Withdrawn: Prenatal thoraco-amniotic chest drain insertion to manage a case of fetal hydrops secondary to FOXC2

http://bit.ly/2MCL7l4

Glucose control in the ICU

Purpose of review Critically ill patients usually develop hyperglycemia, which is associated with adverse outcome. Controversy exists whether the relationship is causal or not. This review summarizes recent evidence regarding glucose control in the ICU. Recent findings Despite promising effects of tight glucose control in pioneer randomized controlled trials, the benefit has not been confirmed in subsequent multicenter studies and one trial found potential harm. This discrepancy could be explained by methodological differences between the trials rather than by a different case mix. Strategies to improve the efficacy and safety of tight glucose control have been developed, including the use of computerized treatment algorithms. Summary The ideal blood glucose target remains unclear and may depend on the context. As compared with tolerating severe hyperglycemia, tight glucose control is well tolerated and effective in patients receiving early parenteral nutrition when provided with a protocol that includes frequent, accurate glucose measurements and avoids large glucose fluctuations. All patient subgroups potentially benefit, with the possible exception of patients with poorly controlled diabetes, who may need less aggressive glucose control. It remains unclear whether tight glucose control is beneficial or not in the absence of early parenteral nutrition. Correspondence to Greet Van den Berghe, MD, PhD, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium. Tel: +32 16 344021; fax +32 16 344015; e-mail: greet.vandenberghe@kuleuven.be Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2DGGzHt

Thoracic trauma in military settings: a review of current practices and recommendations

Purpose of review To examine current literature on thoracic trauma related to military combat and to explore its relevance to the civilian population. Recent findings Damage control resuscitation (DCR) has improved the management of hemorrhaging trauma patients. Permissive hypotension below 110 mmHg and antifibrinolytic use during DCR is widely accepted, whereas the use of freeze-dried plasma and whole blood is gaining popularity. The Modified Physiologic Triaging Tool can be used for primary triage and it may have applications in civilian trauma systems. Although Tactical Combat Casualty Care protocol recommends the Cric-Key device for surgical cricothyroidotomies, other devices may offer comparable performance. Recommendations for regional anesthesia after blunt trauma are not well defined. Increasing amounts of evidence favor the use of extracorporeal membrane oxygenation for refractory hypoxemia and resuscitative endovascular balloon occlusion of the aorta (REBOA) for severe hemorrhage. REBOA outcomes are potentially improved by partial occlusion and small 7 Fr catheters. Summary The Global War on Terror has provided opportunities to better understand and treat thoracic trauma in military settings. Trauma registries and other data sources have contributed to significant advancements in the management of thoracic trauma in military and civilian populations. Correspondence to Robert Mansky, 545 First Ave, Apt 8I, New York, NY 10016, USA. Tel: +1 516 672 5589; e-mail: rmansky@gmail.com Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2UoSVJW

Noninvasive ventilation versus oxygen therapy in patients with acute respiratory failure

Purpose of review High-flow nasal cannula oxygen therapy (HFOT) is becoming an alternative to noninvasive ventilation (NIV) and standard oxygen in management of patients with acute respiratory failure. Recent findings Patients with de novo acute respiratory failure should be managed with HFOT rather than NIV. Indeed, the vast majority of patients with de novo respiratory failure meet the criteria for ARDS, and NIV does not seem protective, as patients generate overly high tidal volume that may worsen underlying lung injury. However, NIV remains the first-line oxygenation strategy in postoperative patients and those with acute hypercapnic respiratory failure when pH is equal to or below 7.35. During preoxygenation, NIV also seems to be more efficient than standard oxygen using valve-bag mask to prevent profound oxygen desaturation. In postoperative cardiothoracic patients, HFOT could be an alternative to NIV in the management of acute respiratory failure. Summary Recent recommendations for managing patients with acute respiratory failure have been established on the basis of studies comparing NIV with standard oxygen. Growing use of HFOT will lead to new studies comparing NIV versus HFOT in view of more precisely defining the appropriate indications for each treatment. Correspondence to Jean-Pierre Frat, Médecine Intensive Réanimation, CHU de Poitiers, 2 rue la Milétrie, 86021 Poitiers Cedex, France. Tel: +33 5 49 44 40 07; e-mail: jean-pierre.frat@chu-poitiers.fr Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2DJ5pa0

Telemedicine in the ICU: clinical outcomes, economic aspects, and trainee education

Purpose of review The evidence base for telemedicine in the ICU (tele-ICU) is rapidly expanding. The last 2 years have seen important additions to our understanding of when, where, and how telemedicine in the ICU adds value. Recent findings Recent publications and a recent meta-analysis confirm that tele-ICU improves core clinical outcomes for ICU patients. Recent evidence further demonstrates that comprehensive tele-ICU programs have the potential to quickly recuperate their implementation and operational costs and significantly increase case volumes and direct contribution margins particularly if additional logistics and care standardization functions are embedded to optimize ICU bed utilization and reduce complications. Even though the adoption of tele-ICU is increasing and the vast majority of today's medical graduates will regularly use some form of telemedicine and/or tele-ICU, telemedicine modules have not consistently found their way into educational curricula yet. Tele-ICU can be used very effectively to standardize supervision of medical trainees in bedside procedures or point-of-care ultrasound exams, especially during off-hours. Lastly, tele-ICUs routinely generate rich operational data, as well as risk-adjusted acuity and outcome data across the spectrum of critically ill patients, which can be utilized to support important clinical research and quality improvement projects. Summary The value of tele-ICU to improve patient outcomes, optimize ICU bed utilization, increase financial performance and enhance educational opportunities for the next generation of providers has become more evident and differentiated in the last 2 years. Correspondence to Christian D. Becker, MD, PhD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. Tel: +1 914 493 1040; fax: +1 914 493 8373; e-mail: christian.becker@wmchealth.org Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2DHWsxz

Cancers, Vol. 11, Pages 156: High-Throughput Screening Identified Compounds Sensitizing Tumor Cells to Glucose Starvation in Culture and VEGF Inhibitors In Vivo

Cancers, Vol. 11, Pages 156: High-Throughput Screening Identified Compounds Sensitizing Tumor Cells to Glucose Starvation in Culture and VEGF Inhibitors In Vivo

Cancers doi: 10.3390/cancers11020156

Authors: Ran Marciano Manu Prasad Tal Ievy Sapir Tzadok Gabriel Leprivier Moshe Elkabets Barak Rotblat

Tumor cells utilize glucose to fuel their anabolic needs, including rapid proliferation. However, due to defective vasculature and increased glucose uptake, tumor cells must overcome glucose deprivation. Accordingly, tumor cells depend on cellular pathways promoting survival under such conditions. Targeting these survival mechanisms can thus serve as a new therapeutic strategy in oncology. As such, we sought to identify small-molecule inhibitors which sensitize tumor cells to glucose starvation by high-throughput drug screening in vitro. Specifically, we searched for inhibitors that selectively killed tumor cells growing in glucose-free but not in normal medium. This phenotypic drug screen of 7000 agents with MCF7 cells led to the identification of 67 potential candidates, 31 of which were validated individually. Among the identified compounds, we found a high number of compounds known to target mitochondria. The efficacies of two of the identified compounds, QNZ (EVP4593) and papaverine, were validated in four different tumor cell lines. We found that these agents inhibited the mTOR(Mechamistic\Mammilian Target of Rapamycin) pathway in tumor cells growing under glucose starvation, but not under normal conditions. The results were validated and confirmed in vivo, with QNZ and papaverine exhibiting superior antitumor activity in a tumor xenograft model when combined with the VEGF inhibitor bevacizumab (avastin). Administering these drug combinations (i.e., avastin and papaverine, and avastin and QNZ) led to significant reductions in proliferation and mTOR activity of the aggressive DLD1 colon cell line in mice. Given our findings, we propose that compounds targeting metabolically challenged tumors, such as inhibitors of mitochondrial activity, be considered as a therapeutic strategy in cancer.

http://bit.ly/2MHlkbo

Intensivists in U.S. Acute Care Hospitals

Objectives: To determine the total numbers of privileged and full-time equivalent intensivists in acute care hospitals with intensivists and compare the characteristics of hospitals with and without intensivists. Design: Retrospective analysis of the American Hospital Association Annual Survey Database (Fiscal Year 2015). Setting: Two-thousand eight-hundred fourteen acute care hospitals with ICU beds. Patients: None. Interventions: None. Measurements and Main Results: Of the 2,814 acute care hospitals studied, 1,469 (52%) had intensivists and 1,345 (48%) had no intensivists. There were 28,808 privileged and 19,996 full-time equivalent intensivists in the 1,469 hospitals with intensivists. In these hospitals, the median (25–75th percentile) numbers of privileged and full-time equivalent intensivists were 11 (5–24) and 7 (2–17), respectively. Compared with hospitals without intensivists, hospitals with privileged intensivists were primarily located in metropolitan areas (91% vs 50%; p

http://bit.ly/2TrkUsB

Emergency department patients with a prolonged corrected QT interval do not have increased thirty‐day mortality

Abstract

Prolonged QT interval (long QTc) predisposes to torsades de pointes, which can present with seizures, syncope, and sudden death. (1) While one‐third of emergency department (ED) patients may have a prolonged corrected QT (QTc) interval, (2) often discovered incidentally, clinical significance is uncertain. In hospitalized patients or long‐term community studies, long QTc is associated with increased mortality. (1, 3) The only ED‐based study estimating mortality found that 5% of admitted patients died, although discharged patients—nearly half the cohort—were not evaluated. (2) Our study purpose was to compare the 30‐day mortality rate of ED patients with long and normal QTc, including those discharged from the ED.

This article is protected by copyright. All rights reserved.

http://bit.ly/2UpMaHN

Benchmarking Complications Associated with Esophagectomy

Objective: Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy. Summary of Background Data: Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects. Methods: The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period. Results: Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively. Conclusion: Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.

http://bit.ly/2AB89ny

How ARVC-related mutations destabilize desmoplakin: an MD study

Arrythmogenic right ventricular cardiomiopathy (ARVC) is a familial heart disease linked to mutations in several desmosomal proteins, but the specific effects of these mutations on the molecular level are poorly understood. Among the many documented ARVC-related genetic variants, a striking hotspot of 9 mutations has been identified in the plakin domain of desmoplakin. This hotspot can be found at the meeting point of three different subdomains of desmoplakin: two spectrin repeats (SRs) and a Src homology 3 domain (SH3).

http://bit.ly/2B9HoHm

A two-pulse cellular stimulation test elucidates variability and mechanisms in signaling pathways

Mammalian cells respond in a variable manner when provided with physiological pulses of ligand, such as low concentrations of acetylcholine present for just tens of seconds or TNFα for just tens of minutes. For a two-pulse stimulation, some cells respond to both pulses, some do not respond, and yet others respond to only one or the other pulse. Are these different response patterns the results of the small number of ligands being able to only stochastically activate the pathway at random times, or an output pattern from a deterministic algorithm responding differently to different stimulation intervals? If the response is deterministic in nature, what parameters determine whether a response is generated or skipped? To answer these questions, we developed a two-pulse test that utilizes different rest periods between stimulation pulses.

http://bit.ly/2Tkv7qp

Anomalous diffusion in inverted variable-lengthscale fluorescence correlation spectroscopy

Using fluorescence correlation spectroscopy (FCS) to distinguish between different types of diffusion processes is often a perilous undertaking, as the analysis of the resulting autocorrelation data is model-dependant. Two recently introduced strategies, however, can help move towards a model-independent interpretation of FCS experiments: 1) the obtention of correlation data at different length-scales and 2) its inversion to retrieve the mean-squared displacement associated with the process under study.

http://bit.ly/2TlX4hR

Correction: Mobile phone use and incidence of brain tumour histological types, grading or anatomical location: a population-based ecological study

Karipidis K, Elwood M, Benke G, et al. Mobile phone use and incidence of brain tumour histological types, grading or anatomical location: a population-based ecological study. BMJ Open 2018;8:e024489. doi: 10.1136/bmjopen-2018-024489.

The previous version of this manuscript contains some error in figure 2 legends. Since the paper was first published online the legend in the first graph of figure 2 has been edited. It should appear as follows:

Giloma, Glioblastoma, Other_glioma, Meningioma, Other, Unspecified.

­

Instead of

­

Frontal, Temporal, Parietal, Other locations, Overlapping, Unspecified.

http://bit.ly/2UvfnBl

Accelerometer compared with questionnaire measures of physical activity in relation to body size and composition: a large cross-sectional analysis of UK Biobank

Objectives

Previous studies of the association between physical activity and adiposity are largely based on physical activity and body mass index (BMI) from questionnaires, which are prone to inaccurate and biased reporting. We assessed the associations of accelerometer-measured and questionnaire-measured physical activity with BMI, waist circumference and body fat per cent measured by bioelectrical impedance and dual-energy X-ray absorptiometry (DXA).

Design

Cross-sectional analysis of UK Biobank participants.

Setting

UK Biobank assessment centres.

Participants

78 947 UK Biobank participants (35 955 men and 42 992 women) aged 40–70 at recruitment, who had physical activity measured by both questionnaire and accelerometer.

Main outcome measures

BMI, waist circumference and body fat per cent measured by bioelectrical impedance.

Results

Greater physical activity was associated with lower adiposity. Women in the top 10th of accelerometer-measured physical activity had a 4.8 (95% CI 4.6 to 5.0) kg/m² lower BMI, 8.1% (95% CI 7.8% to 8.3%) lower body fat per cent and 11.9 (95% CI 11.4 to 12.4) cm lower waist circumference. Women in the top 10th of questionnaire-measured physical activity had a 2.5 (95% CI 2.3 to 2.7) kg/m² lower BMI, 4.3% (95% CI 4.0% to 4.5%) lower body fat per cent and 6.4 (95% CI 5.9 to 6.9) cm lower waist circumference, compared with women in the bottom 10th. The patterns were similar in men and also similar to body fat per cent measured by DXA compared with impedance.

Conclusion

Our findings of approximately twofold stronger associations between physical activity and adiposity with objectively measured than with self-reported physical activity emphasise the need to incorporate objective measures in future studies.

http://bit.ly/2DKsLfd

Prehospital factors associated with death on hospital arrival after traffic crash in Japan: a national observational study

Objective

Although it is important to assess prehospital factors associated with traffic crash fatalities to decrease them as a matter of public health, such factors have not been fully revealed.

Methods

Using data from the Japanese Trauma Data Bank, a large hospital-based trauma registry in Japan, we retrospectively analysed traffic crash patients transported to participating facilities that treated patients with severe trauma from 2004 to 2015. This study defined registered emergency patients whose systolic blood pressure was 0 mm Hg or heart rate was 0 bpm at hospital arrival as being in prehospital cardiopulmonary arrest (CPA). Prehospital factors associated with prehospital CPA due to traffic crash were assessed with multivariable logistic regression analysis.

Results

In total, 66 243 patients were eligible for analysis. Of them, 3390 (5.1%) patients were in CPA at hospital arrival. A multivariable logistic regression model showed the following factors to be significantly associated with prehospital CPA: ages 60–74 years (adjusted OR (AOR) 1.256, 95% CI 1.142 to 1.382) and ≥75 years (AOR 1.487, 95% CI 1.336 to 1.654), male sex (AOR 1.234, 95% CI 1.139 to 1.338), night-time (AOR 1.575, 95% CI 1.458 to 1.702), weekend including holiday (AOR 1.078, 95% CI 1.001 to 1.161), rural area (AOR 1.181, 95% CI 1.097 to 1.271), back seat passenger (AOR 1.227, 95% CI 0.985 to 1.528) and pedestrian (AOR 1.754, 95% CI 1.580 to 1.947) as types of patients.

Conclusion

In this population, factors associated with prehospital CPA due to a traffic crash were elderly people, male sex, night-time, weekend/holiday, back seat passenger, pedestrian and rural area. These fundamental data may be of help in reducing and preventing traffic crash deaths.

http://bit.ly/2UoL8vG

Reporting, presentation and wording of recommendations in clinical practice guideline for gout: a systematic analysis

Objectives

We systematically analysed recommendations from gout guidelines as an example, to provide a basis for developing a reporting standard of recommendations in clinical practice guidelines (CPGs).

Design

Systematic review without meta-analysis.

Methods

We systematically searched MEDLINE and all relevant guideline websites (National Institute for Health and Care Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, WHO, Guidelines International Network, DynaMed, UpTodate, Best Practice) from their inception to January 2017 to identify and select gout CPGs. We used search terms such as 'gout', 'hyperuricemia' and 'guideline'. We included the eligible CPGs of gout according to the predefined inclusion and exclusion criteria after screening titles, abstracts and full texts. The characteristics of recommendations reported in the included guidelines were extracted and analysed.

Results

A total of 15 gout guidelines with a range of 5–80 recommendations were retrieved. Several indicators were used in the gout guidelines to facilitate identification of recommendations, including grouping all recommendations in a summary section, formatting recommendations in a particular or special way, using locating words for recommendations and indicating the strength of recommendation and quality of evidence. We found some components commonly used in the recommendations. The wording of recommendations varied across guidelines. Recommendations were detailed and explained in the section of rationale and explanation of recommendations. In some guidelines, recommendations were accompanied with other material to assist their reporting.

Conclusions

Variability and inconsistency were found on the reporting and presentation of recommendations in gout guidelines. Several points for reporting recommendation can be summarised. First, we suggested summarising and highlighting the core recommendations in a guideline. Second, guideline developers should try to structure and write recommendations reasonably. Third, it was necessary to detail and explain the recommendations and their rationale. Finally, describing and providing other potential useful contents was also a helpful way for clear reporting.

http://bit.ly/2DJTzMR

Evaluating the impact of global fund withdrawal on needle and syringe provision, cost and use among people who inject drugs in Tijuana, Mexico: a costing analysis

Objective

From 2011 to 2013, the Global Fund (GF) supported needle and syringe programmes in Mexico to prevent transmission of HIV among people who inject drugs. It remains unclear how GF withdrawal affected the costs, quality and coverage of needle and syringe programme provision.

Design

Costing study and longitudinal cohort study.

Setting

Tijuana, Mexico.

Participants

Personnel from a local needle and syringe programme (n=6) and people who inject drugs (n=734) participating in a longitudinal study.

Primary outcome measures

Provision of needle and syringe programme services and cost (per contact and per syringe distributed, in 2017 $USD) during GF support (2012) and after withdrawal (2015/16). An additional outcome included needle and syringe programme utilisation from a concurrent cohort of people who inject drugs during and after GF withdrawal.

Results

During the GF period, the needle and syringe programme distributed 55 920 syringes to 932 contacts (60 syringes/contact) across 14 geographical locations. After GF withdrew, the needle and syringe programme distributed 10 700 syringes to 2140 contacts (five syringes/contact) across three geographical locations. During the GF period, the cost per harm reduction contact was approximately 10-fold higher compared with after GF ($44.72 vs $3.81); however, the cost per syringe distributed was nearly equal ($0.75 vs $0.76) due to differences in syringes per contact and reductions in ancillary kit components. The mean log odds of accessing a needle and syringe programme in the post-GF period was significantly lower than during the GF period (p=0.02).

Conclusions

Withdrawal of GF support for needle and syringe programme provision in Mexico was associated with a substantial drop in provision of sterile syringes, geographical coverage and recent clean syringe utilisation among people who inject drugs. Better planning is required to ensure harm reduction programme sustainability is at scale after donor withdrawal.

http://bit.ly/2UtIk0y

Alternative service models for delivery of healthcare services in high-income countries: a scoping review of systematic reviews

Introduction

Costs associated with the delivery of healthcare services are growing at an unsustainable rate. There is a need for health systems and healthcare providers to consider the economic impacts of the service models they deliver and to determine if alternative models may lead to improved efficiencies without compromising quality of care. The aim of this protocol is to describe a scoping review of the extent, range and nature of available synthesised research on alternative delivery arrangements for health systems relevant to high-income countries published in the last 5 years.

Design

We will perform a scoping review of systematic reviews of trials and economic studies of alternative delivery arrangements for health systems relevant to high-income countries published on 'Pretty Darn Quick' (PDQ)-Evidence between 1 January 2012 and 20 September 2017. All English language systematic reviews will be included. The Cochrane Effective Practice and Organisation of Care taxonomy of health system interventions will be used to categorise delivery arrangements according to: how and when care is delivered, where care is provided and changes to the healthcare environment, who provides care and how the healthcare workforce is managed, co-ordination of care and management of care processes and information and communication technology systems. This work is part of a 5-year Partnership Centre for Health System Sustainability aiming to investigate and create interventions to improve health-system-performance sustainability.

Ethics and dissemination

No primary data will be collected, so ethical approval is not required. The study findings will be published and presented at relevant conferences.

http://bit.ly/2DI62R6

Nordic Innovative Trials to Evaluate osteoPorotic Fractures (NITEP) Collaboration: The Nordic DeltaCon Trial protocol--non-operative treatment versus reversed total shoulder arthroplasty in patients 65 years of age and older with a displaced proximal humerus fracture: a prospective, randomised controlled trial

Introduction

The proximal humerus fracture (PHF) is one of the most common fractures in the elderly. The majority of PHFs are treated non-operatively, while 15%–33% of patients undergo surgical treatment. Recent randomised controlled trial (RCT) and meta-analyses have shown that there is no difference in outcome between non-operative treatment and locking plate or hemi-arthroplasty. During the past decade, reverse total shoulder arthroplasty (RTSA) has gained popularity in the treatment of PHF, although there is a lack of RCTs comparing RTSA to non-operative treatment.

Methods

This is a prospective, single-blinded, randomised, controlled, multicentre and multinational trial comparing RTSA with non-operative treatment in displaced proximal humeral fractures in patients 65–85 years. The primary outcome in this study is QuickDASH-score measured at 2 years. Secondary outcomes include visual analogue scale for pain, grip strength, Oxford shoulder score, Constant score and the number of reoperations and complications.

The hypothesis of the trial is that operative treatment with RTSA produces better outcome after 2 and 5 years measured with QuickDASH.

Ethics and dissemination

In this protocol, we describe the design, method and management of the Nordic DeltaCon trial. The ethical approval for the trial has been given by the Regional Committee for Medical and Health Research Ethics, Norway. There have been several examples in orthopaedics of innovations that result in failure after medium-term follow-ups . In order to prevent such failures and to increase our knowledge of RSTA, we feel a large-scale study of the effects of the surgery on the outcome that focuses on the complications and reoperations is warranted. After the trial 2-year follow-up, the results will be disseminated in a major orthopaedic publication.

Trial registration number

NCT03531463; Pre-Results.

http://bit.ly/2UveWab

School-based educational and on-site vaccination intervention among adolescents: study protocol of a cluster randomised controlled trial

Introduction

Childhood vaccination programmes have been established in all Organisation for Economic Co-operation and Development (OECD) countries; however, measles, mumps and rubella (MMR) as well as diphtheria, tetanus, pertussis and polio (Tdap-IPV) vaccination rates are not optimal in adolescents. Education in combination with easy access vaccination may be a promising approach to improve vaccination rates. We aim at improving MMR and Tdap-IPV rates in a school setting in the context of a planned cluster randomised controlled trial (cRCT), the present paper describes the detailed protocol of this trial.

Methods and analysis

We will conduct a school-based cRCT, where schools will be randomised to either an educational condition addressing knowledge, risk communication and enhancing self-efficacy regarding vaccination or a low-intensity information condition. In both conditions, a bus equipped with medical staff and materials, will be delivering MMR and Tdap-IPV vaccine directly after the intervention. Schools in the city centre of Berlin, Germany, will be stratified by percentage of migration and type of school. Primary outcome is the number of students who receive vaccination in the bus. Secondary outcomes are knowledge and self-efficacy. An estimated sample size of 355 school classes with approximately 25 students per class is required. The planned analyses will take the nested structure of students, classes and schools into account.

Ethics and dissemination

The study will be performed according to the principles of Good Clinical Practice and the Declaration of Helsinki. Approval was obtained by the local ethics committee. Parents of all students will be informed in advance. Their written consent will be obtained, in case students are underage. For dissemination, we will engage with governmental organisations to create potential of our educational unit to be included in future public health prevention schemes.

Trial registration number

ISRCTN18026662;Pre-results.

http://bit.ly/2UrVwmh

Prevalence and determinants of serological evidence of atrophic gastritis among Arab and Jewish residents of Jerusalem: a cross-sectional study

Objective

Understanding the correlates of premalignant gastric lesions is essential for gastric cancer prevention. We examined the prevalence and correlates of serological evidence of atrophic gastritis, a premalignant gastric condition, using serum pepsinogens (PGs) in two populations with differing trends in gastric cancer incidence.

Methods

In a cross-sectional study, using ELISA we measured serum PGI and PGII concentrations (Biohit, Finland), Helicobacter pylori serum IgG and cytotoxin-associated gene A (CagA) antigen IgG antibodies in archived sera of 692 Jews and 952 Arabs aged 25–78 years, randomly selected from Israel's population registry in age–sex and population strata. Multivariable logistic regression analyses were performed.

Results

Using cut-offs of PGI <30µg/L or PGI:PGII <3.0, the prevalence of atrophic gastritis was higher among Arab than Jewish participants: 8.8% (95% CIs 7.2% to 10.8%) vs 5.9% (95% CI 4.4% to 7.9%), increasing with age in both groups (p<0.001 for trend). Among Jewish participants, infection with H. pylori CagA phenotype was positively related to atrophic gastritis: adjusted OR (aOR) 2.16 (95% CI 0.94 to 4.97), but not to non-CagA infections aOR 1.17 (95% CI 0.53 to 2.55). The opposite was found among Arabs: aOR 0.09 (95% CI 0.03 to 0.24) for CagA positive and aOR 0.15 (95% CI 0.06 to 0.41) for Cag A negative phenotypes (p<0.001 for interaction). Women had a higher atrophic gastritis prevalence than men. Obesity and smoking were not significantly related to atrophic gastritis; physical activity tended to be inversely associated in Arabs (p=0.08 for interaction).

Conclusions

The prevalence of atrophic gastritis was higher among Arabs than Jews and was differently associated with the CagA phenotype.

http://bit.ly/2DJ58Ui

Effectiveness of intravenous albumin therapy to prevent spontaneous bacterial peritonitis, renal dysfunction and death in adults with cirrhosis: a protocol for a systematic review

Introduction

Use of albumin therapy is recommended for management of disease complications in cirrhosis. The effectiveness of albumin to prevent specific disease complications and death, however, is less clear.

Methods and analysis

We will search Medline (Ovid), Embase (Ovid), Cochrane Hepato-Biliary Controlled Trials Register and Cochrane Central Register of Controlled Trials for published reports on randomised controlled trials and observational studies on the effectiveness of intravenous albumin therapy to prevent spontaneous bacterial peritonitis, renal dysfunction and death in cirrhotic patients. Two independent reviewers will screen the studies for eligibility, extract data and assess risk of bias and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation system. Random effects meta-analyses will be performed when appropriate.

Ethics and dissemination

As no primary data will be collected, a formal ethical approval is not required. We plan to publish the results of this study in a relevant peer-reviewed journal or journals. The study results may also be presented at relevant conferences and meetings.

PROSPERO registration number

CRD42018100798.

http://bit.ly/2Uq4PmX

Changes in vulnerability among older patients with cardiovascular disease in the first 90 days after hospital discharge: A secondary analysis of a cohort study

Objectives

(1) To compare changes in vulnerability after hospital discharge among older patients with cardiovascular disease who were discharged home with self-care versus a home healthcare (HHC) referral and (2) to examine factors associated with changes in vulnerability in this period.

Design

Secondary analysis of longitudinal data from a cohort study.

Participants and setting

834 older (≥65 years) patients hospitalised for acute coronary syndromes and/or acute decompensated heart failure who were discharged home with self-care (n=713) or an HHC referral (n=121).

Outcome

Vulnerability was measured using Vulnerable Elders Survey 13 (VES-13) at baseline (prior to hospital admission) and 30 days and/or 90 days after hospital discharge. Effects of HHC referral on postdischarge change in vulnerability were examined using three linear regression approaches, with potential confounding on HHC referral adjusted by propensity score matching.

Results

Overall, 44.4% of the participants were vulnerable at prehospitalisation baseline and 34.4% were vulnerable at 90 days after hospital discharge. Compared with self-care patients, HHC-referred patients were more vulnerable at baseline (66.9% vs 40.3%), had more increase (worsening) in VES-13 score change (B=–1.34(–2.07, –0.61), p<0.001) in the initial 30 days and more decrease (improvement) in VES-13 score change (B=0.83(0.20, 1.45), p=0.01) from 30 to 90 days after hospital discharge. Baseline vulnerability and the HHC referral attributed to 14%–16% of the variance in vulnerability change during the 90 postdischarge days, and 6% was attributed by patient age, race (African-American), depressive symptoms, and outpatient visits and hospitalisations in the past year.

Conclusion

After adjusting for preceding vulnerability and covariates, older hospitalised patients with cardiovascular disease referred to HHC had delayed recovery in vulnerability in first initial 30 days after hospital discharge and greater improvement in vulnerability from 30 to 90 days after hospital discharge. HHC seemed to facilitate improvement in vulnerability among older patients with cardiovascular disease from 30 to 90 days after hospital discharge.

http://bit.ly/2DI61N2

Developing evidence-based recommendations for optimal interpregnancy intervals in high-income countries: protocol for an international cohort study

Introduction

Short interpregnancy interval (IPI) has been linked to adverse pregnancy outcomes. WHO recommends waiting at least 2 years after a live birth and 6 months after miscarriage or induced termination before conception of another pregnancy. The evidence underpinning these recommendations largely relies on data from low/middle-income countries. Furthermore, recent epidemiological investigations have suggested that these studies may overestimate the effects of IPI due to residual confounding. Future investigations of IPI effects in high-income countries drawing from large, population-based data sources are needed to inform IPI recommendations. We aim to assess the impact of IPIs on maternal and child health outcomes in high-income countries.

Methods and analysis

This international longitudinal retrospective cohort study will include more than 18 million pregnancies, making it the largest study to investigate IPI in high-income countries. Population-based data from Australia, Finland, Norway and USA will be used. Birth records in each country will be used to identify consecutive pregnancies. Exact dates of birth and clinical best estimates of gestational length will be used to estimate IPI. Administrative birth and health data sources with >99% coverage in each country will be used to identify maternal sociodemographics, pregnancy complications, details of labour and delivery, birth and child health information. We will use matched and unmatched regression models to investigate the impact of IPI on maternal and infant outcomes, and conduct meta-analysis to pool results across countries.

Ethics and dissemination

Ethics boards at participating sites approved this research (approval was not required in Finland). Findings will be published in peer-reviewed journals and presented at international conferences, and will inform recommendations for optimal IPI in high-income countries. Findings will provide important information for women and families planning future pregnancies and for clinicians providing prenatal care and giving guidance on family planning.

http://bit.ly/2UoL7rC

Living with dementia with Lewy bodies: an interpretative phenomenological analysis

Objective

To explore the subjective experience of living with dementia with Lewy bodies (DLB).

Design

A qualitative study of in-depth interviews using interpretative phenomenological analysis.

Setting

A memory clinic in Malmö, southern Sweden.

Participants

A purposive sample of five male participants with DLB between the ages of 78 and 88 years and disease duration of 1.5–7 years.

Results

Three themes were identified in relation to the participants' experiences of living with DLB: (1) disease impact, in terms of symptom experience and restricted participation and activities; (2) self-perception and coping strategies; (3) importance of others, such as healthcare, family and friends.

Conclusions

This study provides a broad insight into the first-hand experience of living with DLB and how it compares with other dementia types. Findings highlight factors characterising the disease experience and well-being, and how persons with DLB address challenges arising secondary to disease. These findings are important for both research and clinical practice, demonstrating the feasibility of direct involvement of DLB persons in identifying important aspects of care, which include improved healthcare services.

http://bit.ly/2DIRccU

Meta-analysis of the diagnostic value of Wisteria floribunda agglutinin-sialylated mucin1 and the prognostic role of mucin1 in human cholangiocarcinoma

Objective

Serum carbohydrate antigen 19–9 (CA19-9) is a widely used tumour marker for cholangiocarcinoma (CCA). However, it is not a necessarily good CCA marker in terms of diagnostic accuracy. The purpose of this study is to evaluate the diagnostic value of Wisteria floribundaagglutinin-sialylated Mucin1 (WFA-MUC1) and the prognostic role of Mucin1 (MUC1) in human CCA.

Design

Meta-analysis.

Data sources

Studies published in PubMed, Web of Science, The Cochrane Library and the China National Knowledge Infrastructure up to 11 October 2017.

Eligibility criteria

We included reports assessing the diagnostic capacity of WFA-MUC1 and the prognostic role of MUC1 in CCA. The receiver operating characteristic curve (ROC) of WFA-MUC1 and/or CA19-9 was described, and the HRs including 95% CI and the corresponding p value for MUC1 can be extracted.

Data extraction and synthesis

Two independent researchers extracted data and assessed risk of bias. The diagnostic sensitivity and specificity data of WFA-MUC1 were extracted and analysed as bivariate data. Pooled HRs and its 95% CI for MUC1 were calculated with a random-effects meta-analysis model on overall survival of resectable CCA.

Results

Sixteen reports were included in this study. The pooled sensitivity and specificity of WFA-MUC1 were 0.76 (95% CI 0.71 to 0.81) and 0.72 (95% CI 0.59 to 0.83) in serum, 0.85 (95% CI 0.81 to 0.89) and 0.72 (95% CI 0.64 to 0.80) in bile and 0.72 (95% CI 0.50 to 0.87) and 0.85 (95% CI 0.70 to 0.93) in tissue, respectively. The summary ROC (SROC) were 0.77 (95% CI 0.73 to 0.81) in serum, 0.88 (95% CI 0.85 to 0.90) in bile and 0.86 (95% CI 0.83 to 0.89) in tissue, respectively. Furthermore, the pooled sensitivity and specificity and the SROC of CA19-9 in serum were 0.67 (95% CI 0.61 to 0.72), 0.86 (95% CI 0.75 to 0.93) and 0.75 (95% CI 0.71 to 0.79), respectively. The pooled HRs for MUC1 was 2.20 (95% CI 1.57 to 3.01) in CCA and 4.17 (95% CI 1.71 to 10.17) in mass-forming intrahepatic CCA.

Conclusions

Compared with CA19-9, WFA-MUC1 was shown to possess stronger diagnostic capability. MUC1 could serve as a prognosis factor for poor outcomes of CCA, particularly, mass-forming intrahepatic CCA.

http://bit.ly/2UpCEV5

Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study

Introduction

Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemoradiotherapy. Four separate dose escalation accelerated radiotherapy schedules have been completed in UK (CHART-ED, IDEAL-CRT, I-START and Isotoxic IMRT). This study will compare these schedules with a UK standard sequential chemoradiotherapy schedule of 55 Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in a phase III study, the aim is to use a combined randomised phase II screening/'pick the winner' approach to identify the best schedule to take into a randomised phase III study against conventionally fractionated radiotherapy.

Methods and analysis

Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2–4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local–regional failure, toxicity and cost-effectiveness as secondary objectives.

Ethics and dissemination

The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally.

Trial registration number

ISRCTN47674500.

http://bit.ly/2UpCxZF

Intra-atrial course of the right coronary artery: depiction of a potentially hazardous entity on dual-source CT

http://bit.ly/2Upm8o7

Placental chorioangioma associated with polyhydramnios and hydrops fetalis

A 27-year-old multigravida woman was noted on routine growth scan at 27 weeks gestation to have a central placental hypoechoic area measuring 6.7x6.0x4.4 cm. A subsequent magnetic resonance scan confirmed a solid mass in the placenta lying anteriorly; therefore, a preliminary diagnosis of giant placental chorioangioma was made. A repeat ultrasound scan at 30 weeks gestation indicated that the mass had increased, with the presence of polyhydramnios. The patient experienced reduced fetal movements at 31 weeks gestation. There was persistent fetal tachycardia at 33 weeks gestation, and consequently the neonate was delivered by emergency caesarean section. The placenta revealed a large chorioangioma. The neonate's birth weight was 2.85 kg and non-immune hydrops fetalis was diagnosed. The neonate improved significantly in the neonatal intensive care unit and is currently well with no medical problems.

http://bit.ly/2Upm4ET

Bacteraemia and multiple liver abscesses due to Fusobacterium nucleatum in a patient with oropharyngeal malignancy

Fusobacterium infections can have a wide clinical spectrum, ranging from mild infections to severe sepsis and abscess formation. This range depends partly on the patient's underlying conditions, such as immunosuppression or malignancy. Fusobacteria are commensal rods in the oropharyngeal cavity and digestive tract, but should mucosal barrier disruption occur, in the presence of the above-mentioned predisposing conditions, fusobacteria can spread and cause infections in the soft tissues, liver and so on. An elderly woman was admitted with an altered level of consciousness (lethargy). The ensuing workup revealed a posterior oral cavity tumour (squamous cell carcinoma), Fusobacterium nucleatum bacteraemia and liver abscesses. Due to the severe sepsis, the patient was referred to our intensive care unit, but she passed away despite antibiotic treatment.

http://bit.ly/2Upm1sH

Alports syndrome and intracranial aneurysm: mere coincidence or undiscovered causal relationship

A 44-year-old Caucasian man with a history of deceased donor renal transplant for end-stage renal disease from Alport's syndrome (AS), presented with a spontaneous subarachnoid haemorrhage and hydrocephalus. Following an external ventricular drain for the hydrocephalus, a CT angiography revealed a dissection of the left vertebral artery extending into vertebro-basilar junction necessitating a bypass between left occipital artery to left posterior inferior cerebellar artery. He had a posterior fossa Craniectomy, C1 laminectomy and coiling off, of the left vertebral artery. Postprocedure course was prolonged but uneventful with complete recovery and normal renal function 18 months postpresentation. AS, a disease caused by abnormalities in the synthesis of type IV collagen, can cause aneurysms with severe and permanent neurological sequalae. We present a case of AS with intracranial arterial dissection with potential life-threatening consequences and discuss the genetic and molecular basis of AS along with review of the relevant literature.

http://bit.ly/2DI3Vg8

Disseminated intestinal basidiobolomycosis with mycotic aneurysm mimicking obstructing colon cancer

Basidiobolomycosis is a rare fungal infection that may affect the gastrointestinal tract. It is caused by Basidiobolus ranarum and less than 80 cases have been reported in the literature. The incidence seems to be higher in the Middle East and in particular Saudi Arabia where most cases are diagnosed in the south-western region. An 18-year-old woman presented to the emergency department with an obstructing caecal mass initially suspected to be malignant. Surgical resection was complicated by bowel perforation, histology and cultures confirmed basidiobolomycosis infection. The postoperative course was complicated by an enterocutaneous fistula, fungal intra-abdominal abscesses, liver and lung abscesses, formation of mycotic hepatic artery aneurysm and meningoencephalitis. The patient eventually expired due to sepsis despite aggressive treatment. Diagnosis and management of such rare cases are very challenging and require a multidisciplinary approach. Complications are common and associated with a high mortality.

http://bit.ly/2UplW8n

Fusobacterium necrophorum sepsis after tonsillitis/pharyngitis

Fusobacterium necrophorum is a rare infection most notable for causing Lemierre's syndrome. This consists of a primary oropharyngeal infection and septic thrombophlebitis, and one or more metastatic focus. Prior to the widespread use of antibiotics, Lemierre's syndrome commonly followed a rapidly progressing course, with a high mortality. We describe a case of a previously well 18-month-old boy who presented to the emergency department with a 3-week history of progressive, right-sided, painful neck swelling and systemic sepsis. He was initially treated conservatively with intravenous antibiotics, but ultimately required surgical drainage. Lemierre's syndrome is a rare condition with increasing incidence which can have significant adverse outcomes including death. Early recognition and treatment are essential, but identifying Lemierre's disease is challenging.

http://bit.ly/2DJfFPp

Emergency management of massive haemoptysis

In this manuscript, we present a rare case of massive haemoptysis secondary to rupture of a pulmonary artery aneurysm, which was unusual for having occurred in the absence of tuberculosis or a vasculitis. We describe the emergency management of this that ultimately resulted in the patient's survival from both an anaesthetic and surgical perspective, as well as discuss the role of interventional radiology in this situation.

http://bit.ly/2UwbJqV

Takotsubo cardiomyopathy triggered by status epilepticus: case report and literature review

Takotsubo cardiomyopathy (TC) is acute stress-induced cardiomyopathy with characteristic transient wall motion abnormalities. TC has a clinical presentation similar to an acute coronary syndrome, including chest pain or dyspnoea, ECG changes and elevated cardiac enzymes. TC often occurs after emotional stress. There are approximately 50 TC cases reported related to seizure activity, and our review revealed 15 articles which were associated with status epilepticus. This condition can be a serious complication of seizures. We report a case of TC after status epilepticus in a patient who had been seizure-free for 20 years.

http://bit.ly/2DI3TVy

Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

We describe three cases of pulmonary aspergillosis (PA) in three patients without traditional risk factors for invasive aspergillosis infection, such as prolonged neutropenia or high dose systemic corticosteroid therapy. All three patients developed PA while taking tyrosine kinase inhibitors (TKI) and sustained greater clinical improvement once TKI were withdrawn. Our case series supports the theory TKI treatment can increase susceptibility to PA without causing neutropenia. Recognition that TKI treatment may predispose to invasive aspergillosis will allow for rapid recognition of affected patients and more effective management of future cases.

http://bit.ly/2UplJlB

Tubulointerstitial nephritis and uveitis syndrome in a female adult

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease characterised by the association of acutetubulointerstitial nephritis and uveitis. It affects mainly children and young women. Drugs and infections may be precipitating factors. It is a diagnosis of exclusion. The mainstays of treatment are topical and systemic corticosteroids. Prognosis is usually favourable. We report a case of TINU which occurred in our unit. A 37-year-old woman presented with an influenza-like illness, bilateral ocular pain and blurred vision. Ophthalmological evaluation revealed bilateral anterior uveitis and later renal involvement was seen as acute tubulointerstitial nephritis. A diagnosis of TINU was assumed after exclusion of other systemic diseases. She was treated with topical corticosteroids for the uveitis and evolved favourably, with resolution of ocular symptoms and normalisation of serum creatinine and proteinuria. This case highlights the importance of a high degree of clinical suspicion to make the diagnosis of TINU syndrome.

http://bit.ly/2DK2EVT

Acute ischaemic stroke-related choreoathetosis treated with arterial thrombectomy

A rare case of acute choreoathetosis after acute stroke is presented. This 66-years-old, right-handed Caucasian woman presented with weakness of her right arm and right leg with dysarthria, which resolved by the time she arrived in the emergency department. No obvious focal sign apart from the abnormal choreoathetoid movement of the right arm and leg and of the neck was present. Her medical history included atrial fibrillation without anticoagulation. CT head was nil acute (Alberta Stroke Program Early CT Score of 10). CT angiography of the carotids showed a hyperdense M2 segment of the left middle cerebral artery. Intravenous thrombolysis immediately followed by thrombectomy was decided. Using the Penumbra aspiration device (ACE 68) two clots were removed with two aspirations. A small distal clot remained but partial recanalisation (Thrombolysis in Myocardial Infarction/Thrombolysis in Cerebral Infarction 2b) was achieved. 30 seconds after restoring blood flow, the choreoathetoid movements ceased. The patient was brought to intensive care for further monitoring, which was uneventful.

http://bit.ly/2Um2CsG

Persistent sciatic artery resembles a soft-tissue sarcoma in presentation

Persistent sciatic artery (PSA) is a rare vascular anomaly with estimated incidence of 0.03%–0.06%. It has high incidence of complications including aneurysmal formation and ischaemia that may lead to amputation. During early embryonic development, the sciatic artery (which usually supply fetal lower buds and caudal part) disappears when the superficial femoral artery develops properly and the lower limbs grow. On clinical examination, usually a pulsating gluteal mass (the aneurysm) is appreciated with weak or absent femoral artery (Cowie's sign). However, our patient had presented in a different way. She was referred from peripheral clinic as a case of possible liposarcoma in the gluteal region. On examination, there was obvious asymmetry between both buttocks. The affected side was hard, firm in consistency with no appreciable pulsation. Nevertheless, on auscultation there was a bruit of low grade. Peripheral pulses were palpable. Our clinical impression was towards a sarcoma namely a liposarcoma. MRI was requested to evaluate the mass. The radiology report suggested that most probably it is an angiosarcoma with slim possibility of being a cavernous haemangioma. The trucut biopsy was deferred, in view of the high vascular nature of the lesion. The plan was as follow: To do angiography and embolisation of the main feeding vessels, with the possibility of biopsy in a second incident if indicated.During the conventional angiography, the pathology revealed itself. The patient was type 3 according to Pillet-Gauffre classification (PSA is limited to gluteal area and the popliteal artery arising from the femoral artery) associated with huge arteriovenous malformation. Embolisation with different materials including coils, beads and foam was ineffective. Finally, the radiologist excluded the root of the sciatic artery by a stent bridging from common iliac to external iliac artery. This successfully occluded the PSA.

http://bit.ly/2DIn55e

Congenital lateral cleft palate with unilateral craniofacial microsomia and lateral ankyloglossia

Craniofacial microsomia is a group of anomalies that occur due to developmental defects in the first and second branchial arches during the embryological period. The disease has various craniofacial and extracraniofacial presentation patterns. Lateral cleft palate is distinct from the most common palate clefts because it is located lateral to the uvula. The presence of a lateral cleft palate has been very rarely reported in the literature, and the aetiopathogenesis of the disease is still not well understood. We aimed to report a case of the coexistence of lateral cleft palate and craniofacial microsomia and discuss the aetiopathogenesis of these diseases.

http://bit.ly/2Un2mte

Stroke or side effect? dofetilide associated facial paralysis after direct current cardioversion for atrial fibrillation

Dofetilide is a class III antiarrhythmic drug that has proven efficacious in maintaining sinus rhythm in up to 60% of patients with persistent atrial fibrillation. Dofetilide's most concerning adverse effect is QT prolongation and polymorphic VT, but providers should be aware of other rare significant side effects. We report a case of dofetilide associated Bell's palsy masquerading as stroke that developed shortly after a cardioversion. The patient's facial weakness, a side effect of dofetilide, resolved relatively quickly after discontinuation of the medication and a short course of oral corticosteroids.

http://bit.ly/2UsZSd3

Rivaroxaban-related acute kidney injury in a patient with IgA vasculitis

Anticoagulants have recently been recognised as a cause of acute kidney injury (AKI). We describe the case of a 75-year-old man with IgA vasculitis and atrial fibrillation treated with rivaroxaban, who presented with macroscopic haematuria and an acute decline in renal function. Two months before referral, he noted palpable purpuric lesions and was diagnosed with IgA vasculitis based on skin biopsy findings; the skin lesion disappeared following treatment with a steroid external preparation. Renal biopsy revealed glomerular haemorrhage and red blood cell casts. Although rivaroxaban was withdrawn, his kidney function worsened and he was started on haemodialysis. His renal function did not recover. To the best of our knowledge, this is the first case of direct oral anticoagulant (DOAC)-related AKI in systemic vasculitis. During DOAC therapy, close monitoring of a patient's urinalysis results and their renal function may be required for patients with systemic vasculitis to avoid AKI.

http://bit.ly/2DImUqA

Gross anterior segment ischaemia following vitreoretinal surgery for sickle-cell retinopathy

We report the case of a 32-year-old Afrocaribbean man with known stage 3 proliferative sickle-cell retinopathy who presented with a mixed picture of tractional and rhegmatogenous macula off detachment. He underwent left primary 25 g vitrectomy with silicone oil, delamination and endolaser photocoagulation under a general anaesthetic. He, however, presented 48 hours postoperatively with gross anterior segment ischaemia. His pain and ocular signs settled over the course of a few days following administration of supplemental oxygen, oral steroids, analgesia and intravenous hydration. Examination showed resolution of his proptosis and orbital signs as well as anterior segment inflammation. He remains under follow-up.

http://bit.ly/2DImO2c

Radiosensitivity nomogram based on circulating neutrophils in thoracic cancer

Future Oncology, Ahead of Print.


http://bit.ly/2DJqwc5

Guidance of sentinel lymph node biopsy decisions in patients with T1–T2 melanoma using gene expression profiling

Future Oncology, Ahead of Print.


http://bit.ly/2UpzP6p

Patient preferences for treatment of metastatic melanoma

Future Oncology, Ahead of Print.


http://bit.ly/2DGsPMT

Prostate Magnetic Resonance Imaging: Lesion Detection and Local Staging

Annual Review of Medicine, Volume 70, Issue 1, Page 451-459, January 2019.


http://bit.ly/2FW1ZCY

The Global Landscape of Tuberculosis Therapeutics

Annual Review of Medicine, Volume 70, Issue 1, Page 105-120, January 2019.


http://bit.ly/2CQ06Ul

PD-1 Blockade in Early-Stage Lung Cancer

Annual Review of Medicine, Volume 70, Issue 1, Page 425-435, January 2019.


http://bit.ly/2RYf8ld

Non–Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation

Annual Review of Medicine, Volume 70, Issue 1, Page 61-75, January 2019.


http://bit.ly/2CQyrmm

Clinical Application and Potential of Fecal Microbiota Transplantation

Annual Review of Medicine, Volume 70, Issue 1, Page 335-351, January 2019.


http://bit.ly/2S2eHXq

Postpartum Depression: Pathophysiology, Treatment, and Emerging Therapeutics

Annual Review of Medicine, Volume 70, Issue 1, Page 183-196, January 2019.


http://bit.ly/2CVGoqn

Arrhythmogenic Right Ventricular Cardiomyopathy: Progress Toward Personalized Management

Annual Review of Medicine, Volume 70, Issue 1, Page 1-18, January 2019.


http://bit.ly/2RW3qYs

Gastric Cancer Etiology and Management in Asia and the West

Annual Review of Medicine, Volume 70, Issue 1, Page 353-367, January 2019.


http://bit.ly/2S14KcN

Sodium–Glucose Cotransporter–2 (SGLT-2) Inhibitors and the Treatment of Type 2 Diabetes

Annual Review of Medicine, Volume 70, Issue 1, Page 323-334, January 2019.


http://bit.ly/2CRXFAQ

Molecular Diagnostics for Mycobacterium tuberculosis Infection

Annual Review of Medicine, Volume 70, Issue 1, Page 77-90, January 2019.


http://bit.ly/2RWz8EX

Metformin for Treatment of Fragile X Syndrome and Other Neurological Disorders

Annual Review of Medicine, Volume 70, Issue 1, Page 167-181, January 2019.


http://bit.ly/2CUlVSQ

Entering the Modern Era of Gene Therapy

Annual Review of Medicine, Volume 70, Issue 1, Page 273-288, January 2019.


http://bit.ly/2RVW8E1

Zika Virus Vaccine Development: Progress in the Face of New Challenges

Annual Review of Medicine, Volume 70, Issue 1, Page 121-135, January 2019.


http://bit.ly/2CRp2Lg

Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis

Annual Review of Medicine, Volume 70, Issue 1, Page 211-224, January 2019.


http://bit.ly/2RYSV6w

Cystic Fibrosis: Emerging Understanding and Therapies

Annual Review of Medicine, Volume 70, Issue 1, Page 197-210, January 2019.


http://bit.ly/2CVzTDR

New and Emerging Therapies for Pulmonary Arterial Hypertension

Annual Review of Medicine, Volume 70, Issue 1, Page 45-59, January 2019.


http://bit.ly/2RXMMYv

Abbreviated Magnetic Resonance Imaging (MRI) for Breast Cancer Screening: Rationale, Concept, and Transfer to Clinical Practice

Annual Review of Medicine, Volume 70, Issue 1, Page 501-519, January 2019.


http://bit.ly/2CRp1aa

TP901-1 Phage Recombinase Facilitates Genome Engineering in Drosophila melanogaster

Molecular biology techniques have a large impact on biomedical research and the availability of diverse tools to perform genome manipulations advances the ease of executing complicated genetic research. Here, we introduce in the fruit fly another such tool by harnessing the phage recombinase TP901-1 to perform site-directed recombination that leads to recombinase-mediated cassette exchange (RMCE). The TP901-1 system complements already existing recombination systems and enhances genome engineering in the fruit fly and other organisms.

http://bit.ly/2BaHNcB

Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and has subsequently been found in this breed in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine single nucleotide variant genotyping chip was used to identify a candidate genetic region. There was a highly significant peak of association over chromosome 17, with a p-value of 2 x 10^–13. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Whole genome sequences of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous for the risk allele in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one was homozygous for this variant (offspring of parents both with goniodysgenesis who were also homozygous for the variant). Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. The identification of a candidate genetic region and putative causative variant will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.

http://bit.ly/2TlaOcF

Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

Resveratrol alleviates DOX‐resistance in breast cancer cells. Resveratrol reverses EMT properties. Resveratrol modulates SIRT1/β‐catenin signaling pathway.

Abstract

Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX‐resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial‐mesenchymal transitions (EMTs) in adriamycin‐resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and β‐catenin, which provides a hopeful therapeutic avenue to conquer DOX‐resistance and thereby prolong survival rates in breast cancer patients.

http://bit.ly/2HEaCns

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

We sequenced viral DNA from paraffin‐embedded tissues of PTLD and associated to clinical severity and outcomes. Certain EBV genes had higher proportions of nonsynonymous variants. Anellovirus tissue positivity associated with earlier patient death.

Abstract

Posttransplant lymphoproliferative disorders (PTLDs), 50%‐80% of which are strongly associated with Epstein‐Barr virus (EBV), carry a high morbidity and mortality. Most clinical/epidemiological/tumor characteristics do not consistently associate with worse patient survival, so our aim was to identify if other viral genomic characteristics associated better with survival. We extracted DNA from stored paraffin‐embedded PTLD tissues at our center, identified viral sequences by metagenomic shotgun sequencing (MSS), and analyzed the data in relation to clinical outcomes. Our study population comprised 69 PTLD tissue samples collected between 1991 and 2015 from 60 subjects. Nucleotide sequences from at least one virus were detected by MSS in 86% (59/69) of the tissues (EBV in 61%, anelloviruses 52%, gammapapillomaviruses 14%, CMV 7%, and HSV in 3%). No viruses were present in higher proportion in EBV‐negative PTLD (compared to EBV‐positive PTLD). In univariable analysis, death within 5 years of PTLD diagnosis was associated with anellovirus (P = 0.037) and gammapapillomavirus (P = 0.036) detection by MSS, higher tissue qPCR levels of the predominant human anellovirus species torque teno virus (TTV; P = 0.016), T cell type PTLD, liver, brain or bone marrow location. In multivariable analyses, T cell PTLD (P = 0.006) and TTV PCR level (P = 0.012) remained significant. In EBV‐positive PTLD, EBNA‐LP, EBNA1 and EBNA3C had significantly higher levels of nonsynonymous gene variants compared to the other EBV genes. Multiple viruses are detectable in PTLD tissues by MSS. Anellovirus positivity, not EBV positivity,was associated with worse patient survival in our series. Confirmation and extension of this work in larger multicenter studies is desirable.

http://bit.ly/2ShRmjy

Olaratumab for STS Disappoints in Phase III [News in Brief]

Anti-PDGFRα antibody plus doxorubicin does not improve survival over doxorubicin alone.

http://bit.ly/2DJ4qqi

Challenges with Novel Clinical Trial Designs: Master Protocols

The 2018 Accelerating Anticancer Agent Development (AAADV) Workshop assembled a panel of experts for an in-depth discussion session to present Challenges with Novel Clinical Trial Designs. This panel offered assessments of the challenges faced by industry, the Food and Drug Administration, investigators, institutional review boards, and patients. The panel focused on master protocols, which include umbrella trials, platform trials, and basket trials. Umbrella trials and platform trials share many commonalities, while basket trials are more distinct. Umbrella and platform trials are generally designed with multiple arms where patients of the same histology or other unifying characteristics are enrolled into different arms and multiple investigational agents are evaluated in a single protocol. In contrast, basket studies generally enroll patients with different tumor types based on the presence of a specific mutation or biomarker regardless of histology; these trials may include expansion cohorts. These novel designs offer the promise of expedited drug assessment and approval, but they also place new challenges on all the stakeholders involved in the drug development process. Only by identifying the challenges of these complex innovative clinical trial designs and highlighting challenges from each perspective, can we begin to address these challenges. The 2018 AAADV Workshop convened a panel of experts from relevant disciplines to highlight the challenges that are created by master protocols, and where appropriate, offer strategies to address these challenges.

http://bit.ly/2TmQA1Y

Nod1 imprints inflammatory and carcinogenic responses toward the gastric pathogen Helicobacter pylori

Helicobacter pylori is the strongest known risk for gastric cancer. The H. pylori cag type IV secretion system is an oncogenic locus which translocates peptidoglycan into host cells where it is recognized by NOD1, an innate immune receptor. Beyond this, the role of NOD1 in H. pylori-induced cancer remains undefined. To address this knowledge gap, we infected two genetic models of Nod1 deficiency with the H. pylori cag+ strain PMSS1: C57BL/6 mice which rarely develop cancer, and INS-GAS FVB/N mice which commonly develop cancer. Infected C57BL/6Nod1-/- and INS-GASNod1-/- mice acutely developed more severe gastritis, and INS-GASNod1-/- mice developed gastric dysplasia more frequently compared to Nod1+/+ mice. Because Nod1 genotype status did not alter microbial phenotypes of in vivo-adapted H. pylori, we investigated host immunological responses. H. pylori infection of Nod1-/- mice led to significantly increased gastric mucosal levels of Th1, Th17, and Th2 cytokines compared to Nod1 wild-type mice. To define the role of specific innate immune cells, we quantified cytokine secretion from H. pylori-infected primary gastric organoids generated from WT or Nod1-/- mice, that were co-cultured with or without WT or Nod1-/- macrophages. Infection increased cytokine production from gastric epithelial cells and macrophages and elevations were significantly increased with Nod1 deficiency. Further, H. pylori infection altered the polarization status of Nod1-/- macrophages compared to Nod1+/+ macrophages. Collectively, these studies demonstrate that loss of Nod1 augments inflammatory and injury responses to H. pylori. Nod1 may exert its restrictive role by altering macrophage polarization, leading to immune evasion and microbial persistence.

http://bit.ly/2Bkxtin

Pomalidomide alters pancreatic macrophage populations to generate an immune-responsive environment at precancerous and cancerous lesions

During development of pancreatic cancer, alternatively-activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively-activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4 (IRF4), a transcription factor for M2 macrophage polarization. Pomalidomide-induced absence of alternatively-activated macrophages led to a decrease in fibrosis at PanIN lesions and in syngeneic tumors; this was due to generation of an inflammatory, immune-responsive environment with increased expression of IL-1α and presence of activated (IFNγ positive) CD4+ and CD8+ T cell populations. Our results indicate that pomalidomide could be used to decrease fibrogenesis in pancreatic cancer and may be ideal as a combination treatment with chemotherapeutic drugs or other immunotherapies.

http://bit.ly/2CSeDPj

Cervical cancer-instructed stromal fibroblasts enhance IL-23 expression in dendritic cells to support expansion of Th17 cells

Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV-transformed cells actively instruct their microenvironment, promoting chronic inflammation and cancer progression. We previously demonstrated that cervical cancer cells contribute to T-helper-17 (Th17) cell recruitment, a cell type with pro-tumorigenic properties. In this study we analysed the expression of the Th17-promoting cytokine Interleukin(IL)-23 in the cervical cancer micromilieu and found CD83+ mature dendritic cells (mDC) co-expressing IL-23 in the stroma of cervical squamous cell carcinomas in situ. This expression of IL-23 correlated with stromal Th17 cells, advanced tumor stage, lymph node metastasis, and cervical cancers recurrence. Co-cultures of cervical cancer-instructed mDC and cervical fibroblasts led to potent pro-tumorigenic expansion of Th17 cells in vitro but failed to induce anti-tumor Th1 differentiation. Correspondingly, cervical cancer-instructed fibroblasts increased IL-23 production in co-cultured cervical cancer-instructed mDC, which mediated subsequent Th17 cell expansion. In contrast, production of the Th1-polarizing cytokine IL-12 in cancer-instructed mDC was strongly reduced. This differential IL-23 and IL-12 regulation was the consequence of an increased expression of IL-23 subunits IL-23p19 and IL-12p40 but decreased expression of the IL-12 subunit IL-12p35 in cervical cancer-instructed mDC. Cervical cancer cell-derived IL-6 directly suppressed IL-12p35 in mDC but indirectly induced IL-23 expression in fibroblasts-primed mDC via CAAT/enhancer-binding protein β (C/EBPβ)-dependent induction of IL-1β. In summary, our study defines a mechanism by which the cervical cancer micromilieu supports IL-23-mediated Th17 expansion associated with cancer progression.

http://bit.ly/2Th8OCc

Effect of IL-6 Receptor Blockade on Proprotein Convertase Subtilisin/Kexin Type-9 and Cholesterol Efflux Capacity in Rheumatoid Arthritis Patients

Horm Metab Res
DOI: 10.1055/a-0833-4627

The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 [median % change 32 (3–141), p=0.021]. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

http://bit.ly/2S0X7CT

Bovine teeth can reliably substitute human dentine in an intra‐tooth push‐out bond strength model?

Abstract

Aim

To investigate the reliability of using bovine teeth as an alternative to human teeth in an intra‐tooth push‐out model by comparing the bond strength of three root canal sealers in both tooth substrates.

Methodology

From human and bovine incisors (12 per group), one 1‐mm disc was obtained from each root. On each disc, three standard 0.8mm‐diameter holes were drilled through the dentine. After irrigation, the holes were filled with one of the three tested root canal sealers: AH Plus, MTA Fillapex or Total Fill BC Sealer. Tooth slices were kept in contact with sterile gauze moistened in PBS solution (pH=7.2) for 7 days at 37°C, and finally, a push‐out load was applied until sealer dislocation. The bonded interface area was calculated to obtain data in MPa. The push‐out data for each sealer and the overall push‐out data for human and bovine teeth were compared (Mann‐Whitney U). Kruskal‐Wallis was used to study the sealers behavior at each of the dental substrates. Multiple comparisons were performed using Mann‐Whitney U after Bonferroni correction (P<0.05).

Results

Dentine substrate did not influence the push‐out of either, individual sealers or overall sealers tested (Mann‐Whitney U,P>0.05). In both human and bovine samples, AH Plus performed better than BC Sealer and MTA Fillapex, while BC Sealer also provided a superior push‐out compared to MTA Fillapex (Mann‐Whitney U, P<0.05).

Conclusion

When using an intra‐tooth model, bovine teeth do not significantly influence the bond strength of sealers.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Urq73k

Treatment of Ethylene Glycol Poisoning with Oral Ethyl Alcohol

Ethylene glycol poisoning is not uncommon in India. The ill effects are primarily caused by its toxic metabolites: glycolic acid and oxalic acid. A 70-year-old female presented to our hospital with ataxia after ingestion of ethylene glycol. The reported case describes the management of ethylene glycol poisoning using oral ethyl alcohol as an alternative to the recommended intravenous ethyl alcohol and fomepizole that are not available for use in India. The need for high degree of clinical suspicion, targeted investigations, and early instigation of treatment is of prime importance in cases of ethylene glycol poisoning as it can lead to long-term complications or even death.

http://bit.ly/2B9Jbfs

Comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

Comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

Comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis', Published online: 30 January 2019; doi:10.1038/s41416-018-0361-x

Comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

https://go.nature.com/2ME2li4

Reply to comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

Reply to comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

Reply to comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis', Published online: 30 January 2019; doi:10.1038/s41416-018-0362-9

Reply to comment on 'D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis'

https://go.nature.com/2sVspMt

Benefits, Barriers to Exercise Examined for Patients With ESKD

TUESDAY, Jan. 29, 2019 -- Patients with end-stage kidney disease (ESKD) undergoing maintenance dialysis express a desire to exercise to regain energy and strength, but many report barriers to exercise, according to a study published online Jan. 29...

http://bit.ly/2SinLq8

9/11 Responders May Have Higher Head, Neck Cancer Risk

TUESDAY, Jan. 29, 2019 -- There may be a significant, emerging risk for human papillomavirus (HPV)-related head and neck cancers (HNC) among workers and volunteers who responded to the 9/11 terrorist attacks on the World Trade Center (WTC),...

http://bit.ly/2HHhRuK

Large Insulin Price Hike to Be Investigated by U.S. Congress

TUESDAY, Jan. 29, 2019 -- The soaring cost of insulin will be investigated as the U.S. Congress holds hearings into the high cost of prescription drugs, a lawmaker says. "I have heard stories about people reducing their lifesaving medicines, like...

http://bit.ly/2SdB4bu

Prophylaxis for Gonococcal Eye Infections in Newborns Advised

TUESDAY, Jan. 29, 2019 -- The U.S. Preventive Services Task Force (USPSTF) has reaffirmed the recommendation for use of ocular prophylaxis for gonococcal ophthalmia neonatorum. This recommendation forms the basis of a final recommendation statement...

http://bit.ly/2HHhPTE

1976 to 2016 Saw Drop in Firearm Ownership in Families

TUESDAY, Jan. 29, 2019 -- From 1976 to 2016, there was a decrease in the proportion of families who had young children and owned firearms, although an increase was seen in the proportion who owned handguns, according to a study published online Jan....

http://bit.ly/2Sh3FNc

Significant Hematochezia and Intracranial Bleeding in Neonatal Hereditary Hemorrhagic Telangiectasia

AJP Rep 2019; 09: e10-e14
DOI: 10.1055/s-0039-1677735

Hereditary hemorrhagic telangiectasia (HHT) is an underreported autosomal dominant vascular dysplasia. Neonatal presentations of HHT are rare, as this disorder typically presents in adolescence or beyond with epistaxis. We report a female neonate with hematochezia on the 1st day of life secondary to multiple gastrointestinal arteriovenous malformations (AVMs) along with intracranial hemorrhage. We describe her clinical course and management, as well as her novel family mutation in ENG. This is the first reported HHT case with significant gastrointestinal bleeding in the newborn. We review neonatal HHT and raise the consideration for more directed prenatal imaging and delivery options for fetuses at high risk of HHT.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

http://bit.ly/2RmOCNf

Obstetrical Outcomes of Head and Neck (Nonthyroid) Cancers: A 27-Year Retrospective Series and Literature Review

AJP Rep 2019; 09: e15-e22
DOI: 10.1055/s-0039-1677876

Objective To describe the clinical presentation and obstetrical outcomes of nonthyroid head and neck cancers (HNCs), and to review literature on this rare condition in pregnancy. Study Design Pregnant women with nonthyroid HNC were identified retrospectively from 1990 to 2017. Maternal, neonatal, pregnancy, and demographic data were collected. A review of the literature from January 1980 to May 2018 was performed. Results Over the 27-year time period, 16 women with history of nonthyroid HNC were identified (9 diagnosed during and 7 diagnosed before current pregnancy). The cases were analyzed in detail and the most updated review of management of each type of HNC was provided. Conclusions HNCs are rare with diagnosis and management challenges during pregnancy. In this series, the cases diagnosed and managed previously to pregnancy presented better perinatal outcomes than the cases presented during pregnancy. The maternal outcomes appeared similar for HNC diagnosed before or after pregnancy.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

http://bit.ly/2WuD8uR

Large care gaps in primary care management of asthma: a longitudinal practice audit

Objectives

Care gaps in asthma may be highly prevalent but are poorly characterised. We sought to prospectively measure adherence to key evidence-based adult asthma practices in primary care, and predictors of these behaviours.

Design

One-year prospective cohort study employing an electronic chart audit.

Setting

Three family health teams (two academic, one community-based) in Ontario, Canada.

Participants

884 patients (72.1% female; 46.0±17.5 years old) (4199 total visits; 4.8±4.8 visits/patient) assigned to 23 physicians (65% female; practising for 10.0±8.6 years).

Main outcome measures

The primary outcome was the proportion of visits during which practitioners assessed asthma control according to symptom-based criteria. Secondary outcomes included the proportion of: patients who had asthma control assessed at least once; visits during which a controller medication was initiated or escalated; and patients who received a written asthma action plan. Behavioural predictors were established a priori and tested in a multivariable model.

Results

Primary outcome: Providers assessed asthma control in 4.9% of visits and 15.4% of patients. Factors influencing assessment included clinic site (p=0.019) and presenting symptom, with providers assessing control more often during visits for asthma symptoms (35.0%) or any respiratory symptoms (18.8%) relative to other visits (1.6%) (p<0.01). Secondary outcomes: Providers escalated controller therapy in 3.3% of visits and 15.4% of patients. Factors influencing escalation included clinic site, presenting symptom and prior objective asthma diagnosis. Escalation occurred more frequently during visits for asthma symptoms (21.0%) or any respiratory symptoms (11.9%) relative to other visits (1.5%) (p<0.01) and in patients without a prior objective asthma diagnosis (3.5%) relative to those with (1.3%) (p=0.025). No asthma action plans were delivered.

Conclusions

Major gaps in evidence-based asthma practice exist in primary care. Targeted knowledge translation interventions are required to address these gaps, and can be tailored by leveraging the identified behavioural predictors.

Trial registration number

NCT01070095; Pre-results.

http://bit.ly/2sSpjJn

All-cause mortality among young men 24-26 years after a lifestyle health dialogue in a Swedish primary care setting: a longitudinal follow-up register study

Objectives

To compare mortality and socioeconomic status among men invited to a health dialogue with men from all of Sweden approximately 24 years after the start of the study, and to analyse the associations between lifestyle and all-cause mortality, incidence of cardiovascular disease (CVD) and cancer.

Design

Longitudinal follow-up register study of men 33–42 years old at baseline.

Setting

Primary care in a community in Sweden.

Subjects

All 757 men aged 33–42 years old in a community in southern Sweden, and 652 of these men who participated in a health examination between 1985 and 1987.

Interventions

Health examination, lifestyle-directed health dialogue and group activities in primary care in cooperation with local associations.

Primary and secondary outcome measures

All-cause mortality, income and educational level, and associations between lifestyle at baseline and all-cause mortality, incidence of CVD and cancer.

Results

At follow-up, all-cause mortality was 29% lower (OR=0.71, 95% CI 0.53 to 0.95) among all men invited to the health dialogue compared with all men from the same age cohort in all of Sweden (intention-to-treat) and 43% lower (OR=0.57, 95% CI 0.40 to 0.81) among participating men (on-treatment). A healthy lifestyle was associated with lower mortality (OR=0.16, 95% CI 0.07 to 0.36), with the strongest association for no smoking (OR=0.38, 95% CI 0.21 to 0.68) and a healthy diet (OR=0.37, 95% CI 0.20 to 0.68). A healthy lifestyle was also associated with a decreased incidence of CVD and cancer. There was a significantly higher proportion with short education among invited men compared with men from the same age cohort in all of Sweden.

Conclusions

This study indicates that a combination of low-risk and high-risk strategies, combining a health examination with a lifestyle-directed health dialogue conducted in an ordinary primary care setting in cooperation with local associations, may have contributed to reduced premature mortality. However, we cannot exclude that there may be other factors explaining the lower mortality.

http://bit.ly/2MHolbH

The Case of the False Dichotomy

Often in the interpretation of medical literature we are forced into false dichotomies. Compelled to choose between two hypotheses, neither of which are representative of the data presented. Such is the case with a recent trial published in Intensive Care Medicine in which Guitton et al1 examine the efficacy of apneic oxygenation during RSI in critically […]

EMCrit Project by Rory Spiegel.

http://bit.ly/2HD1Vd1

First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan

Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormal white matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done using genetic testing such as next-generation sequencing. The aim of this study is to identify the genetic causes of LD in two independent Jordanian cases that exhibit MRI findings confirming LD with no definitive diagnosis using whole exome sequencing (WES). The most likely causative variants were identified. In one case, the homozygous pathogenic variant NM_000049.2:c.914C>A;p.Ala305Glu, which is previously reported in ClinVar, in the gene ASPA was identified causing Canavan disease. In the second case, the homozygous novel variant NM_000487.5:c.256C>G;p.Arg86Gly in the gene ARSA was identified causing metachromatic leukodystrophy. The two variants segregate in their families. The phenotypes of the two studied cases overlap with assigned diseases. The present study raises the importance of using WES to identify the precise neurodevelopmental diseases in Jordan.

http://bit.ly/2TnRSKc

New Gene Markers of Angiogenesis and Blood Vessels Development in Porcine Ovarian Granulosa Cells during Short-Term Primary Culture In Vitro

The physiological processes that drive the development of ovarian follicle, as well as the process of oogenesis, are quite well known. Granulosa cells are major players in this occurrence, being the somatic element of the female gamete development. They participate directly in the processes of oogenesis, building the cumulus-oocyte complex surrounding the ovum. In addition to that, they have a further impact on the reproductive processes, being a place of steroid sex hormone synthesis and secretion. It is known that the follicle development creates a major need for angiogenesis and blood vessel development in the ovary. In this study, we use novel molecular approaches to analyze markers of these processes in porcine granulosa cultured primarily in vitro. The cells were recovered from mature sus scrofa specimen after slaughter. They were then subjected to enzymatic digestion and culture primarily for a short term. The RNA was extracted from cultures in specific time periods (0h, 24h, 48h, 96h, and 144h) and analyzed using expression microarrays. The genes that exhibited fold change bigger than , and adjusted p-value lower than 0.05, were considered differentially expressed. From these, we have chosen the members of "angiogenesis," "blood vessel development," "blood vessel morphogenesis," "cardiovascular system development," and "vasculature development" for further selection. CCL2, FGFR2, SFRP2, PDPN, DCN, CAV1, CHI3L1, ITGB3, FN1, and LOX which are upregulated, as well as CXCL10, NEBL, IHH, TGFBR3, SCUBE1, IGF1, EDNRA, RHOB, PPARD, and SLITRK5 genes whose expression is downregulated through the time of culture, were chosen as the potential markers, as their expression varied the most during the time of culture. The fold changes were further validated with RT-qPCR. The genes were described, with special attention to their possible function in GCs during culture. The results broaden the general knowledge about GC's in vitro molecular processes and might serve as a point of reference for further in vivo and clinical studies.

http://bit.ly/2B9Ti3L

The Analysis of Risk Factors for Hemorrhage Associated with Minimally Invasive Percutaneous Nephrolithotomy

Objective. This study investigated the risk factors for bleeding during minimally invasive percutaneous nephrolithotomy, so as to prevent the occurrence of bleeding and improve the surgical effect. Patients and Methods. The data of 396 patients who underwent percutaneous nephrolithotomy by an experienced surgeon between May 2014 and December 2017 were retrospectively analyzed. To identify the risk factors for bleeding during percutaneous nephrolithotomy, each group was stratified according to the decrease in median hemoglobin. Age, gender, body mass index, stone size, operation time, stone type, degree of hydronephrosis, number of accesses, puncture guidance, underlying disease (diabetes; hypertension), and previous surgical history were evaluated. Univariate analysis was performed to calculate the potential factors. In order to determine the independence of each factor, we finally selected stone size, staghorn stone, degree of hydronephrosis, and operation time. Multivariate logistic regression analysis was used to identify the risk factors for bleeding during minimally invasive percutaneous nephrolithotomy. Results. A total of 396 patients were successfully treated with percutaneous nephrolithotomy. The univariate analysis demonstrated that the potential risk factors for bleeding during percutaneous nephrolithotomy included stone size, type of stone, operative time, and degree of hydronephrosis. According to the previous studies, stone size, staghorn stone, degree of hydronephrosis, and operation time were ultimately selected. Multivariate logistic regression analysis was used to identify the risk factors for bleeding during percutaneous nephrolithotomy. According to the outcome of logistic regression analysis, stone size, staghorn stone, operation time, and degree of hydronephrosis were the risk factors for bleeding during minimally invasive percutaneous nephrolithotomy. Conclusions. Percutaneous nephrolithotomy is an effective method for the treatment of upper urinary calculi with few complications. According to the results achieved by an experienced surgeon, the size of stone, staghorn stone, operation time, and degree of hydronephrosis were associated with the bleeding during minimally invasive percutaneous nephrolithotomy.

http://bit.ly/2Tk1HsE

traG Gene Is Conserved across Mesorhizobium spp. Able to Nodulate the Same Host Plant and Expressed in Response to Root Exudates

Evidences for an involvement of the bacterial type IV secretion system (T4SS) in the symbiotic relationship between rhizobia and legumes have been pointed out by several recent studies. However, information regarding this secretion system in Mesorhizobium is still very scarce. The aim of the present study was to investigate the phylogeny and expression of the traG gene, which encodes a substrate receptor of the T4SS. In addition, the occurrence and genomic context of this and other T4SS genes, namely, genes from tra/trb and virB/virD4 complexes, were also analyzed in order to unveil the structural and functional organization of T4SS in mesorhizobia. The location of the T4SS genes in the symbiotic region of the analyzed rhizobial genomes, along with the traG phylogeny, suggests that T4SS genes could be horizontally transferred together with the symbiosis genes. Regarding the T4SS structural organization in Mesorhizobium, the virB/virD4 genes were absent in all chickpea (Cicer arietinum L.) microsymbionts and in the Lotus symbiont Mesorhizobium japonicum MAFF30309. Interestingly, the presence of genes belonging to another secretion system (T3SS) was restricted to these strains lacking the virB/virD4 genes. The traG gene expression was detected in M. mediterraneum Ca3 and M. ciceri LMS-1 strains when exposed to chickpea root exudates and also in the early nodules formed by M. mediterraneum Ca3, but not in older nodules. This study contributes to a better understanding of the importance of T4SS in mutualistic symbiotic bacteria.

http://bit.ly/2Bb295s

Biological activities associated with the volatile compound 2,5-bis(1-methylethyl)-pyrazine

Abstract

Pyrazines are 1,4- diazabenzene based volatile organic compounds and known for their broad-spectrum antimicrobial activity. In the present study we assessed the antimicrobial activity of 2,5-bis(1-methylethyl)-pyrazine, produced by Paenibacillus sp. AD87 during co-culture with Burkholderia sp. AD24. In addition, we were using transcriptional reporter assays in E. coli and mammalian cells to decipher the possible mode of action. Bacterial and mammalian luciferase reporter strains were deployed to elucidate antimicrobial and toxicological effects of 2,5-bis(1-methylethyl)-pyrazine. At high levels of exposure, 2,5-bis(1-methylethyl)-pyrazine exerted strong DNA damage response. At lower concentrations, cell-wall damage response was observed. The activity was corroborated by a general toxicity reporter assay in E. coli ΔampD, defective in peptidoglycan turnover. The maximum E. coli cell-wall stress activity was measured at a concentration close to the onset of the mammalian cytotoxicity, while other adverse outcome pathways, such as the activation of aryl hydrocarbon and estrogenic receptor, the p53 tumor suppressor, and the oxidative stress related Nrf2 transcription factor, were induced at elevated concentrations compared to the response of mammalian cells. Because of its broad-spectrum antimicrobial activity at lower concentrations and the relatively low mammalian toxicity, 2,5-bis(1-methylethyl)-pyrazine is a potential bio-based fumigant with possible applications in food industry, agriculture or logistics.

http://bit.ly/2GbAIeT