3D-Printed Biomimetic Super-Hydrophobic Structure for Microdroplet Manipulation and Oil/Water Separation

Abstract

Biomimetic functional surfaces are attracting increasing attention for various technological applications, especially the superhydrophobic surfaces inspired by plant leaves. However, the replication of the complex hierarchical microstructures is limited by the traditional fabrication techniques. In this paper, superhydrophobic micro-scale artificial hairs with eggbeater heads inspired by Salvinia molesta leaf was fabricated by the Immersed surface accumulation three dimensional (3D) printing process. Multi-walled carbon nanotubes were added to the photocurable resins to enhance the surface roughness and mechanical strength of the microstructures. The 3D printed eggbeater surface reveals interesting properties in terms of superhydrophobilicity and petal effect. The results show that a hydrophilic material can macroscopically behave as hydrophobic if a surface has proper microstructured features. The controllable adhesive force (from 23 μN to 55 μN) can be easily tuned with different number of eggbeater arms for potential applications such as micro hand for droplet manipulation. Furthermore, a new energy-efficient oil/water separation solution based on our biomimetic structures was demonstrated. The results show that the 3D-printed eggbeater structure could have numerous applications, including water droplet manipulation, 3D cell culture, micro reactor, oil spill clean-up, and oil/water separation.

A super-hydrophobic microsized eggbeater structure inspired by Salvinia molesta leaves is fabricated by an immersed surface accumulation 3D printing process. The 3D-printed eggbeater structure shows potential applications such as nonloss microdroplet manipulation and as 3D cell culture platform in biomedical engineering. Furthermore, it demonstrates a new energy-efficient solution for oil absorption and oil/water separation.

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Genetically Engineered Liposome-like Nanovesicles as Active Targeted Transport Platform

Abstract

Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. Here, as a proof of concept, genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.

Genetically engineered biofunctionalized liposome-like nanovesicles (BLNs) serve as active targeted transport platform with higher efficacy and improved safety profiles. The designed BLNs have great potential for precision nanomedicine by engineering a wide range of functional protein moieties and encapsulating drugs in a versatile manner.

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Interstitial P-Doped CdS with Long-Lived Photogenerated Electrons for Photocatalytic Water Splitting without Sacrificial Agents

Abstract

Photocatalytic hydrogen evolution from pure water is successfully realized by using interstitial P-doped CdS with rich S vacancies (CdS-P) as the photocatalyst in the absence of any electron sacrificial agents. Through interstitial P doping, the impurity level of S vacancies is located near the Fermi level and becomes an effective electron trap level in CdS-P, which can change dynamic properties of photogenerated electrons and thus prolong their lifetimes. The long-lived photogenerated electrons are able to reach the surface active sites to initiate an efficient photocatalytic redox reaction. Moreover, the photocatalytic activity of CdS-P can be further improved through the loading of CoP as a cocatalyst.

Photocatalytic hydrogen evolution from pure water is realized by CdS-P. Through interstitial P doping, the impurity level of S vacancies is located near the Fermi level and becomes an effective electron trap level, which can change the dynamics of photogenerated electrons. The long-lived photogenerated electrons can reach the surface active sites for initiating the photocatalytic reaction.

http://ift.tt/2lcrkM6

Blocking Energy-Loss Pathways for Ideal Fluorescent Organic Light-Emitting Diodes with Thermally Activated Delayed Fluorescent Sensitizers

Abstract

Organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence-sensitized fluorescence (TSF) offer the possibility of attaining an ultimate high efficiency with low roll-off utilizing noble-metal free, easy-to-synthesize, pure organic fluorescent emitters. However, the performances of TSF-OLEDs are still unsatisfactory. Here, TSF-OLEDs with breakthrough efficiencies even at high brightnesses by suppressing the competitive deactivation processes, including direct charge recombination on conventional fluorescent dopants (CFDs) and Dexter energy transfer from the host to the CFDs, are demonstrated. On the one hand, electronically inert terminal-substituents are introduced to protect the electronically active core of the CFDs; on the other hand, delicate device structures are designed to provide multiple energy-funneling paths. As a result, unprecedentedly high maximum external quantum efficiency/power efficiency of 24%/71.4 lm W⁻¹ in a green TSF-OLED are demonstrated, which remain at 22.6%/52.3 lm W⁻¹ even at a high luminance of 5000 cd m⁻². The work unlocks the potential of TSF-OLEDs, paving the way toward practical applications.

By blocking energy-loss pathways for fluorescent organic light-emitting diodes with thermally activated delayed fluorescent sensitizers, high maximum external quantum efficiency/power efficiency of 24%/71.4 lm W⁻¹ are demonstrated, which remain at 22.6%/52.3 lm W⁻¹ even at a high luminance of 5000 cd m⁻².

http://ift.tt/2l6WvJJ

Perspectives on Research Participation and Facilitation Among Dialysis Patients, Clinic Personnel, and Medical Providers: A Focus Group Study

Most prospective studies involving individuals receiving maintenance dialysis have been small, and many have had poor clinical translatability. Research relevance can be enhanced through stakeholder engagement. However, little is known about dialysis clinic stakeholders' perceptions of research participation and facilitation. The objective of this study was to characterize the perspectives of dialysis clinic stakeholders (patients, clinic personnel, and medical providers) on: (1) research participation by patients and (2) research facilitation by clinic personnel and medical providers.

http://ift.tt/2zzWoe5

Clinical Snippets

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Medial gastrocnemius muscle stiffness cannot explain the increased ankle joint range of motion following passive stretching in children with cerebral palsy

Abstract

Stretching is often used to increase/maintain joint range of motion (ROM) in children with cerebral palsy (CP) but the effectiveness of these interventions is limited. Therefore, this study aimed to determine the acute changes in muscle-tendon lengthening properties that contribute to increased ROM after a bout of stretching in children with CP. Eleven children with spastic CP (age:12.1(3)y, 5/6 hemiplegia/diplegia, 7/4 GMFCS level I/II) participated in this study. Each child received 3 sets of 5 × 20 s passive, manual static dorsiflexion stretches separated by 30 s rest, and 60 s rest between sets. Pre- and immediately post-stretching, ultrasound was used to measure medial gastrocnemius fascicle lengthening continuously over the full ROM and an individual common ROM pre- to post-stretching. Simultaneously, 3D motion of two marker clusters on the shank and the foot was captured to calculate ankle angle, and ankle joint torque was calculated from manually applied torques and forces on a 6DoF load cell. After stretching, ROM was increased (9.9° (12.0), P = 0.005). Over a ROM common to both pre and post measurements, there were no changes in fascicle lengthening or torque. The maximal ankle joint torque tolerated by the participants increased (2.9(2.4) Nm, P = 0.003) and at this highest passive torque maximal fascicle length was 2.8(2.4) mm greater (P = 0.009) when compared to before stretching. These results indicate that the stiffness of the muscle fascicles in children with CP remain unaltered by an acute bout of stretching.

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Retroperitoneal ectopic brain: Case report and literature review

Heterotopic neural tissue (HNT) has been identified in many sites. In our literature review, we have found only two cases of HNT located in the retroperitoneum. As far as we know, cytological features of HNT have not been described. We here report a case of retroperitoneal HNT diagnosed by fine-needle aspiration (FNA) cytology and subsequent resection. Our patient was a male infant born at 26 weeks' gestation. A retroperitoneal solid-cystic lesion measuring 3.8 cm was identified by abdominal ultrasound. FNA was performed and cytology showed highly cellular smears with single cells and masses of fibrillary material. Cells were small with rounded irregular nuclei and variable cytoplasm. Multinucleated cells, cells with neuronal morphology, calcifications, and hemosiderophages could also be seen. The lesion was excised and histology showed fibrillary areas, glial cells, neurons, and ependymal cells. Synaptophysin, GFAP, and EMA were expressed in distinct areas and cell types. No recurrences were observed.

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Letter to the editor: Uncommon cells in cerebrospinal fluid cytology

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Cytological features in eight patients with ALK-rearranged lung cancer

Background

ALK-rearranged lung cancer has been recently identified. Although signet-ring cell morphology and mucinous cribriform pattern are considered to be characteristic of ALK-rearranged lung cancer. Some studies have also suggested cytological features.

Methods

This study investigated cytological features of ALK-rearranged lung cancer in eight patients.

Results

Cytologically, the tumor cell group varied from isolated to large clusters. Small nucleoli, fine granular to vesicular chromatin, and nuclear groove were observed in all patients. Furthermore, extracellular and intracellular mucin and signet-ring cells were identified in five patients.

Conclusion

This study demonstrated that the presence of extracellular and intracellular mucin, signet-ring cells, small nucleoli, fine granular to vesicular chromatin, and nuclear groove in cytological samples may be a diagnostic clue for ALK-rearranged lung cancer.

http://ift.tt/2l1W5nI

Endoscopic ultrasound guided fine-needle aspiration: What variables influence diagnostic yield?

Background

Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) plays an important role in the diagnosis of various lesions. We sought to determine factors that influence the diagnostic yield of EUS–FNA, specifically, the presence of a cytopathologist, FNA site, and the endoscopist's skill.

Methods

The data on cytopathologist's availability, duration of procedure, number of passes made, and diagnostic material for cell block (CB) preparation was collected over an 18 months period.

Results

230 specimens (218 patients) were obtained from pancreas (114), lymph node (64), submucosal lesions of the gastrointestinal tract (27), liver (8), and miscellaneous (17) sites. The results were classified as informative (77.8%) and non-informative (NI) (22.2%). The NI rate was significantly high, when a cytopathologist was absent (P = .0008). As the likelihood of cytopathologist's presence increased from 35.8% to 82.9%, the CB quality increased (P < .0001). In the absence of a cytopathologist, the likelihood of NI result increased more than 2-fold (P = .03) and of an inadequate CB increased 3-fold (P < .0001). The more experienced endoscopist "C" (compared to the less experienced "A + B") was less likely to get inadequate material (40.5% vs. 66.3%) (P = .0001).

Conclusion

The diagnostic yield of EUS–FNA is significantly related to the presence of an on-site cytopathologist and endoscopist's skill in procuring diagnostic material.

http://ift.tt/2lep470

Amyloidosis diagnosed in cytology specimen of pleural effusion: A case report

Amyloidosis is a rare condition resulting from extracellular deposition of amyloid, a fibrillary material derived from various precursor proteins. Involvement of the pleura by amyloidosis is a rare but serious complication. Pleural amyloidosis is primarily diagnosed by identifying amyloid deposition by histology on pleural biopsy specimens. Hereby, we report a case of systemic amyloidosis where we were able to identify amyloid in a pleural effusion specimen sent for cytopathology evaluation. A 59-year-old male with newly diagnosed multiple myeloma and systemic amyloidosis underwent therapeutic thoracentesis. The H&E stained cell block sections revealed a single, less than one millimeter focus of waxy material surrounded by a rim of reactive mesothelial cells suspicious for amyloid deposit in a background of fibrin, lymphocytes, and reactive mesothelial cells. The focus stained salmon pink with Congo-red special stain and showed apple-green birefringence under polarized light. Our finding suggests that pleural involvement in patients with systemic amyloidosis can be identified on effusion specimens and avert the need for more invasive procedures like pleural or pulmonary parenchymal biopsies.

http://ift.tt/2l46CPc

PKCε promotes human Th17 differentiation: implications in the pathophysiology of Psoriasis

Abstract

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4⁺-T cells from patients with autoimmune Hashimoto's Thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4⁺-T cells from patients with Psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4⁺ subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: i)PKCε is overexpressed in CD4⁺-T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; ii)PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4⁺-T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.

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Effect of second child intent on delivery mode after Chinese two child policy implementation: a cross sectional and prospective observational study of nulliparous women in Chongqing

Objectives

To assess the influence of second child intent on the delivery preferences and final delivery modes of nulliparous women, particularly caesarean delivery on maternal request (CDMR), after implementation of China's two child policy.

Design

Cross sectional and prospective observational study.

Setting

A tertiary teaching hospital in Chongqing, China.

Participants

1000 low risk nulliparous women were initially involved, and were divided into two groups based on their intent on having a second child. 814 women who completed all interviews were analysed.

Main outcome measures

Preferred mode of delivery in second trimester and at admission; final delivery mode, CDMR.

Results

814 women who completed all interviews were analysed, in whom 51.2% intended to have a second child. The preference for caesarean delivery (CD) at the second trimester between the intent and no intent group was 6.2% versus 17.9% (adjusted RR 0.35, 95% CI 0.20 to 0.63) and increased to 24.2% versus 37.3% (adjusted RR 0.65, 95% CI 0.45 to 0.94) at admission, respectively. The overall CD rates between the two groups were 41.0% versus 50.4% (adjusted RR 0.84, 95% CI 0.60 to 1.18), and the CDMR rates were 16.7% versus 29.0% (adjusted RR 0.56, 95% CI 0.37 to 0.86), respectively.

Conclusions

Women who intend to have a second child are less likely to request a CD, and high rates of CD and CDMR in nulliparous women may have decreased after implementation of China's two child policy.

http://ift.tt/2pALeFS

Does the implementation of a novel intensive care discharge risk score and nurse-led inpatient review tool improve outcome? A prospective cohort study in two intensive care units in the UK

Objective

To develop a clinical prediction model for poor outcome after intensive care unit (ICU) discharge in a large observational data set and couple this to an acute post-ICU ward-based review tool (PIRT) to identify high-risk patients at the time of ICU discharge and improve their acute ward-based review and outcome.

Design

Retrospective patient cohort of index ICU admissions between June 2006 and October 2011 receiving routine inpatient review. Prospective cohort between March 2012 and March 2013 underwent risk scoring (PIRT) which subsequently guided inpatient ward-based review.

Setting

Two UK adult ICUs.

Participants

4212 eligible discharges from ICU in the retrospective development cohort and 1028 patients included in the prospective intervention cohort.

Interventions

Multivariate analysis was performed to determine factors associated with poor outcome in the retrospective cohort and used to generate a discharge risk score. A discharge and daily ward-based review tool incorporating an adjusted risk score was introduced. The prospective cohort underwent risk scoring at ICU discharge and inpatient review using the PIRT.

Outcomes

The primary outcome was the composite of death or readmission to ICU within 14 days of ICU discharge following the index ICU admission.

Results

PIRT review was achieved for 67.3% of all eligible discharges and improved the targeting of acute post-ICU review to high-risk patients. The presence of ward-based PIRT review in the prospective cohort did not correlate with a reduction in poor outcome overall (P=0.876) or overall readmission but did reduce early readmission (within the first 48 hours) from 4.5% to 3.6% (P=0.039), while increasing the rate of late readmission (48 hours to 14 days) from 2.7% to 5.8% (P=0.046).

Conclusion

PIRT facilitates the appropriate targeting of nurse-led inpatient review acutely after ICU discharge but does not reduce hospital mortality or overall readmission rates to ICU.

http://ift.tt/2DXPToK

Comprehensive assessment of health education and health promotion in five non-communicable disease demonstration districts in China: a cross-sectional study

Objectives

This study aims to develop assessment indicators of health education and promotion for non-communicable disease (NCD) demonstration districts in China and to identify significant factors associated with NCD health education and promotion work.

Methods

Three complementary techniques were used to conduct this study in Hunan Province, China, between late 2013 and 2015. The Delphi technique was used to develop weighted assessment indicators, followed by the rank sum ratio (RSR) to normalise the weights through rank conversion. Lastly, the technique for order of preference by similarity to ideal solution was conducted to assess five randomly selected NCD demonstration districts representing five different orientations in the province.

Results

A total of 24 assessment indicators were constructed covering the following sections: organisational management, fund support, personnel supplies, health education and promotion, people's awareness of NCDs, management and control of patients with NCD, satisfaction with health education and promotion and health literacy of residents. Five districts were selected as samples for evaluation (Furong District, Ziyang District, Shaodong County, Shuangfeng County and Luxi County). Performance varied among the sites, with Furong District greatly surpassing the other sites, especially in fund support, media promotion, technical support for publicity materials, community promotion and supportive environment supplies. The latter four factors were also much greater in the second-ranked Luxi County site than those in the other sites (except Furong District).

Conclusions

There were gaps in health education and promotion work in NCD demonstration districts in Hunan Province. The districts that performed better had obvious advantages in fund support, media promotion, technical support, community promotion and supportive environment supplies. Our study provided both a methodological reference and an assessment indicator framework for similar future studies.

http://ift.tt/2pEwtSx

Association of socioeconomic status with outcomes in older adult community-dwelling patients after visiting the emergency department: a retrospective cohort study

Objectives

Older adults frequently visit the emergency department (ED). Socioeconomic status (SES) has an important impact on health and ED utilisation; however, the association between SES and ED utilisation in elderly remains unclear. The aim of this study was to investigate the association between SES in older adult patients visiting the ED on outcomes.

Design

A retrospective study.

Participants

Older adults (≥65 years) visiting the ED, in the Netherlands. SES was stratified into tertiles based on average household income at zip code level: low (<1800/month), intermediate (1800–2300/month) and high (>2300/month).

Primary outcomes

Hospitalisation, inhospital mortality and 30-day ED return visits. Effect of SES on outcomes for all groups were assessed by logistic regression and adjusted for confounders.

Results

In total, 4828 older adults visited the ED during the study period. Low SES was associated with a higher risk of hospitalisation among community-dwelling patients compared with high SES (adjusted OR 1.3, 95% CI 1.1 to 1.7). This association was not present for intermediate SES (adjusted OR 1.1, 95% CI 0.95 to 1.4). Inhospital mortality was comparable between the low and high SES group, even after adjustment for age, comorbidity and triage level (low OR 1.4, 95% CI 0.8 to 2.6, intermediate OR 1.3, 95% CI 0.8 to 2.2). Thirty-day ED revisits among community-dwelling patients were also equal between the SES groups (low: adjusted OR 1.0, 95% CI 0.7 to 1.4, and intermediate: adjusted OR 0.8, 95% CI 0.6 to 1.1).

Conclusion

In older adult ED patients, low SES was associated with a higher risk of hospitalisation than high SES. However, SES had no impact on inhospital mortality and 30-day ED revisits after adjustment for confounders.

http://ift.tt/2DTHHpo

Barriers and facilitators of physical activity in knee and hip osteoarthritis: a systematic review of qualitative evidence

Physical activity (PA), including engagement in structured exercise, has a key role in the management of hip and knee osteoarthritis (OA). However, maintaining a physically active lifestyle is a challenge for people with OA. PA determinants in this population need to be understood better so that they can be optimised by public health or healthcare interventions and social policy changes.

Objectives

The primary aim of this study is to conduct a systematic review of the existing qualitative evidence on barriers and facilitators of PA for patients with hip or knee OA. Secondary objective is to explore differences in barriers and facilitators between (1) lifestyle PA and exercise and (2) PA uptake and maintenance.

Methods

Medline, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus, Scopus, Grey literature and qualitative journals were searched. Critical Appraisal Skills Programme—Qualitative checklist and Lincoln and Guba's criteria were used for quality appraisal. Thematic synthesis was applied.

Findings

Ten studies were included, seven focusing on exercise regimes, three on overall PA. The findings showed a good fit with the biopsychosocial model of health. Aiming at symptom relief and mobility, positive exercise experiences and beliefs, knowledge, a 'keep going' attitude, adjusting and prioritising PA, having healthcare professionals' and social support emerged as PA facilitators. Pain and physical limitations; non-positive PA experiences, beliefs and information; OA-related distress; a resigned attitude; lack of motivation, behavioural regulation, professional support and negative social comparison with coexercisers were PA barriers. All themes were supported by high and medium quality studies. Paucity of data did not allow for the secondary objectives to be explored.

Conclusion

Our findings reveal a complex interplay among physical, personal including psychological and social-environmental factors corresponding to the facilitation and hindrance of PA, particularly exercise, engagement. Further research on the efficacy of individualised patient education, psychological interventions or social policy change to promote exercise engagement and lifestyle PA in individuals with lower limb OA is required.

Trial registration number

CRD42016030024.

http://ift.tt/2pF7s9Z

Stepped care approach for medial tibiofemoral osteoarthritis (STrEAMline): protocol for a randomised controlled trial

Introduction

Current guidelines recommend tailored interventions to optimise knee osteoarthritis (OA) management. However, models of care still have a 'one size fits all' approach, which is suboptimal as it ignores patient heterogeneity. This study aims to compare a stepped care strategy with standard care for overweight and obese persons with medial tibiofemoral OA.

Methods and analysis

Participants will be randomised into two groups (85 each). The intervention will receive a diet and exercise programme for 18 weeks in the first step of the study. Disease remission will then be assessed using the Patient Acceptable Symptom State (PASS). PASS is defined as the highest level of symptom beyond which patients consider themselves well and takes into account pain intensity, patient's global assessment of disease activity and degree of functional impairment. In the second step, participants in remission will continue with diet and exercise. If remission is not achieved, participants will be assigned in a hierarchical order to cognitive behavioural therapy, knee brace or muscle strengthening for 12 weeks. The intervention will be decided based on their clinical presentation for symptoms of depression and varus malalignment. Participants without depression or varus malalignment will undertake a muscle strengthening programme. The control group will receive educational material related to OA management. Main inclusion criteria are age ≥50 years, radiographic medial tibiofemoral OA, body mass index (BMI) ≥28 kg/m², knee pain ≥40 (Visual Analogue Scale, 0–100), PASS (0–100) >32 for pain and global assessment, and 31 for functional impairment. Outcomes will be measured at 20-week and 32-week visits. The primary outcome is disease remission at 32 weeks. Other outcomes include functional mobility; patient-reported outcomes; BMI; waist-hip ratio; quadriceps strength; symptoms of depression, anxiety and stress; and knee range of motion. The analysis will be performed according to the intention-to-treat principle.

Ethics and dissemination

The local ethics committee approved this protocol (HREC/14/HAWKE/381). Dissemination will occur through presentations at international conferences and publication in peer-reviewed journals.

Trial registration number

ACTRN12615000227594.

http://ift.tt/2pFmNay

Is sexual minority status associated with poor sleep quality among adolescents? Analysis of a national cross-sectional survey in Chinese adolescents

Objectives

Recent studies have suggested that sexual minorities are more likely to have poor sleep quality. This study aims to explore sleep quality among sexual minority adolescents and examines the association between sexual minority status and sleep quality.

Design

Cross-sectional survey.

Setting

A total of 506 high schools in seven Chinese provinces.

Participants

A total of 150 822 students in grades 7–12 completed the questionnaires, and 123 459 students who reported being aware of their sexual orientation were included in analyses.

Main outcome measures

The Pittsburgh Sleep Quality Index, sexual attraction and school bullying victimisation.

Results

Of the 123 459 students who were analysed, 5.00% self-reported as sexual minorities. Only 26.67% of sexual minority students slept 8 or more hours/day, which is less than their heterosexual peers (35.70%; ²=130.04, P<0.001). Of the total sample, 22.41% of the students reported poor sleep quality, and this prevalence was significantly higher in sexual minority students than in heterosexual students (32.56% vs 21.87%; ²=281.70, P<0.001). After controlling for social demographics, lifestyle and depressive symptoms, sexual minority students had higher odds of poor sleep quality (adjusted OR=1.41, 95% CI 1.31 to 1.51) than their heterosexual peers. The indirect effect of school bullying victimisation (standardised β estimate=0.007, 95% CI 0.006 to 0.009) was significant, indicating that school bullying victimisation partially mediated the association between sexual minority status and sleep quality.

Conclusions

Our study suggested that poor sleep quality was common in sexual minority adolescents, and more attention should be paid to sleep problems in this population. Conducting interventions to reduce school bullying behaviours is an important step to improving sleep quality in sexual minority adolescents. Further, studies are warranted that focus on the risk factors and mechanisms of and interventions for sleep problems in sexual minority adolescents.

http://ift.tt/2pFFZVB

Circulating tumour cells as a potential screening tool for lung cancer (the AIR study): protocol of a prospective multicentre cohort study in France

Introduction

Lung cancer (LC) is the leading cause of death from cancer. Early diagnosis of LC is of paramount importance in terms of prognosis. The health authorities of most countries do not accept screening programmes based on low-dose chest CT (LDCT), especially in Europe, because they are flawed by a high rate of false-positive results, leading to a large number of invasive diagnostic procedures. These authorities advocated further research, including companion biological tests that could enhance the effectiveness of LC screening. The present project aims to validate early diagnosis of LC by detection and characterisation of circulating tumour cells (CTCs) in a peripheral blood sample taken from a prospective cohort of persons at high-risk of LC.

Methods and analysis

The AIR Project is a prospective, multicentre, double-blinded, cohort study conducted by a consortium of 21 French university centres. The primary objective is to determine the operational values of CTCs for the early detection of LC in a cohort of asymptomatic participants at high risk for LC, that is, smokers and ex-smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 years, with chronic obstructive pulmonary disease (COPD). The study participants will undergo yearly screening rounds for 3 years plus a 1-year follow-up. Each round will include LDCT plus peripheral blood sampling for CTC detection. Assuming 5% prevalence of LC in the studied population and a 10% dropout rate, a total of at least 600 volunteers will be enrolled.

Ethics and dissemination

The study sponsor is the University Hospital of Nice. The study was approved for France by the ethical committee CPP Sud-Méditerranée V and the ANSM (Ministry of Health) in July 2015. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations.

Trial registration number

NCT02500693.

http://ift.tt/2DXsPXh

Exercise response in Parkinsons disease: insights from a cross-sectional comparison with sedentary controls and a per-protocol analysis of a randomised controlled trial

Objectives

To investigate the acute and adaptation cardiovascular and metabolic training responses in people with Parkinson's disease (pwP).

Design

(1) A cross-sectional study of exercise response of pwP compared with sedentary controls and (2) an interventional study of exercise training in pwP.

Setting

Community leisure facilities.

Participants

pwP (n=83) and sedentary controls (n=55).

Interventions

Study 1 included participants from a two-arm-parallel single-blind phase II randomised controlled trial (RCT), that undertook a baseline maximal incremental exercise test and study 2 included those randomised to the exercise group in the RCT, who completed a 6-month weekly exercise programme (n=37). The intervention study 2 was a prescribed exercise program consisting of sessions lasting 60 min, two times a week over a 6-month period. The control group followed the same protocol which derived the same cardiorespiratory parameters, except that they were instructed to aim for a cadence of ~60 revolutions per minute and the unloaded phase lasted 3 min with an initial step of 25 W.

Primary and secondary outcome measures

Stepwise incremental exercise test to volitional exhaustion was the primary outcome measure.

Results

Study 1 showed higher maximum values for heart rate (HR), VO₂ L/min, VCO₂ L/min and ventilation L/min for the control group; respiratory exchange ratio (RER), perceived exertion and O₂ pulse (VO₂ L/min/HR) did not differ between groups. In study 2, for pwP who adhered to training (n=37), RER increased significantly and although there was no significant change in aerobic capacity or HR response, reduced blood pressure was found.

Conclusions

An abnormal cardiovascular response to exercise was observed in pwP compared to controls. After the exercise programme, metabolic deficiencies remained for pwP. These observations add to the pathogenic understanding of PD, acknowledge an underling metabolic contribution and support that certain cardiovascular symptoms may improve as a result of this type of exercise.

http://ift.tt/2DWjGhD

Comparing the diagnostic accuracy of five common tumour biomarkers and CA19-9 for pancreatic cancer: a protocol for a network meta-analysis of diagnostic test accuracy

Introduction

Surgical resection is the only curative treatment for patients with resectable pancreatic cancer. Unfortunately, 80%–85% of patients present with locally advanced or metastatic unresectable pancreatic cancer at the time of diagnosis. Detection of pancreatic cancer at early stages remains a great challenge due to lack of accurate detection tests. Recommendations in existing clinical practice guidelines on early diagnosis of pancreatic cancer are inconsistent and based on limited evidence. Most of them endorse measuring serum CA19-9 as a complementary test, but also state that it is not recommended for diagnosing early pancreatic cancer. There are currently no other tumour-specific markers recommended for diagnosing early pancreatic cancer. This study aims to evaluate and compare the accuracy of five common tumour biomarkers (CA242,carcino-embryonic antigen (CEA)), CA125, microRNAs and K-ras gene mutation) and CA19-9 and their combinations for diagnosing pancreatic cancer using network meta-analysis method, and to rank these tests using a superiority index.

Methods and analysis

PubMed, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception to April 2017. The search will include the above-mentioned tumour biomarkers for diagnosing pancreatic cancer, including CA19-9. The risk of bias for each study will be independently assessed as low, moderate or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2. Network meta-analysis will be performed using STATA V.12.0 and R software V.3.4.1. The competing diagnostic tests will be ranked by a superiority index.

Ethics and dissemination

Ethical approval and patient consent are not required since this study is a network meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication.

PROSPERO registration number

CRD42017064627.

http://ift.tt/2pBQXeJ

Chronic non-bacterial osteitis from the patient perspective: a health services research through data collected from patient conferences

Objective

Although chronic non-bacterial osteitis (CNO) is an ever-increasingly recognised illness in the paediatric community and the adult healthcare community, a study to assess diagnosing, treatment and the psychosocial aspect of CNO from a large population pool was not available. We aimed to investigate CNO from the patient perspective.

Design

Health services research, patient survey.

Setting

Ludwig-Maximilians-University (LMU) Pediatric Rheumatology Department CNO Conferences held in June 2013 and June 2015.

Participants

Using a patient survey developed by the LMU Pediatric Rheumatology Department, 105 patients from ages 5 to 63 years were assessed regarding CNO to include epidemiological data, medical history and treatment, initial symptoms, diagnostic procedures, current symptoms, associated diseases, current treating physicians, absences in school and work due to illness and the impact of illness on patient, family and friends.

Results

Active CNO was reported in 90% of patients present, with 73% being women and 27% being men. An overwhelming majority (70%) reported being diagnosed within 18 months of onset of symptoms; however, the initial diagnoses were wide-ranged to include malignancies in 36% to bacterial osteomyelitis in 30%, where the majority were treated with an antibiotic and/or were biopsied. When asked about the psychosocial aspect of this illness, 83% reported that non-bacterial osteitis (NBO) negatively impacted the family, 79% reported that NBO has negatively affected either school or work and 56% reported a negative impact on friendships.

Conclusion

Delay of diagnosis, living with differential diagnoses like malignancies and finding specialists for medical care are a few examples of what leads patients into searching for more information. The negative impact on daily life including family relationships, friendships and work/school highlights a need for better psychosocial support such as guidance counselling or psychological support due to three-quarters of patients receiving no such said support.

http://ift.tt/2pD4cf9

Senior high-cost healthcare users resource utilization and outcomes: a protocol of a retrospective matched cohort study in Canada

Introduction

Senior high-cost users (HCUs) are estimated to represent 60% of all HCUs in Ontario, Canada's most populous province. To improve our understanding of individual and health system characteristics related to senior HCUs, we will examine incident senior HCUs to determine their incremental healthcare utilisation and costs, characteristics of index hospitalisation episodes, mortality and their regional variation across Ontario.

Methods and analysis

A retrospective, population-based cohort study using administrative healthcare records will be used. Incident senior HCUs will be defined as Ontarians aged ≥66 years who were in the top 5% of healthcare cost users during fiscal year 2013 but not during fiscal year 2012. Each HCU will be matched to three non-HCUs by age, sex and health planning region. Incremental healthcare use and costs will be determined using the method of recycled predictions. We will apply multivariable logistic regression to determine patient and health service factors associated with index hospitalisation and inhospital mortality during the incident year. The most common causes of admission will be identified and contrasted with the most expensive hospitalised conditions. We will also calculate the ratio of inpatient costs incurred through admissions of ambulatory care sensitive conditions to the total inpatient expenditures. The magnitude of variation in costs and health service utilisation will be established by calculating the extremal quotient, the coefficient of variation and the Gini mean difference for estimates obtained through multilevel regression analyses.

Ethics and dissemination

This study has been approved by Hamilton Integrated Research Ethics Board (ID#1715-C). The results of the study will be distributed through peer-reviewed journals. They also will be disseminated at research events in academic settings, national and international conferences as well as with presentations to provincial health authorities.

http://ift.tt/2DVzpx8

ABC Index: quantifying experienced burden of COPD in a discrete choice experiment and predicting costs

Objective

The Assessment of Burden of COPD (ABC) tool supports shared decision making between patient and caregiver. It includes a coloured balloon diagram to visualise patients' scores on burden indicators. We aim to determine the importance of each indicator from a patient perspective, in order to calculate a weighted index score and investigate whether that score is predictive of costs.

Design

Discrete choice experiment.

Setting and participants

Primary care and secondary care in the Netherlands. 282 patients with chronic obstructive pulmonary disease (COPD) and 252 members of the general public participated.

Methods

Respondents received 14 choice questions and indicated which of two health states was more severe. Health states were described in terms of specific symptoms, limitations in physical, daily and social activities, mental problems, fatigue and exacerbations, most of which had three levels of severity. Weights for each item-level combination were derived from a Bayesian mixed logit model. Weights were rescaled to construct an index score from 0 (best) to 100 (worst). Regression models were used to find a classification of this index score in mild, moderate and severe that was discriminative in terms of healthcare costs.

Results

Fatigue, limitations in moderate physical activities, number of exacerbations, dyspnoea at rest and fear of breathing getting worse contributed most to the burden of disease. Patients assigned less weight to dyspnoea during exercise, listlessness and limitations with regard to strenuous activities. Respondents from the general public mostly agreed. Mild, moderate and severe burden of disease were defined as scores <20, 20–39 and ≥40. This categorisation was most predictive of healthcare utilisation and annual costs: 1368, 2510 and 9885, respectively.

Conclusions

The ABC Index is a new index score for the burden of COPD, which is based on patients' preferences. The classification of the index score into mild, moderate and severe is predictive of future healthcare costs.

Trial registration number

NTR3788; Post-results.

http://ift.tt/2pD4anx

Is computer-assisted instruction more effective than other educational methods in achieving ECG competence among medical students and residents? Protocol for a systematic review and meta-analysis

Introduction

Although ECG interpretation is an essential skill in clinical medicine, medical students and residents often lack ECG competence. Novel teaching methods are increasingly being implemented and investigated to improve ECG training. Computer-assisted instruction is one such method under investigation; however, its efficacy in achieving better ECG competence among medical students and residents remains uncertain.

Methods and analysis

This article describes the protocol for a systematic review and meta-analysis that will compare the effectiveness of computer-assisted instruction with other teaching methods used for the ECG training of medical students and residents. Only studies with a comparative research design will be considered. Articles will be searched for in electronic databases (PubMed, Scopus, Web of Science, Academic Search Premier, CINAHL, PsycINFO, Education Resources Information Center, Africa-Wide Information and Teacher Reference Center). In addition, we will review citation indexes and conduct a grey literature search. Data extraction will be done on articles that met the predefined eligibility criteria. A descriptive analysis of the different teaching modalities will be provided and their educational impact will be assessed in terms of effect size and the modified version of Kirkpatrick framework for the evaluation of educational interventions. This systematic review aims to provide evidence as to whether computer-assisted instruction is an effective teaching modality for ECG training. It is hoped that the information garnered from this systematic review will assist in future curricular development and improve ECG training.

Ethics and dissemination

As this research is a systematic review of published literature, ethical approval is not required. The results will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement and will be submitted to a peer-reviewed journal. The protocol and systematic review will be included in a PhD dissertation.

PROSPERO registration number

CRD42017067054; Pre-results.

http://ift.tt/2DXvOPs

BRain health and healthy AgeINg in retired rugby union players, the BRAIN Study: study protocol for an observational study in the UK

Introduction

Relatively little is known about the long-term health of former elite rugby players, or former sportspeople more generally. As well as the potential benefits of being former elite sportspersons, there may be potential health risks from exposures occurring during an individual's playing career, as well as following retirement. Each contact sport has vastly different playing dynamics, therefore exposing its players to different types of potential traumas. Current evidence suggests that these are not necessarily comparable in terms of pathophysiology, and their potential long-term adverse effects might also differ. There is currently limited but increasing evidence that poorer age-related and neurological health exists among former professional sportsmen exposed to repetitive concussions; however the evidence is limited on rugby union players, specifically.

Methods and analysis

We present the protocol for a cross-sectional study to assess the association between self-reported history of concussion during a playing career, and subsequent measures of healthy ageing and neurological and cognitive impairment. We are recruiting a sample of approximately 200 retired rugby players (former Oxford and Cambridge University rugby players and members of the England Rugby International Club) aged 50 years or more, and collecting a number of general and neurological health-related outcome measures though validated assessments. Biomarkers of neurodegeneration (neurofilaments and tau) will be also be measured. Although the study is focusing on rugby union players specifically, the general study design and the methods for assessing neurological health are likely to be relevant to other studies of former elite sportspersons.

Ethics and dissemination

The study has been approved by the Ethical Committee of London School of Hygiene and Tropical Medicine (reference: 11634-2). It is intended that results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders.

http://ift.tt/2DXsuUv

Frailty measurement and outcomes in interventional studies: protocol for a systematic review of randomised control trials

Introduction

Frailty is associated with reduced functional capacity, decreased resistance to stressors and is predictive of a range of adverse health outcomes, including dependency, hospitalisation and mortality. Early identification of frailty may prevent, reduce and postpone adverse health outcomes. However, there is a need for additional evidence to guide decision-making for the care of frail patients since frail persons are frequently excluded from studies, the differential impact of frailty is often not examined in clinical trials and few large-scale clinical trials examining frail cohorts have been conducted. Randomised control trials (RCTs) published to date have used a diverse range of definitions of frailty, as well as a variety of outcome measures. The objective of this systematic review is to comprehensively characterise the frail populations enrolled and the end points reported in frailty RCTs.

Methods and analysis

We will identify all RCTs reporting on the outcome of interventions in adult (age ≥18 years) frail populations as defined by authors, in all settings of care. Databases will include MEDLINE, CINAHL, EMBASE, PsycInfo, Global Health, the Joanna Briggs database and Cochrane Library. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, inter-rater reliability, risk of bias assessment and evaluation of the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach.

Ethics and dissemination

This systematic review will comprehensively identify RCTs including frail patients to identify how frailty is measured and which outcomes are reported. The results of this systematic review may inform clinicians caring for persons with frailty, facilitate conduct of future RCTs and inform future efforts to develop common data elements and core outcomes for frailty studies. Our findings will be disseminated through conference presentation and publication in peer-reviewed journals.

PROSPERO registration number

CRD42017065233.

http://ift.tt/2pG47Ht

Feasibility of 2-D ultrasound shear wave elastography of fetal lungs in case of threatened preterm labour: a study protocol

Introduction

2-D ultrasound shear wave elastography (SWE) could be considered as a new noninvasive tool for monitoring fetal lung development based on evaluation of mechanical properties during pregnancy. Interesting results are available concerning the use of SWE on developing organs, especially on premature infants and animal models. The main objective in this study is to evaluate the feasibility of 2-D SWE in human fetal lungs between 24 and 34 weeks of gestation (WG). The secondary objective is to modellise fetal lung-to-liver elastography ratio (LLE ratio) and to assess variations between normal lung and lung surfactant-enriched after a corticosteroids course indicated for a threatened preterm labour (TPL).

Methods/design

A prospective case-control study will be performed between 24 and 34 WG. Fetal lungs and liver will be explored by SWE into two groups: fetuses of women with an uncomplicated pregnancy (control group) and fetuses of women with a TPL requiring administration of corticosteroids (cases group). LLE ratio will be defined as the value of the lung elasticity divided by the value of the liver elasticity.

Primary judgement criterion is the value of elasticity modulus expressed in kilopascal. Lungs and liver will be explored through three measurements to define the most reproducible regions with the lowest intra- and inter-observer variability. Feasibility will be evaluated by assessing the number of examinations performed and the number of examinations with interpretable results. Intra- and inter-observer reproducibility will be evaluated by means of the intra-class correlation coefficient.

Ethics and dissemination

Approval of the study protocol was obtained from the human ethical research committee (Comité de Protection des Personnes EST II, process number 15/494) and the French National Agency for Medicines and Health Products Safety (process number 2015-A01575-44). All participants will sign a statement of informed consent.

Trial registration number

NCT02870608; Recruiting.

http://ift.tt/2pHD9iG

Our Health Counts Toronto: using respondent-driven sampling to unmask census undercounts of an urban indigenous population in Toronto, Canada

Objectives

To provide evidence of the magnitude of census undercounts of 'hard-to-reach' subpopulations and to improve estimation of the size of the urban indigenous population in Toronto, Canada, using respondent-driven sampling (RDS).

Design

Respondent-driven sampling.

Setting

The study took place in the urban indigenous community in Toronto, Canada. Three locations within the city were used to recruit study participants.

Participants

908 adult participants (15+) who self-identified as indigenous (First Nation, Inuit or Métis) and lived in the city of Toronto. Study participants were generally young with over 60% of indigenous adults under the age of 45 years. Household income was low with approximately two-thirds of the sample living in households which earned less than $C20 000 last year.

Primary and secondary outcome measures

We collected baseline data on demographic characteristics, including indigenous identity, age, gender, income, household type and household size. Our primary outcome asked: 'Did you complete the 2011 Census Canada questionnaire?'

Results

Using RDS and our large-scale survey of the urban indigenous population in Toronto, Canada, we have shown that the most recent Canadian census underestimated the size of the indigenous population in Toronto by a factor of 2 to 4. Specifically, under conservative assumptions, there are approximately 55 000 (95% CI 45 000 to 73 000) indigenous people living in Toronto, at least double the current estimate of 19 270.

Conclusions

Our indigenous enumeration methods, including RDS and census completion information will have broad impacts across governmental and health policy, potentially improving healthcare access for this community. These novel applications of RDS may be relevant for the enumeration of other 'hard-to-reach' populations, such as illegal immigrants or homeless individuals in Canada and beyond.

http://ift.tt/2pFRfBm

Developing and validating a novel multisource comorbidity score from administrative data: a large population-based cohort study from Italy

Objective

To develop and validate a novel comorbidity score (multisource comorbidity score (MCS)) predictive of mortality, hospital admissions and healthcare costs using multiple source information from the administrative Italian National Health System (NHS) databases.

Methods

An index of 34 variables (measured from inpatient diagnoses and outpatient drug prescriptions within 2 years before baseline) independently predicting 1-year mortality in a sample of 500 000 individuals aged 50 years or older randomly selected from the NHS beneficiaries of the Italian region of Lombardy (training set) was developed. The corresponding weights were assigned from the regression coefficients of a Weibull survival model. MCS performance was evaluated by using an internal (ie, another sample of 500 000 NHS beneficiaries from Lombardy) and three external (each consisting of 500 000 NHS beneficiaries from Emilia-Romagna, Lazio and Sicily) validation sets. Discriminant power and net reclassification improvement were used to compare MCS performance with that of other comorbidity scores. MCS ability to predict secondary health outcomes (ie, hospital admissions and costs) was also investigated.

Results

Primary and secondary outcomes progressively increased with increasing MCS value. MCS improved the net 1-year mortality reclassification from 27% (with respect to the Chronic Disease Score) to 69% (with respect to the Elixhauser Index). MCS discrimination performance was similar in the four regions of Italy we tested, the area under the receiver operating characteristic curves (95% CI) being 0.78 (0.77 to 0.79) in Lombardy, 0.78 (0.77 to 0.79) in Emilia-Romagna, 0.77 (0.76 to 0.78) in Lazio and 0.78 (0.77 to 0.79) in Sicily.

Conclusion

MCS seems better than conventional scores for predicting health outcomes, at least in the general population from Italy. This may offer an improved tool for risk adjustment, policy planning and identifying patients in need of a focused treatment approach in the everyday medical practice.

http://ift.tt/2DZ4ShV

Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)

Abstract

Background

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.

Methods

This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.

Results

173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.

Conclusion

These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

http://ift.tt/2BVIPM3

Adaptive and reversible resistance to Kras inhibition in pancreatic cancer cells

Activating mutations in KRAS are the hallmark genetic alterations in pancreatic ductal adenocarcinoma (PDAC) and the key drivers of its initiation and progression. Longstanding efforts to develop novel KRAS inhibitors have been based on the assumption that PDAC cells are addicted to activated KRAS, but this assumption remains controversial. In this study, we analyzed the requirement of endogenous Kras to maintain survival of murine PDAC cells, using an inducible shRNA-based system that enables temporal control of Kras expression. We found that the majority of murine PDAC cells analyzed tolerated acute and sustained Kras silencing by adapting to a reversible cell state characterized by differences in cell morphology, proliferative kinetics, and tumor-initiating capacity. While we observed no significant mutational or transcriptional changes in the Kras-inhibited state, global phosphoproteomic profiling revealed significant alterations in cell signaling, including increased phosphorylation of focal adhesion pathway components. Accordingly, Kras-inhibited cells displayed prominent focal adhesion plaque structures, enhanced adherence properties, and increased dependency on adhesion for viability in vitro. Overall, our results call into question the degree to which PDAC cells are addicted to activated KRAS, by illustrating adaptive non-genetic and non-transcriptional mechanisms of resistance to Kras blockade. However, by identifying these mechanisms, our work also provides mechanistic directions to develop combination strategies that can help enforce the efficacy of KRAS inhibitors.

http://ift.tt/2leFzzX

GADD45{beta} loss ablates innate immunosuppression in cancer

T cell exclusion from the tumour microenvironment (TME) is a major barrier to overcoming immune escape. Here we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumour-associated inflammation and T cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma (HCC) and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of pro-inflammatory tumour-associated macrophages (TAM) and intratumoural immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Further, they suggest a therapeutic target in GADD45β for re-programming TAM to overcome immunosuppression and T cell exclusion from the TME.

http://ift.tt/2l2A7kA

Germinal centers determine the prognostic relevance of tertiary lymphoid structures and are impaired by corticosteroids in lung squamous cell carcinoma

In solid tumors, the presence of lymph node-like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS form in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multi-spectral microscopy, quantitative pathology and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of germinal centers (GC). In untreated patients, TLS density was the strongest independent prognostic marker. Further, TLS density correlated with GC formation and expression of adaptive immune response-related genes. In patients treated with neoadjuvant chemotherapy, TLS density was similar but GC formation was impaired and the prognostic value of TLS density was lost. Corticosteroids are co-administered with chemotherapy to manage side effects in LSCC patients, so we evaluated whether they impaired TLS development independently of chemotherapy. TLS density and GC formation were each reduced in chemotherapy-naive LSCC patients treated with corticosteroids before surgery, compared to untreated patients, a finding that we confirmed in the experimental model of lung TLS induction. Overall, our results highlight the importance of GC formation in TLS during tumor development and treatment.

http://ift.tt/2CckzSI

Survival of cancer stem-like cells under metabolic stress via CaMK2{alpha}-mediated upregulation of sarco/endoplasmic reticulum calcium ATPase expression

Purpose: Cancer cells grow in an unfavorable metabolic milieu in the tumor microenvironment and are constantly exposed to metabolic stress such as chronic nutrient depletion. Cancer stem-like cells (CSCs) are intrinsically resistant to metabolic stress, thereby surviving nutrient insufficiency and driving more malignant tumor progression. In this study, we aimed to demonstrate the potential mechanisms by which CSCs avoid Ca2+-dependent apoptosis during glucose deprivation. Experimental design: We investigated cell viability and apoptosis under glucose deprivation, performed genome-wide transcriptional profiling of paired CSCs and parental cells, studied the effect of calcium/calmodulin-dependent protein kinase 2 alpha (CaMK2α) gene knockdown, and investigated the role of nuclear factor kappa B (NFB) in CSCs during time-dependent Ca2+-mediated and glucose deprivation-induced apoptosis. We also observed the effect of combined treatment with 2-deoxy-d-glucose, a metabolic inhibitor that mimics glucose deprivation conditions in mouse xenograft models, and thapsigargin, a specific inhibitor of SERCA. Results: We demonstrated the coordinated up-regulation of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in CSCs. SERCA, in turn, is transcriptionally regulated by CaMK2α via NFB activation. Combined treatment with 2-deoxy-d-glucose and thapsigargin, a specific inhibitor of SERCA, significantly reduced tumor growth compared to that in untreated control animals or those treated with the metabolic inhibitor alone. Conclusions: The current study provides compelling evidence that CaMK2α acts as a key anti-apoptosis regulator in metabolic stress-resistant CSCs by activating NFB. The latter induces expression of SERCA, allowing survival in glucose-deprived conditions. Importantly, our combination therapeutic strategy provides a novel approach for the clinical application of CSC treatment.

http://ift.tt/2lejktT

Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies

Purpose: Both objective response rate (ORR) and progression-free survival as defined by RECIST are weakly associated with overall survival (OS) in trials evaluating immunotherapy drug products.  We proposed a novel intermediate response endpoint (IME) for evaluating immunotherapies.  Experimental Design: We defined IME response as having no non-target lesion progression, no new lesion appearance, and reaching a target lesion response determined by baseline tumor burden, tumor reduction depth, and tumor change dynamic within one year after randomization. Database used consisted of data from randomized active-controlled immunotherapy trials. Criterion for IME was developed based on patient level data from a training dataset, and further evaluated using independent testing dataset. A patient level responder analysis comparing OS between patients with and without an IME response was conducted using combined data.  Association between trial level OS hazard ratio (HR) and IME odds ratio was analyzed using a weighted linear regression model. Results: A total of 5806 patients from 9 randomized studies were included in the database. At patient level, patients with IME response had improved OS compared to non-responders (HR 0.09). At trial level, association between OS and IME was moderate (R2 = 0.68). Conclusion: The IME was moderately associated with OS, and the association appeared to be stronger than the association observed between RECIST-defined ORR and OS.  However, the analyses conducted in this research are exploratory and further evaluation is needed before using this endpoint in future studies.

http://ift.tt/2l5StBl

Fine Mapping of QUICK ROOTING 1 and 2, Quantitative Trait Loci Increasing Root Length in Rice

The volume that the root system can occupy is associated with the efficiency of water and nutrient uptake from soil. Genetic improvement of root length, which is a limiting factor for root distribution, is necessary for increasing crop production. In this report, we describe identification of two QTLs for maximal root length, QUICK ROOTING 1 (QRO1) on chromosome 2 and QRO2 on chromosome 6 in cultivated rice (Oryza sativa L.). We measured the maximal root length in 26 lines carrying chromosome segments from the long-rooted upland rice cultivar Kinandang Patong in the genetic background of the short-rooted lowland cultivar IR64. Five lines had longer roots than IR64. By rough mapping of the target regions in BC₄F₂ populations, we detected putative QTLs for maximal root length on chromosomes 2, 6, and 8. To fine-map these QTLs, we used BC₄F₃ recombinant homozygous lines. QRO1 was mapped between markers RM5651 and RM6107, which delimit a 1.7-Mbp interval on chromosome 2, and QRO2 was mapped between markers RM20495 and RM3430-1, which delimit an 884-kbp interval on chromosome 6. Both QTLs may be promising gene resources for improving root system architecture in rice.

http://ift.tt/2C8nZs1

Genetic Evidence for Roles of Yeast Mitotic Cyclins at Single-Stranded Gaps Created by DNA Replication

Paused/stalled replication forks are major threats to genome integrity; unraveling the complex pathways that contribute to fork stability/restart is crucial. Experimentally, fork stalling is induced by growth in presence of hydroxyurea (HU), which depletes the pool of deoxynucleoside triphosphates (dNTPs) and slows down replication progression in yeast. Here, I report an epistasis analysis, based on sensitivity to HU, between CLB2, the principal mitotic cyclin gene in S. cerevisiae, and genes involved in fork stability and recombination. clb2 cells are not sensitive to HU, but the strong synergistic effect of clb2 with most genes tested indicates, unexpectedly, that CLB2 plays an important role in DNA replication, in the stability and restart of stalled forks, in pathways dependent and independent of homologous recombination. Results indicate that CLB2 functions in parallel to SGS1 helicase-EXO1 exonuclease to allow proper Rad51 recombination, but also regulates a combined Sgs1-Exo1 activity in a Mec1- and a Rad53- checkpoint protein kinase dependent pathway. Data argue that Mec1 regulates Clb2 to prevent a deleterious Sgs1-Exo1 activity at paused/stalled forks, while Rad53 checkpoint activation regulates Clb2 to allow a necessary Sgs1-Exo1 activity at stalled/collapsed forks. Altogether, this study indicates that Clb2 regulates the activity of numerous nucleases at single-stranded gaps created by DNA replication. A model is proposed for the function and regulation of Clb2 at stalled forks. These data open new perspectives on the role of mitotic cyclins at the end of S phase.

http://ift.tt/2BGDZhe

The ‘could’ and the ‘should’ of reconstructing severe hind-foot injuries

Publication date: Available online 26 December 2017
Source:Injury
Author(s): Jowan G. Penn-Barwell, Philippa M. Bennett, Andrew C. Gray




http://ift.tt/2Ccx6rw

The influence of local bone quality on fracture pattern in proximal humerus fractures

Publication date: Available online 26 December 2017
Source:Injury
Author(s): Ruben A. Mazzucchelli, Katharina Jenny, Vilijam Zdravkovic, Johannes B. Erhardt, Bernhard Jost, Christian Spross
IntroductionBone mineral density and fracture morphology are widely discussed and relevant factors when considering the different treatment options for proximal humerus fractures. It was the aim of this study to investigate the influence of local bone quality on fracture patterns of the Neer classification as well as on fracture impaction angle in these injuries.Materials and MethodsAll acute, isolated and non-pathological proximal humerus fractures admitted to our emergency department were included. The fractures were classified according to Neer and the humeral head impaction angle was measured. Local bone quality was assessed using the Deltoid Tuberosity Index (DTI). The distribution between DTI and fracture pattern was analysed.Results191 proximal humerus fractures were included (61 men, mean age 59 years; 130 women, mean age 69.5). 77 fractures (40%) were classified as one-part, 72 (38%) were two-part, 24 (13%) were three- and four-part and 18 (9%) were fracture dislocations. 30 fractures (16%) were varus impacted, whereas 45 fractures (24%) were classified as valgus impacted. The mean DTI was 1.48. Valgus impaction significantly correlated with good bone quality (DTI ≥ 1.4; p = 0.047) whereas no such statistical significance was found for the Neer fracture types.DiscussionWe found that valgus impaction significantly depended on good bone quality. However, neither varus impaction nor any of the Neer fracture types correlated with bone quality. We conclude that the better bone quality of valgus impacted fractures may be a reason for their historically benign amenability to ORIF. On the other hand, good local bone quality does not prevent fracture comminution.



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Vaccination protects against invasive HPV-associated cancers

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Memory Improvement Effect of Ethanol Garlic (A. sativum) Extract in Streptozotocin-Nicotinamide Induced Diabetic Wistar Rats Is Mediated through Increasing of Hippocampal Sodium-Potassium ATPase, Glutamine Synthetase, and Calcium ATPase Activities

Studies suggest that garlic (A. sativum) improves memory dependent on the hippocampus. However, the effect of ethanol garlic extract on hippocampus Na+/K+ ATPase, Ca2+ ATPase, and glutamine synthetase (GS) activities as possible mechanisms in memory improvement in diabetic Wistar rats has not been reported. Twenty-four male Wistar rats weighing 200–250 g were divided into three groups with 8 rats each. Group (A), normal control rats, and Group (B), diabetic rats, received 1 ml of normal saline; diabetic rats in Group (C) received 1000 mg/kg of garlic extract orally for 21 days. Hyperglycemia was induced by a single intraperitoneal injection of streptozotocin 60 mg/kg followed by 120 mg/kg nicotinamide while extraction of garlic was done by cold maceration method. Memory was tested in all groups. After that, the rats were sacrificed, the brain was removed, and the hippocampi were carefully excised and then homogenized. Activities of Na+/K+ ATPase, calcium ATPase, and GS were analyzed from the homogenate. Results showed improvement in memory and a significant increase in hippocampus Na+/K+ ATPase, Ca2+ ATPase, and GS activities in diabetic rats treated with garlic extract. In conclusion, the increased activity of hippocampus Na+/K+ ATPase, calcium ATPase, and glutamine synthetase may account for the memory improvement.

http://ift.tt/2DU4u4v

Hemorrhoids

Each of us has veins around the anus that stretch under pressure. Some of the veins are inside the rectum (internal) and others are under the skin around the anus (external). When the veins become swollen, they are called hemorrhoids.

http://ift.tt/2lge3lx

Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine

Sulfur amino acids are a kind of amino acids which contain sulfhydryl, and they play a crucial role in protein structure, metabolism, immunity, and oxidation. Our review demonstrates the oxidation resistance effect of methionine and cysteine, two of the most representative sulfur amino acids, and their metabolites. Methionine and cysteine are extremely sensitive to almost all forms of reactive oxygen species, which makes them antioxidative. Moreover, methionine and cysteine are precursors of S-adenosylmethionine, hydrogen sulfide, taurine, and glutathione. These products are reported to alleviate oxidant stress induced by various oxidants and protect the tissue from the damage. However, the deficiency and excess of methionine and cysteine in diet affect the normal growth of animals; thereby a new study about defining adequate levels of methionine and cysteine intake is important.

http://ift.tt/2DWCXiC

Linezolid Injection by Auromedics Pharma: Voluntary Recall 600mg/300mL flexible bags- Due to Presence White Particle Matter That Has Been Identified as Mold

Audience: Risk Manager, Pharmacy, Nurse ISSUE: AuroMedics Pharma is voluntarily recalling one lot of Linezolid Injection 600mg/300mL flexible bags, NDC 55150 -242 -51 batch CLZ160007 expiration August 2018 to the hospital level. This batch was...

http://ift.tt/2l1lX32

Tarsometatarsal joint communication during fluoroscopy-guided therapeutic joint injections and relationship with patient age and degree of osteoarthritis

Abstract

Objective

Although the tarsometatarsal joints are separated into three distinct synovial compartments, communications between adjacent compartments are often noted during image-guided injections. This study aims to determine whether abnormal inter-compartment tarsometatarsal joint communication is associated with patient age or degree of tarsometatarsal osteoarthritis.

Materials and methods

One hundred forty tarsometatarsal injections were retrospectively reviewed by two radiologists. Extent of inter-compartment communication and degree of osteoarthritis were independently scored. Univariate and multivariable analyses were performed to assess whether the presence of and number of abnormal joint communications were related to age and degree of osteoarthritis.

Results

Forty out of 140 tarsometatarsal joints showed abnormal communication with a separate synovial compartment, and 3 of the 40 showed abnormal communication with two separate compartments. On univariate analysis, higher grade osteoarthritis (p < 0.001) and older age (p = 0.014) were associated with an increased likelihood of abnormal inter-compartment tarsometatarsal communication and a greater number of these abnormal communications. On multivariate analysis, the degree of osteoarthritis remained a significant predictor of the presence of (p < 0.001) and number of (p < 0.001) abnormal communications, while the association of age was not statistically significant. There was significant correlation between age and degree of osteoarthritis (p < 0.001).

Conclusion

Higher grade osteoarthritis increases the likelihood of abnormal inter-compartment tarsometatarsal joint communication and is associated with a greater number of abnormal communications. Diagnostic injection to localize a symptomatic tarsometatarsal joint may be less reliable in the setting of advanced osteoarthritis.

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Reduction of artifacts caused by orthopedic hardware in the spine in spectral detector CT examinations using virtual monoenergetic image reconstructions and metal-artifact-reduction algorithms

Abstract

Objective

Aim of this study was to assess the artifact reduction in patients with orthopedic hardware in the spine as provided by (1) metal-artifact-reduction algorithms (O-MAR) and (2) virtual monoenergetic images (MonoE) as provided by spectral detector CT (SDCT) compared to conventional iterative reconstruction (CI).

Methods

In all, 28 consecutive patients with orthopedic hardware in the spine who underwent SDCT-examinations were included. CI, O-MAR and MonoE (40–200 keV) images were reconstructed. Attenuation (HU) and noise (SD) were measured in order to calculate signal-to-noise ratio (SNR) of paravertebral muscle and spinal canal. Subjective image quality was assessed by two radiologists in terms of image quality and extent of artifact reduction.

Results

O-MAR and high-keV MonoE showed significant decrease of hypodense artifacts in terms of higher attenuation as compared to CI (CI vs O-MAR, 200 keV MonoE: −396.5HU vs. –115.2HU, −48.1HU; both p ≤ 0.001). Further, artifacts as depicted by noise were reduced in O-MAR and high-keV MonoE as compared to CI in (1) paravertebral muscle and (2) spinal canal—CI vs. O-MAR/200 keV: (1) 34.7 ± 19.0 HU vs. 26.4 ± 14.4 HU, p ≤ 0.05/27.4 ± 16.1, n.s.; (2) 103.4 ± 61.3 HU vs. 72.6 ± 62.6 HU/60.9 ± 40.1 HU, both p ≤ 0.001. Subjectively both O-MAR and high-keV images yielded an artifact reduction in up to 24/28 patients.

Conclusion

Both, O-MAR and high-keV MonoE reconstructions as provided by SDCT lead to objective and subjective artifact reduction, thus the combination of O-MAR and MonoE seems promising for further reduction.

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Progressive loss of supination of the wrist

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Scapulothoracic pathology: review of anatomy, pathophysiology, imaging findings, and an approach to management

Abstract

Symptomatic scapulothoracic disorders, including scapulothoracic crepitus and scapulothoracic bursitis are uncommon disorders involving the scapulothoracic articulation that have the potential to cause significant patient morbidity. Scapulothoracic crepitus is the presence of a grinding or popping sound with movement of the scapula that may or may not be symptomatic, while scapulothoracic bursitis refers to inflammation of bursa within the scapulothoracic articulation. Both entities may occur either concomitantly or independently. Nonetheless, the constellation of symptoms manifested by both entities has been referred to as the snapping scapula syndrome. Various causes of scapulothoracic crepitus include bursitis, variable scapular morphology, post-surgical or post-traumatic changes, osseous and soft tissue masses, scapular dyskinesis, and postural defects. Imaging is an important adjunct to the physical examination for accurate diagnosis and appropriate treatment management. Non-operative management such as physical therapy and local injection can be effective for symptoms secondary to scapular dyskinesis or benign, non-osseous lesions. Surgical treatment is utilized for osseous lesions, or if non-operative management for bursitis has failed. Open, arthroscopic, or combined methods have been performed with good clinical outcomes.

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Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD): syndactyly type IX

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Voriconazole-induced periostitis deformans: serial imaging in a patient with ANCA vasculitis

Abstract

Objectives

A 61-year-old with acute granulomatosis and polyangiitis developed Aspergillus fumigatus pneumonia after admission to the intensive care unit with a small bowel perforation. This occurred after immunosuppression (intravenous methylprednisolone, intravenous cyclophosphamide, and plasmapheresis) for his initial presentation with stage 3 acute kidney injury.

Materials and methods

The mycologist recommended long-term treatment with voriconazole after initial recovery.

Results

After 7 months of treatment, the patient complained of joint pain and swelling in his hands. Radiographs, computed tomography, and single-photon emission computed tomography appearances were consistent with periostitis. A diagnosis of Voriconazole-induced periostitis deformans was made and the voriconazole was stopped. Plasma fluoride level was 278 μg/L (normal range < 50 μg/L). Discontinuation of voriconazole led to clinical improvement.

Conclusions

Periostitis deformans due to fluorosis is a rare complication of voriconazole treatment. The imaging in our case is unusually dramatic. We were able to track the evolution of periosteal reactions over serial imaging.

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MRI findings associated with microscopic residual tumor following unplanned excision of soft tissue sarcomas in the extremities

Abstract

Introduction

MRI is often used to determine the presence of residual disease following unplanned excisions (UPE) of soft tissue sarcomas (STS). We sought to identify MRI features associated with histologic evidence of residual disease after TBE.

Materials and methods

This was an IRB-approved retrospective review of 27 patients with R1-type UPE of STS over a 32-month period, with subsequent MRI and TBE. MRI studies were retrospectively evaluated to determine depth of tissue involvement, presence of nodular enhancement, and maximum length of soft tissue edema normalized to extremity size. MRI findings were correlated with histology from unplanned excision and TBE.

Results

Among the 21 subjects, there were 13 males and 8 females, mean age 58. Eighteen of 21 STS were grade 2 or 3. Deep compartments were involved in 5/21 cases. Original margins were positive in 17/21 UPE, with inadequate margin assessment in the remaining 4 cases. Residual tumor was present at TBE in 11/21 cases; it was found in 4/6 cases with nodular enhancement and 7/15 cases without nodular enhancement (sensitivity = 0.36; specificity = 0.80; PPV = 0.67; NPV = 0.53). Increased extent of soft tissue edema increased the likelihood of residual tumor at TBE (OR = 35.0; 95% CI = 1.6 to 752.7; p = 0.023).

Conclusion

Nodular enhancement is neither sensitive nor specific in predicting residual microscopic tumor in TBE following UPE. Extensive soft tissue edema on MRI after UPE increases the likelihood of finding a residual microscopic tumor, justifying ample margins at TBE and consideration of adjuvant therapy.

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Detection of femoroplasty on pre- and post-arthroscopic comparison radiographs following treatment of femoroacetabular impingement syndrome: multi-reader accuracy and agreement study

Abstract

Objective

To assess diagnostic accuracy and agreement among radiologists in detecting femoroplasty on pre- and post-arthroscopic comparison frog lateral and anteroposterior (AP) pelvic radiographs after treatment of femoroacetabular impingement (FAI) syndrome.

Materials and methods

In this retrospective, cross-sectional study, 86 patients underwent hip arthroscopy (52 with and 34 without femoroplasty) for treatment of FAI syndrome. Three radiologists blinded to clinical data and chronological order of the pre- and post-arthroscopic comparison radiographs independently examined AP pelvis and frog lateral radiographs to detect femoroplasty changes. Statistical analysis outputs included diagnostic accuracy parameters and inter- and intra-observer agreement.

Results

Identification of femoroplasty in the frog lateral projection has mean sensitivity 70%, specificity 82%, inter-observer agreement κ 0.74–0.76 and intra-observer agreement κ 0.72–0.85. Using the AP pelvis projection to detect femoroplasty has mean sensitivity 32%, specificity 71%, inter-observer agreement κ 0.47–0.65, and intra-observer agreement κ, 0.56–0.84.

Conclusions

Radiologists are only moderately sensitive, though more specific, in femoroplasty detection in the frog lateral projection. The AP pelvis projection yields lower sensitivity and specificity. Both projections have moderate inter- and intra-observer agreement.

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Progressive loss of supination of the wrist

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Browser’s notes

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Giant angioleiomyoma of the sacral foramina: an unusual location

Abstract

Angioleiomyoma is a benign, vascular smooth muscle tumor originating from the tunica media of the vessel wall. In general, it typically arises in the cutaneous, subcutaneous tissue or fascia of the lower extremities in middle-aged women and is less than 2 cm in diameter. We report an unusual case of an angioleiomyoma of the sacral foramina in an 82-year-old man. MRI revealed a well-defined irregular-shaped deep-seated mass in the sacral foramina, showing branching pattern of growth associated with pressure bony erosion of the adjacent bones, with isointense to hypointense signal on T2-weighted images. Surgical excision was performed and the mass was diagnosed as angioleiomyoma on pathological examination. To the best of our knowledge, there has been no report of an angioleiomyoma involving the sacral foramina.

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Clinical efficacy of transforaminal epidural injection for management of zoster-associated pain: a retrospective analysis

Abstract

Objectives

Transforaminal epidural injection (TFEI) has superior accessibility to the dorsal root ganglion, which is an essential location of pain signaling in herpes zoster. However, the effectiveness of TFEI for herpes zoster patients has not previously been studied. We retrospectively analyzed the efficacy of TFEI for pain control and prevention of PHN in patients with acute and subacute herpes zoster.

Methods

Medical records of 137 patients who underwent TFEI for zoster-associated pain (ZAP) were reviewed. The participants were divided into two groups: acute TFEI group (TFEI within 30 days after zoster) and subacute TEEI group (TFEI between 30 and 90 days). The efficacy of TFEI was assessed by a numerical rating scale (NRS), doses of medications, and time to relief of ZAP. Incidence of PHN at 1 week to 6 months after TFEI was evaluated.

Results

Time to ZAP relief was significantly shorter and the incidence of PHN was significantly lower in the acute TFEI group than in the subacute TFEI group. Rate of medication discontinuation was significantly higher in the acute TFEI group than in the subacute TFEI group.

Conclusions

Early application of TFEI in the acute phase of zoster can be a useful option for ZAP control and prevention of chronic neuropathic pain such as PHN.

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T2 signal intensity as an imaging biomarker for patients with superficial Fibromatoses of the hands (Dupuytren’s disease) and feet (Ledderhose disease) undergoing definitive electron beam irradiation

Abstract

Objective

Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI.

Materials and methods

The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7 years. Standard 6 MeV electron beam treatment included 3 Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1–5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain.

Results

Mean volume decreased from 1.5 to 1.2 cm³ (p = 0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p < 0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p < 0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p = 0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p = 0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ = −0.37 and 0.16, respectively).

Conclusions

MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

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Society of Skeletal Radiology 2017 annual meeting summary

Abstract

Peer-reviewed abstracts presented at the 2017 Society of Skeletal Radiology (SSR) Annual Meeting were reviewed following oral presentation. Topics felt to be of potential interest to musculoskeletal (MSK) investigators and practicing clinicians are highlighted in this compilation and analysis of the meeting. New concepts regarding MSK imaging and intervention, MSK protocols and techniques and quality improvement are included. ePoster highlights are also presented.

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Dose reduction for fluoroscopically guided injections: phantom simulation and patient procedures

Abstract

Objective

To demonstrate fluoroscopy dose reduction through both simulated injections on a phantom and patient injections.

Materials and methods

Our study was IRB-approved and HIPAA-compliant. Simulation on a phantom was used to estimate effective dose, entrance dose, and organ doses for hip joint injections without and with dose minimization technique (DMT). Additionally, 1,094 joint, bursae, and tendon sheath injections performed by three operators in the same fluoroscopy suite were evaluated both before and after application of DMT. Fluoroscopy time (FT), dose, and dose area product (DAP) of injections were compared using unpaired t-tests with P > 0.05 considered statistically significant.

Results

For the phantom simulation comparing injections without DMT and with DMT, the total DAP was 191.7 vs 18.7 μGy·m², and the entrance dose was 10.2 vs 3.6 mGy, respectively. For both men and women, DMT reduces effective dose and organ doses.

For all injections, the FT (0.7 to 0.2 min), dose (5.6 to 1.9 mGy), and DAP (56.9 to 19.1 μGy·m²) for all three operators decreased with DMT and remained statistically significant when stratified by the two most common injections, glenohumeral and hip joint injections (P < 0.05).

Conclusions

FT, effective dose, entrance dose, and DAP can be reduced with the use of simple easy-to-learn techniques, which will benefit both the patient and the radiologist.

http://ift.tt/2pGhZ4S

Hyperextension injuries of the knee: do patterns of bone bruising predict soft tissue injury?

Abstract

Objective

To establish whether patterns of soft tissue injury following knee hyperextension are associated with post-traumatic 'bone bruise' distribution.

Materials and methods

Patients with a knee MRI within one year of hyperextension injury were identified at our institution over a 7 year period. MRIs, plain radiographs and clinical details of these patients were reviewed.

Results

Twenty-five patients were identified (median time from injury to MRI = 24 days). The most common sites of bone bruising were the anteromedial tibial plateau (48%) and anterolateral tibial plateau (44%). There were high rates of injury to the posterior capsule (52%), ACL (40%) and PCL (40%) but lower rates of injury to the menisci (20%), medial and lateral collateral ligaments (16%) and posterolateral corner (16%). Anterior tibial plateau oedema and rupture of the posterior capsule predicted cruciate ligament injury [OR = 10.5 (p = 0.02) and 24.0 (p = 0.001) respectively]. Whilst anterolateral tibial plateau oedema strongly predicted PCL injury [OR = 26.0, p = 0.003], ACL injury was associated with a variable pattern of bone bruising. Meniscal injury was unrelated to the extent or pattern of bone bruising. 5 out of 8 patients with a 'double sulcus' on the lateral radiograph had ACL injury. The presence of a double sulcus showed significant association with anteromedial kissing contusions (OR = 7.8, p = 0.03).

Conclusions

Following knee hyperextension, bone bruising patterns may be associated with cruciate ligament injury. Other structures are injured less frequently and have weaker associations with bone bruise distribution. The double sulcus sign is a radiographic marker that confers a high probability of ACL injury.

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Highlights of the 44th Annual Scientific Congress of the International Skeletal Society (ISS) 2017, New York, New York

Abstract

This paper summarizes the highlights of the Special Scientific Sessions of the 44th Annual Scientific Meeting of the International Skeletal Society (ISS), which was hosted in New York, NY, in August 2017.

http://ift.tt/2pGhY0O

Safety of omitting routine bleeding tests prior to image-guided musculoskeletal core needle biopsy

Abstract

Purpose

To evaluate the safety of withholding preprocedure international normalized ratio (INR) and platelet testing in patients undergoing musculoskeletal (MSK) core needle biopsy (CNB).

Material and methods

Initially, a retrospective review of 1,162 consecutive patients undergoing MSK CNB with preprocedural INR and platelet testing was performed. Clinical (age, gender, bleeding disorder, liver disease, anticoagulation use, INR > 2, platelet count <50,000/ul) and biopsy factors (imaging modality, lesion type, biopsy needle gauge, number biopsy samples) were tested for association with bleeding complications. During the second phase, an additional 188 biopsies performed without preprocedural coagulation testing were studied. Categorical variables were compared using Chi-squared or Fisher's exact tests, continuous variables with a student t-test. Multivariate analysis was performed using logistic regression.

Results

In the first phase, there was a complication rate of 2.6%, 30/1162. Of the 11 clinical and biopsy factors, soft tissue lesions (p = 0.029) and lesions biopsied under ultrasound (p = 0.048) had a higher rate of bleeding than bone lesions or lesions biopsied under CT, respectively. Only three patients had an INR >2, 0.3% (3/1162) and only four patients had platelet count <50,000/ul, 0.3% (4/1162). No patient with a bleeding complication had an abnormal preprocedure bleeding test. In the second phase, there was a bleeding complication rate of 1.1% (2/188).

Conclusion

Bleeding complications from MSK biopsy are low, even when preprocedure coagulation testing is omitted.

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Frequency of inflammatory-like MR imaging findings in asymptomatic fingers of healthy volunteers

Abstract

Objective

To describe the frequency of inflammatory-like findings on MR imaging in asymptomatic volunteers and compare them with patients with known rheumatoid arthritis and psoriatic arthritis.

Materials and methods

MR images of fingers in 42 asymptomatic volunteers and 33 patients with rheumatoid/psoriatic arthritis were analyzed. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid/Psoriatic Arthritis MRI Scoring System (RAMRIS/PsAMRIS) and tenosynovitis scoring system were used to assess: bone marrow edema (BME), erosions, tendon sheath fluid/tenosynovitis, joint effusion, and soft-tissue edema. Findings and scores were compared between volunteers and patients. Inter-reader agreement was calculated (intraclass correlation coefficients, ICC).

Results

In volunteers, tendon sheath fluid was very common in at least one location (42/42 volunteers for reader 1, 34/42 volunteers for reader 2). BME, erosions, joint effusion, and soft-tissue edema were absent (except one BME in the 3rd proximal phalanx for reader 1). Tendon sheath fluid scores in volunteers and tenosynovitis scores in patients were high (reader 1, 7.17 and 5.39; reader 2, 2.31 and 5.45). Overall, inter-reader agreement was substantial (ICC = 0.696–0.844), except for tendon sheath fluid (ICC = 0.258).

Conclusion

Fluid in the finger flexor tendon sheaths may be a normal finding and without gadolinium administration should not be interpreted as tenosynovitis. Bone marrow edema, erosions, joint effusion, and soft-tissue edema in the fingers most likely reflect pathology if present.

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Assessment of the zonal variation of perfusion parameters in the femoral head: a 3-T dynamic contrast-enhanced MRI pilot study

Abstract

Objective

The objective was to describe MR perfusion characteristics of the femoral head, with a focus on the subchondral bone.

Materials and methods

This prospective monocentric study was approved by our local Ethics Committee. Written informed consent was obtained from all subjects. Dynamic contrast-enhanced MRI of the right hip was performed in 59 adults with suspected spondyloarthritis (32 women, 28 men). Mean age was 37.5 (±12.5) years. Regions of interest were drawn in the femoral head epiphysis, in the subchondral areas the most exposed to mechanical load (superolateral, anterosuperior, and posterior zones) and in areas less exposed to mechanical load (inferior subchondral zone and center of the femoral head). Semi-quantitative and pharmacokinetic parameters were calculated using the Tofts model. Statistical analysis was performed with a linear mixed model to compare the perfusion parameters in the different femoral head zones.

Results

Extravascular extracellular volume and area under the curve were lower in the superolateral zone than in the inferior zone (p = 0.0135 and p < 0.0001 respectively) and the central zone (p = 0.007 and p = 0.0134 respectively). Extravascular extracellular volume and rate constant were lower in the anterosuperior zone than in the inferior zones (p = 0.011 and p = 0.029). In the anterosuperior zone, extravascular extracellular volume was lower, and time to peak was higher than in the central zones (p = 0.0056 and p = 0.0013 respectively). No significant differences were found for any values between other paired zones.

Conclusion

The perfusion of femoral head subchondral bone assessed with dynamic contrast-enhanced magnetic resonance imaging is not homogeneous: the areas exposed to more mechanical loading are less perfused.

http://ift.tt/2DV05yg

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation

Antibody-based drugs have revolutionized treatment for inflammatory diseases. In addition to having direct effects on specific targets, antibodies can activate macrophages to become anti-inflammatory. This protocol describes how anti-inflammatory macrophage activation can be assessed in vitro, using mouse bone marrow macrophages, and in vivo, using peritoneal macrophages.

http://ift.tt/2C7wC6d

Studying Diabetes Through the Eyes of a Fish: Microdissection, Visualization, and Analysis of the Adult tg(fli:EGFP) Zebrafish Retinal Vasculature

Here, we discuss a method protocol which will allow an easy analysis of the adult tg(fli:EGFP) zebrafish retinal vasculature as a fast read-out in settings of long-term vascular pathologies linked to neoangiogenesis and structural changes.

http://ift.tt/2ldnnXq

Ultrathin Porated Elastic Hydrogels As a Biomimetic Basement Membrane for Dual Cell Culture

Current bilayer culture models do not allow for functional in vitro studies that mimic in vivo microenvironments. Using polyethylene glycol and a zinc oxide templating method, this protocol describes the development of an ultrathin biomimetic basement membrane with tunable stiffness, porosity, and biochemical composition that closely mimics in vivo extracellular matrices.

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The promises of microalgae—still a long way to go

Abstract

Over the past decades, interest in microalgae has grown exponentially. Especially industrial applications, such as biodiesel production from microalgae were hyped in the early 2000s. But since the first attempts to commercialise microalgae-derived products for energy applications, only a few developments made it to the market. What is hindering the full exploitation of this valuable resource for food, feed, and energy applications? This opinion paper reflects on the state of the art of industrial microalgae culturing and the knowledge gaps which still need to be filled jointly by academia and industry.

http://ift.tt/2C7iJ5w