bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic burden of IADPSG gestational diabetes diagnostic criteria in China: propensity score matching analysis from a 7-year retrospective cohort
Authors: He Zonglin , Tang Yuan , Xie Huatao , Lin Yuchen , Liang Shangqiang , Xu Yuyuan , Chen Zhili , Wu Liang-zhi , Sheng Jie , Bi Xiaoyu , Pang Muyi , Akinwunmi Babatunde , Xiao Xiaomin , Ming Wai-kit
Published: August 2020

Introduction

The International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) increased the morbidity significantly, but the cost and effectiveness of its application are still unclear. This study aimed to analyze the impact of the IADPSG criteria for diagnosing GDM in China on the perinatal outcomes, and medical expenditure of GDM women versus those with normal glucose tolerance (NGT).

Research design and methods

We conducted a retrospective cohort study involving 7794 women admitted at the First Affiliated Hospital of Jinan University (Guangzhou, China), from November 1, 2010 to October 31, 2017. The perinatal outcomes and medical expenditure were retrieved from the electronic medical records in the hospital. Propensity score matching (PSM, in a 1:1 ratio) algorithm was used to minimize confounding effects on the difference in the two cohorts.

Results

PSM minimized the difference of baseline characteristics between women with and without GDM. Of 7794 pregnant women, half (n=3897) were all of the pregnant women with GDM admitted to the hospital during the period, the other half women had NGT and were selected randomly to match with their counterparts. Adopting the IADPSG criteria was associated with reduced risk of emergency cesarean section, polyhydramnios, turbid amniotic fluid and perineal injury (p<0.01 for all) and having any one of the adverse fetal outcomes (p<0.01), including fetal distress, umbilical cord around the neck, neonatal encephalopathy, admission to neonatal intensive care unit, birth trauma, neonatal hypoglycemia and fetal death. After PSM, the median total medical expenditure by the GDM women was ¥912.9 (US$140.7 in 2015) more than that of the the NGT women (p=0.09).

Conclusions

Despite the increasing medical expenditure, screening at 24–28 gestational weeks under the IADPSG guidelines with the 2-hour, 75 g oral glucose tolerance test can improve short-term maternal and neonatal outcomes.
Animal models of ischemic limb ulcers: a systematic review and meta-analysis
Authors: Thanigaimani Shivshankar , Phie James , Golledge Jonathan
Published: August 2020

The aims of this systematic review were to assess the clinical relevance and quality of previously published animal models of ischemic ulceration and examine the available evidence for interventions improving ulcer healing in these models. Publicly available databases were searched for original studies investigating the effect of limb ischemia on wound healing in animal models. The quality of studies was assessed using two tools based on the Animal research: Reporting of In Vivo Experiments (ARRIVE) guidelines and the clinical relevance of the models. A total of 640 wounds (ischemic=314; non-ischemic=326) were assessed in 252 animals (92 mice, 140 rats, 20 rabbits) from 7 studies. Meta-analyses showed that wound healing was consistently delayed by ischemia at all time-points examined (day-7 standard median difference (SMD) 5.36, 95% CI 3.67 to 7.05; day-14 SMD 4.50, 95% CI 2.90 to 6.10 and day-21 SMD 2.53, 95% CI 1.25 to 3.80). No significant difference in wound healing was observed between 32 diabetic and 32 non-diabetic animals with ischemic wounds. Many studies lacked methods to reduce bias, such as outcome assessors blinded to group allocation and sample size calculations and clinically relevant model characteristics, such as use of older animals and a peripheral location of the wound. Five different interventions were reported to improve wound healing in these models. The impaired wound healing associated with limb ischemia can be modeled in a variety of different animals. Improvements in study design could increase clinical relevance, reduce bias and aid the discovery of translatable therapies.
Increased cardiovascular risk and reduced quality of life are highly prevalent among individuals with hepatitis C
Authors: McPherson Stuart , Gosrani Shion , Hogg Sarah , Patel Preya , Wetten Aaron , Welton Rachael , Hallsworth Kate , Campbell Matthew
Published: August 2020

Objective

Hepatitis C virus (HCV) infection is common. Although treatment is effective, with oral antivirals curing >95% of patients, most individuals have comorbidities that persist long term. Therefore, our aim was to determine the prevalence of potentially modifiable health problems in patients with HCV and develop an HCV care bundle to identify and target comorbidities.

Design

Cross-sectional, observational single-centre study that recruited consecutive patients with HCV from our viral hepatitis clinics. Data were collected on cardiovascular (CV) risk factors, lifestyle behaviours, anthropometry and health-related quality of life (HRQoL). QRISK 3 was used to predict 10-year CV event risk.

Results

100 patients were recruited (67% male, 93% white, median age 52 years (range 24–80); 71% were treated for HCV; 34% had cirrhosis; 14% had diabetes; 61% had hypertension; 31% had metabolic syndrome; and 54% were smokers). The median 10-year CV event risk was 8.3% (range 0.3%–63%). 45% had a predicted 10-year CV event risk of >10%. Only 10% of individuals were treated with statins and 27% with antihypertensives. 92% had a predicted ‘heart age’ greater than their chronological age (median difference +7 (−4 to +26) years). HRQoL was reduced in all SF36v2 domains in the cohort. Factors independently associated with HRQoL included cirrhosis, metabolic syndrome, history of mental health disorder, sedentary behaviour and HCV viraemia.

Conclusion

A large proportion of patients with HCV presented with increased risk of CV events, and rates of smoking and sedentary behaviour were high, while prescribing of primary prophylaxis was infrequent. HRQoL was also reduced in the cohort. A ‘care bundle’ was developed to provide a structured approach to treating potentially modifiable health problems.
Implementation of health and health-related sustainable development goals: progress, challenges and opportunities – a systematic literature review
Authors: Aftab Wafa , Siddiqui Fahad Javaid , Tasic Hana , Perveen Shagufta , Siddiqi Sameen , Bhutta Zulfiqar Ahmed
Published: August 2020

Introduction

While health is one of the Sustainable Development Goals (SDGs), many other ‘health-related’ goals comprise determinants of health. Integrated implementation across SDGs is needed for the achievement of Agenda 2030. While existing literature is rich in normative recommendations about potentially useful approaches, evidence of implementation strategies being adopted by countries is limited.

Methods

We conducted a systematic review with qualitative synthesis of findings using peer reviewed and grey literature from key databases. We included publications examining implementation of health and health-related SDGs (HHSDGs) at national or subnational level published between June 2013 and July 2019.

Results

Of the 32 included publications, 24 provided information at the national level while eight provided information for multiple countries or regions. Our findings indicate that high-level political commitment is evident in most countries and HHSDGs are being aligned with existing national development strategies and plans. A multisectoral, integrated approach is being adopted in institutional setups but evidence on effectiveness of these approaches is limited. Funding constraints are a major challenge for many countries. HHSDGs are generally being financed from within existing funded plans and, in some instances, through SDG-specific budgeting and tracking; additional funding is being mobilised by increasing domestic taxation and subsidisation, and by collaborating with development partners and private sector. Equity is being promoted by improving health service access through universal health coverage and social insurance schemes, especially for disadvantaged populations. Governments are collaborating with development partners and UN agencies for support in planning, institutional development and capacity building. However, evidence on equity promotion, capacity building initiatives and implementation approaches at subnational level is limited. Lack of coordination among various levels of government emerges as a key challenge.

Conclusion

strengthening implementation of multisectoral work, capacity building, financial sustainability and data availability are key considerations to accelerate implementation of HHSDGs.
Associations between maternal age and socioeconomic status with smoking during the second and third trimesters of pregnancy: a register-based study of 932 671 women in Finland from 2000 to 2015
Authors: Roustaei Zahra , Räisänen Sari , Gissler Mika , Heinonen Seppo
Published: August 2020

Objectives

This study aimed to explore the association between maternal age and smoking during the second and third trimesters of pregnancy across socioeconomic groups and to evaluate the interacting effect of maternal age and socioeconomic status on smoking with a view to informing public health interventions.

Design

This is a register-based study.

Settings

Data from the Finnish Medical Birth Register were cross-linked with background data from Statistics Finland.

Participants

The information of 932 671 pregnant women who gave birth in Finland from 2000 to 2015.

Main outcome measures

Maternal smoking during the second and third trimesters of pregnancy by occupation and maternal age.

Results

The proportion of women who smoked during the second and third trimesters of pregnancy was 10.5%. Using women 30–34 years as the reference group, adjusted ORs (aOR) and 95% CIs for smoking were 6.02 (5.81 to 6.24) in women below 20 years and 2.77 (2.71 to 2.84) in women 20 to 24 years. The prevalence of smoking across socioeconomic groups compared with upper-level employees increased, peaking for women in manual occupations (aOR 3.39, 95% CI 3.25 to 3.52) and unemployed women (aOR 4.49, 95% CI 4.30 to 4.68). Significant interactions on the additive scale with the relative excess risk due to interaction >2 were found for unemployed women aged 25–29 years and for teenage mothers and mothers aged 20–24 years across all socioeconomic groups, but not for self-employed women.

Conclusions

Smoking during the second and third trimesters of pregnancy was most common among teenage mothers across all socioeconomic groups. The association between maternal age and smoking differed by socioeconomic status for young mothers. Interventions should address a wider range of maternal risk factors among young mothers with low socioeconomic status and simultaneously target a broader number of women who smoke during the pregnancy.
Current provision of myelopathy education in medical schools in the UK: protocol for a national medical student survey
Authors: Mowforth Oliver , Davies Benjamin , Stewart Max , Smith Sam , Willison Alice , Ahmed Shahzaib , Starkey Michelle , Sadler Iwan , Sarewitz Ellen , Stacpoole Sybil , Kotter Mark
Published: August 2020

Introduction

Degenerative cervical myelopathy (DCM) is a common, disabling and progressive neurological condition triggered by chronic compression of the cervical spinal cord by surrounding degenerative changes. Early diagnosis and specialist management are essential to reduce disability, yet time to diagnosis is typically prolonged. Lack of sufficient representation of DCM in undergraduate and postgraduate medical curricula may contribute to the poor recognition of DCM by non-specialist doctors in clinical practice.

In this study, our objective, therefore, is to assess DCM teaching provision in medical schools throughout the UK and to assess the impact of teaching on the DCM knowledge of UK medical students.

Methods and analysis

A 19-item questionnaire capturing data on medical student demographics, myelopathy teaching and myelopathy knowledge was designed. Ethical approval was granted by the Psychology Research Ethics Committee, University of Cambridge. An online survey was hosted on Myelopathy.org, an international myelopathy charity. Students studying at a UK medical school are eligible for inclusion. The survey is advertised nationally through university social media pages, university email bulletins and the national student network of Myelopathy.org. Advertisements are scheduled monthly over a 12-month recruitment period. Participation is incentivised by entering consenting participants of completed surveys to an Amazon voucher prize draw. Responses are anonymised using participant-chosen unique identifier codes. A participant information sheet followed by an explicit survey question captures participant informed consent. Regular updates on the progress of the study will be published on Myelopathy.org.

Ethics and Dissemination

Ethical approval for the study was granted by the Psychology Research Ethics Committee, University of Cambridge (PRE.2018.099). The findings of the study described in this protocol, and all other related work, will be submitted for publication in a peer-reviewed journal and will be presented at scientific conferences.
What are the elements of a whole system approach to community-centred public health? A qualitative study with public health leaders in England’s local authority areas
Authors: Stansfield Jude , South Jane , Mapplethorpe Tom
Published: August 2020

Objectives

The aim of the study was to identify key elements of whole system approaches to building healthy communities and putting communities at the heart of public health with a focus on public health practice to reduce health inequalities.

Design

A mixed-method qualitative study was undertaken. The primary method was semi-structured interviews with 17 public health leaders from 12 local areas. This was supplemented by a rapid review of literature, a survey of 342 members of the public via Public Health England’s (PHE) People’s Panel and a round-table discussion with 23 stakeholders.

Setting

Local government in England.

Results

Eleven elements of community-centred public health practice that constitute taking a whole system approach were identified. These were grouped into the headings of involving, strengthening, scaling and sustaining. The elements were underpinned by a set of values and principles.

Conclusion

Local public health leaders are in a strong position to develop a whole system approach to reducing health inequalities that puts communities at its heart. The elements, values and principles summarise what a supportive infrastructure looks like and this could be further tested with other localities and communities as a framework for scaling community-centred public health.
Health impacts and environmental footprints of diets that meet the Eatwell Guide recommendations: analyses of multiple UK studies
Authors: Scheelbeek Pauline , Green Rosemary , Papier Keren , Knuppel Anika , Alae-Carew Carmelia , Balkwill Angela , Key Timothy J , Beral Valerie , Dangour Alan D
Published: August 2020

Objectives

To assess the health impacts and environmental consequences of adherence to national dietary recommendations (the Eatwell Guide (EWG)) in the UK.

Design and setting

A secondary analysis of multiple observational studies in the UK.

Participants

Adults from the European Prospective Investigation into Cancer - Oxford(EPIC-Oxford), UK Biobank and Million Women Study, and adults and children aged 5 and over from the National Diet and Nutrition Survey (NDNS).

Primary and secondary outcome measures risk of total mortality from Cox proportional hazards regression models, total greenhouse gas emissions (GHGe) and blue water footprint (WF) associated with ‘very low’ (0–2 recommendations), ‘low’ (3–4 recommendations) or ‘intermediate-to-high’ (5–9 recommendations) adherence to EWG recommendations.

Results

Less than 0.1% of the NDNS sample adhere to all nine EWG recommendations and 30.6% adhere to at least five recommendations. Compared with ‘very low’ adherence to EWG recommendations, ‘intermediate-to-high adherence’ was associated with a reduced risk of mortality (risk ratio (RR): 0.93; 99% CI: 0.90 to 0.97) and −1.6 kg CO2eq/day (95% CI: −1.5 to −1.8), or 30% lower dietary GHGe. Dietary WFs were similar across EWG adherence groups. Of the individual Eatwell guidelines, adherence to the recommendation on fruit and vegetable consumption was associated with the largest reduction in total mortality risk: an RR of 0.90 (99% CI: 0.88 to 0.93). Increased adherence to the recommendation on red and processed meat consumption was associated with the largest decrease in environmental footprints (−1.48 kg CO2eq/day, 95% CI: −1.79 to 1.18 for GHGe and −22.5 L/day, 95% CI: −22.7 to 22.3 for blue WF).

Conclusions

The health and environmental benefits of greater adherence to EWG recommendations support increased government efforts to encourage improved diets in the UK that are essential for the health of people and the planet in the Anthropocene.
Cumulative social disadvantage and hospitalisations due to ambulatory care-sensitive conditions in Finland in 2011─2013: a register study
Authors: Lumme Sonja , Manderbacka Kristiina , Arffman Martti , Karvonen Sakari , Keskimaki Ilmo
Published: August 2020

Objectives

To study the interplay between several indicators of social disadvantage and hospitalisations due to ambulatory care-sensitive conditions (ACSC) in 2011─2013. To evaluate whether the accumulation of preceding social disadvantage in one point of time or prolongation of social disadvantage had an effect on hospitalisations due to ACSCs. Four common indicators of disadvantage are examined: living alone, low level of education, poverty and unemployment.

Design

A population-based register study.

Setting

Nationwide individual-level register data on hospitalisations due to ACSCs for the years 2011–2013 and preceding data on social and socioeconomic factors for the years 2006─2010.

Participants

Finnish residents aged 45 or older on 1 January 2011.

Outcome measure

Hospitalisations due to ACSCs in 2011–2013. The effect of accumulation of preceding disadvantage in one point of time and its prolongation on ACSCs was studied using modified Poisson regression.

Results

People with preceding cumulative social disadvantage were more likely to be hospitalised due to ACSCs. The most hazardous combination was simultaneously living alone, low level of education and poverty among the middle-aged individuals (aged 45–64 years) and the elderly (over 64 years). Risk ratio (RR) of being hospitalised due to ACSC was 3.16 (95% CI 3.03–3.29) among middle-aged men and 3.54 (3.36–3.73) among middle-aged women compared with individuals without any of these risk factors when controlling for age and residential area. For the elderly, the RR was 1.61 (1.57–1.66) among men and 1.69 (1.64–1.74) among women.

Conclusions

To improve social equity in healthcare, it is important to recognise not only patients with cumulative disadvantage but also—as this study shows—patients with particular combinations of disadvantage who may be more susceptible. The identification of these vulnerable patient groups is also necessary to reduce the use of more expensive treatment in specialised healthcare.
Insulin glucose infusion versus nebulised salbutamol versus combination of salbutamol and insulin glucose in acute hyperkalaemia in the emergency room: protocol for a randomised, multicentre, controlled study (INSAKA)
Authors: Montassier Emmanuel , Lemoine Loic , Hardouin Jean Benoit , Rossignol Patrick , Legrand Matthieu
Published: August 2020

Introduction

Hyperkalaemia is a common electrolyte disorder and can be life-threatening. In the emergency room (ER), interventions aim to protect patients from the immediate dangers of elevated serum potassium by redistributing potassium ions from the bloodstream into the cells via intravenous insulin or nebulised beta2-agonists. However, to date, evidence for acute management of hyperkalaemia is limited. The aim of this randomised controlled trial is therefore to compare three strategies, namely insulin/glucose intravenous infusion, nebulised salbutamol or a combination of nebulised salbutamol and insulin/glucose intravenous infusion to reduce serum potassium concentration at 60 min as a first-line treatment in patients admitted to the ER with serum potassium concentrations superior or equal to 6 mmol/L.

Methods and analysis

INSAKA is a prospective, multicentre, controlled, open-label, parallel-group, randomised in a 1:1:1 ratio clinical trial. Patients will be eligible for randomisation if they have serum potassium concentrations superior or equal to 6 mmol/L measured in the ER. Patients will receive either: (1) 10 mg of nebulised salbutamol, (2) 10 units of short-acting insulin in an intravenous bolus with 500 mL of 10% glucose or (3) 10 units of short-acting insulin in an intravenous bolus with 500 mL of 10% glucose combined with 10 mg of nebulised salbutamol. The primary endpoint will be the mean change in the absolute serum potassium level from baseline to 60 min measured in mmol/L. We plan to include 525 patients.

Ethics and dissemination

The INSAKA trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practices. All trial documents and procedures have been reviewed and approved by the Ethics Committee Sud Méditerranée III (approval ID number: 19.07.16.36428). The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, broadcast media, print media and the internet.

Trial registration

EudraCT number: 2019-002710-39, Clinicaltrials.gov identifier: NCT04012138.
Systematic mixed-method review of barriers to end-of-life communication in the family context
Authors: Nagelschmidt Katharina , Leppin Nico , Seifart Carola , Rief Winfried , von Blanckenburg Pia
Published: August 2020

Background

Communication about the end of life is especially important in the family context, as patients and their families are considered as the care unit in palliative care. Open end-of-life communication can positively affect medical, psychological and relational outcomes during the dying process for patient and family. Regardless of the benefits of end-of-life conversations, many patients and their family caregivers speak little about relevant end-of-life issues.

Aim

To identify barriers that hinder or influence the discussion of end-of-life issues in the family context.

Design

A systematic mixed-method review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Data sources

A systematic search of PsycInfo, CINAHL, PubMed and Web of Science was conducted and extended with a hand search. Peer-reviewed primary studies reporting on the barriers to or difficulties in end-of-life conversations experienced by terminally ill patients and/or family caregivers were included in this review.

Results

18 qualitative and two quantitative studies met the inclusion criteria. The experiences of n=205 patients and n=738 family caregivers were analysed qualitatively; n=293 patients and n=236 caregivers were surveyed in the questionnaire studies. Five overarching categories emerged from the extracted data: emotional, cognitive, communicative, relational and external processes can hinder end-of-life communication within the family. The most frequently reported barriers are emotional and cognitive processes such as protective buffering or belief in positive thinking.

Conclusions

Research on end-of-life communication barriers in the family context is scarce. Further research should enhance the development of appropriate assessment tools and interventions to support families with the challenges experienced regarding end-of-life conversations.
How do early-life adverse childhood experiences mediate the relationship between childhood socioeconomic conditions and adolescent health outcomes in the UK?
Authors: Straatmann Viviane S , Lai Eric , Law Catherine , Whitehead Margaret , Strandberg-Larsen Katrine , Taylor-Robinson David
Published: August 2020

Background

Both adverse childhood experiences (ACEs) and adverse childhood socioeconomic conditions (SECs) in early life are associated with poor outcomes across the life course. However, the complex interrelationships between childhood SECs and ACEs are unclear, as are the consequences for health outcomes beyond childhood. We therefore assessed the extent to which early-life ACEs mediate the relationship between SECs and socioemotional behavioural problems, cognitive disability and overweight/obesity in adolescence.

Methods

We used longitudinal data from the UK Millennium Cohort Study (MSC). Outcomes assessed at age 14 were socioemotional behavioural problems, cognitive disability and overweight/obesity. SECs at birth were measured by maternal education. Potentially mediating ACEs measured up to 5 years were verbal and physical maltreatment, parental drug use, domestic violence, parental divorce, maternal mental illness and high frequency of parental alcohol use. We used counterfactual mediation analysis to assess the extent to which ACEs mediate the association between SECs at birth and behavioural, cognitive and physical outcomes at age 14, estimating total (TE), natural direct and indirect effects, and mediated proportions.

Results

Children with disadvantaged SECs were more likely to have socioemotional behavioural problems (relative risk (RR) 3.85, 95% CI 2.48 to 5.97), cognitive disability (RR 3.87, 95% CI 2.33 to 6.43) and overweight/obesity (RR 1.61, 95% CI 1.32 to 1.95), compared to those with more advantaged SECs. Overall, 18% of the TE of SECs on socioemotional behavioural problems was mediated through all ACEs investigated. For cognitive disability and overweight/obese, the proportions mediated were 13% and 19%, respectively.

Conclusion

ACEs measured up to age 5 years in the MCS explained about one-sixth of inequalities in adolescents behavioural, cognitive and physical outcomes.
Durvalumab activity in previously treated patients who stopped durvalumab without disease progression
Authors: Sheth Siddharth , Gao Chen , Mueller Nancy , Angra Natasha , Gupta Ashok , Germa Caroline , Martinez Pablo , Soria Jean-Charles
Published: August 2020

Background

Limited data exist on potential clinical benefit with anti-programmed cell death ligand-1 (PD-L1) retreatment in patients who stop initial therapy for reasons other than disease progression or toxicity and develop disease progression while off treatment.

Patients and methods

NCT01693562 was a phase I/II study evaluating durvalumab monotherapy in advanced solid tumors. Patients benefiting from treatment were taken off durvalumab at 1 year per protocol and prospectively followed. At disease progression, they were eligible for durvalumab retreatment. Outcomes evaluated during retreatment included best overall response (BOR2), duration of response (DoR2), disease control rate (DCR2), and progression-free survival (PFS2).

Results

Of 980 patients enrolled and treated with durvalumab 10 mg/kg every 2 weeks (Q2W) in the dose-expansion cohorts, 168 completed 1 year of initial durvalumab treatment with confirmed BOR1 of complete response in 20 (11.9%), partial response (PR) in 84 (50%), stable disease (SD) in 52 (31%), and disease progression in 12 (7.1%). All 168 patients stopped treatment and were eligible for retreatment at progression; 70 patients (41.7%) representing 14 primary tumor types were retreated and response evaluable. Confirmed BOR2 was PR in 8 patients (11.4%), SD in 42 (60.0%), disease progression in 16 (22.9%), and unevaluable in 4 (5.7%). Median DoR2 was 16.5 months. DCR2 ≥24 weeks (DCR2 24) was 47.1%. PFS2 rate at 12 months was 34.2%, and median PFS2 was 5.9 months. Median overall survival (OS2) was 23.8 months. Response rates, DCR2 24, and median DoR2 were generally greater in patients with high PD-L1 expression than those with low/negative expression. No new safety signals were observed during retreatment.

Conclusion

Retreatment restored antitumor activity, resulting in high rates of durable disease control with an acceptable safety profile. This evidence supports retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity, and supports further investigation.
Guillain-Barré syndrome after adoptive cell therapy with tumor-infiltrating lymphocytes
Authors: Orcurto Angela , Hottinger Andreas , Wolf Benita , Navarro Rodrigo Blanca , Ochoa de Olza Maria , Auger Aymeric , Kuntzer Thierry , Comte Denis , Zimmer Virginie , Gannon Philippe , Kandalaft Lana , Michielin Olivier , Zimmermann Stefan , Harari Alexandre , Trueb Lionel , Coukos George
Published: August 2020

Background

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising experimental immunotherapy that has shown high objective responses in patients with melanoma. Current protocols use a lymphodepletive chemotherapy before infusion of ex vivo expanded TILs, followed by high-dose interleukin-2 (IL-2). Treatment-related toxicities are mainly attributable to the chemotherapy regimen and to the high-dose IL-2 and are generally reversible. Neurological side effects have rarely been described. Nevertheless, due to improvements in cell production techniques and due to combinations with other immunomodulating molecules, side effects not previously described may be encountered.

Case presentation

We report the case of a 53-year-old heavily pretreated patient with melanoma who developed Guillain-Barré syndrome (GBS) 19 days after ACT using autologous TILs, given in the context of a phase I trial. He presented with dorsal back pain, unsteady gait and numbness in hands and feet. Lumbar puncture showed albuminocytological dissociation, and nerve conduction studies revealed prolonged distal motor latencies in median, ulnar, tibial and peroneal nerves, compatible with a GBS. The patient was treated with intravenous immunoglobulins and intensive neurological rehabilitation, with progressive and full recovery at 21 months post-TIL-ACT. Concomitant to the onset of GBS, a cytomegalovirus reactivation on immunosuppression was detected and considered as the most plausible cause of this neurological side effect.

Conclusion

We describe for the first time a case of GBS occurring shortly after TIL-ACT for melanoma, even though we could not identify with certainty the triggering agent. The report of such rare cases is of extreme importance to build on the knowledge of immune cellular therapies and their specific spectrum of toxicities.
Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity
Authors: Lemos Henrique , Ou Rong , McCardle Caroline , Lin Yijun , Calver Jessica , Minett Jack , Chadli Ahmed , Huang Lei , Mellor Andrew L
Published: August 2020

Background

Activating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors.

Methods

Mice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways.

Results

CDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity.

Conclusions

STING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.
Exposure to additives or multigrain flour is associated with high risk of work-related allergic symptoms among bakers
Authors: Olivieri Mario , Murgia Nicola , Spiteri Gianluca , Biscardo Carlo Alberto , Marchetti Pierpaolo , Folletti Ilenia , Verlato Giuseppe
Published: August 2020

Objectives

Wheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved.

Methods

Of the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010–2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models.

Results

The prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected.

Conclusions

Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.
Short-term effects of outdoor air pollution on acute ischaemic stroke occurrence: a case-crossover study in Tianjin, China
Authors: Qi Xuemei , Wang Zhongyan , Guo Xiaokun , Xia Xiaoshuang , Xue Juanjuan , Jiang Guojing , Gu Yumeng , Han Suqin , Yao Qing , Cai Ziying , Wang Xiaojia , Wang Lin , Leng Sean X , Li Xin
Published: August 2020

Objective

Ambient air pollution is associated with ischaemic stroke incidence. However, most of the previous studies used stroke-related hospital admission rather than stroke onset itself. This study aimed to evaluate the relationship between ambient air pollutant exposures and acute ischaemic stroke based on the timing of symptom onset.

Methods

A time-stratified, case-crossover analysis was performed among 520 patients who had ischaemic stroke admitted to the Second Hospital of Tianjin Medical University (Tianjin, China) between 1 April 2018 and 31 March 2019 (365 days). Daily air pollutant concentrations of particulate matter with aerodynamic diameter 2.5 µm, particulate matter with aerodynamic diameter 10 µm (PM10), sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone were obtained from fixed-site monitoring stations. We used conditional logistic regression to estimate OR and 95% CI corresponding to an increase in IQR of each air pollutant after adjusting for the effects of temperature and relative humidity.

Results

Overall, a higher risk of ischaemic stroke was found between April and September. During this period PM10 was associated with an increased risk of ischaemic stroke (1-day lag: OR=1.49, 95% CI 1.09 to 2.02; 3-day mean: OR=1.58, 95% CI 1.09 to 2.29) among patients between 34 and 70 years old. Positive associations were also observed between PM10 (1-day lag: OR=1.51, 95% CI 1.10 to 2.07; 3-day mean: OR=1.57, 95% CI 1.08 to 2.29), ozone (1-day lag: OR=1.83, 95% CI 1.16 to 2.87; 3-day mean: OR=1.90, 95% CI 1.06 to 3.42) and ischaemic stroke occurrence among those with hyperlipidaemia.

Conclusion

Our results suggest that air pollution is associated with a higher risk of ischaemic stroke in younger people or people with hyperlipidemia. These findings still need to be further investigated.
The impact of the COVID-19 pandemic on cardiology services
Authors: Fersia Omar , Bryant Sue , Nicholson Rachael , McMeeken Karen , Brown Carolyn , Donaldson Brenda , Jardine Aaron , Grierson Valerie , Whalen Vanessa , Mackay Alistair
Published: August 2020

Objective

The COVID-19 pandemic resulted in prioritisation of National Health Service (NHS) resources to cope with the surge in infected patients. However, there have been no studies in the UK looking at the effect of the COVID-19 work pattern on the provision of cardiology services. We aimed to assess the impact of the pandemic on cardiology services and clinical activity.

Methods

We analysed key performance indicators in cardiology services in a single centre in the UK in the periods prior to and during lockdown to assess reduction or changes in service provision.

Results

There has been a greater than 50% drop in the number of patients presenting to cardiology and those diagnosed with myocardial infarction. All areas of cardiology service provision sustained significant reductions, which included outpatient clinics, investigations, procedures and cardiology community services such as heart failure and cardiac rehabilitation.

Conclusions

As ischaemic heart disease continues to be the leading cause of death nationally and globally, cardiology services need to prepare for a significant increase in workload in the recovery phase and develop new pathways to urgently help those adversely affected by the changes in service provision.
Descriptive neuroradiology: beyond the hummingbird
Authors: Page Inna , Gaillard Frank
Published: August 2020

Radiology signs have long been described in ways that communicate the imagery around us to enhance our cognitive perception. Here, we describe the use and limitations of 10 such signs in neuroradiology, divided into three groups. The first are signs that are reliable for a specific diagnosis, such as the Medusa head sign indicating a developmental venous anomaly, or a racing car sign in agenesis of corpus callosum. The second group of signs helps us to diagnose rare conditions, such as the onion skin sign in Balo’s concentric sclerosis. The third group is of unreliable signs that may lead clinicians astray. For example, the absence of a swallow-tail sign in Parkinson’s disease or the presence of a hummingbird sign and Mickey Mouse sign in progressive supranuclear palsy. The appropriate use of these signs in clinical practice is essential.
Duodenal duplication cyst masquerading as a pancreatic abscess in a cat
Authors: Tryon Emily , Kalamaras Alexandra , Yang Ching , Wavreille Vincent , Selmic Laura Elizabeth
Published: August 2020

This report details a cat with a duodenal duplication cyst in the region of the right distal pancreas. The cat presented with vomiting, anorexia, pancreatitis and a palpable abdominal mass that was visible on abdominal ultrasound as a thick‐rimmed, cavitated structure with echogenic contents. As such, an initial clinical diagnosis of pancreatic abscess or cyst was suspected. After an exploratory coeliotomy to assess the lesion, a definitive diagnosis of duodenal duplication cyst was determined based on the histopathological findings of a wall with features of the intestinal tract and no communication with the intestinal lumen. The clinical signs, physical examination findings and advanced imaging characteristics of pancreatic abscess and duodenal duplication cyst are discussed in this report to aid clinicians with differentiating between these two rare lesions.
Genotyping by sequencing for SNP marker development in onion
Authors: Labate Joanne A. , Glaubitz Jeffrey C. , Havey Michael J.
Published: August 2020

Onion (Allium cepa) is not highly tractable for development of molecular markers due to its large (16 gigabases per 1C) nuclear genome. Single nucleotide polymorphisms (SNPs) are useful for genetic characterization and marker-aided selection of onion because of codominance and common occurrence in elite germplasm. We completed genotyping by sequencing (GBS) to identify SNPs in onion using 46 F2plants, parents of the F2plants (Ailsa Craig 43 and Brigham Yellow Globe 15-23), two doubled haploid (DH) lines (DH2107 and DH2110), and plants from 94 accessions in the USDA National Plant Germplasm System (NPGS). SNPs were called using the TASSEL 3.0 Universal Network Enabled Analysis (UNEAK) bioinformatics pipeline. Sequences from the F2and DH plants were used to construct a pseudo-reference genome against which genotypes from all accessions were scored. Quality filters were used to identify a set of 284 high quality SNPs, which were placed onto an existing genetic map for the F2family. Accessions showed a moderate level of diversity (mean He= 0.341) and evidence of inbreeding (mean F = 0.592). GBS is promising for SNP discovery in onion, although lack of a reference genome required extensive custom scripts for bioinformatics analyses to identify high quality markers.
Energy resolution and linearity of XENON1T in the MeV energy range
Authors: Aprile E. , Aalbers J. , Agostini F. , Alfonsi M. , Althueser L. , Amaro F. D. , Antochi V. C. , Angelino E. , Angevaare J. , Arneodo F. , Barge D. , Baudis L. , Bauermeister B. , Bellagamba L. , Benabderrahmane M. L. , Berger T. , Breur P. A. , Brown A. , Brown E. , Bruenner S. , Bruno G. , Budnik R. , Capelli C. , Cardoso J. M. R. , Cichon D. , Cimmino B. , Clark M. , Coderre D. , Colijn A. P. , Conrad J. , Cussonneau J. P. , Decowski M. P. , Depoian A. , Di Gangi P. , Di Giovanni A. , Di Stefano R. , Diglio S. , Elykov A. , Eurin G. , Ferella A. D. , Fulgione W. , Gaemers P. , Gaior R. , Rosso A. Gallo , Galloway M. , Gao F. , Garbini M. , Grandi L. , Hasterok C. , Hils C. , Hiraide K. , Hoetzsch L. , Hogenbirk E. , Howlett J. , Iacovacci M. , Itow Y. , Joerg F. , Kato N. , Kazama S. , Kobayashi M. , Koltman G. , Kopec A. , Landsman H. , Lang R. F. , Levinson L. , Lin Q. , Lindemann S. , Lindner M. , Lombardi F. , Lopes J. A. M. , Fune E. López , Macolino C. , Mahlstedt J. , Manenti L. , Manfredini A. , Marignetti F. , Undagoitia T. Marrodán , Martens K. , Masbou J. , Masson D. , Mastroianni S. , Messina M. , Miuchi K. , Molinario A. , Morå K. , Moriyama S. , Mosbacher Y. , Murra M. , Naganoma J. , Ni K. , Oberlack U. , Odgers K. , Palacio J. , Pelssers B. , Peres R. , Pienaar J. , Pizzella V. , Plante G. , Qin J. , Qiu H. , García D. Ramírez , Reichard S. , Rocchetti A. , Rupp N. , dos Santos J. M. F. , Sartorelli G. , Šarčević N. , Scheibelhut M. , Schindler S. , Schreiner J. , Schulte D. , Schumann M. , Lavina L. Scotto , Selvi M. , Semeria F. , Shagin P. , Shockley E. , Silva M. , Simgen H. , Takeda A. , Therreau C. , Thers D. , Toschi F. , Trinchero G. , Tunnell C. , Vargas M. , Volta G. , Wack O. , Wang H. , Wei Y. , Weinheimer C. , Xu M. Weiss , Wenz D. , Wittweg C. , Wulf J. , Xu Z. , Yamashita M. , Ye J. , Zavattini G. , Zhang Y. , Zhu T. , Zopounidis J. P.
Published: August 2020

Xenon dual-phase time projection chambers designed to search for weakly interacting massive particles have so far shown a relative energy resolution which degrades with energy above $$\sim $$∼ 200 keV due to the saturation effects. This has limited their sensitivity in the search for rare events like the neutrinoless double-beta decay of $$^{136} \hbox {Xe}$$136Xe at its Q value, $$Q_{\beta \beta }\simeq 2.46\,\hbox {MeV}$$Qββ≃2.46MeV. For the XENON1T dual-phase time projection chamber, we demonstrate that the relative energy resolution at $$1\,\sigma /\mu $$1σ/μ is as low as ($$0.80 \pm 0.02$$0.80±0.02) % in its one-ton fiducial mass, and for single-site interactions at $$Q_{\beta \beta }$$Qββ. We also present a new signal correction method to rectify the saturation effects of the signal readout system, resulting in more accurate position reconstruction and indirectly improving the energy resolution. The very good result achieved in XENON1T opens up new windows for the xenon dual-phase dark matter detectors to simultaneously search for other rare events.
Dust content solutions for the Alcubierre warp drive spacetime
Authors: Santos-Pereira Osvaldo L. , Abreu Everton M. C. , Ribeiro Marcelo B.
Published: August 2020

The Alcubierre metric is a spacetime geometry where a massive particle inside a spacetime distortion, called warp bubble, is able to travel at velocities arbitrarily higher than the velocity of light, a feature known as the warp drive. This is a consequence of general relativity, which allows for global superluminal velocities but restricts local speeds to subluminal ones as required by special relativity. In this work we solved the Einstein equations for the Alcubierre warp drive spacetime geometry considering the dust matter distribution as source, since the Alcubierre metric was not originally advanced as a solution of the Einstein equations, but as a spacetime geometry proposed without a source gravity field. We found that all Einstein equations solutions of this geometry containing pressureless dust lead to vacuum solutions. We also concluded that these solutions connect the Alcubierre metric to the Burgers equation, which describes shock waves moving through an inviscid fluid. Our results also indicated that these shock waves behave as plane waves.
Static wormhole solutions and Noether symmetry in modified Gauss–Bonnet gravity
Authors: Sharif M. , Nawazish Iqra , Hussain Shahid
Published: August 2020

In this paper, we analyze static traversable wormholes via Noether symmetry technique in modified Gauss–Bonnet $$f(\mathcal {G})$$f(G) theory of gravity (where $$\mathcal {G}$$G represents Gauss–Bonnet term). We assume isotropic matter configuration and spherically symmetric metric. We construct three $$f(\mathcal {G})$$f(G) models, i.e, linear, quadratic and exponential forms and examine the consistency of these models. The traversable nature of wormhole solutions is discussed via null energy bound of the effective stress–energy tensor while physical behavior is studied through standard energy bounds of isotropic fluid. We also discuss the stability of these wormholes inside the wormhole throat and conclude the presence of traversable and physically stable wormholes for quadratic as well as exponential $$f(\mathcal {G})$$f(G) models.