bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular treatment of aortic coarctation using covered balloon-expandable stents—a systematic review and meta-analysis
Authors: He Fei , Cao Zhongze , Wang Chen , Premaratne Shyamal , Starnes Benjamin W. , Shu Chang , Zhang Wayne W. 
Published: October 2024

ObjectivesBalloon dilation followed by balloon-expandable stent implantation is an effective treatment for improving hemodynamic status in patients with coarctation of the aorta (CoA). However, limited evidence exists regarding the safety and efficacy of covered balloon-expandable stents (CBSs) in a large cohort. In this meta-analysis, we aimed to evaluate the overall success rates, hemodynamic and anatomical benefits, complications, and mid-term results of CBSs in treating CoA.MethodsThe PubMed, Embase, and Cochrane Library databases were systemically searched for studies reporting outcomes of CBSs in treating CoA. Single-group rate meta-analyses were performed to calculate estimated pooled procedural success rates, the incidence of complications, and re-coarctation rates. A meta-analysis using standardized mean differences was conducted to compare pre- and postoperative trans-coarctation pressure gradients (PGs), coarctation diameter, and overall changes in systolic blood pressure (SBP). Subgroup analyses were performed to identify potential sources of heterogeneity.ResultsThe final analysis included 12 studies with a total of 411 patients. The estimated pooled procedural success rate was 100% [95% confidence interval (CI): 98%–100%, I2 = 0, P = 0.78]. Significant decreases in trans-coarctation PGs and SBP were observed. The pooled incidences of stent-related, aortic, and access site complications were 2% (95% CI: 0%–5%, I2 = 30.4%, P = 0.15), 2% (95% CI: 0%–4%, I2 = 0%, P = 0.76), and 3% (95% CI: 1%–7%, I2 = 52.9%, P = 0.02), respectively. Subgroup analyses showed that implantation of BeGraft stents was related to a significantly higher incidence of access site complications.ConclusionCovered balloon-expandable stent implantation in treating CoA is safe and effective with high procedural success rates, an acceptable incidence of complications, and a low incidence of re-coarctation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023430356).
Recommendations for prediction models in clinical practice guidelines for cardiovascular diseases are over-optimistic: a global survey utilizing a systematic literature search
Authors: Jing Cheng-yang , Zhang Le , Feng Lin , Li Jia-chen , Liang Li-rong , Hu Jing , Liao Xing 
Published: October 2024

BackgroundThis study aimed to synthesize the recommendations for prediction models in cardiovascular clinical practice guidelines (CPGs) and assess the methodological quality of the relevant primary modeling studies.MethodsWe performed a systematic literature search of all available cardiovascular CPGs published between 2018 and 2023 that presented specific recommendations (whether in support or non-support) for at least one multivariable clinical prediction model. For the guideline-recommended models, the assessment of the methodological quality of their primary modeling studies was conducted using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).ResultsIn total, 46 qualified cardiovascular CPGs were included, with 69 prediction models and 80 specific recommendations. Of the 80 specific recommendations, 74 supported 57 models (53 were fully recommended and 4 were conditionally recommended) in cardiovascular practice with moderate to strong strength. Most of the guideline-recommended models were focused on predicting prognosis outcomes (53/57, 93%) in primary and tertiary prevention, focusing primarily on long-term risk stratification and prognosis management. A total of 10 conditions and 7 types of target population were involved in the 57 models, while heart failure (14/57, 25%) and a general population with or without cardiovascular risk factor(s) (12/57, 21%) received the most attention from the guidelines. The assessment of the methodological quality of 57 primary studies on the development of the guideline-recommended models revealed that only 40% of the modeling studies had a low risk of bias (ROB). The causes of high ROB were mainly in the analysis and participant domains.ConclusionsGlobal cardiovascular CPGs presented an unduly positive appraisal of the existing prediction models in terms of ROB, leading to stronger recommendations than were warranted. Future cardiovascular practice may benefit from well-established clinical prediction models with better methodological quality and extensive external validation.
Associations of thyroid hormones with chronic diarrhea and constipation in euthyroid individuals
Authors: Zeng Weiwei , Wang Yanjun , Zhang Luofang 
Published: October 2024

BackgroundAbnormalities in thyroid function affect bowel health. However, the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation remain unclear. Thus, the aim of this study was to investigate the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation in euthyroid US adults.MethodsThe data for this population-based study were taken from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 datasets. The relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation were examined via multivariate regression. Smoothed curve fitting and threshold effects analysis were used to test for nonlinear relationships and inflection points.ResultsThis study involved 4999 participants ranging in age from 20 to 80 years. Multivariate logistic regression analysis revealed a significant positive correlation between FT3 concentrations and the risk of developing chronic diarrhea [1.37 (1.00, 1.88), P=0.049]. Multivariate linear regression analysis revealed a significant positive correlation between FT3 concentrations and the number of bowel movements [0.84 (0.39, 1.28), P&lt;0.001]. Using smoothed curve fitting and the two-stage regression model, we found a nonlinear relationship between FT4 concentrations and chronic diarrhea, with a breakpoint of 0.79 ng/dl.ConclusionsThere were associations between thyroid hormone concentrations and abnormal bowel habits, particularly between FT3 concentrations and the risk of developing chronic diarrhea. A higher FT3 level was associated with an increased risk of developing chronic diarrhea and more frequent bowel movements. To validate our results, further large-scale prospective studies are needed.
Evaluation of a three-gene methylation model for correlating lymph node metastasis in postoperative early gastric cancer adjacent samples
Authors: Chen Shang , Long Shoubin , Liu Yaru , Wang Shenglong , Hu Qian , Fu Li , Luo Dixian 
Published: October 2024

BackgroundLymph node metastasis (LNM) has a profound impact on the treatment and prognosis of early gastric cancer (EGC), yet the existing evaluation methods lack accuracy. Recent research has underscored the role of precancerous lesions in tumor progression and metastasis. The objective of this study was to utilize the previously developed EGC LNM prediction model to further validate and extend the analysis in paired adjacent tissue samples.MethodsWe evaluated the model in a monocentric study using Methylight, a methylation-specific PCR technique, on postoperative fresh-frozen EGC samples (n = 129) and paired adjacent tissue samples (n = 129).ResultsThe three-gene methylation model demonstrated remarkable efficacy in both EGC and adjacent tissues. The model demonstrated excellent performance, with areas under the curve (AUC) of 0.85 and 0.82, specificities of 85.1% and 80.5%, sensitivities of 83.3% and 73.8%, and accuracies of 84.5% and 78.3%, respectively. It is noteworthy that the model demonstrated superior performance compared to computed tomography (CT) imaging in the adjacent tissue group, with an area under the curve (AUC) of 0.86 compared to 0.64 (p &lt; 0.001). Furthermore, the model demonstrated superior diagnostic capability in these adjacent tissues (AUC = 0.82) compared to traditional clinicopathological features, including ulceration (AUC = 0.65), invasional depth (AUC = 0.66), and lymphovascular invasion (AUC = 0.69). Additionally, it surpassed traditional models based on these features (AUC = 0.77).ConclusionThe three-gene methylation prediction model for EGC LNM is highly effective in both cancerous and adjacent tissue samples in a postoperative setting, providing reliable diagnostic information. This extends its clinical utility, particularly when tumor samples are scarce, making it a valuable tool for evaluating LNM status and assisting in treatment planning.
Molecular characteristics, risk factors, and clinical outcomes of methicillin-resistant Staphylococcus aureus infections among critically ill pediatric patients in Shanghai, 2016–2021
Authors: Dai Congyi , Ji Wenting , Zhang Yufei , Huang Weichun , Wang Haiying , Wang Xing 
Published: October 2024

ObjectiveMethicillin-resistant Staphylococcus aureus (MRSA) infection in children has been on the rise, which poses a serious threat to their health and life in China. The purpose of this study was to determine the molecular characteristics, risk factors, and clinical outcomes of MRSA infections among critically ill pediatric patients.MethodsA retrospective case-control study was performed in the pediatric intensive care unit (PICU) of a tertiary university teaching hospital. All children infected with culture-positive S. aureus in the PICU between January 2016 and December 2021 were included. Univariate and multivariable logistic regression analyses were used to identify potential risk factors for MRSA infection and clinical outcomes of S. aureus infection. All S. aureus isolates were characterized based on antimicrobial resistance, multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing.ResultsOf 3,974 patients admitted to the PICU, 280 were diagnosed with a S. aureus infection during the 6-year study period. Among them, 43.2% (121/280) were MRSA. All MRSA isolates showed significantly higher rates of resistance to penicillin, erythromycin, clindamycin and tetracycline than MSSA strains. The MRSA strains consisted of 45 spa types and 20 sequence types (STs) (20 clonal complexes), among which the most frequently represented were ST59-t437and ST398-t034. Multivariable logistic regression revealed vaginal delivery, respiratory failure, co-infection with a virus, C-reactive protein (CRP) &gt; 8 mg/L as significant risk factors for MRSA infection. There was no significant difference in all-cause mortality during hospitalization between the MRSA group and the MSSA group. Furthermore, independent predictors for mortality in patients with S. aureus infections were the presence of hypoproteinemia, hematopathy, septic shock, respiratory failure, fever, and white blood cell (WBC) &gt; 15.0 × 109/L.ConclusionsThe study revealed a high proportion of MRSA infections among critically ill pediatric patients, and found significant risk factors for MRSA infection and poor prognosis of S. aureus infection. Methicillin resistance did not contribute to the mortality in the current study. These findings will provide evidence-based practices to make the strategies of prevention and rational use of antibiotics for pediatric patients with S. aureus infection in the ICU.
Clinical prognostic models in children with sepsis in low- and middle-income countries: a systematic review and meta-analysis
Authors: Jordan Jessica , Nguyen Celinie M. , Fletcher Lauren M. , Garbern Stephanie C. 
Published: October 2024

IntroductionSepsis is the leading cause of child death worldwide, with the majority of these deaths occurring in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to describe clinical prognostic scores and models for pediatric sepsis outcomes and assess the performance of these scores for predicting mortality in LMICs.MethodsOvid Medline, CINAHL, Cochrane Library, EBSCO Global Health, and Web of Science, were searched through September 2022 for citations related to the development or validation of a clinical prognostic score or model among children with sepsis, conducted in LMIC. Titles, abstracts, and full texts were screened by two independent reviewers and data extracted included population characteristics, variables included, outcomes, and model performance. Risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST).Results4,251 titles/abstracts and 315 full-text studies were screened, with 12 studies meeting inclusion criteria. Study countries included India, China, Egypt, Indonesia, Tanzania, and a multi-site study in Latin America. Prognostic scores/models included existing scores such as PELOD-2, pSOFA, PRISM, P-MODS, refractory shock criteria. There was high risk of bias in all studies. Meta-analysis was possible for pSOFA, PELOD-2, PRISM, and P-MODS, with pooled area under the receiver-operator characteristic curve of 0.86 (95%CI 0.78–0.94), 0.83 (95% CI 0.76–0.91), respectively.ConclusionRelatively few clinical scores and models have been externally validated for prognostication and risk-stratification among children with sepsis in diverse LMIC settings. Notably there were no studies from low-income countries. Some potentially relevant studies were excluded due to lack of clarity regarding the presence of sepsis in the study populations. More widespread and standardized use of sepsis criteria may aid in better understanding the burden of sepsis and prognostic model performance at the bedside among children in LMICs. Further research to externally validate, implement and adapt these models is needed to account for challenges in use of these scores in resource-limited settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126, PROSPERO [CRD42022340126].
Comparative analysis of the therapeutic efficacy of remimazolam tosylate and propofol in older adults undergoing painless endoscopic retrograde cholangiopancreatography
Authors: Tian Yu-quan , Chen Di-kun , Zhang He-ming , Sun Yong-mei 
Published: October 2024

ObjectiveThe aim of this study is to conduct a comparative analysis of the therapeutic outcomes associated with the administration of remimazolam and propofol during painless endoscopic retrograde cholangiopancreatography (ERCP) procedures in older adults.MethodsA total of 140 older adults who underwent elective painless ERCP were randomly assigned to two groups using the random number table method: the remimazolam group and the propofol group, each consisting of 70 patients. In the remimazolam group, anesthesia was administered using a combination of remimazolam and opioids, while in the propofol group, a combination of propofol and opioids was used. Comparative assessments between the two groups included anesthesia induction time, first induction success rate, intraoperative hemodynamics, awakening duration, stress response index, and the incidence of adverse reactions.ResultsThe remimazolam group exhibited a prolonged anesthesia induction time compared to the propofol group and a lower success rate of first induction (P &lt; 0.05). At the point of endoscope entry (T2) and 10 min post-operation (T3), patients in the remimazolam group demonstrated higher mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values compared to those in the propofol group (P &lt; 0.05). Furthermore, the remimazolam group had shorter durations for eye-opening, consciousness recovery, and residence in the recovery room compared to the propofol group (P &lt; 0.05). Post-surgery levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) at 24 h were lower in the remimazolam group than in the propofol group (P &lt; 0.05). The incidence of adverse reactions was significantly lower in the remimazolam group (18.57%) compared to the propofol group (31.43%) (P &lt; 0.05).ConclusionRemimazolam exhibits a longer induction time compared to propofol in the painless diagnosis and treatment of ERCP in older adults. However, it provides a more stable circulatory state post-induction and throughout the operation, reduces stress response, enables rapid recovery, and has a lower incidence of serious adverse reactions. These attributes suggest that remimazolam has potential for widespread clinical application and adoption.Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2400080926.
The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review
Authors: Leen Nadia A. , Kowal Mikael A. , Batalla Albert , Bossong Matthijs G. 
Published: October 2024

IntroductionThere is growing recognition of the potential of cannabis to treat various medical conditions and symptoms, such as chronic pain, spasticity, and epilepsy. However, one of the biggest challenges is the assurance of a standardized cannabis product that contains a consistent amount of its main psychoactive substances delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and which is compliant with predetermined specifications for these compounds. This is crucial not only to ensure consistent cannabis quality and dosage for patients but also to effectively translate research findings into clinical practice.MethodsThis systematic literature review provides an overview of the effects of standardized cannabis products from Bedrocan, a leading Dutch producer of pharmaceutical-quality standardized medicinal cannabis.ResultsCannabis administration to healthy volunteers induces dose-dependent acute effects, such as rapidly rising THC and CBD blood concentrations, the subjective experience of high and anxiety, slower reaction time and impaired attention, learning and working memory. Patient studies suggest that treatment with medicinal cannabis reduces pain intensity across a broad range of chronic pain-related medical conditions. Medicinal cannabis showed a mild safety profile, with minor and transient side effects, such as feeling high, coughing and mental confusion. The strength of acute effects, the experience of side effects and the drop-out rate in patient studies may depend on cannabis dose, cannabis composition (CBD:THC ratio), and cannabis use history of participants.ConclusionSafety and efficacy of standardized medicinal cannabis products should be further investigated in randomized clinical trials with sufficient sample size, with particular focus on cannabis dose and composition, age and differences between males and females.
Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics
Authors: González-Iglesias Eva , Ochoa Dolores , Navares-Gómez Marcos , Zubiaur Pablo , Aldama Marina , Torre Tamara de la , Ríos-Rodríguez Marta de los , Soria-Chacartegui Paula , Rodríguez-Lopez Andrea , Abad-Santos Francisco , Novalbos Jesús 
Published: October 2024

IntroductionEzetimibe inhibits cholesterol uptake by modulation of intestinal sterol absorption. Currently, although some studies have shown alterations in ezetimibe levels caused by alterations in the ABCG5, ABCG8, NPC1L1 or UGT1A1 genes, there are no pharmacogenetic guidelines to confirm these biomarkers. The aim of this work was to evaluate the effect of 49 variants in 22 pharmacogenes related to metabolism and transport.MethodsA total of 96 healthy volunteers from four bioequivalence clinical trials of ezetimibe as monotherapy or in combination with simvastatin were studied. Blood samples were extracted for unconjugated ezetimibe plasma quantification and genotyping.Results and DiscussionNo association of metabolizing enzyme variants with ezetimibe pharmacokinetic parameters was found. The results show some trends in the univariate analysis for ABCB1 rs2032582 or ABCC2 rs2273697 and Cmax (p univariate (puv) = 0.056 and 0.087, respectively), which finally reach significance in the multivariate analysis (p multivariate (pmv) = 0.049 and 0.048, respectively). Nevertheless, these results need to be validated in future studies.
Drug selection for inner ear therapy
Authors: Salt Alec N. , Turner Jeremy G. 
Published: October 2024

IntroductionOne of the primary tenets in pharmacotherapy is that the applied drug must reach the target tissue at therapeutic concentration. For many therapies intended to treat hearing disorders it has become apparent that we have failed to achieve this goal, contributing to poor outcomes in several important clinical trials. The crux of the delivery problem is that small lipophilic molecules pass with relative ease through membranous boundaries of the body. This initially seems advantageous when the drug is applied intratympanically, enabling entry into perilymph through the round window membrane. Unfortunately, the same property also allows the drug to pass through endothelial cells of blood capillaries, allowing it to be eliminated from perilymph. Drugs that are eliminated rapidly as they diffuse along the cochlear scalae will only treat basal high-frequency cochlear regions and will not reach therapeutic concentrations in the apical regions of the human cochlea.MethodsWe have used the FluidSim program, a computer model of the inner ear fluids, to derive perilymph elimination properties for 15 molecules from published and archival data sets, which are compared with calculated molecular properties.ResultsSmaller, lipophilic drugs are shown to be eliminated from perilymph more rapidly, with half-times as fast as 17 min, compared to larger, polar ones, with half-times as long as 1,304 min (21.7 h).DiscussionBased on their molecular properties’ drugs can be identified that distribute well along the cochlea when applied intratympanically. This excludes many drugs that have been used for, or are currently in development for, inner ear therapy. On the other hand, it opens a vast array of less-studied, larger molecules, many of which would be unsuitable for oral delivery (characterized as “not druglike”) but representing promising candidates for local inner ear therapy. In the earliest stages of consideration, drugs need to be selected based on the properties which govern their ability to reach the appropriate target site and not whether they are efficacious in small animals or have high potency in vitro. Confirmation that the selected drug is reaching the target site(s) in a large animal model should ideally precede expensive clinical trials.