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Outcomes of Percutaneous Mechanical Aspiration in Right-Sided Infective Endocarditis: A Multicenter Registry
No full textBACKGROUND: Catheter-based percutaneous mechanical aspiration (PMA) is an emerging acute intervention for debulking infective vegetations in right-sided infective endocarditis (RSIE); however, its outcomes and safety remain undefined.
OBJECTIVES: The authors sought to assess early clinical outcomes and safety of PMA in patients with RSIE.
METHODS: The CLEAR-IE (Cardiac Lesion Extraction and Aspiration Registry for Infective Endocarditis) is a large multicenter retrospective registry of consecutive patients with RSIE who have undergone PMA. Procedural success was defined as a ≥70% reduction in site-reported vegetation size or a residual size ≤1 cm on intraprocedural echocardiography, which included transesophageal echocardiography (TEE), intracardiac echocardiography (ICE), and transthoracic echocardiography (TTE), selected at the operator\u27s discretion to guide the intervention. The primary endpoint was a composite of in-hospital mortality, new pulmonary embolism (PE), or emergency surgery. Secondary endpoints included each component of the primary endpoint and in-hospital worsening tricuspid regurgitation (TR).
RESULTS: Between January 2014 and January 2024, 256 patients from 19 institutions were included. Median age was 43 years; 43% were women, and 51% had history of injection drug use. Acute PE (50.8%) and shock (27%) were frequent at presentation. Tricuspid valve involvement was present in 70%, with a median site-reported vegetation size of 2.4 cm (Q1-Q3: 0.6-9 cm). Severe TR was noted in 31.3% at baseline. Staphylococcus aureus was the predominant pathogen (73.8%). Procedural success was achieved in 89.4%, with a median residual vegetation size of 0.7 cm (Q1-Q3: 0.2-1.1 cm). Overall, 86.9% completed the procedure free from procedure-related complications. The primary endpoint occurred in 18% (mortality: 9.8%; new PE: 8.3%; emergency surgery: 3.1%). Among those without baseline severe TR, worsening TR occurred in 16.9%. On univariate analysis, shock (OR: 2.27; 95% CI: 1.15-4.43; P = 0.03) and hypoxia (OR: 3.62; 95% CI: 1.83-7.17; P \u3c 0.001) were significantly associated with the primary endpoint, whereas worsening TR was not. On multivariate analysis, hypoxia (OR: 2.76; 95% CI: 1.34-5.73; P = 0.006) remained significantly associated with the primary outcome.
CONCLUSIONS: PMA of RSIE is feasible with high procedural success. Adverse events were acceptable and largely driven by underlying RSIE. Randomized trials are warranted to confirm the clinical impact and safety of PMA in RSIE
Molecular mechanisms of phytoconstituents from selected Egyptian plants against non-small cell lung cancer using integrated in vitro network pharmacology and molecular docking approach
No full textNon-small cell lung cancer (NSCLC) is a widespread highly malignant type of lung cancer. Conventional chemotherapeutic drugs may be accompanied by both drug resistance and serious side effects in patients. Therefore, safer and more effective medications are urgently needed for the treatment of NSCLC. This study investigates the mode of action of 21 phytoconstituents previously isolated from the Amaryllidaceous plants Crinum bulbispermum (Burm.f.), Pancratium maritimum L., and Hippeastrum vittatum Herbert alongside the Asteraceous plant Centaurea scoparia Sieb. for therapy of NSCLC via in vitro cytotoxic, network pharmacology, and molecular docking analyses. Despite the in vitro and in vivo cytotoxic studies carried out on phytoconstituents from these plants in treating numerous cancer types, scarce information documenting their cytotoxic activity towards NSCLC cells is available. First, the compounds were tested for their in vitro cytotoxic activities and selectivity on human non-small cell lung cancer cells using disk diffusion assay. Compounds having significant potencies were promoted for network pharmacology analysis. Pharm mapper, Genecards, STRING, and KEGG databases were utilized for surfing target genes and pathways for these compounds, while for construction of compound-target-pathway (C-T-P) network, Cytoscape 3.7.1. freeware was used. Molecular docking and dynamics simulation were run for the top hit constituents against the most enriched molecular targets followed by in silico ADMET studies using Schrodinger(®) suite and Gromacs. In vitro cytotoxicity testing demonstrated that crinamine was the most potent compound followed by lycorine, hemanthidine, and haemanthamine. The network pharmacology approach revealed the enrichment of acetyllycoramine, pluviine, 5-hydroxy-7-methoxy-2-methylchromone, and ismine. Whereas, androgen receptor (AR), epidermal growth factor receptor (EGFR), and estrogen-sensitive receptor alpha (ESR1) were the most enriched target genes. Pathway analysis revealed that central carbon metabolism, EGFR tyrosine kinase inhibitor endocrine resistance, and non-small cell lung cancer were the most enriched cancer-related pathways. Ismine possessed the most stable ligand-protein interactions when docked to the three proteins, with MD simulations further confirming its strong and consistent binding to AR, moderate stability with ESR-1, and lower stability with EGFR over the 100 ns trajectory. ADMET study conducted on the above compounds confirmed their excellent drug-likeness properties, oral bioavailability, and safety profiles highlighting the need for some structural modifications to pluviine to enhance its oral bioavailability. These integrated approaches showed that some constituents from the investigated plants interact synergistically against non-small cell lung cancer-related genes and pathways
Association of Germline Pathogenic Variants in
No full textPURPOSE: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).
MATERIALS AND METHODS: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race.
RESULTS: We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]).
CONCLUSION: Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype
Associations among positive child health measures in the environmental influences on child health outcomes (ECHO) cohort
No full textPURPOSE: Effective measurement of positive child health is critical in improving public health. A proposed measure of positive health, a positive child health index (PCHI), is based on how many of 11 specific physical, developmental, and mental health conditions a child has (ranging from 0 to 11). Accepted measures of positive health, Patient-Reported Outcome Measurement Information System (PROMIS®) measures of global health, meaning and purpose, and life satisfaction, are based on child and caregiver perceptions.
METHODS: The sample comprised 3713 children aged 5 to 17 years from the NIH Environmental influences on Child Health Outcomes (ECHO) Cohort with data to calculate PCHI and at least 1 child- or caregiver-reported PROMIS measure. Linear regressions were performed to test the associations between each PROMIS measure T-score and the PCHI, adjusting for gestational age, child sex, child age, and maternal factors (age, education, income).
RESULTS: The PROMIS measure associated most strongly with PCHI was caregiver-reported global health, followed by child-reported global health. Caregiver-reported life satisfaction and child-reported meaning and purpose were higher for children with a PCHI = 0 compared with children with 3 or more health conditions but not when compared with children with only 1 or 2 conditions. Among children with 4 or more conditions, girls reported lower global health than boys. Sex differences were not found for caregiver-reported measures.
CONCLUSION: PROMIS measures and PCHI offer complementary information on positive child health. PROMIS measures are intended as measures of a person\u27s perception of their health, whereas PCHI reflects a cumulative impact of chronic health conditions from the perspective of health care systems. Both viewpoints are informative in public health promotion
Analysis of longitudinal patterns of child maltreatment reports in the United States
No full textBACKGROUND: Child maltreatment is a continuous and prevalent issue, and victims of maltreatment often suffer adverse effects well into adulthood. Since child maltreatment rates tend to be clustered geographically and temporally, intervention programs are best implemented at a local level, targeting local risk factors for sustained and effective reduction over time.
OBJECTIVE: Quantifying geographic variation in child maltreatment rate trajectories can help states identify local risk factors to guide program development and resource allocation.
PARTICIPANTS AND SETTING: National child maltreatment data from 2011 to 2020 from the National Child Abuse and Neglect Data System (NCANDS) was used to quantify child maltreatment rates (overall and substantiated) over time.
METHODS: Latent trajectory analysis was conducted to identify groups of states in the United States that share distinct temporal patterns of child maltreatment rates. Child maltreatment data was linked to the American Community Survey data to obtain community-level characteristics.
RESULTS: Three groups of states with distinct child maltreatment trajectories were identified: 43 states with stable trajectory, 4 states with increasing number of reports over time, and 5 states with decreasing reports over time. Although states with a stable trajectory had some characteristics associated with higher socioeconomic status, such as lower percentage of families below poverty level, and lower percentage of unemployed laborers, there was not a consistent trend in socioeconomic characteristics between the three groups.
CONCLUSIONS: Our results indicate there to be three groups of states with distinct child maltreatment trajectories, with majority of the states following a stable trajectory over time. There was not a consistent trend in socioeconomic characteristics between the three groups. While the results do not allow us to draw firm conclusions about socioeconomic characteristics associated with maltreatment trajectories, it does provide data-driven evidence for the existing assumption of a national average maltreatment trajectory
Trends in the Perioperative Practices for Immunological Assessment and Immunosuppression Strategies for Patients Undergoing Intestinal Transplantation at American Transplant Centers
No full textBACKGROUND: Intestinal transplantation (IT) is a complex procedure that requires nuanced immunosuppressive strategies to optimize patient outcomes. Despite advancements, significant variability remains in immunosuppressive protocols across transplant centers due to a lack of consensus on the optimal approaches for induction, maintenance, and clinical testing. This variability complicates standardization and identification of best practices for IT recipients.
METHODS: A descriptive survey study was conducted to characterize immunosuppressive and testing strategies in IT at major transplant centers in the United States. Ten centers known to have performed over 10 ITs since 2015 were selected from the Scientific Registry of Transplant Recipients database. A 22-question survey was distributed to surgical directors, collecting data on pre-, peri-, and post-transplant immunological testing, desensitization strategies, immunosuppressive regimens, and management of antibody-mediated rejection (AMR) and acute cellular rejection (ACR).
RESULTS: Nine centers (90%) responded. All centers conducted pretransplant human leukocyte antigen (HLA) and donor-specific antibody (DSA) testing, with varying frequencies and methodologies. Desensitization was reported by 44% of centers for isolated IT and by 22% for multivisceral transplants. Induction therapy predominantly involved antithymocyte globulin (89%) and rituximab (44%). Tacrolimus was universally used for maintenance, with varying trough level targets across centers. Post-transplant DSA testing was performed by all centers, and protocol-driven endoscopic bowel biopsies were routine at 67% of centers. AMR was diagnosed at 89% of centers, with plasmapheresis and IVIG being the most common treatments. Variability was noted in desensitization practices and AMR management.
CONCLUSION: This survey highlights considerable consistency in pre- and post-transplant testing and immunosuppressive regimens for IT recipients, while significant variability exists in desensitization strategies and AMR management. Further research is needed to standardize these practices to improve patient outcomes across transplant centers
Reducing Quotation Errors in Scientific Manuscripts: A Novel Approach from the Global Andrology Forum
No full textPURPOSE: This study investigated 1) the frequency of quotation errors in multi-authored medical manuscripts in andrology, 2) analyzed common types of quotation errors and the methods used to rectify them, and 3) evaluated their impact on manuscript accuracy, credibility, and research conclusions.
MATERIALS AND METHODS: Twelve manuscripts written by the Global Andrology Forum (GAF) members between 2023 and 2024 were randomly selected for this study. The manuscripts and Quotation Verification Sheets were analyzed by senior GAF researchers to detect the number and types of quotation errors. The error rate was calculated by the total number of quotation errors and total number of all cited references in each manuscript. The impact on manuscript sections was assessed using a 0-4 grading scale. The Spearman correlation test was used to assess the correlation between scalar variables, and the Mann-Whitney U test was utilized to compare scalar variables between two groups.
RESULTS: The median value of quotation errors was 10.3%. Factual inaccuracy was the most common type of error, and was observed in all twelve manuscripts at various rates. The number of errors was significantly associated with the number of references (ρ=0.706; p=0.010) and in-text citations (ρ=0.636; p=0.026). Factual inaccuracy (ρ=0.588; p=0.044) and factual interpretation (ρ=0.861; p=0.013) were also correlated with the total number of quotation errors. However, no significant associations were found between quotation errors and author numbers or their qualifications. The quotation errors adversely impacted the manuscript discussion, followed by the overall message.
CONCLUSIONS: Quotation errors are common in multi-authored medical manuscripts in andrology-related scientific articles. Journal editorial offices should incorporate quotation verification into the review process. Limiting references and in-text citations to only strictly necessary ones may help improve quotation accuracy. The quotation verification model proposed by GAF offers a practical and structured approach for detecting and correcting quotation errors
