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Comprehensive Overview of Retrograde-Antegrade Connection Techniques Without Externalization in Chronic Total Occlusion PCI: The Portal Techniques
No full textBACKGROUND: Advancing the retrograde microcatheter (MC) into the antegrade guide catheter during retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be challenging or impossible, preventing guidewire externalization.
OBJECTIVES: To detail and evaluate all the techniques focused on wiring to achieve intubation of the distal tip of a microcatheter, balloon, or stent with an antegrade or retrograde guidewire, aiming to reduce complications by minimizing tension on fragile collaterals during externalization and enabling rapid antegrade conversion in various clinical scenarios.
METHODS: We describe the two main techniques, tip-in and rendezvous, and their derivatives such a facilitated tip-in, manual MC-tip modification, tip-in the balloon, tip-in the stent, deep dive rendezvous, catch-it and antegrade microcatheter probing. We provide case studies that demonstrate the effectiveness of these techniques in complex scenarios involving extreme vessel angulation, severe calcification, fragile collaterals, and challenging retrograde MC crossing without externalization.
CONCLUSION: The development of advanced variants along with traditional techniques to establish retrograde guidewire connection and antegrade conversion has led to the establishment of a cohesive group of methods known as portal techniques. These approaches serve as strategic advantages in retrograde CTO-PCI, providing a valuable and feasible alternative to conventional retrograde connection techniques, particularly when those techniques fail. Their ability to avoid the externalization process reduces potential damage to collateral channels and the ostium of the donor artery, potentially leading to a reduction in complication rates
Association of substance use with suicide mortality: An updated systematic review and meta-analysis
No full textBACKGROUND: Rates of suicide mortality and substance use have increased globally. We updated and extended existing systematic reviews of the association between substance use and suicide.
METHODS: This systematic review and meta-analysis explored the association between substance use and suicide mortality in peer reviewed, longitudinal cohort studies published from 2003 through 2024. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled data were analyzed using a quality effects model. Meta-regression was used to assess the effect of moderation by study quality. Asymmetry in funnel plots and Doi plots were used to detect reporting bias.
FINDINGS: The analysis involved 47 studies from 12 countries. Substance misuse (SMR: 5.58, 95 % CI: 3.63-8.57, I(2): 99 %) was significantly associated with risk for suicide. Alcohol (SMR: 65.39, 95 % CI: 3.02-19.62, I(2): 99 %), tobacco (SMR: 1.83, 95 % CI: 1.20-2.79, I(2): 83 %), opioid (SMR: 5.46, 95 % CI: 3.66-8.15, I(2): 96 %), cannabis (SMR 3.31, 95 % CI: 1.42-7.70, I(2): 95 %), and amphetamine (SMR 11.97, 95 % CI: 3.13-45.74, I(2): 99 %) misuse were each linked to higher rates of suicide mortality. The association between substance misuse and suicide was stronger for females (SMR: 12.37, 95 % CI: 7.07-21.63, I(2): 98 %) than males (SMR: 5.21, 95 % CI: 3.09-8.78, I(2): 99 %) overall and in analyses of specific substances. Further disaggregated data were not available to sufficiently explore for potential health inequities across social factors.
CONCLUSIONS: This meta-analysis highlights that substance misuse remains a significant suicide risk factor. It underscores the need for universal and targeted prevention and equitable access to effective interventions
High-throughput proteomics identifies inflammatory proteins associated with disease severity and genetic ancestry in patients with hidradenitis suppurativa
No full textBACKGROUND: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis.
OBJECTIVE: To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa.
METHODS: We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. We profiled circulating inflammatory proteins using Olink High-throughput proteomics and determined genetic ancestry from whole-genome sequencing data.
RESULTS: Using linear regression, we identified novel proteins associated with HS after adjusting for age, sex, and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of Th1-related inflammatory proteins.
LIMITATIONS: Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines.
CONCLUSION: Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS
Insulin Titration Recommendations When Using Glucagon-Like Peptide 1 Receptor Agonist Therapy in Adults With Type 1 Diabetes
No full textEffect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis
No full textBACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.
AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.
METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.
RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.
CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted
IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products
No full textIN BRIEF: Exposure to phthalates, alone or in mixtures, at different periods of development alters the reproductive function of males and females, especially in rodents, where they have been most studied. This review addressed the most recent data (last 10 years) on exposure to phthalates in different scenarios and how the use of natural products could mitigate the harmful effects caused by exposure at different stages of development.
ABSTRACT: This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review because most studies that have focused on developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of endocrine-disrupting chemicals in humans and animals at different developmental periods. Various food bioactive compounds (FBCs), such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs), present antioxidant, anti-inflammatory, antitumor, and other biological properties with the potential to reduce deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies carried out in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). In addition, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction because there is a lack of studies with females
Feasibility of implementation of the zero suicide model in community-based organizations serving Afghan refugees resettled in Michigan
No full textBACKGROUND: Pioneered at HFH Behavioral Health Services in 2001, the Zero Suicide (ZS) model is comprised of several evidence-based approaches including suicide screening and assessment, caring contacts, care coordination, and suicide specific psychotherapies. The ZS model has been successfully introduced in more than twenty countries; however, to date the model has been primarily introduced in higher income countries within large health systems. It is important to understand the feasibility of this approach in a range of other settings. In the current project, a feasibility study was conducted, and a pilot program is currently underway to adapt the model for use in Community-based Organizations (CBOs) serving refugee populations.
METHODS: This feasibility study focused on Afghan refugees arriving in Michigan as a part of the U.S. government Operation Allies Welcome program. The qualitative study included interviews with social, health, and behavioral health providers and staff at CBOs serving refugee and asylum-seeking populations in Michigan and behavioral health specialists at HFH and Wayne State University. A Stakeholders\u27 Advisory Board was established including HFH and CBO partners.
RESULTS: Afghan refugees encountered challenges on arrival and during their settlement into life in Southeastern Michigan, including linguistic, social, economic, medical, and behavioral health barriers. The data include specific recommendations made by the respondents for adaptations to the Zero Suicide model.
CONCLUSION: While the need for behavioral health services for refugee communities is recognized, challenges remain in the implementation of accessible, acceptable, and adaptable programs. Within Michigan, CBOs have developed strong relationships with refugees and asylum seekers resettled into the state. The current project was designed to build on these existing infrastructures within CBOs and determine the feasibility of integrating an evidence-based suicide prevention program. Through the feasibility study, it was evident that CBOs were interested in including the Zero Suicide model as a part of their health services. However, it was clear that adaptations were needed to support the introduction of the model and that those adaptations would have to account for diverse refugee communities and varied resources and structures within each CBO
Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC
No full textBACKGROUND: Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC) was significantly improved with amivantamab-lazertinib as compared with osimertinib. Results of the protocol-specified final overall survival analysis in this trial have not been reported.
METHODS: We randomly assigned, in a 2:2:1 ratio, participants with previously untreated EGFR-mutated (exon 19 deletion or L858R substitution), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib, osimertinib, or lazertinib. Overall survival (assessed in an analysis of the time from randomization to death from any cause) in the amivantamab-lazertinib group as compared with the osimertinib group was a key secondary end point. Additional end points included safety.
RESULTS: A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up.
CONCLUSIONS: Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated EGFR-mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)