bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous intravenous catheter forceps biopsy in right atrial mass: two case reports and literature review
Authors: Chang Lei , Gong Chenyi , Lu Haitao , Liu Yihai , Kang Lina , Chen Jianzhou , Wang Lian , Xu Biao
Published: February 2022

Background

Primary malignant tumors of the heart are rare. Although preoperative histological diagnosis is difficult, it has paramount value in therapeutic strategy development and prognostic estimation. Herein, we reported 2 cases of intracardiac tumors.

Cases presentation

Both patients presented to the hospital with heart-related symptoms. Echocardiography showed massive masses in the atrium and positron emission tomography–computed tomography (PET/CT) revealed hypermetabolism and invasiveness. One patient cannot take surgery due to extensive metastasis and poor condition. The other patient was primarily diagnosed with lymphoma, and surgery was not recommended. They successfully underwent intravenous atrial biopsy, and histological samples confirmed intimal sarcoma and diffuse large B cell lymphoma. Based on immunohistochemical and molecular assessments, targeted chemotherapy was administered, resulting in clinical and imaging remission at discharge.

Conclusions

Percutaneous intravenous catheter biopsy as a safe invasive test provides an accurate pathological diagnosis after imaging evaluation, and offers a therapeutic direction. Nonmalignant masses and some chemo-radiosensitive malignant tumors in the atrium could have good prognosis after targeted therapy.
Clinical effectiveness and cost-effectiveness of ambulatory heart failure nurse-led services: an integrated review
Authors: Driscoll Andrea , Gao Lan , Watts Jennifer J.
Published: February 2022

Background

Globally the burden of heart failure is rising. Hospitalisation is one of the main contributors to the burden of heart failure and unfortunately, the majority of heart failure patients will experience multiple hospitalisations over their lifetime. Considering the high health care cost associated with heart failure, a review of economic evaluations of post-discharge heart failure services is warranted.

Aim

An integrated review of the economic evaluations of post-discharge nurse-led heart failure services for patients hospitalised with acute heart failure.

Methods

Electronic databases were searched using EBSCOHost: CINAHL complete, Medline complete, Embase, Scopus, EconLit, Global Health, and Health source (Consumer and Nursing/Academic) for published articles until 22nd June 2021. The searches focussed on papers that examined the cost-effectiveness of nurse-led clinics or telemonitoring involving nurses to follow-up patients after hospitalisation for acute heart failure. GRADE criteria and CHEERS checklist were used to determine the quality of the evidence and the quality of reporting of the economic evaluation.

Results

Out of 453 studies identified, eight studies were included: four in heart failure clinics and four in telemonitoring programs. Five of the articles were cost-effectiveness analyses, one a cost comparison and two studies involved economic modelling The GRADE criteria were rated as high in five studies. In which, four studies examined the cost-effectiveness of telemonitoring programs. Based on the CHEERS checklist for reporting quality of economic evaluations, the majority of economic evaluations were rated between 86 and 96%. All the studies found the intervention to be cost-effective compared to usual care with Incremental Cost Effectiveness Ratios ranging from $18 259 (Canadian dollars)/life year gained to €40,321 per Quality Adjusted Life Years gained.

Conclusion

Nurse-led heart failure clinics and telemonitoring programs were found to be cost-effective. Certainly, this review has shown that heart failure clinics and telemonitoring programs do represent value for money with their greatest impact and cost savings through reducing rehospitalisations.
How have governments supported citizens stranded abroad due to COVID-19 travel restrictions? A comparative analysis of the financial and health support in eleven countries
Authors: McDermid Pippa , Craig Adam , Sheel Meru , Seale Holly
Published: February 2022

Background

In response to the continuing threat of importing novel coronavirus disease (COVID-19), many countries have implemented some form of border restriction. A repercussion of these restrictions has been that some travellers have found themselves stranded abroad unable to return to their country of residence, and in need for government support. Our analysis explores the COVID-19-related information and support options provided by 11 countries to their citizens stranded overseas due to travel restrictions. We also examined the quality (i.e., readability, accessibility, and useability) of the information that was available from selected governments’ web-based resources.

Methods

Between June 18 to June 30, 2021, COVID-19-related webpages from 11 countries (Australia, New Zealand, Fiji, Canada, United States of America (USA), United Kingdom (UK), France, Spain, Japan, Singapore, and Thailand) were reviewed and content relating to information and support for citizens stuck overseas analysed. Government assistance-related data from each webpage was extracted and coded for the following themes: travel arrangements, health and wellbeing, finance and accommodation, information needs, and sources. Readability was examined using the Simplified Measure of Gobbledygook (SMOG) and the Flesch Kincaid readability tests; content ‘accessibility’ was measured using the Web Content Accessibility Guidelines (WCAG) Version 2.1; and content ‘usability’ assessed using the usability heuristics for website design tool.

Results

Ninety-eight webpages from 34 websites were evaluated. No country assessed covered all themes analysed. Most provided information and some level of support regarding repatriation options; border control and re-entry measures; medical assistance; and traveller registration. Only three countries provided information or support for emergency housing while abroad, and six provided some form of mental health support for their citizens. Our analysis of the quality of COVID-19-related information available on a subset of four countries’ websites found poor readability and multiple accessibility and usability issues.

Conclusion

This study uniquely analyses government support for citizens stuck abroad during the COVID-19 pandemic. With large variance in the information and services available across the countries analysed, our results highlight gaps, inconsistencies, and potential inequities in support available, and raise issues pertinent to the quality, accessibility, and usability of information. This study will assist policymakers plan and communicate comprehensive support packages for citizens stuck abroad due to the COVID-19 situation and design future efforts to prepare for global public health emergencies.
Hepatitis C seroprevalence among people living with HIV/AIDS and pregnant women in four provinces in Cambodia: an integrated bio-behavioral survey
Authors: Pheng Phearavin , Meyer Laurence , Ségéral Olivier , Chea Phalla , Yi Siyan , Tuot Sovannary , Kaldor John M. , Saphonn Vonthanak
Published: February 2022

Background

Understanding the extent of viral hepatitis burden in specific subgroups, such as pregnant women and people living with HIV/AIDS (PLWHA), and their geographic distribution is essential for evidence-informed policy and mobilizing resources for targeted treatment and prevention efforts. However, in Cambodia, the epidemiology of hepatitis C remains uncertain. We estimated the hepatitis C virus (HCV) burden and transmission risk factors among PLWHA and pregnant women attending antenatal care (ANC) in Cambodia.

Methods

Between March and April 2016, we conducted a cross-sectional survey in four diverse geographical areas: the capital city of Phnom Penh and three provinces. We collected information on demographic characteristics and risk behaviors and performed HCV antibody (Anti-HCV) testing among pregnant women attending public ANC clinics and among those receiving HIV care at the hospitals. We computed the prevalence of HCV among the two population subsets and performed logistic regression analyses to identify risk factors associated with HCV antibody positivity.

Results

Of 935 participants enrolled, 510 (54.6%) were pregnant women and 425 (45.4%) were PLWHA. Anti-HCV prevalence was significantly higher in PLWHA than in pregnant women (29/425, 6.8% vs 5/510, 0.9%, P < 0.001). Of the geographic regions, Preah Sihanouk province (Southwest) had the highest anti-HCV prevalence among PLWHA (12.0%, P = 0.031). There was no significant geographic difference in anti-HCV prevalence among pregnant women. In multivariable analyses (data subset to PLWHA), HCV infection was significantly associated with having a family member positive for HCV (OR = 7.6 [95% CI: 1.01–57.84], P = 0.048) and a history of intravenous medication injection in the last 5 years (OR = 7.1 [95% CI: 2.79–18.10], P < 0.001).

Conclusions

HCV infection is relatively common among Cambodian PLWHA, likely related to intravenous medication injection and intra-familial viral transmission. Systematic HCV testing and care among PLWHA (and possibly their family members) might be necessary. Setting up a surveillance system for HCV might also be beneficial for some geographical regions and populations.
The pregnancy experiences and antenatal care services of Chinese migrants in Switzerland: a qualitative study
Authors: Cai Dingcui , Villanueva Paulina , Stuijfzand Susannah , Lu Hong , Zimmermann Basile , Horsch Antje
Published: February 2022

Background

Differences in reproductive health outcomes according to the mothers’ origins have been reported in Switzerland, for example, women from European countries and non-European countries. The Swiss Federal Office of Public Health has therefore called for specific Swiss-wide studies on migrant populations. This study explores the pregnancy and antenatal care experiences of Chinese migrants in Switzerland, intending to clarify their maternity care needs.

Methods

In-depth interviews of 14 Chinese mothers and 13 family members were conducted in Chinese or English and audio recorded. All audio-recordings were transcribed verbatim. All Chinese transcripts were translated into English. Thematic analysis was performed with the assistance of the qualitative data analysis software, MAXQDA Analytics Pro 2020.

Results

Five themes were extracted from the transcripts: (1) Motivations and concerns about having children, (2) The merits of the Swiss maternity care system, (3) The inconveniences and barriers of accessing Swiss maternity care services, (4) Strategies to deal with the inconveniences of the Swiss maternity care system, and (5) The need for culturally sensitive care.

Conclusions

The results of our study provide new knowledge and understanding of pregnancy experiences and antenatal care services of Chinese mothers and their families in Switzerland. Their unique positive experiences included: family planning, the continuity of maternity services, humane care with the privacy respected, personalized sensitive care needs, preferences for female obstetricians and obstetricians of Asian origin. Several barriers were highlighted, such as information seeking difficulties, communication difficulties, and a rigid appointment system. Reducing barriers enabling access to maternity care services within the Swiss healthcare system is necessary to provide equal quality maternity care for individuals, irrespective of their origins.
The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis
Authors: Zhang Xiaowei , Wu Yuchen , Sun Xuefei , Cui Qu , Bai Xueyan , Dong Gehong , Gao Zifen , Wang Yaming , Gao Chunji , Sun Shengjun , Ji Nan , Liu Yuanbo
Published: February 2022

Background

Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis.

Methods

In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed.

Results

The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P < 0.05). The relative mRNA expression level of MTOR in PCNSL samples was significantly increased (P = 0.013). Correlation analysis revealed that the expression of p-mTOR was correlated with that of p-AKT, p-S6, p-4E-BP1. PTEN deletion was found in 18.9% of PCNSL samples and was correlated with the expression of p-AKT (P = 0.031). Correlation analysis revealed that the PCNSL relapse rate in the p-mTOR-positive group was 64.5%, significantly higher than that in the negative group (P = 0.001). Kaplan-Meier survival analysis showed inferior progression-free survival (PFS) in the p-mTOR- and p-S6-positive groups (P = 0.002 and 0.009, respectively), and PTEN deletion tended to be related to shorter overall survival (OS) (P = 0.072). Cox regression analysis revealed p-mTOR expression as an independent prognostic factor for a shorter PFS (hazard ratio (HR) =7.849, P = 0.046).

Conclusions

Our results suggest that the PI3K/AKT/mTOR signaling pathway is aberrantly activated in PCNSL and associated with a poor prognosis, which might indicate new therapeutic targets and prognostic factors.
Long non-coding RNA AC087388.1 as a novel biomarker in colorectal cancer
Authors: Poursheikhani Arash , Abbaszadegan Mohammad Reza , Kerachian Mohammad Amin
Published: February 2022

Background

Several investigations have reported diverse roles of long non-coding RNA (lncRNA) in biological processes, tumor development, and progression of colorectal cancer (CRC). In this study, we investigated the lncRNA AC087388.1 tumorigenic role in CRC cells.

Methods

The CRC tissues were collected at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. The human SW-48 and HT-29 CRC cell lines were obtained from the national cell bank of Iran. The cells were cultured according to ATCC (the American Type Culture Collection) recommendations. Quantitative real-time PCR was applied to assess the RNA expression. ShRNA transfection was done to downregulate the target gene. MTT and apoptosis assays were conducted to evaluate cell proliferation and viability, respectively. Colony formation assay, wound healing assay, and invasion assay were applied to determine growth, motility, and invasion of the cells, respectively. ENCORI online tool was used as downstream enrichment analysis.

Results

Forty CRC patients were encompassed in this study. The results demonstrated that the lncRNA SLC16A1-AS1, AC087388.1, and ELFN1-AS1 were significantly overexpressed in the CRC tissues in comparison to their normal counterpart margins. All the lncRNAs have shown significant Area Under Curve (AUC) values in the patients. Downregulation of lncRNA AC087388.1 remarkably decreased the cell proliferation and viability of the CRC cells. In addition, the data demonstrated that the downregulation of lncRNA AC087388.1 significantly suppressed cell growth and colony formation capability in the cells. Also, downregulation of lncRNA AC087388.1 attenuated motility and invasion of CRC cells, and significantly decreased the expression of invasion genes. In-silico functional enrichment analysis indicated that the lncRNA AC087388.1 has contributed to crucial signaling pathways in tumorigenesis such as the p53 and Wnt signaling pathways, apoptosis, and cell cycle.

Conclusions

Altogether, we showed that lncRNA AC087388.1 has an oncogenic role in tumorigenesis of CRC, and it can be considered as a novel diagnostic and prognostic biomarker in CRC.
Deep learning identifies Acute Promyelocytic Leukemia in bone marrow smears
Authors: Eckardt Jan-Niklas , Schmittmann Tim , Riechert Sebastian , Kramer Michael , Sulaiman Anas Shekh , Sockel Katja , Kroschinsky Frank , Schetelig Johannes , Wagenführ Lisa , Schuler Ulrich , Platzbecker Uwe , Thiede Christian , Stölzel Friedrich , Röllig Christoph , Bornhäuser Martin , Wendt Karsten , Middeke Jan Moritz
Published: February 2022

Background

Acute promyelocytic leukemia (APL) is considered a hematologic emergency due to high risk of bleeding and fatal hemorrhages being a major cause of death. Despite lower death rates reported from clinical trials, patient registry data suggest an early death rate of 20%, especially for elderly and frail patients. Therefore, reliable diagnosis is required as treatment with differentiation-inducing agents leads to cure in the majority of patients. However, diagnosis commonly relies on cytomorphology and genetic confirmation of the pathognomonic t(15;17). Yet, the latter is more time consuming and in some regions unavailable.

Methods

In recent years, deep learning (DL) has been evaluated for medical image recognition showing outstanding capabilities in analyzing large amounts of image data and provides reliable classification results. We developed a multi-stage DL platform that automatically reads images of bone marrow smears, accurately segments cells, and subsequently predicts APL using image data only. We retrospectively identified 51 APL patients from previous multicenter trials and compared them to 1048 non-APL acute myeloid leukemia (AML) patients and 236 healthy bone marrow donor samples, respectively.

Results

Our DL platform segments bone marrow cells with a mean average precision and a mean average recall of both 0.97. Further, it achieves high accuracy in detecting APL by distinguishing between APL and non-APL AML as well as APL and healthy donors with an area under the receiver operating characteristic of 0.8575 and 0.9585, respectively, using visual image data only.

Conclusions

Our study underlines not only the feasibility of DL to detect distinct morphologies that accompany a cytogenetic aberration like t(15;17) in APL, but also shows the capability of DL to abstract information from a small medical data set, i. e. 51 APL patients, and infer correct predictions. This demonstrates the suitability of DL to assist in the diagnosis of rare cancer entities. As our DL platform predicts APL from bone marrow smear images alone, this may be used to diagnose APL in regions were molecular or cytogenetic subtyping is not routinely available and raise attention to suspected cases of APL for expert evaluation.
Comparative short-term efficacy and acceptability of a combination of pharmacotherapy and psychotherapy for depressive disorder in children and adolescents: a systematic review and meta-analysis
Authors: Xiang Yajie , Cuijpers Pim , Teng Teng , Li Xuemei , Fan Li , Liu Xueer , Jiang Yuanliang , Du Kang , Lin Jingyuan , Zhou Xinyu , Xie Peng
Published: February 2022

Background

Although the clinical efficacy and safety of combination of pharmacotherapy and psychotherapy in the treatment of depressive disorders in children and adolescents have been studied, the results remain controversial. This meta-analysis aimed to study the short-term efficacy and acceptability of combined therapy for children and adolescents with depressive disorders.

Methods

We conducted a systematic search in multiple databases for randomised controlled trials (RCTs), up to 31 December 2020, that assessed the combination of pharmacotherapy and psychotherapy against other active treatment options (pharmacotherapy, psychotherapy and placebo combined psychotherapy) in children and adolescents ( ≤ 18 years old) with depressive disorder. This study was registered with PROSPERO (CRD42020196701).

Results

A total of 14 RCTs involving 1,325 patients were included. For the primary and secondary outcomes, there were no statistically significant differences between the compared interventions in terms of remission (odds ratios [OR] = 1.37; 95% confidence interval [CI]: 0.93 to 2.04), acceptability (OR = 0.99; 95% CI: 0.72 to 1.38), efficacy (standardised mean differences = -0.07; 95% CI: -0.32 to 0.19), and suicidality (OR = 1.17; 95% CI: 0.67 to 2.06). Limited evidence showed that the combination of fluoxetine (OR = 1.90, 95% CI: 1.10 to 3.29) or non-selective serotonin reuptake inhibitors (non-SSRI) (OR = 2.46, 95% CI: 1.06 to 5.72) with cognitive-behavioural therapy (CBT) was superior to other active treatment options. Most included trials were rated as ‘some concerns’ in terms of risk of bias assessment.

Conclusion

There is no evidence from the limited available data that all combined therapies are superior to other active treatment options for the acute treatment of depressive disorder in children and adolescents. However, it showed that fluoxetine or non-SSRI pharmacotherapies combined with CBT might be superior to other therapies in short-term. Mixed characteristics (e.g. age) and small sample size of non-SSRI combined therapy may influence the generalisability of the results.
Optimal dose determination of enerisant (TS-091) for patients with narcolepsy: two randomized, double-blind, placebo-controlled trials
Authors: Inoue Yuichi , Uchiyama Makoto , Umeuchi Hideo , Onishi Koichi , Ogo Hiroki , Kitajima Iwao , Matsushita Isao , Nishino Izumi , Uchimura Naohisa
Published: February 2022

Background

The histamine H3 receptor has emerged as one of the most promising targets of novel pharmacotherapy for narcolepsy. Studies now aim to investigate the optimal dose of enerisant, a novel H3 antagonist/inverse agonist, for the treatment of excessive daytime sleepiness in patients with narcolepsy.

Methods

We conducted two phase 2, fixed-dose, double-blind, randomized, placebo-controlled trials in patients with narcolepsy. The first phase 2 study (Study 1) was conducted to investigate the efficacy and safety of enerisant at dosages of 25, 50, and 100 mg/day administered for 3 weeks based on the results of a phase 1 study conducted on healthy volunteers. The primary endpoint was mean sleep latency in maintenance of wakefulness test (MWT), and the secondary endpoint was the total score on the Epworth Sleepiness Scale (ESS). The dosages of enerisant in the second phase 2 study (Study 2) were set at 5 and 10 mg/day based on the simulation of receptor occupancy results from positron emission tomography study.

Results

Forty-six and fifty-three patients were randomized in Study 1 and Study 2, respectively. The efficacy of enerisant was partially confirmed in Study 1 with ESS; however, the doses were not tolerated, and there were many withdrawals due to adverse events (mainly insomnia, headache, and nausea). The doses in Study 2 were well tolerated, with a lower incidence of adverse events in Study 2 than in Study 1, although the efficacy could not be confirmed with MWT and ESS in Study 2.

Conclusions

The optimal dose of enerisant could not be determined in these two studies. Although enerisant has a favorable pharmacokinetic profile, it is thought to have large interindividual variabilities in terms of efficacy and safety, suggesting the necessity of tailored dosage adjustments.

Trial registration

ClinicalTrials.gov identifier: NCT03267303; Registered 30 August 2017 (Study 2).

Japic identifier: JapicCTI-142529; Registered 7 May 2014 (Study 1) and JapicCTI-173689; Registered 30 August 2017, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?clinicalTrialId=29277 (Study 2).
Adherence to the OARSI recommendations for designing, conducting, and reporting of clinical trials in knee osteoarthritis: a targeted literature review
Authors: Hummer Charles D. , Huang Yili , Sheehan Brendan
Published: February 2022

Background

The Osteoarthritis Research Society International (OARSI) updated their guideline for clinical trials on knee osteoarthritis (KOA) in 2015, which contains recommendations for the conduct, design, and reporting of clinical trials. The purpose of this study was to assess the quality of clinical trials published between 2010 and 2020 investigating intra-articular interventions in patients with KOA using the OARSI recommendations.

Methods

A targeted literature review was conducted to identify randomized controlled trials in patients with KOA receiving intra-articular interventions, published between 2010 and 2020. Included studies were assessed using the OARSI recommendations. For a comparison between the time periods before and after the introduction of the new OARSI recommendations, the year 2016 was selected as the cut-off.

Results

One hundred forty-eight publications, representing 139 unique trials, were included in this review. Included studies adhered to between 9 and 24 recommendations (median: 19). The highest increase in adherence from studies published in 2016 or earlier compared to after 2016 was seen in the reporting and registration of trials and the use of structural outcome measures. Overall, adherence to the recommendations related to the collection of biochemical biomarkers and the use of structural outcome measures remained low.

Conclusion

An improvement can be made in the conduct, design, and reporting of clinical trials for intra-articular therapies in KOA. Despite proper guidelines, quality of clinical trials varies, and the methodological deficiencies found are preventable and can be corrected. The quality of research should be considered when making treatment decisions for patients with KOA in clinical practice.
Predictors of adverse events after percutaneous pedicle screws fixation in patients with single-segment thoracolumbar burst fractures
Authors: Dong Shengtao , Li Zongyuan , Tang Zhi-ri , Zheng Yuanyuan , Yang Hua , Zeng Qiuming
Published: February 2022

Background

Percutaneous pedicle screw fixation (PPSF) is the primary approach for single-segment thoracolumbar burst fractures (TLBF). The healing angle at the thoracolumbar junction is one of the most significant criteria for evaluating the efficacy of PPSF. Therefore, the purpose of this study was to analyze the predictors associated with the poor postoperative alignment of the thoracolumbar region from routine variables using a support vector machine (SVM) model.

Methods

We retrospectively analyzed patients with TLBF operated at our academic institute between March 1, 2014 and December 31, 2019. Stepwise logistic regression analysis was performed to assess potential statistical differences between all clinical and radiological variables and the adverse events. Based on multivariate logistic results, a series of independent risk factors were fed into the SVM model. Meanwhile, the feature importance of radiologic outcome for each parameter was explored. The predictive performance of the SVM classifier was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy (ACC) and confusion matrices with 10-fold cross-validation, respectively.

Results

In the recruited 150 TLBFs, unfavorable radiological outcomes were observed in 53 patients (35.33%). The relationship between osteoporosis (p = 0.036), preoperative Cobb angle (p = 0.001), immediate postoperative Cobb angle (p = 0.029), surgically corrected Cobb angle (p = 0.001), intervertebral disc injury (Score 2 p = 0.001, Score 3 p = 0.001), interpedicular distance (IPD) (p = 0.001), vertebral body compression rate (VBCR) (p = 0.010) and adverse events was confirmed by univariate regression. Thereafter, independent risk factors including preoperative Cobb angle, the disc status and IPD and independent protective factors surgical correction angle were identified by multivariable logistic regression. The established SVM classifier demonstrated favorable predictive performance with the best AUC = 0.93, average AUC = 0.88, and average ACC = 0.87. The variables associated with radiological outcomes, in order of correlation strength, were intervertebral disc injury (42%), surgically corrected Cobb angle (25%), preoperative Cobb angle (18%), and IPD (15%). The confusion matrix reveals the classification results of the discriminant analysis.

Conclusions

Critical radiographic indicators and surgical purposes were confirmed to be associated with an unfavorable radiographic outcome of TLBF. This SVM model demonstrated good predictive ability for endpoints in terms of adverse events in patients after PPSF surgery.
To debate or not to debate? Examining the contribution of debating when studying medical ethics in small groups
Authors: Amar-Gavrilman Nehora , Bentwich Miriam Ethel
Published: February 2022

Background

Medical ethics is a significant learning topic for medical students, and often studied through small group learning (SGL) to encourage critical thinking (CT) and tolerance for ambiguity, both considered particularly important when coping with medical ethics dilemmas. However, a previous study about CT and tolerance for ambiguity in medical ethics SGL produced mixed results. Debating is a pedagogical tool known to enhance CT but never used before in medical ethics learning. This paper examines whether the use of debate may enhance medical ethics SGL by contributing to the CT of students and their tolerance of ambiguity.

Methods

Intervention study using the qualitative microanalysis research method, based on videotaped observations that were analyzed through Kamin’s model of CT and non-CT. The study was conducted at Bar-Ilan University’s Faculty of Medicine in the years 2017–2019. Forty-four students and 4 facilitators participated, equally split between 4 small groups. Twenty-four medical ethics SGL sessions at the beginning and end of the year were videotaped, 2 groups – with no intervention, 1 group included partial debate intervention and 1 group fully used debates. Results were compared for changes in CT and ambiguity before and during the intervention period.

Results

The full intervention (debating) group had the highest increase in utterances reflecting CT, thus actually doubling the median number of CT utterances at the end of the year in comparison to the median number at the beginning of the year. In a similar manner, the debate group exhibited the only group in which there was an increase in the median utterances of tolerance to ambiguity. Nevertheless, the debate group also exhibited the largest increase in the median non-CT utterances and the lowest decrease of intolerance to ambiguity, when comparing the end of the year to the beginning of the year sessions.

Conclusions

Debating is an important enhancement to SGL in medical ethics; however, it does not guarantee a complete absence of non-CT.
Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden
Authors: Wiik Johanna , Kärrberg Cecilia , Nilsson Staffan , Strander Björn , Jacobsson Bo , Sengpiel Verena
Published: February 2022

Background

Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD.

Methods

A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008–2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders.

Results

Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21–2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40–2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66–4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02–1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18–2.54), and pPROM (aOR 2.44, 95% CI 1.40–4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3–10 mm, thereafter increasing by 15% with each additional millimeter.

Conclusions

This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue.

Cone-length should be recorded at treatment, for future prenatal risk estimation.
Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)
Authors: Talaei Mohammad , Faustini Sian , Holt Hayley , Jolliffe David A. , Vivaldi Giulia , Greenig Matthew , Perdek Natalia , Maltby Sheena , Bigogno Carola M. , Symons Jane , Davies Gwyneth A. , Lyons Ronan A. , Griffiths Christopher J. , Kee Frank , Sheikh Aziz , Richter Alex G. , Shaheen Seif O. , Martineau Adrian R.
Published: February 2022

Background

Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods

We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Results

Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06–1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11–1.39), South Asian vs. White ethnicity (1.65, 1.10–2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with  lower risk (0.80, 0.70–0.93, for ≥ 10 vs. 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02–1.19), South Asian vs. White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02–1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions

Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.
Machine learning and bioinformatics analysis revealed classification and potential treatment strategy in stage 3–4 NSCLC patients
Authors: Li Chang , Tian Chen , Zeng Yulan , Liang Jinyan , Yang Qifan , Gu Feifei , Hu Yue , Liu Li
Published: February 2022

Background

Precision medicine has increased the accuracy of cancer diagnosis and treatment, especially in the era of cancer immunotherapy. Despite recent advances in cancer immunotherapy, the overall survival rate of advanced NSCLC patients remains low. A better classification in advanced NSCLC is important for developing more effective treatments.

Method

The calculation of abundances of tumor-infiltrating immune cells (TIICs) was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), xCell (xCELL), Tumor IMmune Estimation Resource (TIMER), Estimate the Proportion of Immune and Cancer cells (EPIC), and Microenvironment Cell Populations-counter (MCP-counter). K-means clustering was used to classify patients, and four machine learning methods (SVM, Randomforest, Adaboost, Xgboost) were used to build the classifiers. Multi-omics datasets (including transcriptomics, DNA methylation, copy number alterations, miRNA profile) and ICI immunotherapy treatment cohorts were obtained from various databases. The drug sensitivity data were derived from PRISM and CTRP databases.

Results

In this study, patients with stage 3–4 NSCLC were divided into three clusters according to the abundance of TIICs, and we established classifiers to distinguish these clusters based on different machine learning algorithms (including SVM, RF, Xgboost, and Adaboost). Patients in cluster-2 were found to have a survival advantage and might have a favorable response to immunotherapy. We then constructed an immune-related Poor Prognosis Signature which could successfully predict the advanced NSCLC patient survival, and through epigenetic analysis, we found 3 key molecules (HSPA8, CREB1, RAP1A) which might serve as potential therapeutic targets in cluster-1. In the end, after screening of drug sensitivity data derived from CTRP and PRISM databases, we identified several compounds which might serve as medication for different clusters.

Conclusions

Our study has not only depicted the landscape of different clusters of stage 3–4 NSCLC but presented a treatment strategy for patients with advanced NSCLC.
The adverse impact of coronary artery disease on left ventricle systolic and diastolic function in patients with type 2 diabetes mellitus: a 3.0T CMR study
Authors: Wang Jin , Li Yuan , Guo Ying-Kun , Huang Shan , Shi Rui , Yan Wei-Feng , Qian Wen-Lei , He Guang-Xi , Yang Zhi-Gang
Published: February 2022

Background

Coronary artery disease (CAD) confers considerable morbidity and mortality in diabetes. However, the role of CAD in additive effect of left ventricular (LV) function has rarely been explored in type 2 diabetes mellitus (T2DM) patients. This study aimed to investigate how CAD affect LV systolic and diastolic function in T2DM patients.

Materials and methods

A total of 282 T2DM patients {104 patients with CAD [T2DM (CAD +)] and 178 without [T2DM (CAD −)]} and 83 sex- and age- matched healthy controls underwent cardiac magnetic resonance scanning. LV structure, function, global strains [including systolic peak strain (PS), peak systolic (PSSR) and diastolic strain rate (PDSR) in radial, circumferential and longitudinal directions] and late gadolinium enhancement (LGE) parameters were measured. T2DM (CAD +) patients were divided into two subgroups based on the median of Gensini score (60) which was calculated to assess the severity of CAD. Multivariable linear regression analyses were constructed to investigate the determinants of reduced LV function.

Results

Compared with normal controls, T2DM (CAD −) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV global strains, while T2DM(CAD +) patients showed more marked increase and decrease than T2DM(CAD-) and healthy controls, except for longitudinal PDSR (PDSR-L) (all P < 0.017). All of LV global strains demonstrated a progressive decrease from normal controls, through Gensini score ≤ 60, to Gensini score > 60 group, except for PDSR-L (all P < 0.017). CAD was an independent predictor of reduced LV global circumferential PS (GCPS, β = 0.22, p < 0.001), PSSR (PSSR-C, β = 0.17, p = 0.005), PDSR (PDSR-C, β = 0.22, p < 0.001), global radial PS (GRPS, β = 0.19, p = 0.001), and global longitudinal PS (GLPS, β = 0.18, p = 0.003) in T2DM. The Gensini score was associated with decreased GCPS, PSSR-C, PDSR-C, GRPS, and GLPS in T2DM (CAD +) (all p < 0.05).

Conclusion

CAD has an additive deleterious effect on LV systolic and diastolic function in T2DM patients. Among T2DM (CAD +) patients, the Gensini score is associated with reduced LV contractile and diastolic function.

Trial registration Retrospectively registered
RNA helicase DHX15 decreases cell apoptosis by NF-κB signaling pathway in Burkitt lymphoma
Authors: Chen Yuan , Chen Xianglei , Pan Lili , Huang Yuanmao , Cai Yuanhua , Li Jinggang , Li Yang , Wang Shaoyuan
Published: February 2022

Background

DHX15 is one of the RNA helicase family members involving in several biological processes. Studies have reported that overexpression of DHX15 is related to cancer progression. However, the role of DHX15 in Burkitt lymphoma (BL) and latent Epstein-Barr virus (EBV) infection remains to be elucidated.

Methods

Expression of DHX15 was measured in BL patient by immunohistochemical staining. In vitro study, a CCK-8 assay was used to analyze cell proliferation and flow cytometry was performed to assess cell cycle, apoptosis and mitochondria membrane potential. Members of NF-κB signaling pathway and apoptotic-related proteins expression were measured by western-blot. EBV latent infection products and RNA polymerase III transcripts expression were determined by quantitative real-time PCR and western-blot. In vivo study, HE, IHC, TUNEL and ISH assays were used to analyze the effect of DHX15 on subcutaneous tumor nodes formation.

Results

DHX15 was overexpressed in Burkitt lymphoma patients and tends to be associated with poor progression-free survival and poor overall survival. Knockdown of DHX15 significantly inhibited BL tumor growth, reduced cell proliferation, induced cell cycle arrest and increased cell apoptosis. Further analysis showed that canonical NF-κB signaling and its downstream targets, mitochondria and Caspase were involved in the increased cell apoptosis after DHX15 gene knockdown. Furthermore, knockdown of DHX15 reduced EBV latent infection products expression and inhibited RNA polymerase III activity.

Conclusion

DHX15 may be an oncogene in the development of BL and a potential therapeutic target for the treatment of BL and latent EBV infection.
Appropriateness of referrals from primary care for lumbar MRI
Authors: Krogh Susanne Brogaard , Jensen Tue Secher , Rolving Nanna , Thomsen Janus Nikolaj Laust , Hansen Casper Brink , Werenberg Christoffer Høj , Rasmussen Erik , Carlson Rune , Jensen Rikke Krüger
Published: February 2022

Background

International guidelines do not recommend routine imaging, including magnetic resonance imaging (MRI), and seek to guide clinicians only to refer for imaging based on specific indications. Despite this, several studies show an increase in the use of MRI among patients with low back pain (LBP) and an imbalance between appropriate versus inappropriate use of MRI for LBP. This study aimed to investigate to what extent referrals from general practice for lumbar MRI complied with clinical guideline recommendations in a Danish setting, contributing to the understanding and approaches to lumbar MRI for all clinicians managing LBP in the primary sector.

Materials and methods

From 2014 to 2018, all referrals for lumbar MRI were included from general practitioners in the Central Denmark Region for diagnostic imaging at a public regional hospital. A modified version of the American College of Radiology Imaging Appropriateness Criteria for LBP was used to classify referrals as appropriate or inappropriate, based on the unstructured text in the GPs’ referrals. Appropriate referrals included fractures, cancer, symptoms persisting for more than 6 weeks of non-surgical treatment, previous surgery, candidate for surgery or suspicion of cauda equina. Inappropriate referrals were sub-classified as lacking information about previous non-surgical treatment and duration.

Results

Of the 3772 retrieved referrals for MRI of the lumbar spine, 55% were selected and a total of 2051 referrals were categorised. Approximately one quarter (24.5%) were categorised as appropriate, and 75.5% were deemed inappropriate. 51% of the inappropriate referrals lacked information about previous non-surgical treatment, and 49% had no information about the duration of non-surgical treatment. Apart from minor yearly fluctuations, there was no change in the distribution of appropriate and inappropriate MRI referrals from 2014 to 2018.

Conclusion

The majority of lumbar MRI referrals (75.5%) from general practitioners for lumbar MRI did not fulfil the ACR Imaging Appropriateness Criteria for LBP based on the unstructured text of their referrals. There is a need for referrers to include all guideline-relevant information in referrals for imaging. More research is needed to determine whether this is due to patients not fulfilling guideline recommendations or simply the content of the referrals.