bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice
Authors: Song Mengqi , Cheng Haoyue , Zou Hao , Ma Kai , Lu Lianfang , Wei Qian , Xu Zejiang , Tang Zirui , Zhang Yuanzheng , Wang Yinan , Sun Chuandong
Published: June 2024

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.
Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning
Authors: Zhou Xiaoli , Zhao Lina , Zhang Zepei , Chen Yang , Chen Guangdong , Miao Jun , Li Xiaohui
Published: June 2024

Background

Prior studies have suggested a potential relationship between osteoporosis and sarcopenia, both of which can present symptoms of compromised mobility. Additionally, fractures among the elderly are often considered a common outcome of both conditions. There is a strong correlation between fractures in the elderly population, decreased muscle mass, weakened muscle strength, heightened risk of falls, and diminished bone density. This study aimed to pinpoint crucial diagnostic candidate genes for osteoporosis patients with concomitant sarcopenia.

Methods

Two osteoporosis datasets and one sarcopenia dataset were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes were identified using Limma and Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analysis, construction of protein–protein interaction (PPI) networks, and application of a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to determine candidate hub genes for diagnosing osteoporosis combined with sarcopenia. Receiver operating characteristic (ROC) curves and column line plots were generated.

Results

The merged osteoporosis dataset comprised 2067 DEGs, with 424 module genes filtered in sarcopenia. The intersection of DEGs between osteoporosis and sarcopenia module genes consisted of 60 genes, primarily enriched in viral infection. Through construction of the PPI network, 30 node genes were filtered, and after machine learning, 7 candidate hub genes were selected for column line plot construction and diagnostic value assessment. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value (area under the curve ranging from 1.00 to 0.93).

Conclusion

We identified 7 candidate hub genes (PDP1, ALS2CL, VLDLR, PLEKHA6, PPP1CB, MOSPD2, METTL9) and constructed column line plots for osteoporosis combined with sarcopenia. This study provides reference for potential peripheral blood diagnostic candidate genes for sarcopenia in osteoporosis patients.
Offering extended use of the contraceptive implant via an implementation science framework: a qualitative study of clinicians’ perceived barriers and facilitators
Authors: Rigler Nicole , Kully Gennifer , Hildebrand Marisa C. , Averbach Sarah , Mody Sheila K.
Published: June 2024

Background

The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years. However, studies that suggest efficacy up to 5 years. There is little information on the prevalence of extended use and the factors that influence clinicians in offering extended use. We investigated clinician perspectives on the barriers and facilitators to offering extended use of the contraceptive implant.

Methods

Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured qualitative interviews. Participants were recruited from a nationwide survey study of reproductive health clinicians on their knowledge and perspective of extended use of the contraceptive implant. To optimize the diversity of perspectives, we purposefully sampled participants from this study. We used content analysis and consensual qualitative research methods to inform our coding and data analysis. Themes arose deductively and inductively.

Results

We interviewed 20 clinicians including advance practice clinicians, family medicine physicians, obstetrician/gynecologist and complex family planning sub-specialists. Themes regarding barriers and facilitators to extended use of the contraceptive implant emerged. Barriers included the FDA approval for 3 years and clinician concern about liability in the context of off-label use of the contraceptive implant. Educational materials and a champion of extended use were facilitators.

Conclusions

There is opportunity to expand access to extended use of the contraceptive implant by developing educational materials for clinicians and patients, identifying a champion of extended use, and providing information on extended use prior to replacement appointments at 3 years.
The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents
Authors: Wang Yanpei , Ma Leilei , Wang Jiali , Ding Yuyin , Liu Ningyu , Men Weiwei , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , He Yong , Dong Qi , Tao Sha
Published: June 2024

Background

The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated.

Methods

In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6–15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS).

Results

This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group.

Conclusions

The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.
Ageism and lookism as stereotypes of health disparity in intensive care units in Iran: a critical ethnography
Authors: Yarahmadi Sajad , Soleimani Mohsen , Gholami Mohammad , Fakhr-Movahedi Ali , Madani Seyed Mohsen Saeidi
Published: June 2024

Background

The intensive care unit presents structural complexities, and the prevailing power imbalance between patients and staff can lead to health disparities. Hence, unveiling the underlying factors that give rise to and reinforce these disparities can contribute to their prevention. This study aims to shed light on the stereotypes linked to ageism and lookism, which perpetuate health disparities within the intensive care unit setting in Iran.

Methods

This critical ethnographic study employed Carsepkan’s approach and was carried out in intensive care units in the west of Iran from 2022 to 2023. The data collection and analysis were conducted through three interconnected stages. In the initial stage, more than 300 h of observations were made at the research site. In the subsequent stage, a horizon analysis was performed. Conversations with 14 informants were conducted in the final stage to enrich the dataset further. Then the analysis process was carried out as in the previous step to uncover an implicit culture of health disparity. To verify the validity and reliability of the study, credibility, conformability, dependability, and transferability were all taken into account.

Findings

The ageism and lookism stereotypes emerged from seven main themes; youth-centric; negative ageism; age-friendliness; age-related priority; centered care for pediatric patients and families; appearance-centeredness; and a contradiction between belief and behavior.

Conclusion

This critical study showed that ageism and lookism stereotypes permeated the intensive care unit’s culture. These stereotypes have the potential to influence equality dynamics, as well as to foster and support health disparity in the intensive care unit.
Association between triglyceride glucose-waist to height ratio and coronary heart disease: a population-based study
Authors: Zhuang Yangping , Wang Yu , Sun Peifen , Ke Jun , Chen Feng
Published: June 2024

Background

The Triglyceride glucose (TyG) index-related indicators improve risk stratification by identifying individuals prone to atherosclerosis early in life. This study aimed to examine the relation between TyG-waist circumference-to-height ratio (TyG-WHtR) and coronary heart disease.

Methods

Data from four National Health and Nutrition Examination Surveys (NHANES) cycles between 2011 and 2018 were used for a cross-sectional study. The association between TyG-WHtR and coronary heart disease risk was examined using a multifactorial logistic regression model, and corresponding subgroup analyses were performed. Nonlinear correlations were analyzed using smooth curve fitting and threshold effects analysis. When nonlinear connections were discovered, appropriate inflection points were investigated using recursive methods.

Results

TyG-WHtR and coronary heart disease were significantly positively correlated in the multifactorial logistic regression analysis. Subgroup analyses and interaction tests revealed that gender, age, smoking status, and cancer were not significantly associated with this correlation (P for interaction > 0.05). Furthermore, utilizing threshold effect analysis and smooth curve fitting, a nonlinear connection with an inflection point of 0.36 was observed between TyG-WHtR and coronary heart disease.

Conclusions

According to this study, the American population is far more likely to have coronary heart disease if they have higher TyG-WHtR levels.
Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018
Authors: Shen Jing , Wang Zhen , Liu Yong , Wang Tao , Wang Xiao-Yu , Qu Xin-Hui , Chen Zhi-Ping , Han Xiao-Jian
Published: June 2024

Objective

Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia.

Methods

This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used.

Results

During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis.

Conclusions

This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.
Country-specific determinants for COVID-19 case fatality rate and response strategies from a global perspective: an interpretable machine learning framework
Authors: Zhou Cui , Wheelock Åsa M. , Zhang Chutian , Ma Jian , Li Zhichao , Liang Wannian , Gao Jing , Xu Lei
Published: June 2024

Background

There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries.

Methods

Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries.

Findings

Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class.

Conclusions

Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.
Cytokines and lymphocyte subsets are associated with disease severity of severe fever with thrombocytopenia syndrome
Authors: Song Li , Zou Wenlu , Wang Gang , Qiu Ling , Sai Lintao
Published: June 2024

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity.

Methods

We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023.

Results

A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity.

Conclusions

Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS.
Traditional Chinese Medicine and renal regeneration: experimental evidence and future perspectives
Authors: Zhang Denglu , Jiang Huihui , Yang Xianzhen , Zheng Sanxia , Li Yi , Liu Shuai , Xu Xiangdong
Published: June 2024

Repair of acute kidney injury (AKI) is a typical example of renal regeneration. AKI is characterized by tubular cell death, peritubular capillary (PTC) thinning, and immune system activation. After renal tubule injury, resident renal progenitor cells, or renal tubule dedifferentiation, give rise to renal progenitor cells and repair the damaged renal tubule through proliferation and differentiation. Mesenchymal stem cells (MSCs) also play an important role in renal tubular repair. AKI leads to sparse PTC, affecting the supply of nutrients and oxygen and indirectly aggravating AKI. Therefore, repairing PTC is important for the prognosis of AKI. The activation of the immune system is conducive for the body to clear the necrotic cells and debris generated by AKI; however, if the immune activation is too strong or lengthy, it will cause damage to renal tubule cells or inhibit their repair. Macrophages have been shown to play an important role in the repair of kidney injury. Traditional Chinese medicine (TCM) has unique advantages in the treatment of AKI and a series of studies have been conducted on the topic in recent years. Herein, the role of TCM in promoting the repair of renal injury and its molecular mechanism is discussed from three perspectives: repair of renal tubular epithelial cells, repair of PTC, and regulation of macrophages to provide a reference for the treatment and mechanistic research of AKI.
Development of eating skills in infants and toddlers from a neuropediatric perspective
Authors: Kalhoff Hermann , Kersting Mathilde , Sinningen Kathrin , Lücke Thomas
Published: June 2024

Early infant feeding and swallowing are complex motor processes involving numerous muscles in coordination, e.g. the orofacial muscles as well as the muscles of the pharynx, larynx and esophagus. The newborn’s reflexive drinking develops into the ability to ingest pureed complementary food as infancy progresses. Finally, in the last part of the first year of life, a differentiated eating, chewing and swallowing process develops allowing the voluntary intake of different foods of the family diet. The dietary schedule for the first year of life, which describes the recommended nutrition of infants in Germany, corresponds to these milestones in eating development. Disturbances in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere with the development of eating skills. Swallowing disorders (dysphagia) in children can have a detrimental effect on food intake and pose a serious risk to growth and development. Their prevention treatment requires a multidisciplinary approach with the aim of enabling the child to eat independently in the long term.
Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer
Authors: Morla-Barcelo Pere Miquel , Laguna-Macarrilla David , Cordoba Octavi , Matheu Gabriel , Oliver Jordi , Roca Pilar , Nadal-Serrano Mercedes , Sastre-Serra Jorge
Published: June 2024

Background

Early-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3–15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.

Methods

RNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.

Results

DEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.

Conclusions

In conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient’s prognosis.
News sequences types of Staphylococcus aureus isolated from human pathologicals fluids in Burkina Faso
Authors: Traoré Roukiatou , Ouédraogo Ganamé Abasse , Ouédraogo Abdoul Salam , Savadogo Aly , Zongo Cheikna , Godreuil Sylvain
Published: June 2024

Staphylococcus aureus is a pathogen with high epidemic potential frequently involved in nosocomials and communities infections. The pathogenicity of Staphylococcus aureus is due to both its ability to resist antibiotics and to Produce toxins. This work aims at studying the resistance and Molecular Epidemiology of Staphylococcus aureus. Antibiotic susceptibility of the 70 strains isolates of Staphylococcus aureus was determined by agar diffusion while Multiplex PCR and MLST were used to search toxin-coding genes and MRSA typing, respectively. 14.28% of isolates were multidrug resistant. Staphylococcus aureus showed high susceptibility to aminoglycoside and Macrolides familly. lukS-PV/lukF-PV and sea genes were detected in 45% and 3% of Staphylococcus aureus respectively. Ten (10) sequence types including ST5710, ST2430, ST5289, ST5786, ST6942, ST6943, ST6944, ST6945, ST6946, ST6947 have been reported. The study showed a diversity of antibiotic resistance phenotypes and a great diversity of MRSA clones causing infections.
Co-production of a systematic review on decision coaching: a mixed methods case study within a review
Authors: Jull Janet , Smith Maureen , Carley Meg , Stacey Dawn , Graham Ian D. ,   The Cochrane Decision Coaching Review Team, Boland Laura , Dunn Sandra , Dwyer Andrew A. , Finderup Jeanette , Kasper Jürgen , Kienlin Simone , Köpke Sascha , Légaré France , Lewis Krystina , Rahn Anne Christin , Rutherford Claudia , Zhao Junqiang
Published: June 2024

Background

Co-production is a collaborative approach to prepare, plan, conduct, and apply research with those who will use or be impacted by research (knowledge users). Our team of knowledge users and researchers sought to conduct and evaluate co-production of a systematic review on decision coaching.

Methods

We conducted a mixed-methods case study within a review to describe team co-production of a systematic review. We used the Collaborative Research Framework to support an integrated knowledge translation approach to guide a team through the steps in co-production of a systematic review. The team agreed to conduct self-study as a study within a review to learn from belonging to a co-production research team. A core group that includes a patient partner developed and conducted the study within a review. Data sources were surveys and documents. The study coordinator administered surveys to determine participant preferred and actual levels of engagement, experiences, and perceptions. We included frequency counts, content, and document analysis.

Results

We describe co-production of a systematic review. Of 17 team members, 14 (82%) agreed to study participation and of those 12 (86%) provided data pre- and post-systematic review. Most participants identified as women (n = 9, 75.0%), researchers (n = 7, 58%), trainees (n = 4, 33%), and/or clinicians (n = 2, 17%) with two patient/caregiver partners (17%). The team self-organized study governance with an executive and Steering Committee and agreed on research co-production actions and strategies. Satisfaction for engagement in the 11 systematic review steps ranged from 75 to 92%, with one participant who did not respond to any of the questions (8%) for all. Participants reported positive experiences with team communication processes (n = 12, 100%), collaboration (n = 12, 100%), and negotiation (n = 10–12, 83–100%). Participants perceived the systematic review as co-produced (n = 12, 100%) with collaborative (n = 8, 67%) and engagement activities to characterize co-production (n = 8, 67%). Participants indicated that they would not change the co-production approach (n = 8, 66%). Five participants (42%) reported team logistics challenges and four (33%) were unaware of challenges.

Conclusions

Our results indicate that it is feasible to use an integrated knowledge translation approach to conduct a systematic review. We demonstrate the importance of a relational approach to research co-production, and that it is essential to plan and actively support team engagement in the research lifecycle.
Factors associated with early inhospital adverse outcome following surgery for acute appendicitis in Uganda: a multicenter cohort
Authors: Farhan Sharif Yusuf , Abraha Demoz , Edyedu Isaac , Molen Selamo Fabrice , Mauricio William , Odong Samuel Oledo , Mugeni Michael , Muhumuza Joshua
Published: June 2024

Introduction

Surgery for acute appendicitis has been associated with significant morbidity. This study aimed to determine the factors associated with early inhospital adverse outcomes following surgery for acute appendicitis in Uganda.

Methods

This was a multicentre, prospective cohort in which early inhospital outcome following surgery for acute appendicitis was assessed at 4 regional referral hospitals in Uganda. The occurrence of complications during the admission period was documented as well as the length of hospital stay. Factors associated with adverse outcomes were determined using Poisson regression.

Results

Of the 102 patients who underwent surgery for acute appendicitis, the majority were males 79(77.5%) with a mean age of 23.8(SD = 12.5) years. The perforated appendix was seen in 26 (25.5%) patients. Post-operative complications occurred in 21(20.6%) with the commonest being surgical site infection in 19(18.6%) patients. The median length of hospital stay was 3(IQR = 3–4) days with 43(42.2%) staying in hospital for more than 3 days. The presence of anemia (Hb < 8) (aRR = 1.376, CI = 1.159–1.634,P =  < 0.001) and having a perforated appendix (aRR = 1.263, CI = 1.026–1.555,P = 0.027) were independently associated with occurrence of complications while being HIV positive (aRR = 1.379, CI = 1.105–1.721,P = 0.005) and having a perforated appendix (aRR = 1.258, CI = 1.019–1.554,P = 0.033) were independently associated with prolonged hospital stay.

Conclusion

Community education about early presentation is still required in order to reduce the number of patients that present late which should, in turn, reduce the risk of complications and length of hospital stay.
Role of EBUS in lymphoma presenting as superior vena cava syndrome: bronchoscopic and sonographic findings: a case report
Authors: Thomas Ancy Elsa , Thangakunam Balamugesh , Mathew Benjamin Barsouma , Kodiatte Thomas Alex
Published: June 2024

Background

The clinical description of superior vena cava syndrome has been widely studied; however, there is limited information on bronchoscopic findings in clinical practice.

Case presentation

A 57-year-old man presented with facial and neck swelling and pedal edema of 6 months duration. Computed tomography showed mediastinal lesions in the right paratracheal stations with thrombosis of the right internal jugular vein and superior vena cava (SVC). Without establishing a diagnosis, he was started on oral steroids elsewhere and his symptoms progressed. He did not receive anticoagulation therapy. Bronchoscopy showed edematous supraglottic and glottic regions with hyperemia of the airway mucosa. Endobronchial Ultrasonography revealed a mediastinal mass of heterogeneous echotexture in the lower right paratracheal region, with mediastinal collateral blood vessels. He underwent EBUS-guided aspiration cytology and intranodal forceps biopsy, which confirmed the diagnosis of non-Hodgkin’s.

Conclusion

In cases with an unconfirmed diagnosis of lymphoma, it is prudent to refrain from administering glucocorticoids, as these medications can exhibit lympholytic properties and may hinder the diagnostic process. Due to extensive collateral formation in superior vena cava syndrome, utilizing Doppler during endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) can identify numerous mediastinal collateral vessels, thus minimizing the risk of bleeding.
President's Page: Advancing the technologies of applied geophysics
Authors: Gelinsky Stephan , Cheng Arthur
Published: June 2024

One of the main goals of SEG is to support the advancement of the science of applied geophysics. In pursuit of this goal, what can we do to give more visibility and focus to the technologies that together create applied geophysics?
Cost–utility analysis of Social Stories™ for children with autism spectrum disorder in mainstream primary schools: results from a randomised controlled trial
Authors: Wang Han-I. , Bell Kerry , Blackwell Jane , Welch Charlie , Mandefield Laura , Watson Judith , Standley Emma , McMillan Dean , Gilbody Simon , Wright Barry , Hewitt Catherine , Parrott Steve
Published: June 2024

Background

One in 57 children are diagnosed with autism in the UK, and the estimated cost for supporting these children in education is substantial. Social Stories™ is a promising and widely used intervention for supporting children with autism in schools and families. It is believed that Social Stories™ can provide meaningful social information to children that can improve social understanding and may reduce anxiety. However, no economic evaluation of Social Stories has been conducted.

Aims

To assess the cost-effectiveness of Social Stories through Autism Spectrum Social Stories in Schools Trial 2, a multi-site, pragmatic, cluster-randomised controlled trial.

Method

Children with autism who were aged 4–11 years were recruited and randomised (N = 249). Costs measured from the societal perspective and quality-adjusted life-years (QALYs) measured by the EQ-5D-Y-3L proxy were collected at baseline and at 6-month follow-up for primary analysis. The incremental cost-effectiveness ratio was calculated, and the uncertainty around incremental cost-effectiveness ratios was captured by non-parametric bootstrapping. Sensitivity analyses were performed to evaluate the robustness of the primary findings.

Results

Social Stories is likely to result in a small cost savings (–£191 per child, 95% CI −767.7 to 337.7) and maintain similar QALY improvements compared with usual care. The probability of Social Stories being a preferred option is 75% if society is willing to pay £20 000 per QALY gained. The sensitivity analysis results aligned with the main study outcomes.

Conclusions

Compared with usual care, Social Stories did not lead to an increase in costs and maintained similar QALY improvements for primary-aged children with autism.
A pilot study of post-consolidation chemoimmunotherapy for high-risk neuroblastoma (ANBL19P1): A report from the Children’s Oncology Group.
Authors: Desai Ami V. , Naranjo Arlene , LaBarre Brian , Goldsmith Kelly C. , Granger Meaghan P. , States Lisa , Green Sean , Trunzo Mariel , Fitzgerald Wendy , DuBois Steven G. , Bagatell Rochelle , Park Julie R. , Marachelian Araz
Published: June 2024

10004

Background: Post-consolidation anti-GD2 antibody-based immunotherapy has improved survival for newly diagnosed patients (pts) with high-risk neuroblastoma (HRNBL). However, nearly half of newly diagnosed pts relapse. Based upon the efficacy of anti-GD2 antibody dinutuximab given with chemotherapy (chemoimmunotherapy) in the relapse setting, we hypothesized that post-consolidation chemoimmunotherapy may further improve frontline outcomes. ANBL19P1 first assessed the feasibility of delivering chemoimmunotherapy after tandem high-dose chemotherapy with autologous stem cell transplant (ASCT). Methods: Pts <31 years old with HRNBL who received 4-6 cycles of Induction chemotherapy +/- up to 4 cycles of post-Induction chemotherapy or chemoimmunotherapy, underwent tandem ASCT, had no evidence of progressive disease (PD), and met organ function criteria were eligible. Therapy, administered every 28 days, consisted of temozolomide and irinotecan on Days 1-5, dinutuximab on Days 2-5, and sargramostim on Days 6-12 during Cycles 1-5; isotretinoin on Days 8-21 during Cycles 1-6. Therapy was deemed feasible if the 95% confidence interval (CI) placed on the percentage of pts that completed 5 cycles of dinutuximab + chemotherapy without PD within 30 weeks contained 75%, and if the interim monitoring rules for feasibility and excessive toxicity were not triggered. Event-free (EFS) and overall survival (OS) were determined from time of enrollment. Results: From 11/30/20-6/30/23, 40 eligible pts enrolled and started protocol therapy. 87.5% (n=35) were ≥18 months old and 97.5% (n=39) had INRG Stage M disease, at diagnosis. 87.5% (95% CI 73.9%, 94.5%) completed 5 cycles of dinutuximab + chemotherapy without PD within 30 weeks, exceeding the feasibility benchmark of 75%. Feasibility and monitoring rules were not triggered. Five pts were removed from protocol therapy prior to Cycle 4 [physician determination (n=2), pt/parent refusal of further therapy (n=2), and PD (n=1)]. No unacceptable toxicities or deaths on protocol therapy were reported. Toxicities of interest are summarized (Table). One-year EFS and OS were 90.0±5.0% and 97.5±2.7%, respectively (median follow-up time for pts without event=1.2 years). Conclusions: Administration of post-consolidation chemoimmunotherapy in pts who underwent tandem ASCT is tolerable and met pre-defined feasibility criteria. The impact of this approach on survival outcomes will be studied in a future COG trial. Clinical trial information: NCT04385277 . [Table: see text]
Radiation dose escalation and local control for intermediate-risk rhabdomyosarcoma on ARST1431: A report from the Children’s Oncology Group
Authors: Jackson Christopher , Xue Wei , GUPTA ABHA A. , Qumseya Amira , Dasgupta Roshni , Hill-Kayser Christine E. , Spalding Aaron , Rodeberg David A. , Harrison Douglas James , Venkatramani Rajkumar , Wolden Suzanne L.
Published: June 2024

10007

Background: The objective of this study was to evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma (IR-RMS) treated on the Children’s Oncology Group (COG) ARST1431 clinical trial. To improve local control, the radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors > 5cm at diagnosis and residual gross disease at the time of RT. Methods: The297 patients randomized on ARST1431 were included. LF was defined as progression or relapse at the primary tumor site. Gray’s test was used to compare the cumulative incidence of LF across variables. Results: There was a trend for lower 3-year LF in group III patients with fusion-positive disease (11.1%, 95% confidence interval (CI) 4.5%-21.1%) compared to patients with fusion-negative disease (21.8%, 95% CI 15.8%-28.4%), p = 0.09.There was no difference in the 3-year LF rate for patients who underwent proton RT (16.3%, 95% CI 9.6%-24.7%) compared to photon RT (16.2%, 95% CI 10.2%-23.6%;), p = 0.8. The 3-year LF rate for all patients with tumors > 5cm at diagnosis (24.9%, 95% CI 18.6%-31.7%) was significantly higher than that of patients with tumors ≤5cm at diagnosis (9.9%, 95% CI 5.2%-16.4%), p < 0.01. Of 81 patients with tumors > 5cm and residual gross disease after induction chemotherapy who went on to receive RT, 62 (76.5%) received the protocol-specified boost to 59.4 Gy. Patients who received the boost had a 3-year LF rate of 32.1% (95% CI 20.1%-44%), while patients who did not undergo an RT boost had a 3-year LF rate of 16.1% (95% CI 3.8%-36.2%), p = 0.3. For patients with group III, non-parameningeal disease, those who underwent delayed primary excision (DPE) had a significantly lower LF rate compared to those who did not undergo DPE (3-year rate of 5.6% (95% CI 1.4%-14.0%) vs. 22.0% (95% CI 14.5-30.7%), p < 0.01). Conclusions: On ARST1431, larger tumors ( > 5cm at diagnosis) were associated with increased risk of LF. Dose escalation to 59.4 Gy did not improve local control for patients with tumors > 5cm at diagnosis with residual gross disease at the time of RT. For a select group of non-parameningeal, group III patients who underwent DPE followed by RT, local control was improved. Clinical trial information: NCT02567435 .
Clinical characteristics, prognosis, and immunotherapy outcome in pediatric melanoma: Analysis from a large Chinese cohort.
Authors: Wang Juan , Song Mengjia , Lan Yingxia , Huang Junting , Zhu Jia , Lu Suying , Sun Feifei , Zhen Zijun , Que Yi , Hu Wanming , Zhang Yu , Zhang Yizhuo
Published: June 2024

10050

Background: Malignant melanoma in children and adolescents is rare, with limited data on Chinese populations.To assess the clinical characteristics, survival, prognostic factors, and the efficacy of immunotherapy in a real-world cohort of Chinese pediatric patients with melanoma. Methods: This is a retrospective, cohort study included pediatric melanoma patients between February, 2005 and May, 2021, with a median follow-up time of 76.7 months. Data analyses were conducted in May, 2023. This study enrolled patients from Sun Yat-sen University Cancer Center, the biggest cancer institution in South China for cancer prevention, diagnosis and treatment. Inclusion criteria for this study were as follows: 1) histopathologically confirmed diagnosis of melanoma; 2) Age ≤18 year; 3) with complete clinical data on sex, age, histopathological features, etc. The exclusion criteria was secondary malignant melanoma. Main outcomes and measures were patient’s OS and EFS. Results: 43 patients were enrolled, with median age of 138.9 (range 13.1-215.0) months, including 30 cutaneous melanoma, 7 meningeal melanoma, 5 mucosal melanoma, and 1 uveal melanoma. The frequency of BRAF V600E mutation was 16.7% (4/24). Mismatch repair proteins were normally expressed (7/7), and the positive rate of programmed cell death ligand 1 expression was 55.6% (5/9). The event-free survival and overall survival of cutaneous, mucosal and meningeal melanoma were 46.7±9.1% vs 75.0±21.7% vs 16.7±15.2% ( P = 0.010), 65.5±8.9% vs 75.0±21.7% vs 16.7±15.2% (P< 0.001), respectively. Survival of cutaneous melanoma were associated with pathological type, ulceration, Clark level, disease spread, sentinel lymph node status, tumor stage and Ki-67 expression. 5 of 9 patients who were treated with PD-1 inhibitors (5 with PD-1 inhibitors alone, 3 with PD-1 inhibitors plus angiogenesis inhibitors, 1 with combination of anti-PD1, anti-angiogenic inhibitors plus chemotherapy) were evaluable with the overall response rate of 20%. The most common immune-related adverse event was hypothyroidism. Conclusions: This is the largest real-world study in pediatric melanoma patients in Asia. The prognosis of mucosal melanoma was favorable, followed by cutaneous melanoma, and meningeal melanoma had the worst prognosis. PD-1 antibody combined with angiogenesis inhibitors maybe a promising choice in pediatric melanoma.
Effect of oncolytic herpes simplex virus on fusion-positive rhabdomyosarcoma to radiotherapy.
Authors: Shaikh Maryam G. , Nazam Nazia , Butey Swatika , Erwin Michael H , Stewart Jerry E. , Aye Jamie , Beierle Elizabeth A
Published: June 2024

10063

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite multimodal interventions including surgery, chemotherapy, and radiotherapy, nearly a third of patients with localized disease will experience tumor recurrence. Patients with tumors harboring an oncogenic FOXO1 fusion are at greater risk of relapse and are most in need of novel therapies. Oncolytic viruses are being explored as treatments for pediatric tumors, and data suggest that oncolytic viruses may enhance responses to chemoradiotherapy. M002 is a genetically engineered oncolytic herpes simplex virus (oHSV) that exhibits aneurovirulence in normal cells. M002 selectively replicates in malignant cells, eliminating these cells through cellular burst during the lytic cycle. In the present study, we explored the efficacy of the M002 virus alone and in combination with low-dose ionizing radiotherapy in a human patient-derived xenograft (PDX) model of fusion-positive RMS (FP-RMS). Methods: A human FP-RMS PDX was established and maintained by injection into the quadriceps femoris muscle of athymic nude mice under Institutional Animal Care and Use Committee guidelines (IACUC-09363). Tumors were dissociated and cells were treated with increasing multiplicity of infection (MOI) of either the oHSV, R3659 or its genetically engineered variant, M002. A colorimetric assay evaluated the cytotoxicity of oHSV treatments on the RMS PDX cells after 24, 48, and 72 hours of infection. In separate experiments, cells treated with vehicle (control) or infected with M002 were exposed to irradiation (2 Gy), and viability was determined at 24, 48, 72, and 96 hours. Results: Treatment with M002 or its parent construct, R3659, significantly reduced RMS PDX cell viability in a dose-dependent manner at all time points. M002 showed slightly higher cytotoxicity than R3659 as measured by lethal dose 50% (LD50, 37±1.25 vs 44±0.95 PFU/cell, M002 vs R3659, at 24 hours, p=0.02). When sub-lethal doses of M002 were combined with low-dose irradiation, RMS PDX cell viability was significantly decreased compared to cells treated with either M002 or irradiation alone (26% decrease at 10 PFU/cell). Conclusions: Our preliminary data highlight that M002 exhibits cytotoxicity in a PDX model of FP-RMS. Treatment with M002 further increased the cytotoxicity of ionizing radiation compared to individual treatments, suggesting that oHSV sensitized the cells to radiotherapy. Future studies in vivo may provide more pre-clinical evidence for the radio-sensitizing and therapeutic potential of M002 in FP-RMS.