bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Systolic Function and Not Genetic Variants Determine Outcome in Pediatric and Adult Left Ventricular Noncompaction Cardiomyopathy
Authors: Schultze-Berndt Alina , Kühnisch Jirko , Herbst Christopher , Seidel Franziska , Al-Wakeel-Marquard Nadya , Dartsch Josephine , Theisen Simon , Knirsch Walter , Jenni Rolf , Greutmann Matthias , Oechslin Erwin , Berger Felix , Klaassen Sabine 
Published: September 2021

Background: Left ventricular noncompaction cardiomyopathy (LVNC CMP) is a genetic cardiomyopathy. Genotype-phenotype correlation and clinical outcome of genetic variants in pediatric and adult LVNC CMP patients are still unclear.Methods: The retrospective multicenter study was conducted in unrelated index patients with LVNC CMP, diagnosed between the years 1987 and 2017, and all available family members. All index patients underwent next-generation sequencing for genetic variants in 174 target genes using the Illumina TruSight Cardio Sequencing Panel. Major adverse cardiac events (MACE) included mechanical circulatory support, heart transplantation, survivor of cardiac death, and/or all-cause death as combined endpoint.Results: Study population included 149 LVNC CMP patients with a median age of 27.8 (9.2–44.8) years at diagnosis; 58% of them were symptomatic, 18% suffered from non-sustained and sustained arrhythmias, and 17% had an implantable cardioverter defibrillator (ICD) implanted. 55/137 patients (40%) were ≤ 18 years at diagnosis.A total of 134 variants were identified in 87/113 (77%) index patients. 93 variants were classified as variant of unknown significance (VUS), 24 as likely pathogenic and 15 as pathogenic. The genetic yield of (likely) pathogenic variants was 35/113 (31%) index patients. Variants occurred most frequently in MYH7 (n=19), TTN (n = 10) and MYBPC3 (n = 8). Altogether, sarcomere gene variants constituted 42.5% (n = 57) of all variants. The presence or absence of (likely) pathogenic variants or variants in specific genes did not allow risk stratification for MACE.Reduced left ventricular (LV) systolic function and increased left ventricular end-diastolic diameter (LVEDD) were risk factors for event-free survival in the Kaplan-Meier analysis. Through multivariate analysis we identified reduced LV systolic function as the main risk factor for MACE. Patients with reduced LV systolic function were at a 4.6-fold higher risk for MACE.Conclusions: Genetic variants did not predict the risk of developing a MACE, neither in the pediatric nor in the adult cohort. Multivariate analysis emphasized reduced LV systolic function as the main independent factor that is elevating the risk for MACE. Genetic screening is useful for cascade screening to identify family members at risk for developing LVNC CMP.
Time of Onset of Necrotizing Enterocolitis and Focal Perforation in Preterm Infants: Impact on Clinical, Surgical, and Histological Features
Authors: Berrington Janet Elizabeth , Embleton Nicholas David 
Published: September 2021

Objective: There is no gold standard test for diagnosis of necrotizing enterocolitis (NEC). Timing of onset is used in some definitions and studies in an attempt to separate NEC from focal intestinal perforation (FIP) with 14 days used as a cutoff. In a large, detailed data set we aimed to compare NEC and FIP in preterm infants born &lt;32 weeks gestation, presenting before 14 days of life in comparison to cases presenting later.Design: Infants with NEC or FIP when parents had consented to enrollment in an observational and sample collection study were included from 2009 to 2019. Clinical, surgical, histological, and outcome data were extracted and reviewed by each author independently.Patients/Episodes: In 785 infants, 174 episodes of NEC or FIP were identified of which 73 (42%) occurred before 14 days, including 54 laparotomies and 19 episodes of medically managed NEC (“early”). There were 56 laparotomies and 45 episodes of medically managed NEC presenting on or after 14 days age (“late”).Results: In early cases, 41% of laparotomies were for NEC (22 cases) and 59% for FIP (32 cases), and in late cases, 91% of laparotomies (51 cases) were for NEC and 9% (five cases) were for FIP. NEC presenting early was more likely to present with an initial septic presentation rather than discrete abdominal pathology and less likely to have clear pneumatosis. Early cases did not otherwise differ clinically, surgically, or histologically or in outcomes compared with later cases. FIP features did not differ by age at presentation.Conclusions: Although most FIP occurred early, 14% occurred later, whereas almost one third (29%) of NEC cases (surgical and medical) presented early. Infant demographics and surgical and histological findings of early- and late-presenting disease did not differ, suggesting that early and late cases are not necessarily different subtypes of the same disease although a common pathway of different pathogenesis cannot be excluded. Timing of onset does not accurately distinguish NEC from FIP, and caution should be exercised in including timing of onset in diagnostic criteria.
Clinical Research in Neonates: Redesigning the Informed Consent Process in the Digital Era
Authors: De Sutter Evelien , Coopmans Birte , Vanendert Femke , Dooms Marc , Allegaert Karel , Borry Pascal , Huys Isabelle 
Published: September 2021

Background: Currently, many initiatives are devoted to optimizing informed consent for participation in clinical research. Due to the digital transformation in health care, a shift toward electronic informed consent (eIC) has been fostered. However, empirical evidence on how to implement eIC in clinical research involving neonates is lacking.Methods: Semi-structured interviews were conducted with 31 health care professionals active in Belgium or the Netherlands. All health care professionals had experience in conducting clinical research involving neonates. Interviews were audio-recorded, transcribed and analyzed using the framework method.Results: Interviewees generally supported the use of eIC in clinical research involving neonates. For example, eIC could enable parents to receive study feedback via the eIC system. Requirements were expressed for parental involvement to decide on which feedback would be appropriate to return. Moreover, experts specialized in presenting information and designing electronic systems should be involved. Broad consensus among health care professionals indicates that the face-to-face-interaction between parents and the research team is vital to establish a relationship of trust. Therefore, it is necessary that the use of eIC runs alongside personal interactions with the parents. Concerns were raised about the accessibility of eIC to parents. For this reason, it was suggested that parents should always be given the possibility to read and sign a paper-based informed consent form or to use eIC.Conclusions: Health care professionals' views indicate that the use of eIC in clinical research with neonates may offer various opportunities. Further development and implementation will require a multi-stakeholder approach.
In-Hospital Outcomes of Acute Kidney Injury After Pediatric Cardiac Surgery: A Meta-Analysis
Authors: Van den Eynde Jef , Rotbi Hajar , Gewillig Marc , Kutty Shelby , Allegaert Karel , Mekahli Djalila 
Published: September 2021

Background: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with increased morbidity and mortality in both adults and children. This study aimed to investigate the in-hospital outcomes of CS-AKI in the pediatric population.Methods: PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for studies published by August 2020. Random-effects meta-analysis was performed, comparing in-hospital outcomes between patients who developed CS-AKI and those who did not.Results: Fifty-eight publications between 2008 and 2020 consisting of 18,334 participants (AKI: 5,780; no AKI: 12,554) were included. Higher rates of in-hospital mortality (odds ratio [OR] 7.22, 95% confidence interval [CI] 5.27–9.88), need for renal replacement therapy (RRT) (OR 18.8, 95% CI 11.7–30.5), and cardiac arrhythmias (OR 2.67, 95% 1.86–4.80) were observed in patients with CS-AKI. Furthermore, patients with AKI had longer ventilation times (mean difference [MD] 1.76 days, 95% CI 1.05–2.47), pediatric intensive care unit (PICU) length of stay (MD 3.31, 95% CI 2.52–4.10), and hospital length of stay (MD 5.00, 95% CI 3.34–6.67).Conclusions: CS-AKI in the pediatric population is associated with a higher risk of mortality, cardiac arrhythmias and need for RRT, as well as greater mechanical ventilation time, PICU and hospital length of stay. These results might help improve the clinical care protocols prior to cardiac surgery to minimize the disease burden of CS-AKI in children. Furthermore, etiology-specific approaches to AKI are warranted, as outcomes are likely impacted by the underlying cause.
Clinical Progress on Management of Pneumonia Due to COVID-19 With Chinese Traditional Patent Medicines
Authors: Wu Ying , Zhong Ping 
Published: September 2021

Background: The outbreak of new coronavirus has tremendously threatened the public health system worldwide, including China. Chinese patent medicines (CPMs) have greatly contributed to the prevention and treatment of this viral infection, as well as the recovery of patients with COVID-19 infection. Therefore, numerous experts and guidelines recommend to take CPMs to treat pneumonia due to COVID-19.Aim of the Study: The present study reviewed CPMs recommended by the &lt; Guidelines for diagnosis and management of COVID-19 (8th edition)&gt; regarding evidence of their efficacy from clinical studies and the underlying mechanisms, which will lay the foundation for clinical use of these CPMs for COVID-19.Methods: The composition, efficacy, indications, history of use, and relevant clinical research on 14 recommended CPMs, including Huoxiangzhengqi capsules (pills, liquid, oral solution), Jinhuaqinggan granules, Lianhuaqingwen capsules (granules), Shufengjiedu capsules, Xiyanping injections, Xuebijing injections, Reduning injections, Tanreqing injections, Xingnaojing injections, Shenfu injections, Shengmai injections, Angongniuhuang pills, Suhexiang pills, were searched in both Chinese and English databases based on differences in stages of the disease and manifestations of such patients. Advantages of these CPMs over conventional treatments and their underlying mechanisms were explored by analyzing results from published articles and undergoing clinical trials.Results: Findings from clinical studies and Chinese experience in using these CPMs showed that CPMs, when used in combination with conventional treatments, were effective in managing COVID-19 with few side effects.Conclusion: CPMs have excellent efficacy in managing COVID-19 with a great potential for clinical use.
Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial
Authors: Chen Chang , Zhang Yi , Huang Jianying , Yin Ping , Cheng Zhenshun , Wu Jianyuan , Chen Song , Zhang Yongxi , Chen Bo , Lu Mengxin , Luo Yongwen , Ju Lingao , Zhang Jingyi , Wang Xinghuan 
Published: September 2021

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19).Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients.Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days.Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: −0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p &lt; 0.0001) and cough (difference: 1.75 days, p &lt; 0.0001). No difference was observed in the AOT or NMV/MV rate (both p &gt; 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014).Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.
Efficacy of Zhuyu Pill Intervention in a Cholestasis Rat Model: Mutual Effects on Fecal Metabolism and Microbial Diversity
Authors: Yu Han , Liu Chao , Zhang Fenghua , Wang Jianfei , Han Jun , Zhou Xin , Wen Yueqiang , Shen Tao 
Published: September 2021

Cholestasis is a clinical condition resulting from impaired bile flow. Currently, patients with cholestasis face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological activity in cholestasis remain to be clarified. In this study, an α-naphthyl-isothiocyanate (ANIT, 50 mg/kg)-induced rat model of cholestasis was treated with ZYP. Serum biochemical indices and histopathological evaluation was performed, together with the metabolomics analyses of feces and 16S rDNA sequencing of the fecal microbiota. We evaluated the anti-cholestatic activity of ZYP and investigated the mechanisms underlying its correlation with fecal microbiota and fecal metabolite regulation. The relationships between biochemical indices and changes in gene expression associated with liver injury, levels fecal metabolites, and composition of fecal microbiota were analyzed. The results showed that both high (1.2 g/kg) and low (0.6 g/kg) doses of ZYP could effectively improve biochemical parameters in the blood of cholestasis-induced rat models; the intervention effect of high dose ZYP was superior to that that of lower dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the fecal microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and of fecal microbiota could effectively be alleviated with ZYP treatment. This study contributes to the “TCM wisdom” applied in clinical diagnosis and treatment of cholestasis.
A Systematic Review and a Meta-Analysis Comparing Prophylactic and Therapeutic Low Molecular Weight Heparins for Mortality Reduction in 32,688 COVID-19 Patients
Authors: Giossi Riccardo , Menichelli Danilo , Pani Arianna , Tratta Elena , Romandini Alessandra , Roncato Rossana , Nani Alessandro , Schenardi Paolo , Diani Erika , Fittipaldo Veronica Andrea , Farcomeni Alessio , Scaglione Francesco , Pastori Daniele 
Published: September 2021

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality.Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS).Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14–3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, −3.87, 5.83 days).Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding.Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955
Therapeutic Effects of Stem Cells From Different Source on Renal Ischemia- Reperfusion Injury: A Systematic Review and Network Meta-analysis of Animal Studies
Authors: Shang Zhizhong , Jiang Yanbiao , Guan Xin , Wang Anan , Ma Bin 
Published: September 2021

Objective: Although stem cell therapy for renal ischemia-reperfusion injury (RIRI) has made immense progress in animal studies, conflicting results have been reported by the investigators. Therefore, we aimed to systematically evaluate the effects of different stem cells on renal function of animals with ischemia-reperfusion injury and to compare the efficacies of stem cells from various sources.Methods: PubMed, Web of Science, Embase, Cochrane, CNKI, VIP, CBM, and WanFang Data were searched for records until April 2021. Two researchers independently conducted literature screening, data extraction, and literature quality evaluation.Results and conclusion: Seventy-two animal studies were included for data analysis. Different stem cells significantly reduced serum creatinine and blood urea nitrogen levels in the early and middle stages (1 and 7 days) compared to the negative control group, however there was no significant difference in the late stage among all groups (14 days); In the early stage (1 day), the renal histopathological score in the stem cell group was significantly lower than that in the negative control group, and there was no significant difference among these stem cells. In addition, there was no significant difference between stem cell and negative control in proliferation of resident cells, however, significantly less apoptosis of resident cells than negative control. In conclusion, the results showed that stem cells from diverse sources could improve the renal function of RIRI animals. ADMSCs and MDMSCs were the most-researched stem cells, and they possibly hold the highest therapeutic potential. However, the quality of evidence included in this study is low, and there are many risks of bias. The exact efficacy of the stem cells and the requirement for further clinical studies remain unclear.
Interventional Efects of the Topical of “Sanse Powder” Essential Oils Nanoemulsion on Knee Osteoarthritis in Rats by Targeting the ERS/TXNIP/NLRP3 Signaling Axis
Authors: Liu Zixiu , Liao Taiyang , Yang Nan , Ding Liang , Li Xiaochen , Wu Peng , Wang Peimin 
Published: September 2021

Purpose: Our recent research is dedicated to finding effective drugs for the treatment of knee osteoarthritis (KOA) from traditional Chinese medicine and trying to make full use of modern science and technology to uncover the mechanisms and targets behind them. Synovial inflammation is one of the key pathological features of KOA, and a growing number of researchers realize that early intervention of synovial inflammation may be able to reverse disease progression. The close association of traditional natural products with modern nanotechnology may be important for improving the anti-synovitis efficacy. The purpose of our research was to explore the anti-synovitis mechanism of NEs-SP-EO that might be associated with the ERS/TXNIP/NLRP3 signalling axis.Methods: Chemical composition of “Sanse Powder” essential oil (SP-EO) and NEs-SP-EO were analyzed by GC-MS. NEs-SP-EO were prepared and characterized by nanoparticle tracking analysis, polydispersity index (PDI), zeta potential (ZP), ultraviolet-visible spectroscopy, and transmission electronic microscopy. The CCK8 assay for cell viability of NEs-SP-EO was performed on fibroblast-like synovial cells (FLSs) and the inflammatory environment was stimulated by LPS to explore the therapeutic mechanisms in vitro. Experiments of NEs-SP-EO in vivo were performed in male SD rats.Results: The GC-MS results showed that 30 compounds were present in SP-EO and 11 components of NEs-SP-EO were identified. The results also showed that the formulation of NEs-SP-EO exhibited suitable particle size, negative charge, and stable system. In vitro and vivo testing, NEs-SP-EO produced anti-synovitis efficacy by reduced the induction of the ERS/TXNIP/NLRP3 signaling axis as well as regulating the overproduction of IL-1β, IL-18.Conclusion: We have developed a new type of essential oil nanoemulsion from “Sanse Powder” and demonstrated that it can managing synovitis of KOA. Besides, we have initially explored the anti-inflammatory mechanism that may be related to the ERS/TXNIP/NLRP3 signaling axis.