bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life analysis of patients treated with cetuximab or cisplatin for locoregionally advanced squamous cell carcinoma of head and neck in the United States
Authors: Aggarwal Himani , Punekar Rajeshwari S. , Li Li , Carter Gebra Cuyun , Walker Mark S.
Published: June 2020

Background

To compare quality of life of patients treated with cetuximab with or without radiation therapy (±RT) vs. cisplatin±RT for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) in the real-world setting.

Methods

In this retrospective observational study, electronic medical records and Patient Care Monitor (PCM) survey data from the Vector Oncology Data Warehouse were utilized from adult patients in the United States who received initial treatment with cetuximab±RT or cisplatin±RT for locoregionally advanced SCCHN between January 1, 2007 and January 1, 2017. Quality of life was assessed using PCM index scores and individual PCM items. Cetuximab±RT and cisplatin±RT cohorts were balanced using propensity score weighting. Linear mixed models were used to assess the impact of baseline demographic and clinical characteristics on PCM endpoints.

Results

Of 531 patients with locoregionally advanced SCCHN, 187 received cetuximab±RT, and 344 received cisplatin±RT. Before propensity score weighting, the cetuximab±RT cohort was older (mean [SD] age of 63.9 [9.6] years vs. 57.4 [8.6] years), and more likely to be white (82.4% vs. 72.4%) compared to the cisplatin±RT cohort. After propensity score weighting, the two cohort subsamples (cetuximab±RT, N = 60; cisplatin±RT, N = 177) with PCM data showed no significant differences in General Physical Symptoms, Treatment Side Effects, Impaired Ambulation, or Impaired Performance index scores. Patients in the cetuximab±RT cohort had higher Acute Distress index (p = 0.023), Despair index (p = 0.011), and rash (p = 0.003) scores but lower numbness/tingling scores (p = 0.022) than patients in the cisplatin±RT cohort.

Conclusions

Significant group differences were observed in this comparative analysis, as the cetuximab±RT cohort had significantly higher Acute Distress index, Despair index, and rash scores compared with the cisplatin±RT cohort but lower numbness/tingling scores. These patterns of symptoms appear consistent with previously reported symptoms associated with the treatment of SCCHN.
The role of physical activity in cancer survivors’ quality of life
Authors: Liska Tayah M. , Kolen Angela M.
Published: June 2020

Purpose

As a result of a cancer diagnosis and treatment, many cancer survivors experience persistent physical, mental, and emotional symptoms that affect their quality of life. Physical activity has been identified as an intervention that may help to manage the side effects of a cancer diagnosis and its treatment. The purpose of this study was to investigate the role of physical activity on overall quality of life in adult cancer survivors.

Methods

One-on-one semi-structured interviews were conducted in person or via telephone with 13 adult (≥18 yrs) cancer survivors who had completed cancer treatment.

Results

These cancer survivors described their physical activity as improving their physical functioning and mental health, as a means of positive social engagement, and adding positivity to their daily life.

Conclusion

Even though the cancer survivors in this study experienced diverse types of cancer and for different lengths of time as well as varying methods of treatment(s), these results support the role of physical activity in enhancing cancer survivors’ quality of life. Further research is warranted to (a) expand this research with a larger sample and quantitative methods, (b) examine healthcare providers’ knowledge and application of exercise guidelines to cancer survivors in cancer care, and (c) explore implementation strategies for greater advocacy for healthcare providers to share the exercise recommendations with cancer survivors.
Clinical impacts of resection margin status and clinicopathologic parameters on pancreatic ductal adenocarcinoma
Authors: Jamiyan Tsengelmaa , Shiraki Takayuki , Kurata Yoshihiro , Ichinose Masanori , Kubota Keiichi , Imai Yasuo
Published: June 2020

Background

The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters.

Patients and methods

We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher’s exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis.

Results

Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter.

Conclusions

PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients’ overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis.
How to strengthen a health research system: WHO’s review, whose literature and who is providing leadership?
Authors: Hanney Stephen R. , Kanya Lucy , Pokhrel Subhash , Jones Teresa H. , Boaz Annette
Published: June 2020

Background

Health research is important for the achievement of the Sustainable Development Goals. However, there are many challenges facing health research, including securing sufficient funds, building capacity, producing research findings and using both local and global evidence, and avoiding waste. A WHO initiative addressed these challenges by developing a conceptual framework with four functions to guide the development of national health research systems. Despite some progress, more is needed before health research systems can meet their full potential of improving health systems. The WHO Regional Office for Europe commissioned an evidence synthesis of the systems-level literature. This Opinion piece considers its findings before reflecting on the vast additional literature available on the range of specific health research system functions related to the various challenges. Finally, it considers who should lead research system strengthening.

Main text

The evidence synthesis identifies two main approaches for strengthening national health research systems, namely implementing comprehensive and coherent strategies and participation in partnerships. The literature describing these approaches at the systems level also provides data on ways to strengthen each of the four functions of governance, securing financing, capacity-building, and production and use of research. Countries effectively implementing strategies include England, Ireland and Rwanda, whereas West Africa experienced effective partnerships. Recommended policy approaches for system strengthening are context specific. The vast literature on each function and the ever-growing evidence-base are illustrated by considering papers in just one key journal, Health Research Policy and Systems, and analysing the contribution of two national studies. A review of the functions of the Iranian system identifies over 200 relevant and mostly national records; an analysis of the creation of the English National Institute for Health Research describes the key leadership role played by the health department. Furthermore, WHO is playing leadership roles in helping coordinate partnerships within and across health research systems that have been attempting to tackle the COVID-19 crisis.

Conclusions

The evidence synthesis provides a firm basis for decision-making by policy-makers and research leaders looking to strengthen national health research systems within their own national context. It identifies five crucial policy approaches — conducting situation analysis, sustaining a comprehensive strategy, engaging stakeholders, evaluating impacts on health systems, and partnership participation. The vast and ever-growing additional literature could provide further perspectives, including on crucial leadership roles for health ministries.
A critical evaluation of systematic reviews assessing the effect of chronic physical activity on academic achievement, cognition and the brain in children and adolescents: a systematic review
Authors: Wassenaar Thomas M. , Williamson Wilby , Johansen-Berg Heidi , Dawes Helen , Roberts Nia , Foster Charlie , Sexton Claire E.
Published: June 2020

Background

International and national committees have started to evaluate the evidence for the effects of physical activity on neurocognitive health in childhood and adolescence to inform policy. Despite an increasing body of evidence, such reports have shown mixed conclusions. We aimed to critically evaluate and synthesise the evidence for the effects of chronic physical activity on academic achievement, cognitive performance and the brain in children and adolescents in order to guide future research and inform policy.

Methods

MedLine, Embase, PsycINFO, Cochrane Library, Web of Science, and ERIC electronic databases were searched from inception to February 6th, 2019. Articles were considered eligible for inclusion if they were systematic reviews with or without meta-analysis, published in peer-reviewed (English) journals. Reviews had to be on school-aged children and/or adolescents that reported on the effects of chronic physical activity or exercise interventions, with cognitive markers, academic achievement or brain markers as outcomes. Reviews were selected independently by two authors and data were extracted using a pre-designed data extraction template. The quality of reviews was assessed using AMSTAR-2 criteria.

Results

Of 908 retrieved, non-duplicated articles, 19 systematic reviews met inclusion criteria. One high-quality review reported inconsistent evidence for physical activity-related effects on cognitive- and academic performance in obese or overweight children and adolescents. Eighteen (critically) low-quality reviews presented mixed favourable and null effects, with meta-analyses showing small effect sizes (0.1–0.3) and high heterogeneity. Low-quality reviews suggested physical activity-related brain changes, but lacked an interpretation of these findings. Systematic reviews varied widely in their evidence synthesis, rarely took intervention characteristics (e.g. dose), intervention fidelity or study quality into account and suspected publication bias. Reviews consistently reported that there is a lack of high-quality studies, of studies that include brain imaging outcomes, and of studies that include adolescents or are conducted in South American and African countries.

Conclusions

Inconsistent evidence exists for chronic physical activity-related effects on cognitive-, academic-, and brain outcomes. The field needs to refocus its efforts towards improving study quality, transparency of reporting and dissemination, and is urged to differentiate between intervention characteristics for its findings to have a meaningful impact on policy.
Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues
Authors: Zhang Qiyao , Zheng Qingyuan , Yu Xiao , He Yuting , Guo Wenzhi
Published: June 2020

Background

Post-transcriptional methylation modifications, including 5-methylcytosine (m5C) modification, are closely related to the tumorigenesis of cancers. However, the mRNA profile of m5C modification in hepatocellular carcinoma (HCC) is unknown.

Methods

Methylated RNA immunoprecipitation sequencing was performed to identify m5C peaks on mRNA of human HCC tissues and adjacent tissues, and differences in m5C between the two groups were analyzed. In addition, we conducted a bioinformatics analysis to predict the function of specific methylated transcripts.

Results

We found that there was a noticeable difference in m5C between HCC and paired non-tumor tissues, suggesting that m5C could play a role in the pathogenesis of HCC. In addition, analyses of gene ontology and the Kyoto Encyclopedia of Genes and Genomes showed that the unique distribution pattern of mRNA m5C in HCC was associated with a wide range of cellular functions.

Conclusions

Our results revealed different distribution patterns of m5C in HCC and adjacent tissues and provided new insights into a novel function of m5C RNA methylation of mRNA in HCC progression.
The unique association between the level of peripheral blood monocytes and the prevalence of diabetic retinopathy: a cross-sectional study
Authors: Wan Heng , Cai Yan , Wang Yuying , Fang Sijie , Chen Chi , Chen Yi , Xia Fangzhen , Wang Ningjian , Guo Minghao , Lu Yingli
Published: June 2020

Objective

The attraction and influx of monocytes into the retina has been considered a critical step in the development of diabetic retinopathy (DR). However, large population studies about the association between peripheral blood monocyte levels, an inexpensive and easily measurable laboratory index, and DR are limited. Thus, we aimed to investigate the association between peripheral blood monocyte levels and DR.

Methods

A total of 3223 participants out of 3277 adults with diabetes were enrolled from seven communities in China in this cross-sectional survey. Participants underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, routinely analyzed leukocyte characteristics, glucose, lipid profiles, urine albumin/creatinine ratio and fundus photographs.

Results

The prevalence of DR among the participants in the highest quartile of peripheral blood monocyte levels significantly decreased by 41% (OR 0.59; 95% CI 0.43, 0.81) compared with the participants in the first quartile (P for trend < 0.05). However, there were no associations between the monocyte level and the prevalence of cardiovascular and cerebrovascular diseases (CVD) and diabetic kidney disease (DKD) (both P for trend > 0.05). Associations between leukocyte, neutrophil and lymphocyte levels and DR were also not found (all P for trend > 0.05). These associations were all fully adjusted for age, sex, education status, duration of diabetes history, current smoking, BMI, HbA1c, dyslipidemia, systolic blood pressure and insulin therapy.

Conclusion

Decreased peripheral blood monocyte levels were associated with increased odds of DR after adjusting for potential confounders in diabetic adults. However, causation remains to be demonstrated.
Adolescents living with HIV, complex needs and resilience in Blantyre, Malawi
Authors: Kaunda-Khangamwa Blessings N. , Kapwata Prosperina , Malisita Kennedy , Munthali Alister , Chipeta Effie , Phiri Sam , Manderson Lenore
Published: June 2020

Background

Adolescents living with HIV (ALHIV) in Malawi experience multiple challenges associated with their illness and various social, environmental, economic and cultural factors. In exploring their various medical concerns and social vulnerabilities, we consider the role of multiple services in creating a pathway for resilience.

Methods

Multiple methods and case studies allowed for triangulation of evidence and provided a holistic understanding of resilience among adolescents with complex needs. The research methods included: (1) a survey to identify examples of young people with complex needs, (2) qualitative interviews and field notes to further explore these needs, (3) patient files and health passports to identify clinical challenges, and (4) ecomapping exercises to personalize cases and identify resilience-enabling resources and supports. We present four case studies to highlight the complex experiences and access to services of ALHIV, and to illustrate their growing power and decision-making capacity over time.

Results

Adversity experienced by ALHIV varied by gender, family situation, years of schooling, and use of teen-clubs for support. The two female adolescents emphasised their need to be accepted and how this impacted sexuality and reproduction. The two males illustrated how ideas of masculinity influenced their sexual practice and involvement with health services and the correctional justice system. Multiple risks (alcohol use, sexual activities) and complex needs (belonging, having a purpose in life/productive activities, autonomy, desire for offspring) influence pathways to resilience. ALHIV were able to strengthen their own wellbeing by resisting negative behaviours and peer pressure and caregiver interactions through ‘strategic silence’.

Conclusion

ALHIV experienced self-transformation as a result of taking ART, with fewer severe episodes of illness and distressing skin conditions. Continuous engagement at the teen-club clinic transformed both productive activities and social relationships among ALHIV as they set life goals, gained a sense of empowerment, requested SRH services, and formed intimate relationships. These transformative opportunities allowed them to learn ways of minimizing risk of reinfection and violence, and of navigating health worker–caregiver–adolescent interactions.
Radiobiological model-based approach to determine the potential of dose-escalated robust intensity-modulated proton radiotherapy in reducing gastrointestinal toxicity in the treatment of locally advanced unresectable pancreatic cancer of the head
Authors: Raturi Vijay P. , Hojo Hidehiro , Hotta Kenji , Baba Hiromi , Takahashi Ryo , Rachi Toshiya , Nakamura Naoki , Zenda Sadamoto , Motegi Atsushi , Tachibana Hidenobu , Ariji Takaki , Motegi Kana , Nakamura Masaki , Okumura Masayuki , Hirano Yasuhiro , Akimoto Tetsuo
Published: June 2020

Background

The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model.

Methods

For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison.

Result

The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT – ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to < 10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCPro-IMPT/NTCPIMRT) reduction was noted (0.16–0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.).

Conclusion

With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.
Identification of a potential gene target for osteoarthritis based on bioinformatics analyses
Authors: Duan Zhi-xi , Li Yu-sheng , Tu Chao , Xie Peng , Li Yi-han , Qi Lin , Li Zhi-hong
Published: June 2020

Background

Osteoarthritis (OA) is the most common chronic joint disease worldwide. It is characterized by pain and limited mobility in the affected joints and may even cause disability. Effective clinical options for its prevention and treatment are still unavailable. This study aimed to identify differences in gene signatures between tissue samples from OA and normal knee joints and to explore potential gene targets for OA.

Methods

Five gene datasets, namely GSE55457, GSE55235, GSE12021, GSE10575, and GSE1919, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the R programming software. The functions of these DEGs were analyzed, and a protein–protein interaction (PPI) network was constructed. Subsequently, the most relevant biomarker genes were screened using a receiver operating characteristic (ROC) curve analysis. Finally, the expression of the protein encoded by the core gene PTHLH was evaluated in clinical samples.

Results

Eleven upregulated and 9 downregulated DEGs were shared between the five gene expression datasets. Based on the PPI network and the ROC curves of upregulated genes, PTHLH was identified as the most relevant gene for OA and was selected for further validation. Immunohistochemistry confirmed significantly higher PTHLH expression in OA tissues than in normal tissues. Moreover, similar PTHLH levels were detected in the plasma and knee synovial fluid of OA patients.

Conclusion

The bioinformatics analysis and preliminary experimental verification performed in this study identified PTHLH as a potential target for the treatment of OA.
Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas
Authors: Hotta Takamasa , Tsubata Yukari , Tanino Akari , Nakao Mika , Amano Yoshihiro , Hamaguchi Megumi , Hamaguchi Shunichi , Kishimoto Koji , Isobe Takeshi
Published: June 2020

Background

Multiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually.

Methods

This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients.

Results

The 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977).

Conclusions

The outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.
Analysis of attempted suicide episodes presenting to the emergency department: comparison of young, middle aged and older people
Authors: Kim Soo Hyun , Kim Han Joon , Oh Sang Hoon , Cha Kyungman
Published: June 2020

Background

Attempted suicide remains difficult for clinicians to predict with some established risk factors. We investigate the detailed characteristics of attempted suicide especially according to age and methods of suicide attempts.

Methods

A retrospective study was conducted to evaluate patients who visited the emergency department due to attempted suicide. A retrospective medical record review of all patients who presented to the emergency department (ED) of two tertiary teaching hospitals in Korea after suicide attempt between January 1, 2010, and December 31, 2017 was performed. Demographic information and detailed variables (methods and reasons of suicide attempts and variables regarding reattempts) were investigated. Total participants were classified into 3 groups according to age, young group, middle aged group and the older group, and each characteristics were compared.

Results

A total of 3698 patients were enrolled in this study. Deliberate self-poisoning (DSP) was the most common method of attempted suicide (66.5%) followed by cutting (24.4%), hanging (7.9%), falling (2.6%), and drowning (1.1%). In patients who had previous suicide attempts (n = 1029, 27.8%), attempted methods were likely to be concordant with previous attempted methods. The most common reason for suicide attempts was interpersonal relationship issues followed by socio-economic reasons. Older patients (n = 412, 11.2%) were significantly different from other 2 groups (n = 3286, 88.8%) regarding gender, suicide re-attempt, occupation, alcohol co-ingestion, previous psychiatric history, and discharge outcomes (all p-values < 0.001). Especially, in older patients, use of critical method and reason of physical illness were more common.

Conclusion

Our findings indicated that people who attempted suicide might have different sociodemographic and clinical factors depending on age group. Depending on age, it is necessary to apply additional suicide intervention programs in different ways.
Genetic associations between voltage-gated calcium channels and autism spectrum disorder: a systematic review
Authors: Liao Xiaoli , Li Yamin
Published: June 2020

Objectives

The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD).

Methods

A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions.

Results

From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca2+pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD.

Conclusions

Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype.
Measurable residual disease in multiple myeloma: ready for clinical practice?
Authors: Burgos Leire , Puig Noemi , Cedena Maria-Teresa , Mateos María-Victoria , Lahuerta Juan José , Paiva Bruno , San-Miguel Jesús F.
Published: June 2020

The landscape of multiple myeloma (MM) has changed considerably in the past two decades regarding new treatments, insight into disease biology and innovation in the techniques available to assess measurable residual disease (MRD) as the most accurate method to evaluate treatment efficacy. The sensitivity and standardization achieved by these techniques together with unprecedented rates of complete remission (CR) induced by new regimens, raised enormous interest in MRD as a surrogate biomarker of patients’ outcome and endpoint in clinical trials. By contrast, there is reluctance and general lack of consensus on how to use MRD outside clinical trials. Here, we discuss critical aspects related with the implementation of MRD in clinical practice.
cGAS-STING, an important pathway in cancer immunotherapy
Authors: Jiang Minlin , Chen Peixin , Wang Lei , Li Wei , Chen Bin , Liu Yu , Wang Hao , Zhao Sha , Ye Lingyun , He Yayi , Zhou Caicun
Published: June 2020

Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.
Comparing complications of small-bore chest tubes to large-bore chest tubes in the setting of delayed hemothorax: a retrospective multicenter cohort study
Authors: Orlando A. , Cordero J. , Carrick M. M , Tanner A. H. , Banton K. , Vogel R. , Lieser M. , Acuna D. , Bar-Or D.
Published: June 2020

Background

Previous studies have provided initial data suggesting that small-bore (SB, ≤ 14Fr) chest tubes have the same efficacy as large-bore (LB, > 14 Fr) chest tubes for acute hemothorax (HTX), but data continue to be lacking in the setting of delayed HTX. This study compared complications of SB chest tubes to LB tubes in patients with delayed HTX.

Methods

This was a retrospective observational study across 7.5 yrs. at 6 Level 1 trauma centers. Patients were included if 1) diagnosed with a HTX or > 1 rib fracture with bloody effusion from chest tube; 2) initial chest tube placed ≥36 h of hospital admission. Patients were excluded for hemopneumothoraces. The primary endpoint was having at least one of the following chest tube complications: tube replacement, VATS, tube falling out, tube clogging, pneumonia, retained HTX, pleural empyema. Secondary outcomes included chest tube output volume and drainage rate. Dependent/independent and parametric/non-parametric analyses were used to assess primary and secondary outcomes.

Results

There were 160 SB patients (191 tubes) and 60 LB patients (72 tubes). Both comparison groups were similar in multiple demographic, injury, clinical features. The median (IQR) tube size for each group was as follows: SB [12 Fr (12–14)] and LB [32 Fr (28–32)]. The risk of having at least one chest tube complication was similar for LB and SB chest tubes (14% vs. 18%, p = 0.42). LB tubes had significantly larger risk of VATS, while SB tubes had significantly higher risk of pneumonia. SB tubes had significantly slower least squares (LS) mean initial output drainage rate compared to LB tubes (52.2 vs. 213.4 mL/hour, p < 0.001), but a non-parametric analysis suggested no significant difference in median drainage rates between groups 39.7 [23.5–242.0] mL/hr. vs. 38.6 [27.5–53.8], p = 0.81. LB and SB groups had similar initial output volume (738.0 mL vs. 810.9, p = 0.59).

Conclusions

There was no clearly superior chest tube diameter size; both chest tube sizes demonstrated risks and benefits. Clinicians must be aware of these potential tradeoffs when deciding on the diameter of chest tube for the treatment of delayed HTXs.
Preventive use of respiratory support after scheduled extubation in critically ill medical patients—a network meta-analysis of randomized controlled trials
Authors: Zhou Xiaoyang , Yao Shengmi , Dong Pingping , Chen Bixin , Xu Zhaojun , Wang Hua
Published: June 2020

Background

Respiratory support has been increasingly used after extubation for the prevention of re-intubation and improvement of prognosis in critically ill medical patients. However, the optimal respiratory support method is still under debate. This network meta-analysis (NMA) aims to evaluate the comparative effectiveness of various respiratory support methods used for preventive purposes after scheduled extubation in critically ill medical patients.

Methods

A systematic database search was performed from inception to December 19, 2019, for randomized controlled trials (RCTs) that compared a preventive use of different respiratory support methods, including conventional oxygen therapy (COT), noninvasive ventilation (NIV), high-flow oxygen therapy (HFOT), and combinational use of HFOT and NIV (HFOT+NIV), after planned extubation in adult critically ill medical patients. Study selection, data extraction, and quality assessments were performed in duplicate. The primary outcomes included re-intubation rate and short-term mortality.

Results

Seventeen RCTs comprising 3341 participants with 4 comparisons were included. Compared with COT, NIV significantly reduced the re-intubation rate [risk ratio (RR) 0.55, 95% confidence interval (CI) 0.39 to 0.77; moderate quality of evidence] and short-term mortality (RR 0.66, 95% CI 0.48 to 0.91; moderate quality of evidence). Compared to COT, HFOT had a beneficial effect on the re-intubation rate (RR 0.55, 95% CI 0.35 to 0.86; moderate quality of evidence) but no effect on short-term mortality (RR 0.79, 95% CI 0.56 to 1.12; low quality of evidence). No significant difference in the re-intubation rate or short-term mortality was found among NIV, HFOT, and HFOT+NIV. The treatment rankings based on the surface under the cumulative ranking curve (SUCRA) from best to worst for re-intubation rate were HFOT+NIV (95.1%), NIV (53.4%), HFOT (51.2%), and COT (0.3%), and the rankings for short-term mortality were NIV (91.0%), HFOT (54.3%), HFOT+NIV (43.7%), and COT (11.1%). Sensitivity analyses of trials with a high risk of extubation failure for the primary outcomes indicated that the SUCRA rankings were comparable to those of the primary analysis.

Conclusions

After scheduled extubation, the preventive use of NIV is probably the most effective respiratory support method for comprehensively preventing re-intubation and short-term death in critically ill medical patients, especially those with a high risk of extubation failure.
Timing of antiretroviral therapy for HIV-infected patients with moderate to severe Pneumocystis pneumonia: study protocol for a multi-centre prospective randomised controlled trial
Authors: Qin Yuanyuan , Lu Yanqiu , Zhou Yihong , Harypursat Vijay , Sun Feng , Yang Sen , Tang Shengquan , Li Yao , He Xiaoqing , Zeng Yanming , Chen Yaokai
Published: June 2020

Background

Pneumocystis pneumonia (PCP) is a common acquired immune deficiency syndrome (AIDS)-related opportunistic infection. Recent reports estimate that more than 400,000 patients with human immunodeficiency virus (HIV) develop PCP each year globally. However, the timing of antiretroviral therapy (ART) initiation for HIV-infected patients with PCP is still controversial, and the benefits and risks of early initiation of ART are not completely clear. We thus designed this study in order to determine the optimal timing for ART initiation for HIV-positive patients with moderate to severe PCP.

Methods

This study will be an open-label, multi-centre, prospective randomised controlled trial. A total of 200 subjects will be randomly assigned to an early ART initiation group (≤14 days after PCP diagnosis) and a deferred ART initiation group (>14 days after PCP diagnosis) at a 1:1 ratio. All subjects will be followed up for 48 weeks after starting ART. The primary endpoint is incidence of disease progression (including new or relapsing opportunistic infections and death) at week 48. The secondary endpoints are the changes in CD4 counts from baseline at weeks 12, 24 and 48; the degree of virological suppression (HIV RNA < 50 copies/mL) at weeks 24 and 48; the rate of development of PCP-associated immune reconstitution inflammatory syndrome; and adverse events over 48 weeks.

Discussion

We hope that the results of this study will reveal the optimal timing for initiation of ART in HIV-infected patients with moderate to severe PCP.

Trial registration

This trial was registered as one of the 12 trials under the name of a general project at chictr.org.cn on February 1, 2019. The registration number of the general project is ChiCTR1900021195.
Defining key design elements of registry-based randomised controlled trials: a scoping review
Authors: Karanatsios Bill , Prang Khic-Houy , Verbunt Ebony , Yeung Justin M. , Kelaher Margaret , Gibbs Peter
Published: June 2020

Background

Traditional randomised controlled trials remain the gold standard for improving clinical care but they do have their limitations, including their associated high costs, high failure rate and limited external validity. An alternative methodology is the newly defined, prospective, registry-based randomised controlled trial (RRCT), where treatment and outcome data is collected in an existing registry. This scoping review explores the current literature regarding RRCTs to help identify the key design elements of RRCTs and the characteristics of clinical registries on which they are reliant on.

Methods

A scoping review methodology conducted in accordance with the Joanna Briggs Institute guidelines was performed. Four databases were searched for articles published from inception to June 2018: Medline; Embase; the Cumulative Index to Nursing and Allied Health Literature and; Scopus. The search strategy included MeSH and text words related to RRCT.

Results

We identified 2369 articles of which 75 were selected for full-text screening. Of these, only 17 articles satisfied our inclusion criteria. All studies were published between 1996 and 2017 and all were investigator-initiated. Study designs were mainly multi-site comparative/effectiveness studies incorporating the use of disease registries (n = 8), procedure registries (n = 8) and a health services registry (n = 1). The low cost, reduced administrative burden and enhanced external validity of RRCTs make them an attractive research methodology which can be used to address questions of public health importance. We identified that that there are variable definitions of what constituted a RRCT and that issues related to ethical conduct and data integrity, completeness, timeliness, validation and endpoint adjudication need to be carefully addressed.

Conclusion

RRCTs potentially have an important role to play in informing best clinical practice and health policy. There are a number of issues that need to be addressed to optimise the utility of this approach, including establishing universally accepted criteria for the definition of a RRCT.
Protocol for a randomised controlled trial to investigate the effect of home- and gym-based resistance exercise training on glycaemic control, body composition and muscle strength
Authors: Al Ozairi Ebaa , Alsaeed Dalal , Taliping Dennis , Jalali Mohamad , El Samad Abeer , Mashankar Anant , Taghadom Etab , Guess Nicola , Gill Jason M. R. , Sattar Naveed , Gray Cindy , Welsh Paul , Gray Stuart R.
Published: June 2020

Background

Resistance exercise is known to be effective in reducing glycated haemoglobin (HbA1c) in people with type 2 diabetes. However, studies, so far, have employed supervised resistance exercise in a laboratory or gym facility which limits the future translation of such exercise in to clinical practice and recommendations. Our primary aim, therefore, is to test the hypothesis, in a randomized controlled trial, that home-based resistance exercise training and gym-based resistance exercise training both reduce HbA1c levels in people with type 2 diabetes compared to control. We will also investigate the effects of home- and gym-based resistance exercise training on muscle strength and body composition.

Methods

The current study is a three-arm randomised controlled trial which will be conducted with 150 eligible people with type 2 diabetes to compare home-and gym-based resistance exercise training with usual care in Kuwait. The interventions will be delivered by exercise specialists and last for 32 weeks. The primary outcomes are HbA1c with secondary outcomes measuring muscle function, body composition, physical activity and quality of life.

Discussion

Ethical approval has been granted by the Dasman Diabetes Institute ethical review committee (RA/197/2019). Study findings will be disseminated through presentation at scientific conferences and in scientific journals.

Trial registration

NCT04136730: Retrospectively registered on 21 October 2019
Clinical efficacy evaluation of a traditional Miao technique of crossbow needle therapy in the treatment of knee osteoarthritis: a multi-center randomized controlled trial
Authors: Fu Jing , Shang Hong-Cai , Wang Li-Ying , Zhao Chen , Yang Xiao-Fang , Guo Wei-Wei , Lu Chun-Xia , Cui Jin , Wang Yan-Ping
Published: June 2020

Background

Knee osteoarthritis (KOA) seriously reduces quality of life and is a major threat to the health of the middle-aged and elderly. This study aimed to assess the efficacy of Miao crossbow needle therapy vs. acupuncture for KOA therapy.

Methods

This multicenter, randomized controlled trial was performed at three hospitals between April 2016 and December 2016. The patients were randomized to receive crossbow needle (CN) or acupuncture (AT). All treatments were completed within 46 days. Evaluation of treatment was conducted on the 46th, 62nd, and 77th days. The primary endpoint was change of Western Ontario and McMaster Osteoarthritis Index (WOMAC) score on the 46th day. The secondary endpoints included WOMAC score, the Lysholm knee score, the Japanese Orthopedic Association (JOA) knee score, visual analog scale (VAS), and the MOS 36-item short-form health survey (SF-36), on the 46th, 62nd, and 77th day.

Results

Finally, data of 301 participants were analyzed for the efficacy of treatment. Compared with AT, there was a larger change of WOMAC score in the CN group after treatment [− 25.0 (95% CI − 27.0, − 23.0) vs. − 18.8 (95% CI − 20.8, − 16.9), P < 0.001]. In the CN group, the WOMAC score was lower at all three time points (P = 0.008, P = 0.003, P < 0.001 respectively), while the Lysholm knee score (P = 0.03) and JOA score (P = 0.013) were higher and the VAS score (P = 0.011) was lower on the 77th day.

Conclusion

Both Miao crossbow needle therapy and acupuncture reduced the WOMAC score. Miao crossbow needle therapy can be an alternative method for treating patients with knee osteoarthritis.

Trial registration

ChiCTR, ChiCTR-INR-16008032. Registered on 12 March 2016.
Correction to: Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial
Authors: Bosteels Cedric , Maes Bastiaan , Van Damme Karel , De Leeuw Elisabeth , Declercq Jozefien , Delporte Anja , Demeyere Bénédicte , Vermeersch Stéfanie , Vuylsteke Marnik , Willaert Joren , Bollé Laura , Vanbiervliet Yuri , Decuypere Jana , Libeer Frederick , Vandecasteele Stefaan , Peene Isabelle , Lambrecht Bart N.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Two Randomized Controlled Trials of Bacillus Calmette-Guérin Vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled trials
Authors: ten Doesschate Thijs , Moorlag Simone J. C. F. M. , van der Vaart Thomas W. , Taks Esther , Debisarun Priya , ten Oever Jaap , Bleeker-Rovers Chantal P. , Verhagen Patricia Bruijning , Lalmohamed Arief , ter Heine Rob , van Crevel Reinout , van de Wijgert Janneke , Janssen Axel B. , Bonten Marc J. , van Werkhoven Cornelis H. , Netea Mihai G. ,   on behalf of the BCG-CORONA study team#
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
The complete mitochondrial genome of the Columbia lance nematode, Hoplolaimus columbus, a major agricultural pathogen in North America
Authors: Ma Xinyuan , Agudelo Paula , Richards Vincent P. , Baeza J. Antonio
Published: June 2020

Background

The plant-parasitic nematode Hoplolaimus columbus is a pathogen that uses a wide range of hosts and causes substantial yield loss in agricultural fields in North America. This study describes, for the first time, the complete mitochondrial genome of H. columbus from South Carolina, USA.

Methods

The mitogenome of H. columbus was assembled from Illumina 300 bp pair-end reads. It was annotated and compared to other published mitogenomes of plant-parasitic nematodes in the superfamily Tylenchoidea. The phylogenetic relationships between H. columbus and other 6 genera of plant-parasitic nematodes were examined using protein-coding genes (PCGs).

Results

The mitogenome of H. columbus is a circular AT-rich DNA molecule 25,228 bp in length. The annotation result comprises 12 PCGs, 2 ribosomal RNA genes, and 19 transfer RNA genes. No atp8 gene was found in the mitogenome of H. columbus but long non-coding regions were observed in agreement to that reported for other plant-parasitic nematodes. The mitogenomic phylogeny of plant-parasitic nematodes in the superfamily Tylenchoidea agreed with previous molecular phylogenies. Mitochondrial gene synteny in H. columbus was unique but similar to that reported for other closely related species.

Conclusions

The mitogenome of H. columbus is unique within the superfamily Tylenchoidea but exhibits similarities in both gene content and synteny to other closely related nematodes. Among others, this new resource will facilitate population genomic studies in lance nematodes from North America and beyond.