bluuebunny/crossref_metadata_2025 huggingface dataset:
Complicated EBV infection in a healthy child
Authors: Teles Hugo , Brito Teresa , Cachão Joana , Parente Susana
Published: March 2021

The Epstein-Barr virus (EBV) is highly prevalent throughout the population. Although in most cases, the infection has a good prognosis, it can cause severe complications. We report a case of a healthy child with a primary EBV infection that evolved with two rare complications. She first presented in the emergency room with fever and sore throat, and was diagnosed with tonsillitis and medicated with antibiotic. She returned 7 days later for fatigue, vomiting and abdominal pain. The examination revealed tonsillitis, swollen cervical lymph nodes and pain in the right hypochondrium. An abdominal ultrasound was performed, compatible with acute acalculous cholecystitis. She was admitted in the paediatric nursery and medicated with intravenous antibiotics. The EBV serology revealed primary infection. Two days later, she developed cardiogenic shock and had to be transferred to an intensive care unit under mechanical ventilation and inotropics. She was discharged 12 days later, keeping a moderate left ventricular dysfunction.
COVID-19-induced granulomatosis with polyangiitis
Authors: Selvaraj Vijairam , Moustafa Abdelmoniem , Dapaah-Afriyie Kwame , Birkenbach Mark P
Published: March 2021

COVID-19 and granulomatosis with polyangiitis share many clinical and radiological features, making it challenging for clinicians to distinguish between the two. In this case report, we describe a patient who was diagnosed with COVID-19 in October 2020. One month later, she presented with persistent fatigue, shortness of breath and anaemia with worsening renal functions, found to have elevated antineutrophil cytoplasmic antibodies and antiproteinase 3 antibodies, and diagnosed with granulomatosis with polyangiitis.
Effect of tap dance on plantar pressure, postural stability and lower body function in older patients at risk of diabetic foot: a randomized controlled trial
Authors: Zhao Yanan , Cai Keshu , Wang Qianwen , Hu Yaqing , Wei Lijun , Gao Huihua
Published: March 2021

Introduction

To examine the effects of tap dance (TD) on dynamic plantar pressure, static postural stability, ankle range of motion (ROM), and lower extremity functional strength in patients at risk of diabetic foot (DF).

Research design and methods

A randomised, single-blinded, two-arm prospective study of 40 patients at risk of DF was conducted. The intervention group (n=20) received 16 weeks of TD training (60 min/session×3 sessions/week). The control group attended four educational workshops (1 hour/session×1 session/month). Plantar pressure, represented by the primary outcomes of peak pressure (PP) and pressure-time integral (PTI) over 10 areas on each foot, was measured using the Footscan platform system. Secondary outcomes comprised static postural stability, ankle ROM and lower extremity functional strength.

Results

Reductions in intervention group PP (right foot: mean differences=4.50~27.1, decrease%=25.6~72.0; left foot: mean differences=−5.90~6.33, decrease%=−22.6~53.2) and PTI at 10 areas of each foot (right foot: mean differences=1.00~12.5, decrease%=10.4~63.6; left foot: mean differences=0.590~25.3, decrease%=21.9~72.6) were observed. Substantial PP and PTI differences were noted at the second through fourth metatarsals, medial heel and lateral heel in the right foot. Substantial PP and PTI differences were detected at metatarsals 1 and 2 and metatarsal 2 in the left foot, respectively. Moderate training effects were found in plantar flexion ROM of both feet, lower extremity functional strength, and length of center-of-pressure trajectory with eyes closed and open (r=0.321–0.376, p<0.05).

Conclusions

A 16-week TD training program can significantly improve ankle ROM, lower extremity functional strength, and static postural stability. To attain greater improvements in plantar pressure, a longer training period is necessary.

Trial registration number

ChiCTR1800014714.
Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study
Authors: Dhayalan Dhanushan , Tveiten Øystein Vesterli , Goplen Frederik Kragerud , Finnkirk Monica Katrine , Storstein Anette Margrethe , Gruner Eli Renate , Lund-Johansen Morten
Published: March 2021

Introduction

The optimal management of small-sized to medium-sized vestibular schwannoma (VS) is a matter of controversy. Clinical results of the prevailing treatment modalities (microsurgery, stereotactic radiosurgery (SRS), and conservative management (CM)) are documented, but comparative studies are few, and none are randomised or blinded. Upfront radiosurgery, or a careful follow-up by MRI with subsequent treatment on growth, are two strategies used at many centres. The present study aims at comparing these strategies by randomising individuals with newly diagnosed tumours to either upfront SRS or initial CM.

Methods and analysis

The Vestibular Schwannoma: Radiosurgery or Expectation study is designed as a randomised, controlled, observer-blinded, single-centre superiority trial with two parallel groups. Eligible patients will be randomised using sequentially numbered opaque sealed envelopes, and the radiosurgery group will undergo standard Gamma Knife Radiosurgery (GKRS) within 2 months following randomisation. The primary endpoint is tumour growth measured as volume ratio V4years/Vbaselineand volume doubling time, evaluated by annual T1 contrast MRI volumetric analysis. Secondary endpoints include symptom and sign development measured by clinical examination, audiovestibular tests, and by patient’s responses to standardised validated questionnaires. In addition, the patient’s working status, and the health economics involved with both strategies will be evaluated and compared. All outcome assessments will be performed by blinded observers. Power analysis indicates that 100 patients is sufficient to demonstrate the effect of GKRS on tumour volume.

Ethics and dissemination

The trial has ethical approval from the Regional Ethical Committee (23503) and funding from The Western Norway Regional Health Authority. Trial methods and results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines in a peer-reviewed journal.

Trial registration number

Clinical trials:NCT02249572. Haukeland University Hospital record: 2014/314. Regional Ethical Committee (REC West): 23 503. The Western Norway Regional Health Authority: 912 281.
Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study
Authors: Rubin Greg , Walter Fiona M , Emery Jon , Hamilton Willie , Hoare Zoe , Howse Jenny , Nixon Catherine , Srivastava Tushar , Thomas Chloe , Ukoumunne Obioha C , Usher-Smith Juliet A , Whyte Sophie , Neal Richard D
Published: March 2021

Objective

To determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer.

Design and setting

Feasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation.

Participants

Patients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer. 530 patients (mean age 68 years, 58% female) participated.

Intervention

Practices randomised 1:1 to usual care (control) or to receive a previously piloted eCDS tool for suspected cancer (intervention), for use at the discretion of the GPs, supported by a theory-based implementation package and ongoing support. We conducted semistructured interviews with GPs in intervention practices. Recruitment lasted 22 months.

Outcomes

Patient participation rate, use of eCDS, referrals and route to diagnosis, O-G cancer diagnoses; acceptability to GPs; cost-effectiveness. Participants followed up 6 months after index encounter.

Results

From control and intervention practices, we screened 3841 and 1303 patients, respectively; 1189 and 434 were eligible, 392 and 138 consented to participate. Ten patients (1.9%) had O-G cancer. eCDS was used eight times in total by five unique users. GPs experienced interoperability problems between the eCDS tool and their clinical system and also found it did not fit with their workflow. Unexpected restrictions on software installation caused major problems with implementation.

Conclusions

The conduct of this study was hampered by technical limitations not evident during an earlier pilot of the eCDS tool, and by regulatory controls on software installation introduced by primary care trusts early in the study. This eCDS tool needed to integrate better with clinical workflow; even then, its use for suspected cancer may be infrequent. Any definitive trial of eCDS for cancer diagnosis should only proceed after addressing these constraints.

Trial registration number

ISRCTN125595588.
Households access to improved drinking water sources and toilet facilities in Ethiopia: a multilevel analysis based on 2016 Ethiopian Demographic and Health Survey
Authors: Andualem Zewudu , Dagne Henok , Azene Zelalem Nigussie , Taddese Asefa Adimasu , Dagnew Baye , Fisseha Roman , Muluneh Atalay Goshu , Yeshaw Yigizie
Published: March 2021

Objective

This study aimed to assess households access to improved drinking water sources and sanitation facilities and their associated factors in Ethiopia.

Design

Cross-sectional study.

Setting

Ethiopia.

Participants

Household heads.

Primary outcomes

Access to improved drinking water sources and toilet facilities.

Methods

We conducted an in-depth secondary data analysis of 2016 Ethiopian Demographic and Health Survey. Data from a total of 16 650 households and 645 clusters were included in the analysis. The households were selected using a stratified two-stage cluster sampling technique. Multilevel binary logistic regression analyses were performed to identify factors associated with access to an improved drinking water source and toilet facilities. Adjusted OR with a 95% CI was reported with p value <0.05 was used to declare a significant association between the covariates and the outcome variables.

Results

The proportions of households’ access to improved sources of drinking water and toilet facilities were 69.94% (95% CI: 69.23% to 70.63%) and 25.36% (95% CI: 24.69% to 26.03%), respectively. Households headed by women and households with a better wealth index were positively associated with access to improved drinking water sources. Whereas rural households, ≥30 min round trip to obtain drinking water and region were factors negatively associated with households access to improved drinking water sources. A higher probability of having access to improved toilet facilities: households with heads who had attained higher education, households having better access to improved sources of drinking water and households with better wealth index. While the following households were less likely to have access to improved toilet facilities: households with heads were widowed, households with four to six members, rural households and region.

Conclusion

The study found that the proportions of households’ access to improved drinking water sources and toilet facilities in Ethiopia were relatively low, which demands the need to tailor strategies to increase the coverage of access to improved drinking water sources and toilet facilities.
Preoperative nivolumab to evaluate pathological response in patients with stage I non-small cell lung cancer: a study protocol of phase II trial (POTENTIAL)
Authors: Kagimoto Atsushi , Tsutani Yasuhiro , Mimae Takahiro , Miyata Yoshihiro , Ikeda Norihiko , Ito Hiroyuki , Maniwa Yoshimasa , Suzuki Kenji , Tsuboi Masahiro , Yoshimura Kenichi , Umemoto Seiji , Okada Morihito
Published: March 2021

Introduction

Recently, inhibition of programmed cell death 1 or its ligand has shown therapeutic effects on non-small cell lung cancer (NSCLC). However, the effectiveness of preoperative nivolumab monotherapy for stage I NSCLC remains unknown. The present study aimed to investigate the pathological response of preoperative treatment with nivolumab for clinically node negative but having a high risk of NSCLC recurrence.

Methods and analysis

The Preoperative Nivolumab (Opdivo) to evaluate pathologic response in patients with stage I non-small cell lung cancer: a phase 2 trial (POTENTIAL) study is a multicentre phase II trial investigating efficacy of preoperative nivolumab for clinical stage I patients at high risk of recurrence. This study includes histologically or cytologically confirmed NSCLC patients with clinical N0 who were found on preoperative high-resolution CT to have a pure solid tumour without a ground-glass opacity component (clinical T1b, T1c or T2a) or a solid component measuring 2–4 cm in size (clinical T1c or T2a). Patients with epidermal growth factor receptor (EGFR) mutation (deletion of exon 19 or point mutation on exon21, L858R), anaplastic lymphoma kinase (ALK) translocation or c-ros oncogene 1 (ROS-1) translocation are excluded from this study. Nivolumab (240 mg/body) is administrated intravenously as preoperative therapy every 2 weeks for three cycles. Afterward, lobectomy and mediastinal lymph node dissection (ND 2a-1 or ND 2a-2) are performed. The primary endpoint is a pathological complete response in the resected specimens. The secondary endpoints are safety, response rates and major pathological response. The planed sample size is 50 patients. Patients have been enrolled since April 2019.

Ethics and dissemination

This trial was approved by the Institutional Review Board of Hiroshima University Hospital and other participating institutions. This trial will help examine the efficacy of preoperative nivolumab therapy for clinical stage I NSCLC.

Trial registration number

jRCT2061180016.
The importance and availability of adjustments to improve access for autistic adults who need mental and physical healthcare: findings from UK surveys
Authors: Brice Samuel , Rodgers Jacqui , Ingham Barry , Mason David , Wilson Colin , Freeston Mark , Le Couteur Ann , Parr Jeremy R
Published: March 2021

Objectives

To investigate autistic people’s views on the importance and availability of adjustments to mental and physical healthcare provision. To explore whether specific categories of adjustments can be identified and to identify any differences in their importance and availability between mental and physical healthcare.

Design

Data from two studies, both employing a cross-sectional survey design.

Setting

UK-based autistic adults registered with the Adult Autism Spectrum Cohort-UK were contacted by post or online. In both studies, recruitment was staged over a 12-month period. Non-responders were sent a single reminder letter 2 weeks after initial contact.

Participants

537 autistic adults completed a survey about mental health services (51% response rate), 407 completed the physical health survey (49% response rate). Within these samples, 221 participants completed both surveys.

Primary outcome measures

Each study developed a bespoke survey to explore participants’ views on mental and physical health services, respectively. Both included an identical list of adjustments that participants rated based on importance and availability.

Results

Three factors of important adjustments were identified: sensory environment, clinical and service context, and clinician knowledge and communication. Adjustments across healthcare settings were widely rated as being important yet rarely available. One significant difference between the importance of adjustments available through mental and physical health services was identified. Participants reported that having access to a clinician who is willing to adapt their approach to suit the person’s preferences was significantly more important for participants attending mental health settings (p=0.001).

Conclusions

Autistic people reported the limited availability of important adjustments in current healthcare provision. To address unmet need and tackle the health inequalities faced by autistic people attending physical and mental healthcare settings, healthcare providers should offer adjustments relating to the three identified factors. Future research should focus on identifying and addressing service provider barriers to implementation.
Detailed study protocol for systematic scoping review of research on child marriage, 2000–2019
Authors: Greene Margaret E. , Siddiqi Manahil
Published: March 2021

Introduction

The global development agenda reflects greater attention to ending child marriage and supporting adolescent girls than ever before. Limited understandings of the evidence base on child marriage, however, make it challenging to assess gaps in the literature and inform policy and programming to respond to the needs of adolescent girls. The goal of this project is to systematically identify, evaluate and synthesise the global evidence on child marriage.

Methods and analysis

We will include articles with a thematic focus on child marriage from all geographic settings, two decades of research (2000–2019) and in four languages (English, Spanish, French and Portuguese). We will search 18 electronic academic databases (7 in English and 4 each in French, Spanish and Portuguese, with 1 overlapping database) and for the grey literature, conduct targeted hand-searches of organisations engaged in work to prevent child marriage. The databases for studies in English are PubMed, PsychINFO, Embase, CINAHL Plus, Popline, Web of Science and Cochrane Library; for studies in French, the databases will be DialNet, Directory of Open Access Journals, Science Direct and Biblioteca CCG-IBT database; in Spanish, DialNet, La Biblioteca Científica Electrónica en Línea, Red Iberoamericana de Innovación y Conocimiento Científico and Jstor and in Portuguese, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Biblioteca Virtual em Saúde, Biblioteca Científica Eletrônica On-line and Biblioteca Digital Brasileira de Teses e Dissertações. We will also review reference lists of select articles and seek input from key authors, field practitioners and participants in international convenings. We will collect and analyse data on publication characteristics, including type of document, institutional affiliation, publication year, language, focus country and region, study objective, specific focus, research method, key findings and recommendations of the material offered for future work. The database searches for publications in English were conducted in January 2020 and we plan to complete the searches in French, Spanish and Portuguese in early 2021.

Ethics and dissemination

As a systematic review of already-published data, this study does not raise ethical or safety concerns. The authors plan to publish the results of the scoping review in a relevant international journal as well as present the results widely following publication. Building on this foundational work, the authors plan to conduct analyses that make use of the rich data.

Registration details

The study design adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our protocol was registered with Open Science Framework on 14 January 2020 (https://osf.io/awh8v).
STEPFORWARD study: a randomised controlled feasibility trial of a self-aligning prosthetic ankle-foot for older patients with vascular-related amputations
Authors: Vanicek Natalie , Coleman Elizabeth , Watson Judith , Bell Kerry , McDaid Catriona , Barnett Cleveland , Twiste Martin , Jepson Fergus , Salawu Abayomi , Harrison Dennis , Mitchell Natasha
Published: March 2021

Objectives

To determine the feasibility of conducting a full-scale randomised controlled trial (RCT) of the effectiveness and cost-effectiveness of a self-aligning prosthetic ankle-foot compared with a standard prosthetic ankle-foot.

Design

Multicentre parallel group feasibility RCT.

Setting

Five prosthetics centres in England recruiting from July 2018 to August 2019.

Participants

Adults aged ≥50 years with a vascular-related or non-traumatic transtibial amputation for 1 year or longer, categorised as having ‘limited community mobility’ and using a non-self-aligning ankle-foot.

Intervention

Participants were randomised into one of two groups for 12 weeks: self-aligning prosthetic ankle-foot or existing non-self-aligning prosthetic ankle-foot.

Outcomes

Feasibility measures: recruitment, consent and retention rates; and completeness of questionnaire and clinical assessment datasets across multiple time points. Feasibility of collecting daily activity data with wearable technology and health resource use data with a bespoke questionnaire.

Results

Fifty-five participants were randomised (61% of the target 90 participants): n=27 self-aligning ankle-foot group, n=28 non-self-aligning ankle-foot group. Fifty-one participants were included in the final analysis (71% of the target number of participants). The consent rate and retention at final follow-up were 86% and 93%, respectively. The average recruitment rate was 1.25 participants/site/month (95% CI 0.39 to 2.1). Completeness of questionnaires ranged from 89%–94%, and clinical assessments were 92%–95%, including the activity monitor data. The average completion rates for the EQ-5D-5L and bespoke resource use questionnaire were 93% and 63%, respectively.

Conclusions

This feasibility trial recruited and retained participants who were categorised as having ‘limited community mobility’ following a transtibial amputation. The high retention rate of 93% indicated the trial was acceptable to participants and feasible to deliver as a full-scale RCT. The findings support a future, fully powered evaluation of the effectiveness and cost-effectiveness of a self-aligning prosthetic ankle-foot compared with a standard non-self-aligning version with some adjustments to the trial design and delivery.

Trial registration number

ISRCTN15043643.
Danish teleophthalmology platform reduces optometry referrals into the national eye care system
Authors: Muttuvelu Danson Vasanthan , Buchholt Heidi , Nygaard Mads , Rasmussen Marie Louise Roed , Sim Dawn
Published: March 2021

Objective

The purpose of this study was to evaluate the stratification of follow-up and referral pathways after implementation of a systematic cloud-based electronic-referral teleophthalmological service for optometry-initiated ocular posterior segment disease referrals to the Danish national eye care system.

Methods and Analysis

A retrospective cohort study was conducted in the period from 1 August 2018 to 31 July 2019. Patients with suspected ocular posterior segment disease reviewed by the telemedical ophthalmology service were included. The service stratified patients into the categories: no need for follow-up, follow-up by optometrist, follow-up by the telemedical service and referral to the national Danish eye care service.

Results

From a pool of 386 361 customers, 9938 patients were enrolled into this study. 19.5% of all patients were referred to the Danish national eye care system, while 80.5% of the patients in the telemedical service were not, in the period from 1 August 2018 to 31 July 2019. 14.4% of the optometrist referrals did not need any follow-up, while a majority of 66.1% needed some follow-up either by the optometrist themselves or within the telemedical service.

Conclusion

Optometrist posterior segment disease referrals can be considerably reduced with a risk stratified approach and optimal use of technology. New models can improve and streamline the healthcare system.
Associations between cardiac troponin I and cardiovascular parameters after 12-week endurance training in young moderately trained amateur athletes
Authors: Tesema Gashaw , George Mala
Published: March 2021

Background

Previous studies were conducted only on elite athletes, and they investigate acute training responses of cardiac troponin I (CTnI). However, cardiac troponin was found to be elevated in young and inexperienced athletes than adults, and immature myocardium is more susceptible to injury, which needs further consideration.

Aim

Therefore, we aimed to observe the association between CTnI and cardiovascular parameters in response to chronic endurance training adaptation in young athletes.

Methods

Fifteen participants aged (19.5±1.3) years were selected and placed in endurance running at 70%–80% HRmax intensity for 35 min per training for the first week and additional 2 min each week from the second to the last week for 12 weeks. Serum cardiac troponin and cardiovascular parameters were assessed at pre-training and after 12 weeks of training.

Result

We find a significant CTnI level (p<0.05) and it is positively correlated with systolic blood pressure (BP) (r=0.425). Moreover, CTnI was statistically significant (p<0.01) and positively associated with mean arterial pressure (r=0.516) with a moderate correlation. Besides, CTnI showed a significant (p<0.001) and positive relationship with resting heart rate (r=0.605) and a moderate correlation. We did not find a significant relationship between CTnI and diastolic BP in response to endurance training adaptation.

Conclusion

In conclusion, serum CTnI was significantly and positively associated with cardiovascular parameters in young amateur athletes in response to 12-week endurance training adaptation.
Palliative medicine referrals for hepatocellular carcinoma: a national survey of gastroenterologists
Authors: Sabih Abdul Hamid , Laube Robyn , Strasser Simone I , Lim Lynn , Cigolini Maria , Liu Ken
Published: March 2021

Objectives

Palliative care (PC) service involvement for hepatocellular carcinoma (HCC) patients is suboptimal and little is known about the underlying reasons for this. We aimed to study clinicians’ experience and attitudes towards PC in HCC.

Methods

A nationwide survey was conducted of consultants/trainees recruited from the Gastroenterological Society of Australia membership directory. Clinician demographics, experience and attitudes towards PC use for HCC patients were collected.

Results

There were 160 participants. Most attended weekly multidisciplinary team meetings (MDTM, 60%) and had no formal PC training (71%). MDTM with PC attendance was reported by 12%. Rates of PC referral increased incrementally from BCLC 0/A to D patients but were not universal even in advanced (46%) or terminal (87%) stages. Most acknowledged PC patient discussions occurred too late (61%). Those with prior PC training were more likely to refer BCLC 0/A and B patients for early PC. Referral rates for outpatient PC were higher in respondents who attended MDTM with PC present across all BCLC stages. PC service was rated good/very good by 70%/81% for outpatients/inpatients. Barriers to PC referral included clinician-perceived negative patient associations with PC (83%), clinician-perceived patient/caregiver lack of acceptance (81%/77%) and insufficient time (70%).

Conclusions

PC referral for HCC patients is not universal and occurs late even in late-stage disease. Prior PC training and/or PC presence at MDTM positively influences referral practices. Barriers to PC referral are not related to quality of PC services but rather to clinician-perceived patients’ negative reactions to or lack of acceptance of PC.
Linked Colour imaging for the detection of polyps in patients with Lynch syndrome: a multicentre, parallel randomised controlled trial
Authors: Houwen Britt B S L , Hazewinkel Yark , Pellisé María , Rivero-Sánchez Liseth , Balaguer Francesc , Bisschops Raf , Tejpar Sabine , Repici Alessandro , Ramsoekh D , Jacobs Maarten A J M , Schreuder Ramon-Michel M , Kaminski Michal Filip , Rupinska Maria , Bhandari Pradeep , van Oijen Martijn G H , Koens Lianne , Bastiaansen Barbara A J , Tytgat Kristien M , Fockens Paul , Vleugels Jasper L A , Dekker E
Published: March 2021

Objective

Despite regular colonoscopy surveillance, colorectal cancers still occur in patients with Lynch syndrome. Thus, detection of all relevant precancerous lesions remains very important. The present study investigates Linked Colour imaging (LCI), an image-enhancing technique, as compared with high-definition white light endoscopy (HD-WLE) for the detection of polyps in this patient group.

Design

This prospective, randomised controlled trial was performed by 22 experienced endoscopists from eight centres in six countries. Consecutive Lynch syndrome patients ≥18 years undergoing surveillance colonoscopy were randomised (1:1) and stratified by centre for inspection with either LCI or HD-WLE. Primary outcome was the polyp detection rate (PDR).

Results

Between January 2018 and March 2020, 357 patients were randomised and 332 patients analysed (160 LCI, 172 HD-WLE; 6 excluded due to incomplete colonoscopies and 19 due to insufficient bowel cleanliness). No significant difference was observed in PDR with LCI (44.4%; 95% CI 36.5% to 52.4%) compared with HD-WLE (36.0%; 95% CI 28.9% to 43.7%) (p=0.12). Of the secondary outcome parameters, more adenomas were found on a patient (adenoma detection rate 36.3%; vs 25.6%; p=0.04) and a colonoscopy basis (mean adenomas per colonoscopy 0.65 vs 0.42; p=0.04). The median withdrawal time was not statistically different between LCI and HD-WLE (12 vs 11 min; p=0.16).

Conclusion

LCI did not improve the PDR compared with HD-WLE in patients with Lynch syndrome undergoing surveillance. The relevance of findings more adenomas by LCI has to be examined further.

Trial registration number

NCT03344289.
Combination immunotherapy using G-CSF and oncolytic virotherapy reduces tumor growth in osteosarcoma
Authors: Morales-Molina Alvaro , Gambera Stefano , Leo Angela , García-Castro Javier
Published: March 2021

Background

Osteosarcoma is the most common malignant solid tumor that affects bones, however, survival rates of patients with relapsed osteosarcoma have not improved in the last 30 years. Oncolytic virotherapy, which uses viruses designed to selectively replicate in cancer cells, has emerged as a promising treatment for solid tumors. Our group uses mesenchymal stem cells (MSCs) to transport oncolytic adenoviruses (OAds) to the tumor site, a therapeutic strategy called Celyvir. This treatment has been already applied in human patients, canine patients and different mouse models. In parallel, previous results have probed that administration of granulocyte-colony stimulating factor (G-CSF) increased immune infiltration in tumors. We then hypothesized that the mobilization of immune cells by G-CSF may increase the antitumor efficacy of Celyvir treatment by increasing the immune infiltration into the tumors.

Methods

In this study, we use a murine version of Celyvir consisting in murine MSCs carrying the murine OAd dlE102—here called OAd-MSCs—in an immunocompetent model of osteosarcoma. We tested the antitumoral efficacy of the combination of OAd-MSCs plus G-CSF.

Results

Our results show that treatment with OAd-MSCs or the union of OAd-MSCs with G-CSF (Combination) significantly reduced tumor growth of osteosarcoma in vivo. Moreover, treated tumors presented higher tumor infiltration of immune cells—especially tumor-infiltrating lymphocytes—and reduced T cell exhaustion, which seems to be enhanced in tumors treated with the Combination. The comparison of our results to those obtained from a cohort of pediatric osteosarcoma patients showed that the virotherapy induces immunological changes similar to those observed in patients with good prognosis.

Conclusions

The results open the possibility of using cellular virotherapy for the treatment of bone cancers. Indeed, its combination with G-CSF may be considered for the improvement of the therapy.
Fast progression in non–small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel
Authors: Gandara David , Reck Martin , Moro-Sibilot Denis , Mazieres Julien , Gadgeel Shirish , Morris Stefanie , Cardona Andres , Mendus Diana , Ballinger Marcus , Rittmeyer Achim , Peters Solange
Published: March 2021

Background

Treatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study.

Methods

The OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non–small cell lung cancer. FP rates and associated baseline factors were analyzed. FP was defined as either a ≥50% increase in the sum of largest diameters (SLDs) within 6 weeks of treatment initiation or death due to cancer progression within 12 weeks (absent post-baseline scan).

Results

Forty-two of 421 patients (10%) receiving atezolizumab and 37 of 402 (9%) receiving docetaxel had FP. Twenty patients with FP (48%) receiving atezolizumab versus 12 (30%) receiving docetaxel had a ≥50% SLD increase within 6 weeks. FP was significantly associated with an ECOG (Eastern Cooperative Oncology Group) performance status of 1 (vs 0), ≥3 metastatic sites at baseline, and failure of preceding first-line treatment within 6 months, but not with epidermal growth factor receptor mutation, programmed cell death 1 ligand 1 or tumor mutational burden. Overall survival in patients with FP and a ≥50% SLD increase at week 6 was similar with atezolizumab and docetaxel (unstratified HR 0.89 (95% CI 0.41 to 1.92)).

Conclusions

FP rates were similar with atezolizumab and docetaxel in the OAK study, suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy. Applying the FP criteria to other phase III checkpoint inhibitor trials may further elucidate the risk factors for FP.

Trial registration number

NCT02008227.
First immunotherapeutic CAR-T cells against the immune checkpoint protein HLA-G
Authors: Anna François , Bole-Richard Elodie , LeMaoult Joel , Escande Marie , Lecomte Martin , Certoux Jean-Marie , Souque Philippe , Garnache Francine , Adotevi Olivier , Langlade-Demoyen Pierre , Loustau Maria , Caumartin Julien
Published: March 2021

Background

CAR-T cells immunotherapy is a breakthrough in the treatment of hematological malignancies such as acute lymphoblastic leukemia (ALL) and B-cell malignancies. However, CAR-T therapies face major hurdles such as the lack of tumor-specific antigen (TSA), and immunosuppressive tumor microenvironment sometimes caused by the tumorous expression of immune checkpoints (ICPs) such as HLA-G. Indeed, HLA-G is remarkable because it is both a potent ICP and a TSA. HLA-G tumor expression causes immune escape by impairing innate and adaptive immune responses and by inducing a suppressive microenvironment. Yet, to date, no immunotherapy targets it.

Methods

We have developed two anti-HLA-G third-generation CARs based on new anti-HLA-G monoclonal antibodies.

Results

Anti-HLA-G CAR-T cells were specific for immunosuppressive HLA-G isoforms. HLA-G-activated CAR-T cells polarized toward T helper 1, and became cytotoxic against HLA-G+tumor cells. In vivo, anti-HLA-G CAR-T cells were able to control and eliminate HLA-G+tumor cells. The interaction of tumor-HLA-G with interleukin (IL)T2-expressing T cells is known to result in effector T cell functional inhibition, but anti-HLA-G CAR-T cells were insensitive to this inhibition and still exerted their function even when expressing ILT2. Lastly, we show that anti-HLA-G CAR-T cells differentiated into long-term memory effector cells, and seemed not to lose function even after repeated stimulation by HLA-G-expressing tumor cells.

Conclusion

We report for the first time that HLA-G, which is both a TSA and an ICP, constitutes a valid target for CAR-T cell therapy to specifically target and eliminate both tumor cells and HLA-G+suppressive cells.
Severity of COVID-19 in patients with lung cancer: evidence and challenges
Authors: Passaro Antonio , Bestvina Christine , Velez Velez Maria , Garassino Marina Chiara , Garon Edward , Peters Solange
Published: March 2021

Cancer patients are highly vulnerable to SARS-CoV-2 infections due to frequent contacts with the healthcare system, immunocompromised state from cancer or its therapies, supportive medications such as steroids and most importantly their advanced age and comorbidities. Patients with lung cancer have consistently been reported to suffer from an increased risk of death compared with other cancers. This is possibly due to the combination of specific pathophysiological aspects, including underlying pulmonary compromise due to smoking history and the increased specific pressures on respiratory healthcare services caused by the related pandemic. Rationally and safely treating patients with lung cancer during the pandemic has become a continuous challenge over the last year. Deciding whether to offer, modify, postpone or even cancel treatments for this particular patient’s population has become the crucial recurrent dilemma for lung cancer professionals. Chemotherapy, immunotherapy and targeted agents represent distinct risks factors in the context of COVID-19 that should be balanced with the short-term and long-term consequences of delaying cancer care. Despite the rapid and persistent trend of the pandemic, declared by WHO on March 11, 2020, and still ongoing at the time of writing (January 2021), various efforts were made by oncologists worldwide to understand the impact of COVID-19 on patients with cancer. Adapted recommendations of our evidence-based practice guidelines have been developed for all stakeholders. Different small and large-scale registries, such as the COVID-19 and Cancer Consortium (CCC19) and Thoracic Cancers International COVID-19 Collaboration quickly collected data, supporting cancer care decisions under the challenging circumstance created by the COVID-19 pandemic. Several recommendations were developed as guidance for prioritizing the various aspects of lung cancer care in order to mitigate the adverse effects of the COVID-19 healthcare crisis, potentially reducing the morbidity and mortality of our patients from COVID-19 and from cancer. These recommendations helped inform decisions about treatment of established disease, continuation of clinical research and lung cancer screening. In this review, we summarize available evidence regarding the direct and indirect impact of the COVID-19 pandemic on lung cancer care and patients.
Factors associated with time to independent walking recovery post-stroke
Authors: Kennedy Caitlin , Bernhardt Julie , Churilov Leonid , Collier Janice M , Ellery Fiona , Rethnam Venesha , Carvalho Lilian B , Donnan Geoffrey A , Hayward Kathryn S
Published: March 2021

Background

Past studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT).

Methods

The outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics: age, sex, handedness; pre-stroke: hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation; stroke-related: stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention.

Results

A total of 2100 participants (median age 73 years, National Institutes of Health Stroke Scale 7, <1% missing data) with stroke were included. The median time to walking 50 m unassisted was 6 days (IQR 2–63) and 75% achieved independent walking by 3 months. Adjusted Cox regression indicated that slower return to independent walking was associated with older age (caHR 0.651, 95% CI 0.569 to 0.746), diabetes (caHR 0.836, 95% CI 0.740 to 0.945), severe stroke (caHR 0.094, 95% CI 0.072 to 0.122), haemorrhagic stroke (caHR 0.790, 95% CI 0.675 to 0.925) and right hemisphere stroke (caHR 0.796, 95% CI 0.714 to 0.887).

Conclusion

Our analysis provides robust evidence for important factors associated with independent walking recovery. These findings highlight the need for tailored mobilisation programmes that target subgroups, in particular people with haemorrhagic and severe stroke.
Hydroxychloroquine is associated with lower platelet activity and improved vascular health in systemic lupus erythematosus
Authors: Cornwell MacIntosh Grant , Luttrell-Williams Elliot S , Golpanian Michael , El Bannoudi Hanane , Myndzar Khrystyna , Izmirly Peter , Belmont H Michael , Katz Stuart , Smilowitz Nathaniel R , Engel Alexis , Clancy Robert , Ruggles Kelly , Buyon Jill P , Berger Jeffrey S
Published: March 2021

Objective

Hydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE.

Methods

Platelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose.

Results

Among 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=−0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=−0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056).

Conclusion

HCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.
Wallerian degeneration as a mimic of recurrence of myelitis
Authors: Patel Arpan , Koul Prateeka , Harel Asaff
Published: March 2021

A middle-aged woman with idiopathic longitudinally extensive myelitis underwent repeat MR scan of cervical spine at 5-month follow-up, which showed new non-enhancing T2 hyperintensities, initially reported as myelitis recurrence. However, the hyperintensities involved both lateral corticospinal tracts caudal to the initial lesion and both dorsal columns rostral to the initial lesion and were therefore compatible with Wallerian degeneration. This radiological mimic should be considered in the differential of recurrence of myelitis.
Venous ligation versus venous repair: does the procedure impact venous thromboembolism risk?
Authors: Farrell Michael Steven , Knudson M Margaret , Stein Deborah M
Published: March 2021

Background

Traumatic lower extremity venous injuries are most commonly managed with either a vein ligation or repair procedure. Venous injuries are associated with an increased risk of developing venous thromboembolisms (VTE), but little is understood with regard to how specific surgical treatments may impact the risk of developing either a deep vein thrombosis (DVT) or a pulmonary embolism (PE). In this study of lower extremity venous injuries, we hypothesized that venous ligation would be associated with an increased risk of DVT but a lower risk of PE when compared with venous repair.

Methods

Patients were identified from the National Trauma Data Bank (2008 to 2014) with at least one iliac, femoral, popliteal, or tibial venous injury and who received either a vein ligation or repair. The patients were then compared based on the type of procedure and the location of the injury to assess the risk of DVT and PE between the groups.

Results

A total of 1214 patients were identified. There was no difference between patients who received a vein ligation versus a repair with respect to age, injury severity score, or initial systolic blood pressure. There was no difference in the odds of developing either a DVT or PE between patients who were treated with vein ligation versus repair. There was also no difference in VTE rates when stratified by the location of the injury.

Conclusions

In individuals with lower extremity venous injuries, there is no difference in the rate of DVT or PE complications when comparing venous repair and ligation procedures. The role of anticoagulation remains to be elucidated following operative treatment.

Level of evidence

Therapeutic/Care Management, Level IV.
Do more mature preterm babies with surgical necrotizing enterocolitis predominantly develop the colonic disease?
Authors: Sinha Chandrasen K , Ashworth Iona , Martin Sarah , Bhayat Sadaf , Kulkarni Anay
Published: March 2021

Background

The primary aim was to scrutinize our hypothesis: “Do more mature preterm (MMP) babies with surgical necrotizing enterocolitis (NEC) predominantly develop the colonic disease and are different in their response and behaviour in comparison to exceedingly preterm (EP) babies?” Secondary outcomes were to define time taken in developing NEC, time from diagnosis to laparotomy, requirement of parenteral nutrition (PN), and ventilatory support.

Methods

We defined MMP babies as ≥30 weeks of gestation and EP babies as ≤29 weeks+6 daysof gestation. Inclusion criteria were all babies <37 weeks with NEC requiring surgery (called surgical NEC group). Data were collected retrospectively and analyzed using QuickCalcs.

Results

Of the total, 41% (97/234) of babies underwent laparotomy between 2010 and 2019. Totally, 81% were EP and 19% were MMP babies. Pure colonic involvement was seen in 9% of EP babies in comparison to 56% in the MMP babies (p=0.0001). Involvement of only the small bowel was seen in two-thirds of EP babies in comparison to only one-third in MMP babies (p=0.01). EP cohort required PN for 82 days (median) in comparison to 17 days (median) in the MMP cohort (p=0.001). Ventilation requirement in the EP group versus the MMP group was 24 vs 9 days (median), respectively (p=0.0006).

Conclusions

MMP babies predominantly developed colonic disease, whereas EP babies predominantly developed small bowel disease. EP babies required a longer duration of PN and ventilation support. This study opens a new area of research to differentiate pathogenesis and maturation patterns of the small and large bowels in babies with NEC.
Snow cornice and snow avalanche monitoring using automatic time lapse cameras in Tasiapik Valley, Nunavik (Québec) during the winter of 2017–2018
Authors: Veilleux Samuel , Decaulne Armelle , Bhiry Najat
Published: March 2021

A series of automatic time-lapse cameras installed along the southwestern side of Tasiapik Valley, near the village of Umiujaq, Nunavik (northern Québec) documented several departure modes and types of snow involved in snow avalanches during winter 2017–2018. These included cornice–avalanche dynamics, slab and loose snow avalanches, and clean and dirty snow avalanches. At the top of the selected slope, a camera monitored the development of a snow cornice beginning in November 2017, detecting multiple cornice failures over the winter and spring. The track and deposition area of the runout paths were monitored from two cameras downslope, revealing the concomitance of snow–cornice fall and snow avalanche triggering. Snow avalanche activity remained relatively infrequent until the end of May 2018. Spring snow avalanche activity is characterized by wet and dirty snow avalanches carrying debris to the foot of the slope and by runout zones located near the road along the slope.