bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial
Authors: Yu Edward , Allan Alison L. , Sanatani Michael , Lewis Debra , Warner Andrew , Dar A. Rashid , Yaremko Brian P. , Lowes Lori E. , Palma David A. , Raphael Jacques , Vincent Mark D. , Rodrigues George B. , Fortin Dalilah , Inculet Richard I. , Frechette Eric , Bierer Joel , Law Jeffery , Younus Jawaid , Malthaner Richard A.
Published: July 2022

Background

Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy.

Methods

We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis.

Results

CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001).

Conclusion

The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.
Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study
Authors: Ivasyk Iryna , Chatterjee Abhinaba , Jordan Catherine , Geiselmann Matthew T. , Chang Peter S. , Kamel Hooman , Khormaee Sariah
Published: July 2022

Background

Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database.

Methods

Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period.

Results

In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA.

Conclusions

The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.
Large hiatus hernia: time for a paradigm shift?
Authors: Rajkomar Kheman , Berney Christophe R.
Published: July 2022

Background

Laparoscopic large hiatal hernia (LHH) repair remains a challenge despite three decades of ongoing attempts at improving surgical outcome. Its rarity and complexity, coupled with suboptimal initial approach that is usually best suited for small symptomatic herniae have contributed to unacceptable higher failure rates.

Results

We have therefore undertaken a systematic appraisal of LHH with a view to clear out our misunderstandings of this entity and to address dogmatic practices that may have contributed to poor outcomes.

Conclusions

First, we propose strict criteria to define nomenclature in LHH and discuss ways of subcategorising them. Next, we discuss preoperative workup strategies, paying particular attention to any relevant often atypical symptoms, indications for surgery, timing of surgery, role of surgery in the elderly and emphasizing the key role of a preoperative CT imaging in evaluating the mediastinum. Some key dissection methods are then discussed with respect to approach to the mediastinal sac, techniques to avoid/deal with pleural breach and rationale to avoid Collis gastroplasty. The issues pertaining to the repair phase are also discussed by evaluating the merits of the cruroplasty, fundoplication types and gastropexy. We end up debating the role of mesh reinforcement and assess the evidence with regards to recurrence, reoperation rate, complications, esophageal dilatation, delayed gastric emptying and mortality. Lastly, we propose a rationale for routine postoperative investigations.
Effect of Enterococcus faecalis OG1RF on human calvarial osteoblast apoptosis
Authors: Li Yang , Sun Shuyu , Wen Cheng , Zhong Jialin , Jiang Qianzhou
Published: July 2022

Background

Enterococcus faecalis is a dominant pathogen in the root canals of teeth with persistent apical periodontitis (PAP), and osteoblast apoptosis contributes to imbalanced bone remodelling in PAP. Here, we investigated the effect of E. faecalis OG1RF on apoptosis in primary human calvarial osteoblasts. Specifically, the expression of apoptosis-related genes and the role of anti-apoptotic and pro-apoptotic members of the BCL-2 family were examined.

Methods

Primary human calvarial osteoblasts were incubated with E. faecalis OG1RF at multiplicities of infection corresponding to infection time points. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, caspase-3/-8/-9 activity assay, polymerase chain reaction (PCR) array, and quantitative real-time PCR were used to assess osteoblast apoptosis.

Results

E. faecalis infection increased the number of early- and late-phase apoptotic cells and TUNEL-positive cells, decreased the mitochondrial membrane potential (ΔΨm), and activated the caspase-3/-8/-9 pathway. Moreover, of all 84 apoptosis-related genes in the PCR array, the expression of 16 genes was upregulated and that of four genes was downregulated in the infected osteoblasts. Notably, the mRNA expression of anti-apoptotic BCL2 was downregulated, whereas that of the pro-apoptotic BCL2L11, HRK, BIK, BMF, NOXA, and BECN1 and anti-apoptotic BCL2A1 was upregulated.

Conclusions

E. faecalis OG1RF infection triggered apoptosis in human calvarial osteoblasts, and BCL-2 family members acted as regulators of osteoblast apoptosis. Therefore, BCL-2 family members may act as potential therapeutic targets for persistent apical periodontitis.
Retraction Note: Chinese medicine Di-Huang-Yi-Zhi protects PC12 cells from H2O2-induced apoptosis by regulating ROS-ASK1-JNK/p38 MAPK signaling
Authors: Zhang Li-Min , Zhen Rong-Rong , Gu Chao , Zhang Tian-Li , Li Yue , Jin Miao , Hu Bing , An Hong-Mei
Published: July 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-020-2834-8.
Early experiences with quality-assured HbA1c and professional glucose point-of-care testing in general practice: a cross-sectional observational study among patients, nurses and doctors
Authors: Smits Marleen , Hopstaken Rogier , Terhaag Lusan , de Kort Gijs , Giesen Paul
Published: July 2022

Background

Point-of-care testing (POCT) is increasingly used in primary care. The rapid availability of the test result during the patient encounter increases the potential for patients and care providers to make a direct and joint decision on disease management. Our aim was to get insight into the first experiences of patients and healthcare professionals after introducing quality-controlled HbA1c and professional glucose POCT in diabetes care in their own general practices.

Methods

A cross-sectional observational study using paper questionnaires for patients, nurses and general practitioners (GPs) in 13 general practices in the Netherlands. HbA1c and professional glucose POCT was introduced after training and under day-to-day quality control. Patients filled in the questionnaire immediately after the test; nurses and GPs after a minimum period of three months from the starting date. Descriptive data analyses were performed.

Results

A total of 1551 fingerstick blood POC tests were performed (1126 HbA1c; 425 Glucose). For HbA1c POCT, 84 patients, 29 nurses and 11 GPs filled in the questionnaires. For professional glucose POCT, 30 patients, 17 nurses and 8 GPs responded. Response rates varied between 24 and 56%. Patients, nurses and GPs were generally (very) satisfied with the novel POC tests. Patients were most positive about the location (in the GPs’ office) and execution of the POC test (by their own nurse), and the speed of the test result. Almost all nurses indicated to have sufficient knowledge and skills to perform the test. Both nurses and GPs had confidence in the test results and indicated they experienced a higher patient satisfaction than with regular blood tests. Perceived disadvantages were the time required to regularly calibrate the devices and the extension of the consultation time because of the test. Patients, nurses and GPs generally expressed they wanted to continue performing these POC tests in routine diabetes care.

Conclusions

Patients, nurses and GPs expressed (very) positive first experiences after introducing HbA1c and professional glucose testing on two high-quality POCT devices in their own general practices. Further research, with a random selection procedure of practices and patients and in other regions and countries, is recommended to confirm these findings.
Evaluation of COVID-19 ECHO training program for healthcare workers in India - A Mixed-Method Study
Authors: Panda Rajmohan , Mishra Nivedita , Lahoti Supriya , Prabhu Rajath R , Mishra Arti , Singh Kalpana , Rai Kumud
Published: July 2022

Background

The Coronavirus Disease 2019 (COVID-19) has severely challenged healthcare delivery systems worldwide. Healthcare Workers were unable to assess and manage the cases due to limited knowledge of treating the virus and inadequate infrastructure. Digital interventions played a crucial role in the training of healthcare workers to get through the pandemic. Project Extension for Community Healthcare Outcomes (ECHO) initiated the COVID-ECHO telementoring program for strengthening the knowledge and skills of healthcare workers. The study aimed at assessing the effects of the ECHO telementoring model in the capacity building of healthcare workers in the context of COVID-19 in India.

Method

We adopted a mixed-method approach with a parallel combination design. A quantitative survey was used to measure changes in the knowledge and self-efficacy among doctors and nurses. In-depth Interviews were used for qualitative exploration of perceptions and experiences of all the study participants. Student t-test and ANOVA were used to assess significant differences between mean scores across participant characteristics for different themes. Statistical significance was set at p < 0.05. In-depth Interviews were analyzed using Framework Analysis. The evaluation followed the first five levels of Moore’s model.

Results

The results highlighted the strengthening of knowledge and skills of healthcare workers in the assessment and management of COVID-19 after the ECHO training. Learning and performance ratings were high as 96% reported an increase in knowledge and 98% were able to apply it in their clinical practices. The key challenges identified were technical issues like internet connectivity and lack of interaction due to limited visual connection. The hybrid sessions, use of video camera, feedback mechanism, and inclusion of Continuing Medical Education were recommended by participants to improve the model.

Conclusions

The findings of this study are an important addition to the pre-existing literature supporting the replicability of the ECHO model in the upskilling of healthcare professionals working in underserved and remote areas, not only in the context of COVID-19 but also in other public health domains. To enhance the effectiveness of this ECHO model, the study findings may be used to refine the model and improve the areas of concern.
Empowerment training to support service user involvement in mental health system strengthening in rural Ethiopia: a mixed-methods pilot study
Authors: Abayneh Sisay , Lempp Heidi , Rai Sauharda , Girma Eshetu , Getachew Medhanit , Alem Atalay , Kohrt Brandon A. , Hanlon Charlotte
Published: July 2022

Background

Increased service user involvement is recommended to improve weak mental health systems in low-and middle-income countries (LMICs). However, involvement is rarely implemented and interventions to support involvement are sparse. In this study we evaluated the acceptability, feasibility and perceived outcomes of an empowerment and training program for service users and health professionals to facilitate service user involvement in mental health system strengthening in rural Ethiopia.

Methods

REducing Stigma among HealthcAreProvidErs (RESHAPE) is a training curriculum for service users, their caregivers and aspirational health workers, which uses PhotoVoice methodology, to prepare them in participation of mental health systems strengthening in LMICs. We delivered the RESHAPE training augmented with empowerment content developed in Ethiopia. The interactive face-to-face training was delivered to service users and caregivers (over 10 days), and health professionals (1 day) separately. The study was an uncontrolled, convergent mixed-methods design. The quantitative data consisted of process data, satisfaction questionnaire, and a retrospective pre-test survey. Qualitative data included exit and follow-up in-depth interviews with the service users. Descriptive statistics were performed for quantitative data, and qualitative data were thematically analysed. The findings were integrated through triangulation for convergent themes following analysis.

Results

Twelve service users, 12 caregivers and 18 health professionals were enrolled, and completed the training. Participants valued the content and delivery process; the standard of the training program met their expectations and participation led to positive gains in understanding about mental illness, stigma, service-user involvement and human rights. The qualitative findings identified positive impacts, including increased self-confidence, sense of empowerment, social - and perceived therapeutic benefits.

Conclusions

We found that the RESHAPE training with added content for Ethiopia, delivered using the PhotoVoice methodology, is feasible, acceptable and of value to develop and implement training programmes which can empower service users to be involved in mental health system strengthening in this setting. Further study to assess the impact on health systems strengthening is warranted.
Carrying both COL1A2 and FBN2 gene heterozygous mutations results in a severe skeletal clinical phenotype: an affected family
Authors: Chen Jing , Xiang Qinqin , Xiao Xiao , Xu Bocheng , Xie Hanbing , Wang He , Yang Mei , Liu Shanling
Published: July 2022

Background

Osteogenesis imperfecta (OI) is the most common monogenic disease of the skeletal system and is usually caused by mutations in the COL1A1 or COL1A2 genes. Congenital contractural arachnodactyly syndrome (CCA) is an autosomal dominant hereditary disease of connective tissue. To date, the FBN2 gene is the only gene reported to cause CCA. Researchers found that COL1A2 and FBN2 are both involved in the extracellular matrix organization pathway. These findings suggest that these two genes play an important role in a similar mechanism and may trigger a synergistic effect.

Methods

Trio-whole-exome sequencing (Trio-WES) was performed to analyse the underlying genetic cause of a proband with OI in a Chinese family. Sanger sequencing was used to validate the mutations in 3 members of the family with OI with varying degrees of severity of skeletal abnormalities and the members with no clinical signs.

Result

A c.3304G > C mutation in the COL1A2 gene (p.Gly1102Arg) and a novel c.4108G > T mutation in the FBN2 gene (p.Glu1370*) were detected in the proband, an affected member of the family. The affected individuals with both mutations present a more severe phenotype, while affected individuals present a milder phenotype if only the mutation in COL1A2 is detected (c.3304G > C). The unaffected individual in this family did not have any mutations in the COL1A2 gene or FBN2 gene.

Conclusion

Our study is the first clinical report to indicate that patients carrying concomitant mutations in both the COL1A2 and FBN2 genes may present with more severe skeletal abnormalities. Furthermore, our study suggests the possibility of synergistic effects between the COL1A2 and FBN2 genes.
A novel signature derived from metabolism-related genes GPT and SMS to predict prognosis of laryngeal squamous cell carcinoma
Authors: Shen Yujie , Huang Qiang , Zhang Yifan , Hsueh Chi-Yao , Zhou Liang
Published: July 2022

Background

A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC.

Methods

We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of The Cancer Genome Atlas (TCGA) and Gene set enrichment analysis (GSEA). After the screening of protein–protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in LSCC cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results.

Results

Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The prognostic signature was proven as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application.

Conclusions

Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified it via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.
Modelling intra-muscular contraction dynamics using in silico to in vivo domain translation
Authors: Ali Hazrat , Umander Johannes , Rohlén Robin , Röhrle Oliver , Grönlund Christer
Published: July 2022

Background

Advances in sports medicine, rehabilitation applications and diagnostics of neuromuscular disorders are based on the analysis of skeletal muscle contractions. Recently, medical imaging techniques have transformed the study of muscle contractions, by allowing identification of individual motor units’ activity, within the whole studied muscle. However, appropriate image-based simulation models, which would assist the continued development of these new imaging methods are missing. This is mainly due to a lack of models that describe the complex interaction between tissues within a muscle and its surroundings, e.g., muscle fibres, fascia, vasculature, bone, skin, and subcutaneous fat. Herein, we propose a new approach to overcome this limitation.

Methods

In this work, we propose to use deep learning to model the authentic intra-muscular skeletal muscle contraction pattern using domain-to-domain translation between in silico (simulated) and in vivo (experimental) image sequences of skeletal muscle contraction dynamics. For this purpose, the 3D cycle generative adversarial network (cycleGAN) models were evaluated on several hyperparameter settings and modifications. The results show that there were large differences between the spatial features of in silico and in vivo data, and that a model could be trained to generate authentic spatio-temporal features similar to those obtained from in vivo experimental data. In addition, we used difference maps between input and output of the trained model generator to study the translated characteristics of in vivo data.

Results

This work provides a model to generate authentic intra-muscular skeletal muscle contraction dynamics that could be used to gain further and much needed physiological and pathological insights and assess and overcome limitations within the newly developed research field of neuromuscular imaging.
Association of Ozone Exposures with the risk of thyroid nodules in Hunan Province: a population-based cohort study
Authors: He Qiao , Wu Min , Shi Qiman , Tan Hailong , Wei Bo , Tang Neng , Chen Jianjun , Liu Mian , Duan Saili , Chang Shi , Huang Peng
Published: July 2022

Background

Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear.

Methods

This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants’ residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors.

Results

In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3–8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels.

Conclusions

High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.
Can prenatal diagnosis of parachute mitral valve be achieved? A case report of fetal parachute mitral valve
Authors: Dai Xiaohui , Chen Jiao , Liu Hanmin , Wu Lin , Zhao Fumin
Published: July 2022

Parachute mitral valve (PMV) is a common form of congenital mitral stenosis and is difficult to diagnose prenatally. This report describes a fetal case of PMV with coarctation of the aorta that was diagnosed at 25 weeks’ gestation by echocardiography and confirmed at autopsy. We describe the ultrasonographic features in this case and present a useful sign for making a prenatal diagnosis of PMV.
How successful was the use of a community of practice for the implementation of evidence-based practices for heart failure within the United States Department of Veterans Affairs: Insights from a formative evaluation
Authors: Sahay Anju , Mittman Brian S. , Gholami Parisa , Lin Shoutzu , Heidenreich Paul A.
Published: July 2022

Background

Communities of Practice (CoPs) are a promising approach to facilitate the implementation of evidence-based practices (EBPs) to improve care for chronic conditions like heart failure (HF). CoPs involve a complex process of acquiring and converting both explicit and tacit knowledge into clinical activities. This study describes the conceptualization, creation, capacity-building and dissemination of a CoP sustained over 9 years, and evaluates its value and impact on EBP.

Methods

In July 2006, a CoP called the Heart Failure Provider Network (HF Network) was established within the United States Department of Veterans Affairs (VA) with the overarching goal of improving the quality of care for HF patients. We assessed (formative) the HF Network in terms of its various activities (inputs) and proximal impacts (mediators) at the individual level, and its distal impacts (outcomes) at the site level including implementation of new/improved EBPs at the systemwide level.

Results

The HF Network membership grew steadily over the 9 years. The CoP has involved a total of 1341 multidisciplinary and multilevel members at all 144 VA Health Care Systems (sites). Most members were practising clinicians (n = 891, 66.4%), followed by administrators (n = 342, 25.5%), researchers (n = 70, 5.2%) and others (n = 38, 2.8%). Participation was assessed to be “active” for 70.6% versus “passive” for 29.4% of members. The distribution of active members (clinicians 64.7%, administrators 21.6%) was similar to the distribution of overall membership.

Conclusions

Survey respondents perceived the HF Network as useful in terms of its varied activities and resources relevant for patient care. Strong evidence shows that these members, particularly those who considered themselves influential in improving quality of care, noted multiple benefits of membership, which included confirmation of their own clinical practices, evidence-based changes to their practice and help in understanding facilitators and barriers in setting up or running HF clinics and other programmes. Such CoPs have strong impacts on the quality of care being delivered for both mandated and non-mandated initiatives.
Determinants of pre-eclampsia among women attending delivery services in public health institutions of Debre Tabor Town: a case–control study
Authors: Ayele Alemu Degu , Tilahun Zemenu Alemu
Published: July 2022

Background

The burden of pre-eclampsia has been continued as a public health importance in both developed and developing countries. However, the consequence of the disease is significantly high in developing countries, where treatment may be unsuccessful due to unclear etiology and late presentation of cases. The determinants of pre-eclampsia are not well known in the Ethiopian population specifically in the study area. Therefore, this study was aimed to identify the determinant factors of pre-eclampsia among women attending delivery services in public health institutions of Debre Tabor Town.

Methods

Unmatched case–control study was conducted from December 1, 2020, to January 15, 2021, among 264 mothers (88 cases and 176 controls). A case–control incidence density sampling technique was applied and data were collected using an interviewer-administered pre-tested questionnaire. Data were entered using Epi-data version 4.2 and analyzed by statistical package for social science (SPSS) version 23. Bivariate and multivariable logistic regression analyses were conducted. Finally, a significant association was declared at a p-value of ≤ 0.05 with 95% CI.

Results

Young age at menarche (10–15 years) (AOR: 7.69; 95% CI: 3.10–25.29), status of the current pregnancy (AOR: 5.88; 95% CI:2.93–22.42), new partner (AOR: 4.16; 95% CI: 3.49–17.03), family history of pre-eclampsia (AOR: 1.52; 95% CI: 1.40–4.18), and alcohol drinking (AOR: 2.18; 95% CI: 2.04–11.79) were found to be significantly associated with pre-eclampsia.

Conclusions

The current study identified that young age at menarche, the status of current pregnancy, new partner, family history of pre-eclampsia, and alcohol drinking were some of the determinant factors of pre-eclampsia. We suggested that health care providers should use these identified factors as a screening means for prediction, early diagnoses, and timely interventions of pre-eclampsia. Health care professionals should also deliver information regarding the risk of alcohol drinking during pregnancy in the preconception period and at early antenatal care services.
Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: a comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats
Authors: Chou Wei-Chun , Cheng Yi-Hsien , Riviere Jim E. , Monteiro-Riviere Nancy A. , Kreyling Wolfgang G. , Lin Zhoumeng
Published: July 2022

Background

Physiologically based pharmacokinetic (PBPK) modeling is an important tool in predicting target organ dosimetry and risk assessment of nanoparticles (NPs). The methodology of building a multi-route PBPK model for NPs has not been established, nor systematically evaluated. In this study, we hypothesized that the traditional route-to-route extrapolation approach of PBPK modeling that is typically used for small molecules may not be appropriate for NPs. To test this hypothesis, the objective of this study was to develop a multi-route PBPK model for different sizes (1.4–200 nm) of gold nanoparticles (AuNPs) in adult rats following different routes of administration (i.e., intravenous (IV), oral gavage, intratracheal instillation, and endotracheal inhalation) using two approaches: a traditional route-to-route extrapolation approach for small molecules and a new approach that is based on route-specific data that we propose to be applied generally to NPs.

Results

We found that the PBPK model using this new approach had superior performance than the traditional approach. The final PBPK model was optimized rigorously using a Bayesian hierarchical approach with Markov chain Monte Carlo simulations, and then converted to a web-based interface using R Shiny. In addition, quantitative structure–activity relationships (QSAR) based multivariate linear regressions were established to predict the route-specific key biodistribution parameters (e.g., maximum uptake rate) based on the physicochemical properties of AuNPs (e.g., size, surface area, dose, Zeta potential, and NP numbers). These results showed the size and surface area of AuNPs were the main determinants for endocytic/phagocytic uptake rates regardless of the route of administration, while Zeta potential was an important parameter for the estimation of the exocytic release rates following IV administration.

Conclusions

This study suggests that traditional route-to-route extrapolation approaches for PBPK modeling of small molecules are not applicable to NPs. Therefore, multi-route PBPK models for NPs should be developed using route-specific data. This novel PBPK-based web interface serves as a foundation for extrapolating to other NPs and to humans to facilitate biodistribution estimation, safety, and risk assessment of NPs.
Acute mitral valve regurgitation secondary to papillary muscle rupture due to infective endocarditis
Authors: Amirkhosravi Farshad , Al Abri Qasim , Lu Alexander J. , El Nihum Lamees I. , Eng Renee K. , von Ballmoos Moritz C. Wyler , Ramchandani Mahesh K.
Published: July 2022

Background

Papillary muscle rupture due to infective endocarditis is a rare event and proper management of this condition has not been described in the literature. Our case aims to shed light on treatment strategies for these patients using the current guidelines.

Case presentation

This case presents a 58-year-old male with acute heart failure secondary to papillary muscle rupture. He underwent an en bloc resection of his mitral valve with a bioprosthetic valve replacement. Specimen pathology later showed necrotic papillary muscle due to infective endocarditis. The patient was further treated with antibiotic therapy. He recovered well post-operatively and continued to do well after discharge.

Conclusion

In patients who present with papillary muscle rupture secondary to infective endocarditis, clinical symptoms should drive the treatment strategy. Despite the etiology, early mitral valve surgery remains treatment of choice for patients who have papillary muscle rupture leading to acute heart failure. Culture-guided prolonged antibiotic treatment is vital in this category of patients, especially those who have a prosthetic valve implanted.
The long-term effect of mTOR inhibition on lipid and glucose metabolism in tuberous sclerosis complex: data from the Dutch TSC registry
Authors: Mulder Femke V. M. , Peeters Evelien F. H. I. , Westerink Jan , Zwartkruis Fried J. T. , de Ranitz-Greven Wendela L.
Published: July 2022

Background

MTOR inhibition is an effective treatment for many manifestations of tuberous sclerosis complex. Because mTOR inhibition is a disease modifying therapy, lifelong use will most likely be necessary. This study addresses the long-term effects of mTOR inhibitors on lipid and glucose metabolism and aims to provide better insight in the incidence and time course of these metabolic adverse effects in treated TSC patients.

Methods

All patients who gave informed consent for the nationwide TSC Registry and were ever treated with mTOR inhibitors (sirolimus and/or everolimus) were included. Lipid profiles, HbA1c and medication were analysed in all patients before and during mTOR inhibitor treatment.

Results

We included 141 patients, the median age was 36 years, median use of mTOR inhibitors 5.1 years (aimed serum levels 3.0–5.0 µg/l). Total cholesterol, LDL- and HDL-cholesterol levels at baseline were similar to healthy reference data. After start of mTOR inhibition therapy, total cholesterol, LDL-cholesterol and triglycerides increased significantly and were higher compared to healthy reference population. Mean total cholesterol levels increased by 1.0 mmol/L after 3–6 months of mTOR inhibition therapy but did not increase further during follow-up. In this study, 2.5% (3/118) of patients developed diabetes (defined as an HbA1c ≥ 48 mmol/mol) during a median follow-up of 5 years.

Conclusions

Hypercholesterolemia is a frequent side effect of mTOR inhibition in TSC patients, and predominantly occurs within the first year of treatment. Although hyperglycemia is a frequent side effect in other indications for mTOR inhibition, incidence of diabetes mellitus in TSC patients was only 2.5%. This may reflect the difference of mTOR inhibition in patients with normal mTOR complex pathway function versus patients with overactive mTOR complex signaling due to a genetic defect (TSC patients).
Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants
Authors: Wang Wenli , Lu Fengying , Zhang Bin , Zhou Qin , Chen Yingping , Yu Bin
Published: July 2022

Objective

This study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women.

Methods

NIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV.

Results

Among the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs < 3 Mb, 41.4% for CNVs falling within 3 ~ 5 Mb, 42.9% for the CNVs falling within 5 ~ 10 Mb, and 14.3% for CNVs > 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups.

Conclusion

NIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.
Effects of a smartphone app-augmented treatment for children with oppositional defiant disorder / conduct disorder and peer-related aggressive behavior – a pilot study
Authors: Görtz-Dorten Anja , Frank Marlin , Fessel Anja , Hofmann Leonie , Döpfner Manfred
Published: July 2022

Background

Social competence training interventions, especially child-focused ones, have proven to be effective in the treatment of children with conduct disorder. Therapy homework assignments implemented between the therapy sessions are essential for practicing strategies developed during treatment sessions and transferring them to everyday life. However, clinical experience shows that patients’ adherence regarding these assignments is often low, thus diminishing the treatment success. One obstacle in this regard is a lack of motivation. The use of smartphone apps in the context of child and adolescent psychotherapy is relatively new, and may provide novel ways to improve the transfer of coping strategies to daily life between treatment sessions. However, only a small number of high-quality studies have analyzed the systematic use of smartphone apps in therapy. The present study will therefore evaluate patients’ homework assignment adherence when using a smartphone app as compared to a paper-and-pencil method.

Method

The study will be conducted as a randomized controlled trial to evaluate the impact of a smartphone app on the adherence to therapy homework assignments (n = 35) in the treatment of children with aggressive behavior aged 6–12 years compared to paper-and-pencil homework assignments (n = 35).

Discussion

This trial is intended as a pilot study and aims to provide a basis for a subsequent multicenter trial. However, the results may already lead to recommendations for the development and use of mental health-related smartphone apps for children and adolescents with aggressive behavior problems.

Trial registration

Trial registration AUTHARK: German Clinical Trials Register (DRKS) DRKS00015625. Registered on 15th October 2019.
Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial
Authors: Marchand A. , Caille A. , Gissot V. , Giraudeau B. , Lengelle C. , Bourgoin H. , Largeau B. , Leducq S. , Maruani A.
Published: July 2022

Background

Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a “watchful waiting” approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment).

Methods

This is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters.

Discussion

Given the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated.

Trial registration

ClinicalTrials.gov NCT04128722. Registered on 24 September 2019.

EudraCT: EUCTR2019-001530-33-FR

Sponsor (University Hospital Center of Tours – CHRU Tours): DR190041-TOPGUN

French regulatory authorities: ID RCB: 2019-001530-33
A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis
Authors: Wen-yue Wang , Ying-peng Xu , Quan-mao Ding , Li-min Xie , De-zhi Wang , Yang Bai , Li-su Wang , Yu-bin Li , Zhi-jun Niu , Yan-xu Ma , Wu-zhong Chen , Li-qun Bai , Yang Liu , Li-kun Jin
Published: July 2022

Background

Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel.

Methods and design

A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3–4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session.

Discussion

This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800014400. Registered on 10 January 2018