating temporal series of wood ring traits of hybrid larch (Larix decidua x L. kaempferi and reciprocal) in relation to soil water availability. Growth rings record the tree plastic responses to past environmental conditions, and we used random regressions to estimate the reaction norms of ring width and wood density with respect to water availability. We investigated the role of phenotypic plasticity on the construction of hybrid larch heterosis and on the expression of its quantitative genetic parameters. The data came from an intra-/interspecific diallel mating design between both parental species. Progenies were grown in two environmentally contrasted sites, in France. Ring width plasticity with respect to water availability was confirmed, as all three taxa produced narrower rings under the lowest water availability. Hybrid larch appeared to be the most plastic taxon as its superiority over its parental species increased with increasing water availability. Despite the low heritabilities of the investigated traits, we found that the expression of a reliable negative correlation between them was conditional to the water availability environment. Finally, by means of a complementary simulation, we demonstrated that random regression can be applied to model the reaction norms of non-repeated records of phenotypic plasticity bound by a family structure. Random regression is a powerful tool for the modeling of reaction norms in various contexts, especially perennial species.

https://ift.tt/2J43bCT

Transcriptomic Plasticity in the Arthropod Generalist Tetranychus urticae Upon Long-Term Acclimation to Different Host Plants

The two-spotted spider mite Tetranychus urticae is an important pest with an exceptionally broad host plant range. This generalist rapidly acclimatizes and adapts to a new host, hereby overcoming nutritional challenges and a novel pallet of constitutive and induced plant defenses. Although recent studies reveal that a broad transcriptomic response upon host plant transfer is associated with a generalist life style in arthropod herbivores, it remains uncertain to what extent these transcriptional changes are general stress responses or host-specific. In the present study, we analyzed and compared the transcriptomic changes that occur in a single T. urticae population upon long-term transfer from Phaseolus vulgaris to a similar, but chemically defended, host (cyanogenic Phaseolus lunatus) and to multiple economically important crops (Glycine max, Gossypium hirsutum, Solanum lycopersicum and Zea mays). These long-term host plant transfers were associated with distinct transcriptomic responses with only a limited overlap in both specificity and directionality, suggestive of a fine-tuned transcriptional plasticity. Nonetheless, analysis at the gene family level uncovered overlapping functional processes, recruiting genes from both well-known and newly discovered detoxification families. Of note, our analyses highlighted a possible detoxification role for Tetranychus-specific short-chain dehydrogenases and single PLAT domain proteins, and manual genome annotation showed that both families are expanded in T. urticae. Our results shed new light on the molecular mechanisms underlying the remarkable adaptive potential for host plant use of generalist arthropods and set the stage for functional validation of important players in T. urticae detoxification of plant secondary metabolites.

https://ift.tt/2OwETHS

Decisionmaking in Emergency Medicine: Experienced-Based and Contextually Anchored Rather Than Evidence Based and Universal

In 2006, Sandhu et al1 called for researchers to undertake more studies to understand how emergency physicians make their decisions. The study by Wright et al2 sheds new light on this field of research in terms of the weight of experience and the role of context in decisionmaking.

https://ift.tt/2QWmJMk

In reply:

We appreciate the opportunity to respond to Dr. Pelaccia's letter,1 which sought to draw some important conclusions for the field of emergency medicine decisionmaking from our recent article.2

https://ift.tt/2AguAP7

Trends in Hospitalization, Readmission, and Diagnostic Testing of Patients Presenting to the Emergency Department With Syncope

Emergency department (ED) visits for syncope are common and routine diagnostic testing is frequently low yield. Our objective is to determine whether recent guidelines emphasizing limiting hospitalization and advanced diagnostic testing to high-risk patients have changed patterns of syncope care.

https://ift.tt/2QWmH7a

Elderly Woman With Severe Dyspnea

A 74-year-old woman with a history of mitral valve replacement was admitted to the emergency department (ED) with severe dyspnea accompanied by diaphoresis. On arrival to the hospital, her blood pressure was 96/60 mm Hg, heart rate was rapid and irregular, at 179 beats/min, and blood oxygen saturation was 90% while she breathed 5 L of oxygen by face mask. The patient's lung examination result was remarkable for the presence of bilateral crackles. The ECG on admission is shown in Figure 1. The patient was administered morphine, furosemide, and cedilanid intravenously and showed no significant improvement after the treatment.

https://ift.tt/2AfRN41

Woman With Headache and Amnesia

A 73-year-old woman presented with a severe headache, confusion, and primarily anterograde amnesia. She was febrile and had no focal neurologic deficits. Her lumbar puncture revealed elevated protein level, hypoglycorrhachia, and a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) of the brain revealed a left-predominant region of hyperintensity on the fluid-attenuated inversion recovery sequence in the anterior medial temporal lobe (Figure 1) including the hippocampus and surrounding structures (Figure 2).

https://ift.tt/2QVSGnW

Elderly Man With Chest Pressure

A 70-year-old man with a remote history of pericarditis and paroxysmal atrial fibrillation was brought to the emergency department (ED) by ambulance after he experienced chest pressure with associated lightheadedness and diaphoresis during a brisk 30-minute walk. An out-of-hospital ECG was performed during symptoms (Figure 1). Shortly after treatment with oxygen and aspirin, the symptoms resolved and a subsequent out-of-hospital ECG was performed before arrival to the ED (Figure 2).

https://ift.tt/2AhrfQ3

Abandoning Further Study of the Application of Computed Tomography Decision Rules to Low-Risk Patients With Head Injury

I read with interest the article by Davey et al.1 The authors explain that despite the presumably low prevalence of intracranial hemorrhage, their "unique cultural practice" involves the performance of head computed tomography (CT) for patients with minimal head injury (head trauma without associated loss of consciousness or disorientation) for various reasons. Unsurprisingly, when Davey et al applied the Canadian CT Head Rule to their cohort, which was at lower risk than the population in which the rule was derived and validated, the rule identified all 5 positive CT results.

https://ift.tt/2QX5SsH

Woman With a Groin Mass

A 63-year-old woman presented with a left-sided groin mass present for 2 months. It became larger and painful 1 month earlier after she lifted furniture. Her surgical history was notable for a remote left iliac endarterectomy. She presented to the emergency department concerned that she had a hernia. A pulsatile, ecchymotic mass was found in the left inguinal region (Figure 1). Bedside ultrasonography revealed a 6-cm fluid collection about the common femoral artery (Figure 2).

https://ift.tt/2AfNGoI

Linkage to Care, Antiretroviral Treatment Initiation, and Viral Suppression of Acute HIV-Infected Individuals Identified From an Emergency Department–Based HIV Screening and Linkage-to-Care Program

We read with great interest the recent article by White et al,1 which portrayed the high diagnostic yield of nontargeted screening for acute HIV infection in emergency departments (EDs). As highlighted by the investigators, diagnosis of acute HIV infection not only provides a critical and time-sensitive opportunity to mitigate the risk of HIV transmission but also significantly improves clinical outcomes for infected ED patients2 through timely linkage to care and initiation of antiretroviral therapy.

https://ift.tt/2QWmmRW

Calendar

▮ Observation Medicine: Science & Solutions. November 1–2, 2018. Charleston, SC. Contact: Christy Snitgen. Email: mcep@mcep.org. Url: www.mcep.org. (12.25)

https://ift.tt/2AfyUhC

Apollo

I came across them in the middle of my afternoon run: 3 women sobbing over a body on the sidewalk. A young man joined the group from the east just as I came upon them from the west.

https://ift.tt/2QXUo8f

Pregnant Woman With Sudden Right Abdominal Pain

A 30-year-old woman at 29 weeks' gestation presented to the emergency department with sudden right-sided abdominal pain. She had a tender abdomen and a WBC count of 14.2×109/L. Emergency transvaginal ultrasonography showed a well-defined mass (Figure 1, left panel) with follicles, and with obvious vascularity (Figure 1, right panel) in the right abdomen. There was a similar mass behind the cervix. Pelvic magnetic resonance imaging (MRI) showed that both ovaries were enlarged, with uneven signal (Figure 2).

https://ift.tt/2AfyQ1m

Young Woman With Thigh Wound and Rash

A healthy 22-year-old woman presented to the emergency department 5 days after developing a right medial thigh wound and petechial rash (Figures 1 and 2). She reported a burning sensation that preceded the rash, followed by rapidly progressing erythema, central necrosis, pain, fever, and fatigue.

https://ift.tt/2QVPHM6

Man With Painless Erythematous Lesions on the Toes

A 58-year-old previously healthy man presented with a 1-day history of erythematous violaceous lesions on his left toes because of possible acute arterial occlusion. On physical examination, erythematous and purpuric lesions were observed on the first and second left toes (Figure 1). Doppler assessment of the dorsalis pedis pulse was normal. Radiograph of the left foot showed no fracture. The patient was advised about a suspected diagnosis of a millipede burn, and 6 hours later, he returned to the emergency department with some millipedes found in his home and work boot (Figure 2).

https://ift.tt/2Ah4P1s

Man With Coughing and Chest Tightness

After a motor vehicle crash, a 45-year-old man presented to a freestanding emergency department, where he received computed tomography (CT) imaging. On administration of intravenous contrast, the patient experienced muscle spasms, coughing, and chest tightness. These symptoms spontaneously resolved within 30 minutes.

https://ift.tt/2QSnfLk

Man With Left-Sided Chest Pain

A 65-year-old man presented to the emergency department with sudden-onset, left-sided chest pain that woke him up from sleep approximately 6 hours before presentation. Nine days earlier, he had had an ST-segment elevation myocardial infarction (STEMI) from a 100% restenosis of a previous proximal left anterior descending stent discovered during coronary angiography. At that time, percutaneous coronary intervention, with the placement of a drug-eluting stent to the proximal and midportions of the left anterior descending stent, was performed.

https://ift.tt/2AfyKH2

Asymptomatic and Under Pressure

SEE RELATED ARTICLE, P. 534.

https://ift.tt/2QW0JBm

What's Coming in Annals ● December 2018

https://ift.tt/2AfQQsC

Clinical Policy: Critical Issues in the Evaluation and Management of Emergency Department Patients With Suspected Non–ST-Elevation Acute Coronary Syndromes (Executive Summary)

This clinical policy from the American College of Emergency Physicians addresses key issues in the evaluation and management of adult emergency department patients with suspected non–ST-elevation acute coronary syndromes. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the below critical questions. For each question a systematic literature search was performed, evidence was graded and synthesized, and recommendations were made based on the strength of the available data.

https://ift.tt/2QSneae

Table of Contents

https://ift.tt/2Ag9tNe

The Future of Virtual Reality in Radiation Oncology

Advances in high-performance computing technology continue to deeply affect the practice of medicine. In radiation oncology we have seen this evolution firsthand as contouring has become completely digital, dose calculation has evolved from approximated 2-dimensional (2D) calculations to 3-dimensional (3D) physics-based simulation, and techniques such as inverse-planned intensity modulated radiation therapy have been introduced to the clinic. The current revolution in machine learning and artificial intelligence has the promise to make even deeper changes to how we work with computers to perform our daily clinical tasks.

https://ift.tt/2OyTEKf

Radiation Therapy Outcomes Models in the Era of Radiomics and Radiogenomics: Uncertainties and Validation

Models by their nature are mathematical approximations of reality, as conveyed by the statement that "all models are wrong but some are useful (1)." Their usefulness in radiation therapy (RT) is highlighted by the roles that outcome models play in improving the quality and efficacy of radiation treatment of tumors by predicting response, individualizing prescriptions, and optimizing and ranking planning options. These models are generally categorized into those for tumor response prediction by tumor control probability (TCP) and those for predicting radiation-induced toxicities by normal-tissue complication probability (NTCP).

https://ift.tt/2J2R7Sz

Precision Medicine—Targeted Therapy

To the Editor: Central nervous system pathologic and normal anatomy have long been regarded as essentially static when planning treatment—motion management was thought to be unimportant because physiologic processes such as respiration or peristalsis do not affect intracranial anatomy. Indeed, 3-dimensional rigid registrations between magnetic resonance imaging (MRI) and computed tomography (CT) scans can be carried out with high degrees of accuracy over months and years to permit the re-establishment of stereotactic coordinates for guidance and monitoring (1).

https://ift.tt/2OxGOvu

Meetings

November 16-17, 2018

https://ift.tt/2J93aOl

Seeing What's Before Us: Imaging in the Electronic Age

If you break your foot and need an x-ray, you are much more likely to be directed to the Department of Diagnostic Imaging than to the Radiology Department. Forward-thinking radiology departments now like to include "imaging" in their titles. It captures the trajectory of growth away from the classic Roentgen ray of 1895 into a boundless visual universe comprised of bits and bytes. Workhorse computed tomography (CT) scans are yielding ground to a complex stew of ultrasound, magnetic resonance, and molecular and nuclear imaging-based technologies, all readily accessible on-screen in just a few clicks.

https://ift.tt/2Oudgzd

Whither Thou Goest, I Will Go

The title of this editorial is from Ruth I:16 (King James version of the Bible), and as with Ruth and Naomi, the disciplines of diagnostic radiology (DR) and radiation oncology (RO) were inexorably linked from their inceptions through the post–World War II era. In the late 1940s, Juan del Regato, MD, one of the early proponents of RO in the United States, corresponded with the American Board of Radiology (ABR) to request a separation of the disciplines within radiology; however, it was not until more than 3 decades later, in 1982, that the ABR administered its last general radiology examination.

https://ift.tt/2J93757

The Importance of Imaging in Radiation Oncology for National Clinical Trials Network Protocols

Imaging is essential in successfully executing radiation therapy (RT) in oncology clinical trials. As technically sophisticated diagnostic imaging and RT were incorporated into trials, quality assurance in the National Clinical Trials Network groups entered a new era promoting image acquisition and review. Most trials involving RT require pre- and post-therapy imaging for target validation and outcome assessment. The increasing real-time (before and during therapy) imaging and RT object reviews are to ensure compliance with trial objectives.

https://ift.tt/2Ouq3Se

Artificial Intelligence in Radiation Oncology Imaging

Artificial intelligence (AI) is emerging as a technology with the power to transform the way we analyze, interpret, and leverage medical imaging data. This power is sure to extend to radiation oncology, which depends on multimodal imaging for most aspects of patient care, including but not limited to clinical decision-making, treatment planning, follow-up care, and quality assessment frameworks. In this editorial, we will comment on the current state and anticipated future impact of AI on radiation oncology, focusing on machine learning and deep learning approaches to medical imaging data analysis and their applications.

https://ift.tt/2J934pX

“Wisest Is He Who Knows What He Does Not Know.”

This issue of the Red Journal contains reports espousing the potential of imaging to improve cancer treatment in general, and radiation therapy (RT) in particular. We share much of that enthusiasm. At the same time, it seems prudent to discuss some of the limits of imaging and the potential downside of overreliance on imaging to define RT targets (1).

https://ift.tt/2OxGFYY

Interim Analysis of a Two-Institution, Prospective Clinical Trial of 4DCT-Ventilation-based Functional Avoidance Radiation Therapy

Functional imaging has been proposed that uses 4DCT images to calculate 4DCT-based lung ventilation (4DCT-ventilation). We have started a 2-institution, phase 2 prospective trial evaluating the feasibility, safety, and preliminary efficacy of 4DCT-ventilation functional avoidance. The trial hypothesis is that the rate of grade ≥2 radiation pneumonitis could be reduced to 12% with functional avoidance, compared with a 25% rate of pneumonitis with a historical control. The trial employed a Simon 2-stage design with a planned futility analysis after 17 evaluable patients.

https://ift.tt/2J931uh

Imaging (R)evolution: Questioning Our Motivations Behind Rapid Adoption of New Technologies in Radiation Oncology

Image-guided treatment has revolutionized the field of radiation oncology. Improved tumor visualization through CT and MRI in the 1970s prompted innovative methods of targeting: intensity modulated radiation therapy and multileaf collimators to deliver complex dose distributions (1). In head and neck cancer, for instance, these innovations are associated with improved survival and quality of life with reduced toxicities (2-4). Advances in functional and metabolic imaging create targets based on tumor biology (1).

https://ift.tt/2OxGCwg

The Influence of Imaging in the Modern Practice of Radiation Oncology

The current practice of radiation oncology now requires a strong relationship with all radiology subspecialists and is embedded with a variety of imaging modalities and formats for both treatment planning and treatment execution. Unlike technology in the past, modern treatment technology delivery systems include kilovoltage imaging and cone beam computed tomography–guided treatment systems for daily patient treatment reproducibility. Today's radiation planning tools include 4-dimensional motion management and fusion software that can routinely blend anatomic and metabolic imaging for target volume definition.

https://ift.tt/2J5cnqT

The EGFR T790M mutation is acquired through AICDA-mediated deamination of 5-methylcytosine following TKI treatment in lung cancer.

Almost all patients with EGFR-driven lung cancer who are treated with EGFR tyrosine kinase inhibitors (TKI) develop resistance to treatment. A single base (c.2369C>T) transition mutation, EGFR T790M, is the most frequent resistance event after first-generation exposure to EGFR TKI. Whether T790M mutation is acquired or is selected from a pre-existing clone has been a matter of significant debate. In this study, we show that treatment with EGFR TKI leads to activation of the NFᴋB pathway, which in turn induces expression of Activation Induced Cytidine Deaminase (AICDA). In turn, AICDA causes deamination of 5-methylcytosine to thymine at position c.2369 to generate the T790M mutation. Pharmacologic inhibition of the NFᴋB pathway or knockout of AICDA decreased the frequency or prevented the development of T790M mutation, respectively. In addition, patients treated with first line EGFR TKI displayed increased expression of AICDA and detection of the T790M mutation upon progression. These results identify the mechanism of T790M acquisition and present an opportunity to target the process to delay or prevent it.

https://ift.tt/2CQWMuA

Glioma Cell Secretion: A Driver of Tumor Progression and a Potential Therapeutic Target

Cellular secretion is an important mediator of cancer progression. Secreted molecules in glioma are key components of complex autocrine and paracrine pathways that mediate multiple oncogenic pathologies. In this review, we describe tumor cell secretion in high-grade glioma and highlight potential novel therapeutic opportunities. Cancer Res; 78(21); 1–9. ©2018 AACR.

https://ift.tt/2CntgLT

JAM-C Expression as a Biomarker to Predict Outcome of Patients with Acute Myeloid Leukemia—Response

https://ift.tt/2yKqyfX

JAM-C Expression as a Biomarker to Predict Outcome of Patients with Acute Myeloid Leukemia—Letter

https://ift.tt/2ymLNVI

Erratum to “Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice”

https://ift.tt/2EvmyX4

Clinical and Mutation Analysis of Patients with Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy in Chinese Population

Mutations in the gene BEST1 usually cause bestrophinopathies, such as the rare progressive diseases Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). This study aimed to investigate the clinical characteristics of patients with BVMD or ARB carrying BEST1 mutations. A total of 12 probands including 9 patients with a clinical diagnosis of BVMD and 3 patients with a clinical diagnosis of ARB were recruited for genetics analysis. All patients underwent detailed ophthalmic examination. All coding exons of the BEST1 gene were screened by PCR-based DNA sequencing. Programs of PolyPhen-2, SIFT, and MutationTaster were used to analyze the potential pathogenicity of the mutations in BEST1. In the 9 unrelated patients with BVMD, one heterozygous BEST1 mutation was revealed in 8 patients and two compound heterozygous mutations in 1 patient. In the 3 unrelated patients with ARB, two compound heterozygous mutations were revealed in 2 patients and three compound heterozygous mutations in 1 patient. Molecular analyses identified a total of 15 mutations, including 3 novel mutations (c.424A>G p.S142G, c.436G>A p.A146T, and c.155T>C p.L52P). Antivascular endothelial growth factor (VEGF) drugs were given to two affected eyes, especially those also exhibiting choroidal neovascularization (CNV), and no serious adverse events occurred. Our study indicates that there is wide genotypic and phenotypic variability in patients with BVMD or ARB in China. The screening of BEST1 gene is significant for the precise diagnosis of BVMD and ARB.

https://ift.tt/2RXGkwP

Protective Effect of Citrulline on the Hearts of Rats with Sepsis Induced by Cecal Ligation and Puncture

Purpose. To investigate the protective effect of citrulline (Cit) on the hearts of rats with sepsis. Methods. Wistar rats were divided into the normal, sham-operated, CLP, Cit, and CLP+Cit groups. Routine blood tests were performed, and the blood biochemical indexes were measured. Pathological changes in the cardiac tissues were observed. The levels of NO and iNOS in blood and SOD activity and MDA levels in the heart were measured. Results. Less inflammatory cell infiltration of the myocardial fibers and significantly decreased white blood cell count, absolute neutrophil count, neutrophil percentage, CK, HBDH, and NO (all P

https://ift.tt/2EtsShN

Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway

Background. BCL6 was a critical prooncogene of human B-cell lymphomas which promoted tumor progress and contributed to malignant behavior in several kinds of cancers. This study was to detect the expression of BCL6 and its biological effect on glioma. Methods. RT-PCR and Western blot were used to detect the expression of BCL6 mRNA and protein in tissues and glioblastoma cell lines. The expression of BCL6 was knockdown in two glioblastoma cell lines (U87 and U251) using BCL6 shRNA. The CCK8, colony-formation, flow cytometry, Transwell, and wound-healing assays were used to evaluate the malignant phenotypic change of glioblastoma cells. Results. The expression of BCL6 was higher in glioma tissues and glioblastoma cell lines than normal tissues. Knockdown of BCL6 expression reduced the proliferation, migration, and invasion of glioblastoma cells. Moreover, knockdown of BCL6 changed expression of proteins related to malignant behaviors of glioblastoma cells. The suppression of BCL6 could increase chemosensitivity of U87 and U251 to temozolomide. Downregulation of BCL6 levels suppressed the expression of BCL2, cyclin D1, MMP2, and MMP9 proteins as well as two classic signaling pathway proteins p-AKT and p-ERK. Simultaneously, BAX and p21 protein levels were upregulated along with knockdown of BCL6. Conclusions. Our results indicated that BCL6 may be a tumor oncogene involved in the progression of glioma via affecting AKT and MAPK signaling pathways.

https://ift.tt/2RXGhkD

Recreational Marijuana Now Legal in Canada

WEDNESDAY, Oct. 17, 2018 -- Recreational marijuana became legal in Canada today, and while many welcome the move, others have serious concerns. An editorial published Oct. 15 in CMAJ, the journal of the Canadian Medical Association, called...

https://ift.tt/2QVLeJG

CDC Warns of Salmonella Illnesses Linked to Raw Chicken

WEDNESDAY, Oct. 17, 2018 -- The number of people sickened in a Salmonella outbreak linked to raw chicken products now stands at 92 people in 29 states, U.S. health officials said today. Of those who have fallen ill, 21 have been hospitalized. No...

https://ift.tt/2AfrDOQ

Hologram-Guided External Ventricular Drain Insertion Feasible

WEDNESDAY, Oct. 17, 2018 -- Hologram-guided external ventricular drain (EVD) insertion is feasible, according to a study published online Oct. 16 in the Journal of Neurosurgery. Ye Li, M.D., Ph.D., from Capital Medical University in Beijing, and...

https://ift.tt/2QXR7G6

Giving Flu Shots in Pharmacies Could Up Vaccination Coverage

WEDNESDAY, Oct. 16, 2018 -- Administering influenza vaccines through pharmacies in addition to traditional locations can increase vaccination coverage in the event of an epidemic, according to a study published online Oct. 16 in Vaccine. Sarah M....

https://ift.tt/2Ag69RS

American Academy of Otolaryngology, Oct. 7-10

The 122nd American Academy of Otolaryngology-Head and Neck Surgery Foundation Annual Meeting and OTO Experience The annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation was held from Oct. 7 to 10 in Atlanta and...

https://ift.tt/2QXR2SO

Regulation of metabolic supply and demand during B cell activation and subsequent differentiation

Takeshi Egawa | Deepta Bhattacharya

https://ift.tt/2yNoBzk

Managing chronic pain in cancer survivors prescribed long-term opioid therapy: a national survey of ambulatory palliative care providers

Chronic pain, or pain lasting > 3 months, is common among cancer survivors, who are often prescribed long-term opioid therapy (LTOT).

https://ift.tt/2P2VZN0

Triggered Palliative Care for Late-stage Dementia: a Pilot Randomized Trial

Persons with late-stage dementia have limited access to palliative care.

https://ift.tt/2PMAOeU

Immune culprits linked to inflammation and bone loss in gum disease identified

An unhealthy population of microbes in the mouth triggers specialized immune cells that inflame and destroy tissues, leading to the type of bone loss associated with a severe form of gum disease, according to a new study in mice and humans. The findings could have implications for new treatment approaches for the condition.

https://ift.tt/2EqVb00

Clinical Characteristics and Outcomes of Patients With Post-Fundoplication Dysphagia

Dysphagia is a consequence of anti-reflux surgery (ARS) for gastroesophageal reflux disease (GERD). We studied patient management and symptomatic outcomes.

https://ift.tt/2ypFlNR

Esophageal Lichen Planus and Squamous Cell Carcinoma: Characteristics and Risk in a Large Tertiary Referral Center

https://ift.tt/2yIq3TP

Characteristics of Opioid Prescriptions to Veterans with Cirrhosis

Despite increased risks for adverse effects in patients with cirrhosis, little is known about opioid prescriptions for this population. We aimed to assess time trends in opioid prescribing and factors associated with receiving opioids among patients with cirrhosis.

https://ift.tt/2yiT0WY

An Anti-Tumor Immune Response is Evoked By Partial-Volume Single Dose Radiation in Two Murine Models

The response of tumors subjected to partial irradiation was studied in two different immunocompetent models. A single dose of 10-20Gy of radiation delivered to half the tumor, reproducibly activates an anti-tumor immune response that eliminates the entire tumor. This response is dependent on vascular adhesion molecules that mediate infiltration of cytotoxic T cells.

https://ift.tt/2P3KtRh

Primary esophageal choriocarcinoma: an unusual cause of myocardial infarction

https://ift.tt/2J4Ikzg

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett’s esophagus over the past 2 decades: data from a multicenter U.S. consortium

Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE associated dysplasia on index endoscopy over the past 25 years.

https://ift.tt/2OtkxPE

Comparison of Flexible Endoscopic Cricopharyngeal Myectomy and Myotomy Approaches for Zenker Diverticulum Repair a

Incision of the cricopharyngeal (CP) muscle with flexible endoscopy is an important approach for Zenker diverticulum (ZD) repair with symptomatic resolution in approximately 90% of cases, but recurrence has been reported in up to 20%. We report our experience with a new endoscopic myectomy of the CP muscle and compare the outcome with conventional myotomy of ZD.

https://ift.tt/2J67vBu

Automated polyp detection in the colorectum: a prospective study (with videos)

Adenoma detection is a highly personalized task that differs markedly between endoscopists. Technical advances are therefore desirable for the improvement of the adenoma detection rate (ADR). An automated computer driven technology would offer the chance to objectively assess the presence of colorectal polyps during colonoscopy. We present here the application of a real-time automatic polyp detection software (APDS) under routine colonoscopy conditions.

https://ift.tt/2OyIV2r

The comparison of monopolar hemostatic forceps with soft coagulation versus hemoclip for peptic ulcer bleeding: a randomized trial (with video)

Although various methods are used in the treatment of peptic ulcer bleeding, there is not a standard recommended approach. The choice depends on multiple factors such as location of the ulcer, clinical experience of endoscopist and local facilities of the clinic. We aimed to compare the efficacy of monopolar hemostatic forceps soft coagulation (MHFSC) and hemoclips (HC) in the treatment of peptic ulcer related upper GI bleeding.

https://ift.tt/2J4YSHJ

Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis

Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis

Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis, Published online: 17 October 2018; doi:10.1038/s41419-018-1118-4

Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis

https://ift.tt/2CTupMc

miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer

miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer

miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer, Published online: 17 October 2018; doi:10.1038/s41419-018-1091-y

miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer

https://ift.tt/2CoqJBc

Tumor suppressive miR-6775-3p inhibits ESCC progression through forming a positive feedback loop with p53 via MAGE-A family proteins

Tumor suppressive miR-6775-3p inhibits ESCC progression through forming a positive feedback loop with p53 via MAGE-A family proteins

Tumor suppressive miR-6775-3p inhibits ESCC progression through forming a positive feedback loop with p53 via MAGE-A family proteins, Published online: 17 October 2018; doi:10.1038/s41419-018-1119-3

Tumor suppressive miR-6775-3p inhibits ESCC progression through forming a positive feedback loop with p53 via MAGE-A family proteins

https://ift.tt/2CNAPMU

Transgenic overexpression of furin increases epileptic susceptibility

Transgenic overexpression of furin increases epileptic susceptibility

Transgenic overexpression of furin increases epileptic susceptibility, Published online: 17 October 2018; doi:10.1038/s41419-018-1076-x

Transgenic overexpression of furin increases epileptic susceptibility

https://ift.tt/2CnjvgJ

Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis

Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis

Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis, Published online: 17 October 2018; doi:10.1038/s41419-018-1074-z

Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis

https://ift.tt/2CRuT5L

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways, Published online: 17 October 2018; doi:10.1038/s41419-018-1059-y

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

https://ift.tt/2Csgo78

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response, Published online: 17 October 2018; doi:10.1038/s41419-018-1084-x

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response

https://ift.tt/2CPFSfL

Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury

Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury

Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury, Published online: 17 October 2018; doi:10.1038/s41419-018-1112-x

Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury

https://ift.tt/2CqhHnq

Umbilical Cord Tissue and Meconium May Not Be Equivalent for Confirming in Utero Substance Exposure

In a retrospective study of 501 neonates with potential in utero substance exposure, the drug detection performance of a commercially available umbilical cord tissue toxicology test was evaluated against a commercially available gold standard meconium toxicology test. Drugs detected in paired meconium and umbilical cord tissue samples were often discordant.

https://ift.tt/2P87iTU

How to manage ambulance safety on the microscopic level

It's important to clean and decontaminate the ambulance interior regularly to prevent the spread of germs

https://ift.tt/2PCPHR1

Combinatorial Prg4 and Il-1ra Gene Therapy Protects Against Hyperalgesia and Cartilage Degeneration in Post-Traumatic Osteoarthritis

Human Gene Therapy, Ahead of Print.


https://ift.tt/2Agt4ge

Optimization and economic evaluation of modified coagulation–flocculation process for enhanced treatment of ceramic-tile industry wastewater

Enhanced treatment of ceramic-tile industry wastewater was investigated by modified coagulation–flocculation process using combination of poly-aluminum chloride (PAC) with anionic (A300), cationic polymer (C270) ...

https://ift.tt/2QYMDzc

Production, purification and characterization of an acid/alkali and thermo tolerant cellulase from Schizophyllum commune NAIMCC-F-03379 and its application in hydrolysis of lignocellulosic wastes

A cellulase producing fungus Schizophyllum commune NAIMCC-F-03379 was isolated from decomposed leaf sample of Lantana camera. The nutritional components (wheat bran, magnesium sulphate and calcium chloride concen...

https://ift.tt/2Agp27D

An AA9-LPMO containing a CBM1 domain in Aspergillus nidulans is active on cellulose and cleaves cello-oligosaccharides

Lytic polysaccharide monooxygenases (LPMOs) are copper dependent enzymes that carry out oxidative cleavage of cellulose and other polysaccharides. Aspergillus nidulans, an ascomycete fungus that contains multiple...

https://ift.tt/2QRueny

Growing Magnetotactic Bacteria of the Genus Magnetospirillum: Strains MSR-1, AMB-1 and MS-1

We present a procedure for growing several strains of Magnetospirillum in two different types of growth media. Magnetospirillum gryphiswaldense strain MSR-1 is grown in both liquid and O2 concentration gradient semi-solid media while M. magneticum strain AMB-1 and M. magnetotacticum strain MS-1 are grown in liquid medium.

https://ift.tt/2yiC9na

Whole Body Vibration Methods with Survivors of Polio

The goal of this article is to highlight the strengths, limitations, and applications of the method used with whole body vibration on polio survivors with and without post-polio syndrome as a feasible and safe form of weight bearing exercise.

https://ift.tt/2yJPHY9

Sub-acute Cerebral Microhemorrhages Induced by Lipopolysaccharide Injection in Rats

We present a protocol to induce and detect CMHs caused by LPS injection in Sprague-Dawley rats, which may be utilized in future research investigations on the pathogenesis of CMHs.

https://ift.tt/2ylU9gu

Gabapentin Beats Pregabalin for Chronic Sciatica

WEDNESDAY, Oct. 17, 2018 -- For patients with chronic sciatica (CS), gabapentin (GBP) is superior to pregabalin (PGB), with fewer and less severe adverse events (AEs), according to a study published online Oct. 15 in JAMA Neurology. Kelvin...

https://ift.tt/2Otr7FZ

Treatment Tied to Survival Benefit in Complex Bladder Cancer

WEDNESDAY, Oct. 17, 2018 -- Cancer treatment is associated with a clinically meaningful survival benefit in older, medically complex patients with superficial bladder cancer (SBC), according to a study published online Oct. 5 in Cancer. Tullika...

https://ift.tt/2OuZgF3

Compression Collar May Protect Brain of Female Soccer Players

WEDNESDAY, Oct. 17, 2018 -- A jugular vein compression collar can prevent white matter alterations associated with head impact exposure among female high school soccer players, according to a study published online Oct. 15 in the British Journal of...

https://ift.tt/2J2EnLy

Fertility Rates Down for Each Urbanization Level 2007 to 2017

WEDNESDAY, Oct. 17, 2018 -- During 2007 to 2017, fertility rates decreased in the United States for each urbanization level, according to an October data brief published by the U.S. Centers for Disease Control and Prevention National Center for...

https://ift.tt/2OrCGx8

Dose Range of IV Ketamine for Adjunct Tx of Depression Tested

WEDNESDAY, Oct. 17, 2018 -- Two subanesthetic dosages of ketamine appear to provide significant symptom relief to patients with treatment-resistant depression (TRD), according to a study published online Oct. 3 in Molecular Psychiatry. Maurizio...

https://ift.tt/2J2Ekzm

Recommendations Developed to Verify NGT Placement in Children

WEDNESDAY, Oct. 17, 2018 -- Recommendations on best practices for nasogastric tube (NGT) placement and verification in pediatric patients have been developed. The best practice recommendations were published online Sept. 6 in Nutrition in Clinical...

https://ift.tt/2J0UHMR

Seven-Day Metronidazole Better for Trichomoniasis Tx in Women

WEDNESDAY, Oct. 17, 2018 -- A seven-day dose of metronidazole is associated with a reduced likelihood of being Trichomonas vaginalis-positive at test-of-cure compared with single-dose treatment, according to a study published online Oct. 5 in The...

https://ift.tt/2OvaNo0

Lung Cancer Deaths 28% Lower in California Than Rest of U.S.

WEDNESDAY, Oct. 17, 2018 -- Annual lung cancer mortality was 28 percent lower in California than in the rest of the United States in 2013, according to a study published online Oct. 10 in Cancer Prevention Research. John P. Pierce, Ph.D., from the...

https://ift.tt/2J0KFv8.

Long-Term Benzodiazepines Do Not Up Mortality in COPD, PTSD

WEDNESDAY, Oct. 17, 2018 -- For patients with chronic obstructive pulmonary disease (COPD) and comorbid posttraumatic stress disorder (PTSD), long-term benzodiazepine use is not associated with mortality, but there is an association for short-term...

https://ift.tt/2OsQYOa

Well-Being of Young Adults on Kidney Replacement Tx Studied

WEDNESDAY, Oct. 17, 2018 -- For young adults receiving kidney replacement therapy (KRT), well-being and medication adherence are associated with psychological morbidity, according to a study published online Oct. 16 in the Clinical Journal of the...

https://ift.tt/2J25Jl8

Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans

To assess the influence of exercise intensity on physiologic and biologic responses, two different exercise testing protocols were utilized. Methods outlining exercise testing on a cycle ergometer as an incremental maximal oxygen consumption test and endurance, steady state submaximal endurance test are described.

https://ift.tt/2Etgn5M

Rigid Embedding of Fixed and Stained, Whole, Millimeter-Scale Specimens for Section-free 3D Histology by Micro-Computed Tomography

We developed protocols and designed a custom apparatus to enable embedding of millimeter-scale specimens. We present sample preparation procedures with an emphasis on embedding in acrylic resin and polyimide tubing to achieve rigid immobilization and long-term storage of specimens for the interrogation of tissue architecture and cell morphology by micro-CT.

https://ift.tt/2RWRMJi

How cardiovascular check-ups save firefighter lives

Decrease your risk of cardiovascular disease and line-of-duty death with these steps to stay firefighter ready to protect your community

https://ift.tt/2CP5NnU

Increasing sensitivity to EMS PTSD

Educating friends about EMS PTSD can prevent innocent questions that can undo years of mental health work and progress

https://ift.tt/2QRhFJ8

Reduced Microglial Activity and Enhanced Glutamate Transmission in the Basolateral Amygdala in Early CNS Autoimmunity

Emotional dysfunction is common in multiple sclerosis (MS) patients and in mouse models of MS, including experimental autoimmune encephalomyelitis (EAE); however, the etiology of these behaviors is poorly understood. To identify CNS changes associated with these behaviors, we focused on the basolateral amygdala (BLA) because of its central role in the regulation of emotional behavior. Whole-cell recordings were performed in the principal neurons of the BLA in early EAE, before demyelination, T-cell invasion, and motor dysfunction. EAE female mice displayed increased frequency of mEPSCs, with no alteration in amplitude or evoked EPSC paired-pulse ratio compared with controls. We found an increase in the AMPA-NMDA ratio and dendritic spine density, indicating increased numbers of glutamatergic synapses. We saw similar electrophysiological changes in BLA principal neurons after microglia were either inactivated (minocycline) or depleted (Mac1-Saporin) in the BLA. Microglia regulate synapses through pruning, directed by complement protein 3 (C3) expression. C3 was downregulated in the BLA in EAE. Ultrastructural analysis of microglia revealed more complex ramifications and reduced extracellular digestion of cellular elements. We also observed reduced IBA-1 and CD68 staining and lack of proinflammatory cytokine expression in the amygdala. Thus, early EAE is a state of microglial "deactivation" associated with reduced synaptic pruning. This contrasts with the prototypic microglial activation commonly associated with inflammatory CNS disease. Additionally, these data support a role for the acquired immune system to influence both neuronal and microglial function in early CNS autoimmunity.

SIGNIFICANCE STATEMENT Microglia help regulate synaptic homeostasis, but there has been little evidence for how this might be important in neuroinflammatory diseases. The data from this study reveal increased synaptic activity and spine density in early stages of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis) in the basolateral amygdala, a nucleus important in the types of behavioral changes we have previously described. These electrophysiological and morphological effects occurred without significant elevation of local inflammatory cytokines or local demyelination. Unexpectedly, in the context of inflammatory state, we found that microglia were "deactivated." This study provides strong evidence for a link between microglial activity and synaptic function; the conclusions contrast with the generally accepted view that microglia are activated in inflammatory disease.

https://ift.tt/2J2CC0U

Hippocampal-Evoked Feedforward Inhibition in the Nucleus Accumbens

The nucleus accumbens (NAc) is critical for motivated behavior and is rewired following exposure to drugs of abuse. Medium spiny neurons (MSNs) in the NAc express either D1 or D2 receptors and project to distinct downstream targets. Differential activation of these MSNs depends on both excitation from long-range inputs and inhibition via the local circuit. Assessing how long-range excitatory inputs engage inhibitory circuitry is therefore important for understanding NAc function. Here, we use slice electrophysiology and optogenetics to study ventral hippocampal (vHPC)-evoked feedforward inhibition in the NAc of male and female mice. We find that vHPC-evoked excitation is stronger at D1+ than D1– MSNs, whereas inhibition is unbiased at the two cell types. vHPC inputs contact both parvalbumin-positive (PV+) and somatostatin-positive (SOM+) interneurons, but PV+ cells are preferentially activated. Moreover, suppressing PV+ interneurons indicates they are primarily responsible for vHPC-evoked inhibition. Finally, repeated cocaine exposure alters the excitation of D1+ and D1– MSNs, without concomitant changes to inhibition, shifting the excitation/inhibition balance. Together, our results highlight the contributions of multiple interneuron populations to feedforward inhibition in the NAc. Moreover, they demonstrate that inhibition provides a stable backdrop on which drug-evoked changes to excitation occur within this circuit.

SIGNIFICANCE STATEMENT Given the importance of the nucleus accumbens (NAc) in reward learning and drug-seeking behaviors, it is critical to understand what controls the activity of cells in this region. While excitatory inputs to projection neurons in the NAc have been identified, it is unclear how the local inhibitory network becomes engaged. Here, we identify a sparse population of interneurons responsible for feedforward inhibition evoked by ventral hippocampal input and characterize their connections within the NAc. We also demonstrate that the balance of excitation and inhibition that projection neurons experience is altered by exposure to cocaine. Together, this work provides insight into the fundamental circuitry of this region as well as the effects of drugs of abuse.

https://ift.tt/2J4KaAm

Dorsal BNST {alpha}2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors

Stress is a precipitating agent in neuropsychiatric disease and initiates relapse to drug-seeking behavior in addicted patients. Targeting the stress system in protracted abstinence from drugs of abuse with anxiolytics may be an effective treatment modality for substance use disorders. α_2A-adrenergic receptors (α_2A-ARs) in extended amygdala structures play key roles in dampening stress responses. Contrary to early thinking, α_2A-ARs are expressed at non-noradrenergic sites in the brain. These non-noradrenergic α_2A-ARs play important roles in stress responses, but their cellular mechanisms of action are unclear. In humans, the α_2A-AR agonist guanfacine reduces overall craving and uncouples craving from stress, yet minimally affects relapse, potentially due to competing actions in the brain. Here, we show that heteroceptor α_2A-ARs postsynaptically enhance dorsal bed nucleus of the stria terminalis (dBNST) neuronal activity in mice of both sexes. This effect is mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels because inhibition of these channels is necessary and sufficient for excitatory actions. Finally, this excitatory action is mimicked by clozapine-N-oxide activation of the G_i-coupled DREADD hM4Di in dBNST neurons and its activation elicits anxiety-like behavior in the elevated plus maze. Together, these data provide a framework for elucidating cell-specific actions of GPCR signaling and provide a potential mechanism whereby competing anxiogenic and anxiolytic actions of guanfacine may affect its clinical utility in the treatment of addiction.

SIGNIFICANCE STATEMENT Stress affects the development of neuropsychiatric disorders including anxiety and addiction. Guanfacine is an α2A-adrenergic receptor (α2A-AR) agonist with actions in the bed nucleus of the stria terminalis (BNST) that produces antidepressant actions and uncouples stress from reward-related behaviors. Here, we show that guanfacine increases dorsal BNST neuronal activity through actions at postsynaptic α2A-ARs via a mechanism that involves hyperpolarization-activated cyclic nucleotide gated cation channels. This action is mimicked by activation of the designer receptor hM4Di expressed in the BNST, which also induces anxiety-like behaviors. Together, these data suggest that postsynaptic α2A-ARs in BNST have excitatory actions on BNST neurons and that these actions can be phenocopied by the so-called "inhibitory" DREADDs, suggesting that care must be taken regarding interpretation of data obtained with these tools.

https://ift.tt/2J4d97c

A child with severe juvenile dermatomyositis treated with ruxolitinib

Sir,

https://ift.tt/2pZaoLM

Reply: A child with severe juvenile dermatomyositis treated with ruxolitinib

Sir,

https://ift.tt/2NO3GBU

Upland soil cluster γ dominates the methanotroph communities in the karst Heshang Cave

ABSTRACT

Microorganisms are thought to play a critical role in methane (CH₄) consumption in karst caves and yet the presence and diversity of methane-oxidizing bacteria (MOB) remain a mystery. In Heshang Cave, CH₄ concentration decreases from 1.9 ppm at the entrance to 0.65 ppm inside the cave. To explore the presence and diversity of MOB in this cave, weathered rocks and sediment samples were collected from the cave and subjected to molecular analysis. The abundances of MOB were 10⁷–10⁸ copies g⁻¹ dry sample via quantification of the pmoA gene, which are comparable to or even higher than those reported in other terrestrial environments, and account for up to 20% of the total microbial communities. Phylogenetically, MOB communities were dominated by the 'high-affinity' upland soil cluster γ (USCγ), although the predominance of Type Ia MOB was also detected in the permanently waterlogged stream sediment. The estimated CH₄ oxidation potential varied dramatically among samples in the range of 0.6–80 CH₄ m⁻³ d⁻¹. Collectively, this study provides compelling evidence that the high-affinity MOB capable of oxidizing CH₄ at the atmospheric level are present in Heshang Cave, which may play an important role in the CH₄ consumption, and supports karst caves as important atmospheric CH₄ sinks.

https://ift.tt/2pZaiUq