bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of the WHIP-PD study: a phase II, twelve-month, dual-site, randomized controlled trial evaluating the effects of a cognitive-behavioral approach for promoting enhanced walking activity using mobile health technology in people with Parkinson-disease
Authors: Rawson Kerri S. , Cavanaugh James T. , Colon-Semenza Cristina , DeAngelis Tami , Duncan Ryan P. , Fulford Daniel , LaValley Michael P. , Mazzoni Pietro , Nordahl Timothy , Quintiliani Lisa M. , Saint-Hilaire Marie , Thomas Cathi A. , Earhart Gammon M. , Ellis Terry D.
Published: April 2020

Background

Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a “connected behavioral approach” that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology.

Methods/design

The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity.

Discussion

We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018.

Trial registration

ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original.
TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma
Authors: Bando Hideaki , Kotani Daisuke , Tsushima Takahiro , Hara Hiroki , Kadowaki Shigenori , Kato Ken , Chin Keisho , Yamaguchi Kensei , Kageyama Shun-ichiro , Hojo Hidehiro , Nakamura Masaki , Tachibana Hidenobu , Wakabayashi Masashi , Fukutani Miki , Togashi Yosuke , Fuse Nozomu , Nishikawa Hiroyoshi , Kojima Takashi
Published: April 2020

Background

The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11–25%, resulting in 9–10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination.

Methods

TENERGY trial is a multicenter, phase II, proof-of-concept study to assess the efficacy and safety of atezolizumab following definitive CRT in patients with locally advanced ESCC. The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1–4, every 28 days), and adequate organ function. Within 6 weeks after CRT, participants will start taking 1200 mg of atezolizumab every three weeks and continue until 12 months or disease progression. The primary endpoint is the confirmed CR rate by the investigator’s assessment. Secondary endpoints include overall response rate, progression-free survival (PFS), OS, adverse events, and confirmed CR rate by central assessment. We will enroll 50 patients (40 with primary locally advanced ESCC and 10 with postoperative locoregionally recurrent ESCC). We will obtain biopsies from the primary site and will collect blood at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab) for an exploratory biomarker study. We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutational burden, PD-L1 status, and Human Leukocyte Antigen haplotyping.

Discussion

The synergistic efficacies of the sequential combination of CRT and atezolizumab should improve the CR rate, resulting in survival improvement for patients with unresectable locally advanced ESCC. Because CRT is a standard treatment option for patients with early stage to locally advanced ESCC, the sequential combination of CRT and atezolizumab has the potential to change the standard ESCC treatments.

Trial registration

UMIN000034373, 10/04/2018 and EPOC1802.
Land and nature as sources of health and resilience among Indigenous youth in an urban Canadian context: a photovoice exploration
Authors: Hatala Andrew R. , Njeze Chinyere , Morton Darrien , Pearl Tamara , Bird-Naytowhow Kelley
Published: April 2020

Background

Population and environmental health research illustrate a positive relationship between access to greenspace or natural environments and peoples’ perceived health, mental health, resilience, and overall well-being. This relationship is also particularly strong among Canadian Indigenous populations and social determinants of health research where notions of land, health, and nature can involve broader spiritual and cultural meanings. Among Indigenous youth health and resilience scholarship, however, research tends to conceptualize land and nature as rural phenomena without any serious consideration on their impacts within urban cityscapes. This study contributes to current literature by exploring Indigenous youths’ meaning-making processes and engagements with land and nature in an urban Canadian context.

Methods

Through photovoice and modified Grounded Theory methodology, this study explored urban Indigenous youth perspectives about health and resilience within an inner-city Canadian context. Over the course of one year, thirty-eight in-depth interviews were conducted with Indigenous (Plains Cree First Nations and Métis) youth along with photovoice arts-based and talking circle methodologies that occurred once per season. The research approach was also informed by Etuaptmumk or a “two-eyed seeing” framework where Indigenous and Western “ways of knowing” (worldviews) can work alongside one another.

Results

Our strength-based analyses illustrated that engagement with and a connection to nature, either by way of being present in nature and viewing nature in their local urban context, was a central aspect of the young peoples’ photos and their stories about those photos. This article focuses on three of the main themes that emerged from the youth photos and follow-up interviews: (1) nature as a calming place; (2) building metaphors of resilience; and (3) providing a sense of hope. These local processes were shown to help youth cope with stress, anger, fear, and other general difficult situations they may encounter and navigate on a day-to-day basis.

Conclusions

This study contributes to the literature exploring Indigenous youths’ meaning-making process and engagements with land and nature in an urban context, and highlights the need for public health and municipal agencies to consider developing more culturally safe and meaningful natural environments that can support the health, resilience, and well-being of Indigenous youth within inner-city contexts.
Case report of endoprosthesis -Y implantation in severe respiratory failure in the MPSII patient; comparison with literature data
Authors: Gocyk Wojciech , Warmus Janusz , Olechnowicz Henryk , Bik-Multanowski Miroslaw , Pawlinski Lukasz , Kiec-Wilk Beata
Published: April 2020

Background

The tracheobronchomalacia is a life-threatening complication of mucopolysaccharidosis (MPS) without known effective, optimal treatment. The severe expiratory collapse of the trachea and bronchi is one of causes of the high rate of deaths in the course of airway impairment in MPSII patients.

Case presentation

Due to the adynamic tracheobronchomalacia despite of enzymatic treatment (ERT) in our MPSII patient, a life-saving tracheal bifurcated type-Y endoprosthesis (a self-expanding, metal stent for the prosthesis of tracheal and bronchial stenosis) was implanted. In the followed months, the breathing efficiency improved, but then gradual worsening, progression of bronchi occlusion at the stent border resulted in patient’s death.

Conclusion

The Y-stent implantation appears to be a short-term, life-saving solution without satisfactory long-term effects due to the progress of peripheral bronchomalacia and increased tissue proliferation and granulation, that arises during the illness’ course.
A case report of fungal infection associated acute fibrinous and organizing pneumonitis
Authors: Zhao Jiangnan , Shi Yi , Yuan Dongmei , Shi Qunli , Wang Weiping , Su Xin
Published: April 2020

Background

Acute fibrinous and organizing pneumonitis (AFOP) is an uncommon variant of acute lung injury, characterized by intra-alveolar fibrin and organizing pneumonia. Proposed etiologies include connective tissue diseases, infections, occupational exposure, drug reactions, and autoimmune disease. Here we present a rare case of fungal infection associated AFOP in patient with diabetes mellitus (DM) and review the relevant literature.

Case presentation

A 67-year-old man complained of cough, fever, dyspnea and hemoptysis. Patient experienced a rapidly progressive course exhibit diffuse predominant consolidation, ground glass opacities, and multifocal parenchymal abnormalities on chest computed tomography (CT). Antibacterial, antifungal, and antiviral treatments were ineffective. A CT-guided percutaneous lung biopsy was performed. Histologically, the predominant findings were as follows: alveolar spaces filled with fibrin and organizing loose connective tissues involving 70% of the observed region, pulmonary interstitial fibrosis, and small abscesses and epithelioid cell granuloma in the focal area. Result of periodic acid-silver methenamine stain was positive. The fungal pathogen from the sputum culture was identified as P. citrinum repeatedly over 3 times. Patient was diagnosed with DM during hospitalization. Corticosteroids combined with an antifungal therapy were effective. Follow-up for 4 months showed complete radiological resolution.

Conclusions

As this common “contaminant” can behave as a pathogen in the immunocompromised host, both clinicians and microbiologists should consider the presence of a serious and potentially fatal fungal infection on isolation of P. citrinum. Based on this case, it could be speculated that AFOP may be associated with fungal infection including P. citrinum.
Radiographic and clinical outcome of lateral lumbar interbody fusion for extreme lumbar spinal stenosis of Schizas grade D: a retrospective study
Authors: Li Jun , Li Hao , Zhang Ning , Wang Zhi-wei , Zhao Teng-fei , Chen Lin-wei , Chen Gang , Chen Qi-xin , Li Fang-cai
Published: April 2020

Background

Extreme lumbar spinal stenosis was thought to be a relative contraindication for lateral lumbar interbody fusion (LLIF) and was excluded in most studies. This is a retrospective study to analyze the radiographic and clinical outcome of LLIF for extreme lumbar spinal stenosis of Schizas grade D.

Methods

For radiographic analysis, we included 181 segments from 110 patients who underwent LLIF between June 2017 and December 2018. Lumbar spinal stenosis was graded according to Schizas’ classification. Anterior and posterior disc heights, disc angle, foramen height, spinal canal diameter and central canal area were measured on CT and MRI. For clinical analysis, 18 patients with at least one segment of grade D were included. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate clinical outcome. Continuous variables were compared using Student’s t-test, with P-values < 0.05 considered to indicate statistically significant differences.

Results

Among the 181 segments included for radiological evaluation, there were 23 grade A segments, 37 grade B segments, 103 grade C segments and 18 grade D segments. Postoperatively, the average change of midsagittal canal diameter of grade D was significantly greater than that of grade A, and not significantly different compared to grades B and C. As to the average change of disc height, bilateral foraminal height, disc angle and central canal area (CCA), grade D was not significantly different from the others. The average postoperative CCA of grade D was significantly smaller than the average preoperative CCA of grade C. Eighteen patients with grade D stenosis were followed up for an average of 19.61 ± 6.32 months. Clinical evaluation revealed an average improvement in the ODI and VAS scores for back and leg pain by 20.77%, 3.67 and 4.15 points, respectively. Sixteen of 18 segments with grade D underwent posterior decompression.

Conclusion

The radiographic decompression effect of LLIF for Schizas grade D segments was comparable with that of other grades. Posterior decompression was necessary for LLIF to achieve a satisfactory clinical outcome for extreme lumbar spinal stenosis of Schizas grade D.
Exercise program combined with electrophysical modalities in subjects with knee osteoarthritis: a randomised, placebo-controlled clinical trial
Authors: de Paula Gomes Cid André Fidelis , Politti Fabiano , de Souza Bacelar Pereira Cheila , da Silva Aron Charles Barbosa , Dibai-Filho Almir Vieira , de Oliveira Adriano Rodrigues , Biasotto-Gonzalez Daniela Aparecida
Published: April 2020

Background

It is not yet clear which of the various electrophysical modalities used in clinical practice is the one that contributes most positively when added to an exercise program in patients with knee osteoarthritis (OA). The aim of the present study was to analyze the clinical effects of the inclusion of interferential current therapy (ICT), shortwave diathermy therapy (SDT) and photobiomodulation (PHOTO) into an exercise program in patients with knee OA.

Methods

This prospective, five-arm, randomised, placebo-controlled trial was carried out with blinded participants and examiners. We recruited 100 volunteers aged 40 to 80 years with knee OA. Participants were allocated into five groups: exercise, exercise + placebo, exercise + ICT, exercise + SDT, and exercise + PHOTO. The outcome measures included Western Ontario and McMaster Universities (WOMAC), numerical rating pain scale (NRPS), pressure pain threshold (PPT), self-perceived fatigue and sit-to-stand test (STST), which were evaluated before and after 24 treatment sessions at a frequency of three sessions per week.

Results

In all groups, there was a significant improvement (p < 0.05) in all variables over time, except pressure pain threshold. We observed significant differences (p < 0.05) between the groups for WOMAC function (exercise vs. exercise + placebo, mean difference [MD] = 5.55, 95% confidence interval [CI] = 3.63 to 7.46; exercise vs. exercise + ICT, MD = 3.40, 95% CI = 1.46 to 5.33; exercise vs. exercise + SDT, MD = 4.75, 95% CI = 1.85 to 7.64; exercise vs. exercise + PHOTO, MD = 5.45, 95% CI = 3.12 to 7.77) and WOMAC pain, with better scores achieved by the exercise group. However, these differences were not clinically relevant when considering the minimum clinically important difference.

Conclusion

The addition of ICT, SDT or PHOTO into an exercise program for individuals with knee OA is not superior to exercise performed in isolation in terms of clinical benefit. clinicaltrials.gov: NCT02636764, registered on March 29, 2014.
Alpine ecology, plant biodiversity and photosynthetic performance of marker plants in a nitrogen gradient induced by Alnus bushes
Authors: Kaltrina Rexha , Kristi Bego , Dea Zyruku , Lulezim Shuka , René Husi , Jakob Schneller , Reinhard Bachofen
Published: April 2020

Background

Alpine alder vegetation acts upon the nearby grass and dwarf shrub vegetation by the nitrogen supply from the symbiotic bacteria Frankia alni of Alnus viridis. This has been studied in two transects concerning plant distribution, plant diversity, nitrate concentration in soil and photosynthetic performance of specific marker plants.

Results

Away from the alder stand, a band of some meters was dominated by Calamagrostis varia which then was followed by alpine dwarf shrub vegetation. Nitrate in the soil showed a concentration decrease away from the alder stand leading to values near the detection limit in the dwarf shrub zone. Within these three zones, plant species were distributed according to their N-index, given in the ecological literature. Three dominant species, Calamagrostis varia, Rhododendron ferrugineum and Vaccinium myrtillus were examined at sites of different N-availability in the horizontal transect for their photosynthetic performance, by measuring the prompt fluorescence, the OJIP named polyphasic rise of chlorophyll-a fluorescence. All three plant species showed signs of stress in the fluorescence rise kinetics at decreased nitrate availability. These are similar to other known stress effects such as faster reduction of the primary acceptor or an electron supply limitation on the donor site of photosystem II.

Conclusion

Prompt chlorophyll-a fluorescence data of the examined leaves in a natural vegetation system showed the effects of a decrease in the essential nutrient nitrogen and in a manner parallel to changes in plant diversity. The selected marker plants behaved differently towards decreasing nitrogen concentrations in soil.
Utilization of dental services among low and middle income pregnant, post-partum and six-month post-partum women
Authors: Baskaradoss Jagan Kumar , Geevarghese Amrita
Published: April 2020

Background

This study aims to explore the difference in the utilization pattern of dental services among pregnant, post-partum and six-month post-partum women.

Methods

This cross-sectional questionnaire survey was performed at two maternity and child care hospitals in India that primarily cater to middle and low income communities. Data were collected from 3 groups: 1) pregnant women in their first trimester; 2) post-partum women (< 48 h after delivery); and 3) six-month post-partum women. The primary outcome of interest was dental service utilization during pregnancy. Self-perceived oral health (SPOH) was calculated based on the four global dimensions- knowledge, function, quality of life and social. Multiple logistic regression analysis was carried out to assess the effect of each independent variable after adjustment for the effect of all other variables in the model.

Results

Responses of 450 (150 pregnant, 150 post-partum and 150 six-month post-partum) women were analyzed (response rate = 72%). Significant differences in the dental attendance pattern was observed between the study groups (p < 0.01). Dental attendance among pregnant and six-month post-partum women were 60 and 75%, respectively, however, only about 15% of the post-partum women reported to have sought dental care within the 6 months prior to the study. Post-partum women had the highest SPOH scores, indicating poor self-perceived oral health, followed by pregnant and then six-month post-partum women, which was statistically significant (p < 0.05). A significantly higher percentage of post-partum women reported to have poor oral and general health, as compared to both, pregnant and six-month post-partum women (p < 0.01). Higher percentage of women reporting ‘good’ oral and general health had sought dental care compared with others (p < 0.01). After adjusting for all the other variables in the model, women with lower levels of education (ORa = 1.42; 95% CI: 1.01–2.00), women with poor self-perceived oral health (ORa = 1.08; 95% CI: 1.02–1.14) and post-partum women (ORa = 0.15; 95% CI: 0.09–0.24) were found to be less likely to seek regular dental care.

Conclusion

Pattern of dental service utilization among women in this population varied according to their pregnancy status, level of education and self-perceived oral health.
The impact of localised general practice training on Queensland’s rural and remote general practice workforce
Authors: Peel Raquel , Young Louise , Reeve Carole , Kanakis Katerina , Malau-Aduli Bunmi , Sen Gupta Tarun , Hays Richard
Published: April 2020

Background

The diverse rural medical education initiatives that have been developed in Australia to address the medical workforce maldistribution have been less successful in many smaller and remote communities. This study explored the factors that attract and retain GP registrars and supervisors and the impact that localised training (i.e., rural and remote workplace-based training and support) has on both GP registrars and supervisors, and the GP workforce in rural and remote underserved areas.

Methods

A purposive sample of 79 GP registrars, supervisors, practice managers, health services staff and community representatives living and working in areas of low GP workforce in rural and remote Australia were invited to participate in semi-structured interviews and one focus group divided over two phases. Thematic analysis was used to explore themes within the data.

Findings

Attractors and barriers to rural and remote practice were identified as the main themes. Attractors include family and community lifestyle factors, individual intrinsic motivators, and remote medicine experiences. In contrast, barriers include work related, location, or family factors. Further, localised GP training was reported to specifically influence GP registrars and supervisors through education, social and financial factors.

Conclusion

The current study has provided a contemporary overview of the issues encountered in expanding GP training capacity in rural and remote communities to improve the alignment of training opportunities with community and workforce needs. Strategies including matching scope of practice to registrar interests have been implemented to promote the attractors and lessen the barriers associated with rural and remote practice.
Physicians’ preventive practices: more frequently performed for male patients and by female physicians
Authors: Delpech Raphaëlle , Bloy Géraldine , Panjo Henri , Falcoff Hector , Ringa Virginie , Rigal Laurent
Published: April 2020

Background

We sought to analyze gender differences in General Practitioners’ (GP) preventive practices: variations according to the GP’s and the patient’s genders, separately and combined, and the homogeneity of GPs’ practices according to gender.

Methods

Fifty-two general practitioners volunteered to participate in a cross-sectional study. A sample of 70 patients (stratified by gender) aged 40–70 years was randomly chosen from each GP’s patient panel. Information extracted from the medical files was used to describe the GPs’ preventive practices for each patient: measurements of weight, waist circumference, glucose, and cholesterol; inquiry and counseling about smoking, alcohol consumption, diet, and physical activity, and dates of cervical smears and mammographies. An aggregate preventive score was calculated to assess the percentage of these practices performed by each GP for patients overall and by gender. Mixed models were used to test for gender differences.

Results

Questionnaires were collected in 2008–2009 for 71% of the 3640 patients and analyzed in June 2017.

Male patients and female GPs were associated with the most frequent performance of many types of preventive care. The aggregate preventive score was higher for male patients (OR = 1.60, 95% CI 1.47–1.75) and female GPs (OR = 1.35, 95% CI 1.05–1.73). There was no combined effect of the genders of the two protagonists. Female patients of male GPs appeared to receive preventive care least frequently and female GPs to deliver preventive care more consistently than their male colleagues.

Conclusion

Physicians need to be aware of these differences, for both patient gender and their own.
Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis
Authors: Zhou Xiaoxiang , Yao Zhuoran , Yang Huaxia , Liang Naixin , Zhang Xuan , Zhang Fengchun
Published: April 2020

Background

A number of studies have reported an association between the occurrence of immune-related adverse events (irAEs) and clinical efficacy in patients undergoing treatment with immune checkpoint inhibitors (ICIs), but the results remain controversial.

Methods

Under the guidance of a predefined protocol and Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, this meta-analysis included cohort studies investigating the association of irAEs and efficacy of ICIs in patients with cancer. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Subgroup analyses involving the cancer type, class of ICIs, combination therapy, sample size, model, landmark analysis, and approach used to extract the data were performed. Specific analyses of the type and grade of irAEs were also performed.

Results

This meta-analysis included 30 studies including 4971 individuals. Patients with cancer who developed irAEs experienced both an OS benefit and a PFS benefit from ICI therapy compared to patients who did not develop irAEs (OS: hazard ratio (HR), 0.54, 95% confidence interval (CI), 0.45–0.65; p < 0.001; PFS: HR, 0.52, 95% CI, 0.44–0.61, p < 0.001). Subgroup analyses of the study quality characteristics and cancer types recapitulated these findings. Specific analyses of endocrine irAEs (OS: HR, 0.52, 95% CI, 0.44–0.62, p < 0.001), dermatological irAEs (OS: HR, 0.45, 95% CI, 0.35–0.59, p < 0.001), and low-grade irAEs (OS: HR, 0.57, 95% CI, 0.43–0.75; p < 0.001) yielded similar results. The association between irAE development and a favorable benefit on survival was significant in patients with cancer who were undergoing treatment with programmed cell death-1 inhibitors (OS: HR, 0.51, 95% CI, 0.42–0.62; p < 0.001), but not cytotoxic T-lymphocyte antigen-4 inhibitors (OS: HR, 0.89, 95% CI, 0.49–1.61; p = 0.706). Additionally, the association was significant in patients with cancer who were treated with ICIs as a monotherapy (OS: HR, 0.53, 95% CI, 0.43–0.65; p < 0.001), but not as a combination therapy (OS: HR, 0.62, 95% CI, 0.36–1.05; p = 0.073).

Conclusions

The occurrence of irAEs was significantly associated with a better ICI efficacy in patients with cancer, particularly endocrine, dermatological, and low-grade irAEs. Further large-scale prospective studies are warranted to validate our findings.

Systematic review registration

PROSPERO CRD42019129310.
Correction to: Integrin-FAK signaling rapidly and potently promotes mitochondrial function through STAT3
Authors: Visavadiya Nishant P. , Keasey Matthew P. , Razskazovskiy Vladislav , Banerjee Kalpita , Jia Cuihong , Lovins Chiharu , Wright Gary L. , Hagg Theo
Published: April 2020

An amendment to this paper has been published and can be accessed via the original article.
Magnetic resonance imaging features of tumor and lymph node to predict clinical outcome in node-positive cervical cancer: a retrospective analysis
Authors: Park Shin-Hyung , Hahm Myong Hun , Bae Bong Kyung , Chong Gun Oh , Jeong Shin Young , Na Sungdae , Jeong Sungmoon , Kim Jae-Chul
Published: April 2020

Background

Current chemoradiation regimens for locally advanced cervical cancer are fairly uniform despite a profound diversity of treatment response and recurrence patterns. The wide range of treatment responses and prognoses to standardized concurrent chemoradiation highlights the need for a reliable tool to predict treatment outcomes. We investigated pretreatment magnetic resonance (MR) imaging features of primary tumor and involved lymph node for predicting clinical outcome in cervical cancer patients.

Methods

We included 93 node-positive cervical cancer patients treated with definitive chemoradiotherapy at our institution between 2006 and 2017. The median follow-up period was 38 months (range, 5–128). Primary tumor and involved lymph node were manually segmented on axial gadolinium-enhanced T1-weighted images as well as T2-weighted images and saved as 3-dimensional regions of interest (ROI). After the segmentation, imaging features related to histogram, shape, and texture were extracted from each ROI. Using these features, random survival forest (RSF) models were built to predict local control (LC), regional control (RC), distant metastasis-free survival (DMFS), and overall survival (OS) in the training dataset (n = 62). The generated models were then tested in the validation dataset (n = 31).

Results

For predicting LC, models generated from primary tumor imaging features showed better predictive performance (C-index, 0.72) than those from lymph node features (C-index, 0.62). In contrast, models from lymph nodes showed superior performance for predicting RC, DMFS, and OS compared to models of the primary tumor. According to the 3-year time-dependent receiver operating characteristic analysis of LC, RC, DMFS, and OS prediction, the respective area under the curve values for the predicted risk of the models generated from the training dataset were 0.634, 0.796, 0.733, and 0.749 in the validation dataset.

Conclusions

Our results suggest that tumor and lymph node imaging features may play complementary roles for predicting clinical outcomes in node-positive cervical cancer.
Deep convolutional neural networks for automated segmentation of brain metastases trained on clinical data
Authors: Bousabarah Khaled , Ruge Maximilian , Brand Julia-Sarita , Hoevels Mauritius , Rueß Daniel , Borggrefe Jan , Große Hokamp Nils , Visser-Vandewalle Veerle , Maintz David , Treuer Harald , Kocher Martin
Published: April 2020

Introduction

Deep learning-based algorithms have demonstrated enormous performance in segmentation of medical images. We collected a dataset of multiparametric MRI and contour data acquired for use in radiosurgery, to evaluate the performance of deep convolutional neural networks (DCNN) in automatic segmentation of brain metastases (BM).

Methods

A conventional U-Net (cU-Net), a modified U-Net (moU-Net) and a U-Net trained only on BM smaller than 0.4 ml (sU-Net) were implemented. Performance was assessed on a separate test set employing sensitivity, specificity, average false positive rate (AFPR), the dice similarity coefficient (DSC), Bland-Altman analysis and the concordance correlation coefficient (CCC).

Results

A dataset of 509 patients (1223 BM) was split into a training set (469 pts) and a test set (40 pts). A combination of all trained networks was the most sensitive (0.82) while maintaining a specificity 0.83. The same model achieved a sensitivity of 0.97 and a specificity of 0.94 when considering only lesions larger than 0.06 ml (75% of all lesions). Type of primary cancer had no significant influence on the mean DSC per lesion (p = 0.60). Agreement between manually and automatically assessed tumor volumes as quantified by a CCC of 0.87 (95% CI, 0.77–0.93), was excellent.

Conclusion

Using a dataset which properly captured the variation in imaging appearance observed in clinical practice, we were able to conclude that DCNNs reach clinically relevant performance for most lesions. Clinical applicability is currently limited by the size of the target lesion. Further studies should address if small targets are accurately represented in the test data.
Nailing of diaphyseal ulna fractures in adults—biomechanical evaluation of a novel implant in comparison with locked plating
Authors: Hopf Johannes Christof , Mehler Dorothea , Nowak Tobias Eckhard , Gruszka Dominik , Wagner Daniel , Rommens Pol Maria
Published: April 2020

Background

Adult forearm fractures require surgical treatment in most cases. Open reduction and internal fixation with plate osteosynthesis is the therapy of choice. Intramedullary fixation offers several advantages compared to plate fixation but is not routinely used. The aim of our study was to compare a newly designed ulna nail with angular stable plating in a biomechanical testing setup of an ulna shaft fracture with a diaphyseal defect.

Methods

Ten pairs of sawbones with a defect osteotomy of the ulna shaft (OTA 2U2C3) were fixed with an interlocked nail or locked plate osteosynthesis. The constructs were tested under four-point bending, torsional loading and axial loading in a servo-pneumatic testing machine to compare the stiffness of both stabilization methods.

Results

The nail constructs show lower yet sufficient bending stiffness (62.25 ± 6.64 N/mm) compared to the plate constructs (71.2 ± 5.98 N/mm, p = 0.005). The torsional loading test shows superior stiffness of the plate constructs (0.24 ± 0.03 Nm/deg vs. 0.1 ± 0.01 Nm/deg; p < 0.001), while the axial loading shows superior stiffness of the nail constructs (1028.9 ± 402.1 N/mm vs. 343.9 ± 112.6 N/mm; p < 0.001).

Conclusions

Intramedullary nailing of ulna shaft fractures obtains sufficient but lower stability in bending and torsional loading when compared to rigid angular stable plating and could be an alternative technique to plate fixation. The lower stability and the closed stabilization technique allow for a rapid periosteal healing, which is not present in stiffer constructs.
Using arterial-venous oxygen difference to guide red blood cell transfusion strategy
Authors: Fogagnolo Alberto , Taccone Fabio Silvio , Vincent Jean Louis , Benetto Giulia , Cavalcante Elaine , Marangoni Elisabetta , Ragazzi Riccardo , Creteur Jacques , Volta Carlo Alberto , Spadaro Savino
Published: April 2020

Background

Guidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference (A-V O2diff), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion.

Methods

A prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0–10.0 g/dL within 72 h after ICU admission. The A-V O2diff, central venous oxygen saturation (ScvO2), and oxygen extraction ratio (O2ER) were noted when a patient’s Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O2diff value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as “appropriate” (patient transfused when the A-V O2diff > 3.7 mL or not transfused when the A-V O2diff ≤ 3.7 mL) or “inappropriate” (patient transfused when the A-V O2diff ≤ 3.7 mL or not transfused when the A-V O2diff > 3.7 mL). The primary outcome was 90-day mortality.

Results

Patients managed with an “appropriate” strategy had lower mortality rates (23/96 [24%] vs. 36/81 [44%]; p = 0.004), and an “appropriate” strategy was independently associated with reduced mortality (hazard ratio [HR] 0.51 [95% CI 0.30–0.89], p = 0.01). There was a trend to less acute kidney injury with the “appropriate” than with the “inappropriate” strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O2diff, but not the ScvO2, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O2diff cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients.

Conclusions

In anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O2diff.

Trial registration

ClinicalTrials.gov, NCT03767127. Retrospectively registered on 6 December 2018.
Under the skin: Ixodes ticks in the subcutaneous tissue of red foxes (Vulpes vulpes) from Germany
Authors: Haut Maja , Król Nina , Obiegala Anna , Seeger Johannes , Pfeffer Martin
Published: April 2020

Background

Ixodes spp. are vectors of zoonotic pathogens. All three active life stages (larvae, nymphs, adults) need to feed on a host in order to develop. Usually ticks parasitize attached to the external surface of their hosts’ skin. Interestingly, in some cases ticks can also be found in the subcutaneous tissue in a variety of hosts, such as red foxes (Vulpes vulpes), raccoon dogs (Nyctereutes procyonoides) and dogs.

Methods

The visceral side of 126 red fox-furs from Germany was examined visually searching for ticks. The localization of ticks was recorded and assigned to ten specific body parts. Morphological identification of ticks was performed according to standardized taxonomic protocols. Ticks which could not be further identified were examined genetically via conventional PCR targeting the 16S rRNA and cox1 gene. Hematoxylin and eosin (H&E) staining was used for histopathological examination.

Results

In 111 out of 126 (88.1%) examined coats, at least one tick was found in the subcutaneous tissue. A total of 1203 ticks were removed from the subcutaneous tissue. Well-preserved ticks could be identified based on morphological criteria, but most ticks were in a progressed state of decomposition. Here, morphological species identification was not successful. Also, PCR methods did not lead to a successful species identification. The following species and development stages were found by morphological identification: Ixodes ricinus (female, n = 289; male, n = 8; nymph, n = 1), I. hexagonus (female, n = 2), I. canisuga (female, n = 1). Male I. ricinus were found individually or copulating in pairs with females. Subcutaneous ticks were localized at three predominant affected body parts: ears, axillar and inguinal region. Histological examination of subcutaneous ticks revealed a granulomatous panniculitis.

Conclusions

To the authors’ knowledge, this is the first finding of highly prevalent subcutaneous ticks in red foxes from Germany. Subcutaneous location of ticks seems to be very common in red foxes and the rule rather than the exception. Deep embedment of longirostra and long feeding times of females seem to put the subcutaneous location in favor. Most foxes were infested in the inguinal area, where the skin is thin and less hairy.
Anal extraskeletal osteosarcoma in a man: a case report and review of the literature
Authors: Saadaat Ramin , Abdul-Ghafar Jamshid , Ud Din Nasir , Haidary Ahmed Maseh
Published: April 2020

Background

Osteosarcoma is a common malignancy of bone that usually occurs in individuals in the age range of 0–24 years. Extraskeletal osteosarcoma is a rare tumor presentation which originates in non-bony tissues. Extraskeletal osteosarcoma comprises 2–5% of all osteosarcomas and less than 1% of all soft tissue sarcomas. As compared to bone-derived osteosarcoma, extraskeletal osteosarcoma occurs in older age groups. Extraskeletal osteosarcoma has a poorer prognosis than bone osteosarcoma. To the best of our knowledge, this is the first case of extraskeletal osteosarcoma in the anal region.

Case presentation

A 70-year-old Hazara man presented to a private hospital with the chief complaints of constipation, bloody defecation, and pain during defecation of 1.5 months’ duration. His past history was unremarkable. A digital rectal examination showed a solid growth in the middle part of his anus. A colonoscopic examination was done and showed a solid mass in his anal region. A computed tomography scan revealed an irregular mural thickening in the anal canal with heterogeneous enhancement. The maximum length of the involved segment was measured to be 4.5 cm. No suspicious lesions were noted in other organs. An abdominoperineal resection was performed on our patient. A 22 cm in length resected segment of his colon, consisting of the lower sigmoid, rectum, and anus was sent to us for histopathological examination. Gross examination revealed a polypoid dark-gray tumor measuring 5 × 3 × 2 cm. The cut section revealed gray and white appearance with firm-to-hard consistency and foci of ossification. Microscopic examination revealed normal anorectal mucosa and a spindle cell malignant neoplasm with osteoid formations. No evidence of epithelial carcinoma was noted. Immunohistochemical stains were positive for stabilin-2 and negative for cytokeratin, which confirmed the diagnosis of osteosarcoma.

Conclusion

Extraskeletal osteosarcoma of the colon is rare and presence of the tumor in the rectum and anal region is extremely rare. Radiology, colonoscopy, and histopathology with immunostaining are required for the diagnosis. The accurate diagnosis of extraskeletal osteosarcoma is important as it has a different regimen of treatment with poorer prognosis compared to primary osteosarcoma of the bone.
Therapeutic strategies for critically ill patients with COVID-19
Authors: Li Lei , Li Ranran , Wu Zhixiong , Yang Xianghong , Zhao Mingyan , Liu Jiao , Chen Dechang
Published: April 2020

Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.
Secure beamforming design for the UAV-enabled transmission over NOMA networks
Authors: Yin Chuan , Yan Leibing
Published: April 2020

This paper considers an unmanned aerial vehicle -enabled multicast-unicast transmit system, in which downlink non-orthogonal multiple access (NOMA) is applied. Since two types of information are broadcast simultaneously, the security of information transmission is a matter of concern. Based on this, we investigate the problem of maximizing the secrecy rate of the particular unicasting user subject to the quality-of-service (QoS) requirements of the multicasting users and the power budget constraint of the UAV base station (BS). Such a problem is non-convex and hard to tackle, and a two-stage procedure is proposed to solve it optimally by dealing with a sequence of semidefinite relaxation (SDR) counterparts. First, fixing the maximal signal to interference plus noise ratio (SINR) of unicasting information in other users, we obtain the corresponding SINR of unicasting information at the particular user. Then, the maximal secrecy unicasting rate is derived by a one-dimension search over the intercepted SINR of unicasting information in other users. Furthermore, two suboptimal solutions with lower complexity are also proposed. Numerical simulation shows that the proposed NOMA assisted schemes always have a better security performance for UAV-enabled transmission.
An annotated and critical glossary of the terminology of inclusion in healthcare and health research
Authors: Islam Shahid , Small Neil
Published: April 2020

The importance of including members of the public has been accorded a significant position in health planning, service delivery and research. But this position masks a lack of clarity about terms that are used. This paper identifies terms that are in common use in the lexicon of community based involvement and engagement in health with the intention of clarifying meaning and thus reducing ambiguity. We define and distinguish between key terms related to inclusion, we consider the terminology attached to community processes and to the challenges of inclusion and we engage with the strengths and weaknesses of the commonly used metaphor of “a ladder of participation”. We wish to contribute to the clear communication of intentions, challenges and achievements in pursuing varied forms of inclusion in health.
Temperature dependent virulence of the entomopathogenic nematodes against immatures of the oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae)
Authors: Aatif Hafiz Muhammad , Hanif Muhammad Shahid , Raheel Muhammad , Ferhan Muhammad , Mansha Muhammad Zeeshan , Khan Azhar Abbas , Ullah Muhammad Irfan , Shakeel Qaiser , Ali Sajjad
Published: April 2020

Fruit flies have a great influence on fruit and vegetable industry of Pakistan. Bactrocera dorsalis Hendel (Tephritidae) is a polyphagous pest in large number of fruit and vegetable crops worldwide. Virulence of 4 entomopathogenic nematodes (EPNs) species, Heterorhabditis bacteriophora, H. indica, Steinernema carpocapsae, and S. asiaticum, was evaluated at different temperature degrees (15, 20, 25, 30 and 35 °C) against the immature stages of fruit fly species, B. dorsalis. The tested EPNs species showed a temperature dependent virulence against the fruit fly immatures. All EPNs showed a poor infectivity at the lowest temperature (15 °C) and a high infectivity at the highest temperature (35 °C). In overall, H. bacteriophora performed the best against the fruit fly larvae and pupae at all temperature degrees. At 35 °C, all the EPNs caused more than 95% mortality in fruit fly maggots, but H. bacteriophora and S. carpocapsae performed better than the others. The EPNs infectivity increased with increasing the temperature and exposure time. Similar results were recorded in case of pupae. H. bacteriophora and S. carpocapsae caused more than 70% pupal mortality rates at 35 °C.