bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving NPVR ≥ 80% as technical success of high-intensity focused ultrasound ablation for uterine fibroids: a cohort study
Authors: Li Shuang , Yang Meijie , Yu Jingwen , Ma Wangwa , Deng Yongbin , Hu Liang , Chen Jin-Yun
Published: May 2024

Objective

To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group.

Materials and methods

Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan–Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group.

Main results

A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR < 70% group, 31.0% in the NPVR 70–79% group, 18.2% in the NPVR 80–89% group and 17.8% in the NPVR ≥ 90% group (P < 0.05). However, no difference was found between the group of NPVR 80−89% and the group of NPVR ≥ 90% (P = 0.499). Age of patients and signal intensity on T2-weighted imaging (T2WI) of tumours were found to be independent risk factors for long-term re-intervention in the NPVR ≥ 80% group. A younger age and greater signal intensity on T2W images corresponded to a greater risk of re-intervention.

Conclusion

USgHIFU, an alternative treatment for uterine fibroids, has reliable long-term efficacy. NPVR ≥ 80% can be used as a sign of technical success, which can reduce re-intervention rates. However, an important step is to communicate with patients in combination with the age of patients and the signal intensity on T2WI of fibroids.

Trial registration

This retrospective study was approved by the ethics committee at our institution (Registration No. HF2023001; Date: 06/04/2023). The Chinese Clinical Trial Registry provided full approval for the study protocol (Registration No. CHiCTR2300074797; Date: 16/08/2023).
Psychometric properties and criterion related validity of the Norwegian version of hospital survey on patient safety culture 2.0
Authors: Olsen Espen , Addo Seth Ayisi Junior , Hernes Susanne Sørensen , Christiansen Marit Halonen , Haugen Arvid Steinar , Leonardsen Ann-Chatrin Linqvist
Published: May 2024

Background

Several studies have been conducted with the 1.0 version of the Hospital Survey on Patient Safety Culture (HSOPSC) in Norway and globally. The 2.0 version has not been translated and tested in Norwegian hospital settings. This study aims to 1) assess the psychometrics of the Norwegian version (N-HSOPSC 2.0), and 2) assess the criterion validity of the N-HSOPSC 2.0, adding two more outcomes, namely ‘pleasure of work’ and ‘turnover intention’.

Methods

The HSOPSC 2.0 was translated using a sequential translation process. A convenience sample was used, inviting hospital staff from two hospitals (N = 1002) to participate in a cross-sectional questionnaire study. Data were analyzed using Mplus. The construct validity was tested with confirmatory factor analysis (CFA). Convergent validity was tested using Average Variance Explained (AVE), and internal consistency was tested with composite reliability (CR) and Cronbach’s alpha. Criterion related validity was tested with multiple linear regression.

Results

The overall statistical results using the N-HSOPSC 2.0 indicate that the model fit based on CFA was acceptable. Five of the N-HSOPSC 2.0 dimensions had AVE scores below the 0.5 criterium. The CR criterium was meet on all dimensions except Teamwork (0.61). However, Teamwork was one of the most important and significant predictors of the outcomes. Regression models explained most variance related to patient safety rating (adjusted R2 = 0.38), followed by ‘turnover intention’ (adjusted R2 = 0.22), ‘pleasure at work’ (adjusted R2 = 0.14), and lastly, ‘number of reported events’ (adjusted R2=0.06).

Conclusion

The N-HSOPSC 2.0 had acceptable construct validity and internal consistency when translated to Norwegian and tested among Norwegian staff in two hospitals. Hence, the instrument is appropriate for use in Norwegian hospital settings. The ten dimensions predicted most variance related to ‘overall patient safety’, and less related to ‘number of reported events’. In addition, the safety culture dimensions predicted ‘pleasure at work’ and ‘turnover intention’, which is not part of the original instrument.
Statin administration or blocking PCSK9 alleviates airway hyperresponsiveness and lung fibrosis in high-fat diet-induced obese mice
Authors: Liang Lin , Chung Sook In , Guon Tae-Eun , Park Kyung Hee , Lee Jae-Hyun , Park Jung-Won
Published: May 2024

Background

Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity.

Methods

Male C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-β1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed.

Results

High-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-β1, IL-1β, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-β1 over-expressed transgenic mice with normal diet.

Conclusions

Lipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity.

Graphical abstract
Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population
Authors: Zhang Shuijing , Liu Wenbing , Xu Bin , Wang Shuguang , Du Zhongyan , Cheng Wenke
Published: May 2024

Background

Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass index (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear.

Methods

This prospective cohort analysis included 355,242 UK Biobank participants with available TyG index and TyG-BMI data and no history of CVD. Cox proportional risk models assessed the association between the TyG index, TyG-BMI and SCA risk. Additionally, Accelerated Failure Time (AFT) models were employed to investigate the timing of SCA onset. The impact of dynamic increases in TyG index and TyG-BMI levels on SCA risk was examined using restricted cubic spline.

Results

Over a median follow-up period of 165.4 months (interquartile range 156.5–174 months), 1,622 cases of SCA were recorded. Multivariate Cox regression analysis revealed a 9% increase in SCA risk per standard deviation increase in TyG index (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04–1.15) and an 14% increase per standard deviation increase in TyG-BMI (aHR 1.14, 95% CI 1.09–1.2). AFT models indicated earlier median times to SCA occurrence with increasing quintiles of TyG index and TyG-BMI compared to the lowest quintile (P for trend < 0.05). SCA risk was linearly (P = 0.54) and non-linearly (P = 0.007) correlated with gradual increases in TyG index and TyG-BMI levels, respectively. Sex-stratified analyses showed stronger associations in women.

Conclusions

Higher TyG index and TyG-BMI levels are associated with an increased SCA risk and earlier onset, particularly in women.
Characteristics of the Western Province, Zambia, trial site for evaluation of attractive targeted sugar baits for malaria vector control
Authors: Arnzen Annie , Wagman Joseph , Chishya Chama , Orange Erica , Eisele Thomas P. , Yukich Joshua , Ashton Ruth A. , Chanda Javan , Sakala Jimmy , Chanda Benjamin , Muyabe Rayford , Kaniki Tresford , Mwenya Mwansa , Mwaanga Gift , Eaton Will T. , Mancuso Brooke , Mungo Alice , Mburu Monicah M. , Bubala Nchimunya , Hagwamuna Ackim , Simulundu Edgar , Saili Kochelani , Miller John M. , Silumbe Kafula , Hamainza Busiku , Ngulube Willy , Moonga Hawela , Chirwa Jacob , Burkot Thomas R. , Slutsker Laurence , Littrell Megan
Published: May 2024

Background

The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites.

Methods

This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area.

Results: Characterization of the trial site

The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older.

Conclusion

Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa.
Trends in the contribution of greenhouse gas emissions from food and beverage purchases in Mexico: 1989–2020
Authors: Canto-Osorio Francisco , Langellier Brent A. , Unar-Munguia Mishel , Barrientos-Gutiérrez Tonatiuh , Rivera Juan A. , Diez-Roux Ana V. , Stern Dalia , López-Olmedo Nancy
Published: May 2024

Background

Assessing the trends in dietary GHGE considering the social patterning is critical for understanding the role that food systems have played and will play in global emissions in countries of the global south. Our aim is to describe dietary greenhouse gas emissions (GHGE) trends (overall and by food group) using data from household food purchase surveys from 1989 to 2020 in Mexico, overall and by education levels and urbanicity.

Methods

We used cross-sectional data from 16 rounds of Mexico’s National Income and Expenditure Survey, a nationally representative survey. The sample size ranged from 11,051 in 1989 to 88,398 in 2020. We estimated the mean total GHGE per adult-equivalent per day (kg CO2-eq/ad-eq/d) for every survey year. Then, we estimated the relative GHGE contribution by food group for each household. These same analyses were conducted stratifying by education and urbanicity.

Results

The mean total GHGE increased from 3.70 (95%CI: 3.57, 3.82) to 4.90 (95% CI 4.62, 5.18) kg CO2-eq/ad-eq/d between 1989 and 2014 and stayed stable between 4.63 (95% CI: 4.53, 4.72) and 4.89 (95% CI: 4.81, 4.96) kg CO2-eq/ad-eq/d from 2016 onwards. In 1989, beef (19.89%, 95% CI: 19.18, 20.59), dairy (16.87%, 95% CI: 16.30, 17.42)), corn (9.61%, 95% CI: 9.00, 10.22), legumes (7.03%, 95% CI: 6.59, 7.46), and beverages (6.99%, 95% CI: 6.66, 7.32) had the highest relative contribution to food GHGE; by 2020, beef was the top contributor (17.68%, 95%CI: 17.46, 17.89) followed by fast food (14.17%, 95% CI: 13.90, 14.43), dairy (11.21%, 95%CI: 11.06, 11.36), beverages (10.09%, 95%CI: 9.94, 10.23), and chicken (10.04%, 95%CI: 9.90, 10.17). Households with higher education levels and those in more urbanized areas contributed more to dietary GHGE across the full period. However, households with lower education levels and those in rural areas had the highest increase in these emissions from 1989 to 2020.

Conclusions

Our results provide insights into the food groups in which the 2023 Mexican Dietary Guidelines may require to focus on improving human and planetary health.
The association between remnant cholesterol and bone mineral density in US adults: the National Health and Nutrition Examination Survey (NHANES) 2013–2018
Authors: Xiao Peilun , Wang Zhihang , Lu Zeyao , Liu Shijia , Huang Chongjun , Xu Ying , Tian Ye
Published: May 2024

Background

Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans.

Methods

This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013–2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD.

Results

This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (β= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P < 0.001). Moreover, RC had a stronger effect on total spine BMD than total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).

Conclusions

This study found that serum RC was negatively related to total spine BMD in U.S. adults. These findings emphasized the important role of RC in bone health in American adults.
A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients
Authors: Xiong Si-Ping , Wang Chun-Hua , Zhang Mei-fang , Yang Xia , Yun Jing-Ping , Liu Li-Li
Published: May 2024

Background

Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC.

Methods

A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell’s concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis.

Results

A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time.

Conclusions

The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.
Scurvy masquerading as IgA vasculitis
Authors: Kassa Hanna L. , Singh S. , Douglas-Jones M. , Schermbrucker Gill , De Lange J , Phoya Frank , Butters Claire , Hlela Carol , Coetzee Ashton , Banderker Ebrahim , Webb Kate
Published: May 2024

Background

Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children.

Case presentation

We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy.

Conclusion

Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential.

Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.
Role of surgical simulation on self-reported confidence level on cardiothoracic surgical trainees
Authors: Yean Len En , Hashim Shahrul Amry bin
Published: May 2024

Background

Simulated self-practice using simulation models could improve fine motor skills and self confidence in surgical trainees.

Aims

The purpose of this study is to evaluate on self-reported confidence level in cardiothoracic surgical trainees by using surgical simulation models.

Methods

We conducted a cross-sectional study on all surgeons (n=10) involved in MIS simulation training. All surgeons are required to perform on three minimally invasive surgery (MIS) procedures (Mitral Valve Repair, Mitral Valve Replacement and Aortic Valve Replacement). A questionnaire was designed based on two existing scales related to self-confidence, the surgical self-efficacy scale [SSES] and the perceived competency scale [PCS]. We assessed their self-confidence (before and after training) in the use of simulation in MIS procedures using rating scales 1-5. The mean score was calculated for each domain and used as the predictor variable. We also developed six questions (PCS) using Objective Structured Assessment of Technical Skills (OSAT) related to each domain and asked participants how confident they were after performing each MICS procedure.

Results

The mean score was 4.7 for all assessed domains, except "knowledge" (3.8). Surgeons who had performed one or more MIS procedures had higher scores (P<0.05). There was no correlation between the number of MIS procedures performed and self-confidence scores.

Conclusions

The results indicate that the cardiac surgery training based on MIS simulation improves trainees and consultants in terms of the level of self-confidence. Although surgeons generally have high levels of self-confidence after simulation training in MIS cardiac procedures, there is still room for improvement with respect to technical skills related to the procedure itself and its results.
Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages
Authors: Nomaki Kohei , Fujikawa Risako , Masuda Takahiro , Tsuda Makoto
Published: May 2024

CD11c-positive (CD11c+) microglia have attracted considerable attention because of their potential implications in central nervous system (CNS) development, homeostasis, and disease. However, the spatiotemporal dynamics of the proportion of CD11c+ microglia in individual CNS regions are poorly understood. Here, we investigated the proportion of CD11c+ microglia in six CNS regions (forebrain, olfactory bulb, diencephalon/midbrain, cerebellum, pons/medulla, and spinal cord) from the developmental to adult stages by flow cytometry and immunohistochemical analyses using a CD11c reporter transgenic mouse line, Itgax-Venus. We found that the proportion of CD11c+ microglia in total microglia varied between CNS regions during postnatal development. Specifically, the proportion was high in the olfactory bulb and cerebellum at postnatal day P(4) and P7, respectively, and approximately half of the total microglia were CD11c+. The proportion declined sharply in all regions to P14, and the low percentage persisted over P56. In the spinal cord, the proportion of CD11c+ microglia was also high at P4 and declined to P14, but increased again at P21 and thereafter. Interestingly, the distribution pattern of CD11c+ microglia in the spinal cord markedly changed from gray matter at P4 to white matter at P21. Collectively, our findings reveal the differences in the spatiotemporal dynamics of the proportion of CD11c+ microglia among CNS regions from early development to adult stages in normal mice. These findings improve our understanding of the nature of microglial heterogeneity and its dynamics in the CNS.
Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction
Authors: Chen Hui , Nie Ping , Li Jingling , Wu Yongqi , Yao Bo , Yang Yabing , Lash Gendie E. , Li Ping
Published: May 2024

Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.
SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure
Authors: Pannu Sonal , Exline Matthew C. , Bednash Joseph S. , Englert Joshua A. , Diaz Philip , Bartlett Amy , Brock Guy , Wu Qing , Davis Ian C. , Crouser Elliott D.
Published: May 2024

Background

The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.

Methods

We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named “SCARLET” (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.

Discussion

Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.

Trial registration

The trial was registered at www.clinicaltrials.gov on 5/31/2023 (NCT05881135).

Trial status

Currently enrolling.
Suppressing random noise in seismic signals using wavelet thresholding based on improved chaotic fruit fly optimization
Authors: Yang Feng , Liu Jun , Hou Qingming , Wu Lu
Published: May 2024

Suppressing random noise in seismic signals is an important issue in research on processing seismic data. Such data are difficult to interpret because seismic signals usually contain a large amount of random noise. While denoising can be used to reduce noise, most denoising methods require the prior estimation of the threshold of the signals to handle random noise, which makes it difficult to ensure optimal results. In this paper, we propose a wavelet threshold-based method of denoising that uses the improved chaotic fruit fly optimization algorithm. Our method of selects uses generalized cross-validation as the objective function for threshold selection. This objective function is optimized by introducing an adjustment coefficient to the chaotic fruit fly optimization algorithm, and the optimal wavelet threshold can then be obtained without any prior information. We conducted denoising tests by using synthetic seismic records and empirical seismic data acquired from the field. We added three types of noise, with different average signal-to-noise ratios, to synthetic seismograms containing noise with original intensities of − 5, − 1, and 4 dB, respectively. The results showed that after denoising, the signal-to-noise ratios of the three types of noise increased to 7.12, 10.04, and 14.26, while the mean-squared errors in the results of the proposed algorithm decreased to 0.006, 0.0031, and 0.0012, respectively.
A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels
Authors: Ho Wei-Min , Chen Chia-Ying , Chiang Tai-Wei , Chuang Trees-Juen
Published: May 2024

Glioblastoma (GBM) is the most common malignant brain tumor in adults, which remains incurable and often recurs rapidly after initial therapy. While large efforts have been dedicated to uncover genomic/transcriptomic alternations associated with the recurrence of GBMs, the evolutionary trajectories of matched pairs of primary and recurrent (P-R) GBMs remain largely elusive. It remains challenging to identify genes associated with time to relapse (TTR) and construct a stable and effective prognostic model for predicting TTR of primary GBM patients. By integrating RNA-sequencing and genomic data from multiple datasets of patient-matched longitudinal GBMs of isocitrate dehydrogenase wild-type (IDH-wt), here we examined the associations of TTR with heterogeneities between paired P-R GBMs in gene expression profiles, tumor mutation burden (TMB), and microenvironment. Our results revealed a positive correlation between TTR and transcriptomic/genomic differences between paired P-R GBMs, higher percentages of non-mesenchymal-to-mesenchymal transition and mesenchymal subtype for patients with a short TTR than for those with a long TTR, a high correlation between paired P-R GBMs in gene expression profiles and TMB, and a negative correlation between the fitting level of such a paired P-R GBM correlation and TTR. According to these observations, we identified 55 TTR-associated genes and thereby constructed a seven-gene (ZSCAN10, SIGLEC14, GHRHR, TBX15, TAS2R1, CDKL1, and CD101) prognostic model for predicting TTR of primary IDH-wt GBM patients using univariate/multivariate Cox regression analyses. The risk scores estimated by the model were significantly negatively correlated with TTR in the training set and two independent testing sets. The model also segregated IDH-wt GBM patients into two groups with significantly divergent progression-free survival outcomes and showed promising performance for predicting 1-, 2-, and 3-year progression-free survival rates in all training and testing sets. Our findings provide new insights into the molecular understanding of GBM progression at recurrence and potential targets for therapeutic treatments.
Interactive Malaysian Childhood Healthy Lifestyle (i-MaCHeL) programme: a single-arm pilot study
Authors: Rashid Ahmad Faezi Ab , Syed Saadun Tarek Wafa Sharifah Wajihah Wafa , Talib Ruzita Abd , Bakar Nor Mazlina Abu
Published: May 2024

Background

The growing obesity epidemic in Malaysia presents a public health challenge that requires innovative intervention strategies. In an effort to address this problem, an Interactive Malaysian Childhood Healthy Lifestyle (i-MaCHeL) programme, which is a web-based initiative designed for preschool child–parent dyads offers a novel approach. Nevertheless, the success of such a web-based intervention depends on several interrelated factors. This research aims to examine the feasibility of i-MaCHeL in the Malaysian context, its usability for preschool child–parent dyads, and the acceptability of the programme among these user groups.

Methods

This was a single-arm pilot study involving 46 child–parent dyads recruited from six government preschools in Terengganu, Malaysia. The preschools were selected using a cluster random sampling technique at the preschool level. The intervention feasibility was determined based on the retention rate of participants in the pilot study. The System Usability Scale (SUS) and intervention process evaluation were used to assess the usability and acceptability of the web-based i-MaCHeL programme.

Results

The retention data demonstrated that 42 out of 46 participants completed the 13-week intervention programme, which showed that the overall retention rate was 91.3%. A mean (SD) SUS score of 84.70 (13.82) was obtained from parents, indicating that the web-based i-MaCHeL had an acceptable usability level. The mean scores of the process evaluation items ranged from 4.52 (0.63) to 4.83 (0.38), demonstrating that the web-based i-MaCHeL was highly accepted by the parents. The acceptability data also indicated that at least 92.9% (39/42) of the parents agreed/strongly agreed that the web content, programme duration, intervention dose, WhatsApp group, and delivery mode were appropriate.

Conclusions

According to these findings, the i-MaCHeL intervention using a web-based approach was feasible, usable, and acceptable as part of a weight-related behaviour change intervention for preschool child–parent dyads. This pilot study demonstrated that the web-based i-MaCHeL was feasible and promising for delivering weight-related behavioural intervention to child–parent dyads.

Trial registration

ClinicalTrials.gov, NCT04711525. Registered on January 15, 2021.
A protocol to determine the acceptability and feasibility of a pilot intervention emergency department virtual observation unit fall prevention program
Authors: Jones Abigail E. , Kennedy Maura , Hayden Emily M. , Ouchi Kei , N. Shankar Kalpana , Chary Anita , Li Angel , Loughlin Kara Mc , White Benjamin , Franco-Garcia Esteban , Dellheim Vanessa , Liu Shan W.
Published: May 2024

Background

As a third of all community dwellers aged 65+ fall each year, falls are common reasons for older adults to present to an Emergency Department (ED). Although EDs should assess patients’ multifactorial fall risks to prevent future fall-related injuries, this frequently does not occur. We describe our protocol to determine the feasibility, acceptability, and safety of a pilot ED Virtual Observation Unit (VOU) Falls program.

Methods

To ensure standardized conduct and reporting, the Standard Protocol Items for Intervention Trials (SPIRIT) guidelines will be used. The VOU is a program where patients are sent home from the ED but are part of a virtual observation unit in that they can call on-call ED physicians while they are being treated for conditions such as cellulitis, congestive heart failure, or pneumonia. A paramedic conducts daily visits with the patient and facilitates a telemedicine consult with an ED physician. VOU nursing staff conduct daily assessments of patients via telemedicine. The ED VOU Falls program is one of the VOU pathways and is a multi-component fall prevention program for fall patients who present after an ED visit. The paramedic conducts a home safety evaluation, a Timed Up and Go Test (TUG). During the VOU visit, the ED physician conducts a telemedicine visit, while the paramedic is visiting the home, to review patients' fall-risk-increasing drugs and their TUG test. We will determine feasibility by calculating rates of patient enrollment refusal, and adherence to fall-risk prevention recommendations using information from 3-month follow-up telephone calls, as well as qualitative interviews with the paramedics. We will determine the acceptability of the ED VOU Falls program based on patient and provider surveys using a Likert scale. We will ask VOU nursing staff to report any safety issues encountered while the patient is in the ED VOU Falls program (e.g., tripping hazards). We will use the chi-square test or Fisher’s exact test for categorical variables, Student’s t-test for continuous variables, and Mann-Whitney for nonparametric data. We will review interview transcripts and generate codes. Codes will then be extracted and organized into concepts to generate an overall theme following grounded theory methods. This is a pilot study; hence, results cannot be extrapolated. However, a definite trial would be the next step in the future to determine if such a program could be implemented as part of fall prevention interventions.

Discussion

This study will provide insights into the feasibility and acceptability of a novel ED VOU Falls program with the aim of ultimately decreasing falls. In the future, such a program could be implemented as part of fall prevention interventions.
Evaluation of MSCT severity scoring for prediction of mortality among patients with COVID-19
Authors: Mohammed Hossam Abd El-Moez , Mansour Tarek Mohamed M. , Abdalla Hytham , Gaber Mostafa A. , Badawy M. Sh. , El-baroudy Mohamed M. , AlAmir Ahmed Yousri , Abdelrazek Ghada M. , Elnabi Mona Gouda Maghrabi Abd
Published: May 2024

Background

Lung CT imaging may reveal COVID-19 abnormalities earlier than RTPCR. CT may be more sensitive than RT-PCR for diagnosing COVID-19-related pneumonia.

Aim

This study assesses the accuracy of multi-slice computed tomography (MSCT) grading in predicting COVID-19 mortality.

Methods

COVID-19 RT-PCR. For severity scores, all patients’ clinical examinations, history, and chest MSCT data were collected.

Results

According to the chest MSCT score, 102 (51.5%), 70 (35%), and 28 (14%) patients had mild, moderate, and severe illness. Out of the patients, 62 (31%) died, and 69% survived. Patients with severe MSCT scores showed a considerably greater mean age than other groups (P < 0.001). Moreover, this group had a considerably higher mean BMI (P < 0.001), and a majority (57.1%) were obese (P < 0.001). Compared to the mild group, the moderate and severe groups had significantly increased rates of diabetes, hypertension, and liver disease (P < 0.001). The moderate group had a greater rate of no comorbidities (P < 0.001). A severe MSCT score was linked to increased leucocytes, C-reactive protein, ESR, ferritin, d-dimer, HbA1c, and fasting blood sugar, as well as decreased mean lymphocytes (P < 0.001). Severe MSCT scores were linked to increased ICU admissions (P < 0.001) and increased demand for advanced mechanical ventilation and oxygen assistance (P < 0.001). A severe MSCT score was associated with the highest death rate, followed by a moderate MSCT score. Low mortality rates were observed in mild MSCT-scored patients (P < 0.001).

Conclusion

MSC T score severity is a reliable and noninvasive way to predict COVID-19 mortality
Analysis of the Trends and Influencing Factors for Postoperative Cough in Patients with Esophageal Cancer Based on Patient-Reported Outcomes
Authors: Sun Jie , Liang Rui , Zhang Qing , Liu Na , Zhu Qingmiao , Li Qi , Yu Dan , Yu Yuan , Qin Jianjun
Published: May 2024

Background

Cough is a common symptom that affects patients’ recovery and quality of life after esophagectomy. This study sought to investigate trends in postoperative cough and the factors that influence cough.

Methods

A total of 208 of 225 patients were enrolled in this study. The Mandarin Chinese version of the Leicester Cough Questionnaire was administered the day before surgery and at three time points (1 week, 1 month, and 3 months) after esophagectomy to assess patient-reported outcomes.

Results

All patients’ LCQ-MC scores after surgery were lower than presurgery (P < 0.05), with the lowest score found 1 week after esophagectomy. Factors associated with a cough 1 week after surgery included clinical stage of cancer (OR 0.782, 95% CI 0.647–0.944, P = 0.011), anastomotic position (OR 1.241, 95% CI 1.069–1.441, P = 0.005), duration of surgery (OR 0.759, 95% CI 0.577–0.998, P = 0.049), and subcarinal lymph node dissection (OR 0.682, 95% CI 0.563–0.825, P < 0.001). Factors associated with a cough one month after surgery included clinical stage (OR 0.782, 95% CI 0.650–0.940, P = 0.009), anastomotic position (OR 1.293, 95% CI 1.113–1.503, P = 0.001), and maintaining a semi-reclining position (OR 1.440, 95% CI 1.175–1.766, P < 0.001). Factors associated with a cough 3 months after surgery were clinical stage (OR 0.741, 95% CI 0.591–0.928, P = 0.009) and anastomotic position (OR 1.220, 95% CI 1.037–1.435, P = 0.016).

Conclusions

This study showed that the factors influencing postoperative cough differed over time following esophagectomy. These results may warrant prospective intervention to better manage patients undergoing surgery for esophageal cancer to prevent postoperative cough.
Long-term Health Outcomes of New Persistent Opioid Use After Gastrointestinal Cancer Surgery
Authors: Khalil Mujtaba , Woldesenbet Selamawit , Munir Muhammad Musaab , Khan Muhammad Muntazir Mehdi , Rashid Zayed , Altaf Abdullah , Katayama Erryk , Endo Yutaka , Dillhoff Mary , Tsai Susan , Pawlik Timothy M.
Published: May 2024

Background

New persistent opioid use (NPOU) after surgery has been identified as a common complication. This study sought to assess the long-term health outcomes among patients who experienced NPOU after gastrointestinal (GI) cancer surgery.

Methods

Patients who underwent surgery for hepato-pancreato-biliary and colorectal cancer between 2007 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Mixed-effect multivariable logistic regression and Cox proportional hazard models were used to estimate the risk of mortality and hospital visits related to falls, respiratory events, or pain symptoms.

Results

Among 15,456 patients who underwent GI cancer surgery, 967(6.6%) experienced NPOU. Notably, the patients at risk for the development of NPOU were those with a history of substance abuse (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14–1.84), moderate social vulnerability (OR, 1.26; 95% CI, 1.06–1.50), an advanced disease stage (OR, 4.42; 95% CI, 3.51–5.82), or perioperative opioid use (OR, 3.07; 95% CI, 2.59–3.63. After control for competing risk factors, patients who experienced NPOU were more likely to visit a hospital for falls, respiratory events, or pain symptoms (OR, 1.45, 95% CI 1.18–1.78). Moreover, patients who experienced NPOU had a greater risk of death at 1 year (hazard ratio [HR], 2.15; 95% CI, 1.74–2.66).

Conclusion

Approximately 1 in 15 patients experienced NPOU after GI cancer surgery. NPOU was associated with an increased risk of subsequent hospital visits and higher mortality. Targeted interventions for individuals at higher risk for NPOU after surgery should be used to help mitigate the harmful effects of NPOU.
Practice Patterns and Outcomes Among Surgical Oncology Fellowship Graduates Performing Complex Cancer Surgery in the United States Across Different Career Stages
Authors: Tsilimigras Diamantis I. , Chatzipanagiotou Odysseas , Woldesenbet Selamawit , Endo Yutaka , Altaf Abdullah , Katayama Erryk , Pawlik Timothy M.
Published: May 2024

Background

Practice patterns and potential quality differences among surgical oncology fellowship graduates relative to years of independent practice have not been defined.

Methods

Medicare claims were used to identify patients who underwent esophagectomy, pancreatectomy, hepatectomy, or rectal resection for cancer between 2016 and 2021. Surgical oncology fellowship graduates were identified, and the association between years of independent practice, serious complications, and 90-day mortality was examined.

Results

Overall, 11,746 cancer operations (pancreatectomy [61.2%], hepatectomy [19.5%], rectal resection [13.7%], esophagectomy [5.6%]) were performed by 676 surgical oncology fellowship graduates (females: 17.7%). The operations were performed for 4147 patients (35.3%) by early-career surgeons (1–7 years), for 4104 patients (34.9%) by mid-career surgeons (8–14 years), and for 3495 patients (29.8%) by late-career surgeons (>15 years). The patients who had surgery by early-career surgeons were treated more frequently at a Midwestern (24.9% vs. 14.2%) than at a Northeastern institution (20.6% vs. 26.9%) compared with individuals treated by late-career surgeons (p < 0.05). Surgical oncologists had comparable risk-adjusted serious complications and 90-day mortality rates irrespective of career stage (early career [13.0% and 7.2%], mid-career [12.6% and 6.3%], late career [12.8% and 6.5%], respectively; all p > 0.05). Surgeon case-specific volume independently predicted serious complications across all career stages (high vs. low volume: early career [odds ratio {OR}, 0.80; 95% confidence interval {CI}, 0.65–0.98]; mid-career [OR, 0.81; 95% CI, 0.66–0.99]; late career [OR, 0.78; 95% CI, 0.62–0.97]).

Conclusion

Among surgical oncology fellowship graduates performing complex cancer surgery, rates of serious complications and 90-day mortality were comparable between the early-career and mid/late-career stages. Individual surgeon case-specific volume was strongly associated with postoperative outcomes irrespective of years of independent practice or career stage.