Variation in perceptions of genital ablation between aspiring eunuchs and individuals with paraphilic sexual fantasies.

Background: Although uncommon, some individuals assigned male at birth (AMAB) seek voluntary genital ablative procedures, and others fantasize about it. Aim: To learn more about the views of genital ablation and injuries in those who aspire to be castrated as compared with those who only fantasize about it. Methods: A survey was run on the Eunuch Archive internet community. Content analysis was conducted on the responses of 342 AMAB individuals with castration fantasy but no desire for actual surgery (fantasizers) vs 294 AMAB individuals who expressed a desire for genital ablation (aspiring). Outcomes: Study outcomes were responses to open-ended questions about genital ablations and injury. Results: Aspiring individuals were more likely to perceive a "physical appearance benefit" from orchiectomy, but fewer could recall how they first learned about the procedure. Some reasons that aspiring persons gave for desiring an orchiectomy included "achieving preferred self" and "health reasons." Fantasizers, in contrast, worried about the potential side effects of orchiectomy, and more believed there to be no benefit to it. Clinical Implications: Psychiatrists and other clinicians need to understand their patients' views on genital ablation to properly diagnose and provide the best personalized care. Strengths and Limitations: Strengths include a large sample of respondents. Limitations include the accuracy of the anonymous survey data. Conclusions: This study demonstrates divergent interests on genital ablation among AMAB individuals who have not had an any genital ablation yet have intense interest in the topic.

Optical coherence tomography-guided versus intravascular ultrasound-guided percutaneous coronary intervention in patients with acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) yields clinical outcomes comparable to intravascular ultrasound (IVUS)-guided PCI in patients with stable ischemic heart disease. However, there is a scarcity of data comparing the clinical outcomes of OCT-guided and IVUS-guided PCI in the setting of acute myocardial infarction (AMI). We sought to compare the clinical outcomes of OCT-guided vs IVUS-guided PCI for patients with AMI in the era of second-generation drug-eluting stent (DES). METHODS: We identified 5260 consecutive patients who underwent PCI with a second-generation DES for AMI under IVUS or OCT guidance from pooled data derived from a series of Korean AMI registries between 2011 and 2020. The primary endpoint was the 1-year rate of target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. RESULTS: A total of 535 (10.2%) and 4725 (89.8%) patients were treated under OCT and IVUS guidance, respectively. The 1-year target lesion failure rates were comparable between the OCT and IVUS groups before and after propensity score matching (hazard ratio, 0.92; 95%CI, 0.42-2.05, P=.84). The OCT utilization rate did not exceed 5% of total patients treated with second-generation DES implantation during the study period. The primary factors for the selection of OCT over IVUS were the absence of chronic kidney disease, non-left main vessel disease, single-vessel disease, stent diameter <3mm, and stent length ≤ 25mm. CONCLUSIONS: OCT-guided PCI in patients with AMI treated with a second-generation DES provided comparable clinical outcomes for 1-year target lesion failure compared with IVUS-guided PCI.

A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis.

Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of quercetin inhibiting macrophage pyroptosis by activating NRF2 through binding to the Arg483 site of KEAP1 competitively. In ApoE-/- mice fed with high fat diet, quercetin administration attenuated atherosclerosis progression by reducing oxidative stress level and suppressing macrophage pyroptosis. At the cellular level, quercetin suppressed THP-1 macrophage pyroptosis induced by ox-LDL, demonstrated by inhibiting NLRP3 inflammasome activation and reducing ROS level, while these effects were reversed by the specific NRF2 inhibitor (ML385). Mechanistically, quercetin promoted NRF2 to dissociate from KEAP1, enhanced NRF2 nuclear translocation as well as transcription of downstream antioxidant protein. Molecular docking results suggested that quercetin could bind with KEAP1 at Arg415 and Arg483. In order to verify the binding sites, KEAP1 mutated at Arg415 and Arg483 to Ser (R415S and R483S) was transfected into THP-1 macrophages, and the anti-pyroptotic effect of quercetin was abrogated by Arg483 mutation, but not Arg415 mutation. Furthermore, after administration of adeno associated viral vector (AAV) with AAV-KEAP1-R483S, the anti-atherosclerotic effects of quercetin were almost abolished in ApoE-/- mice. These findings proved quercetins suppressed macrophage pyroptosis by targeting KEAP1/NRF2 interaction, and provided reliable data on the underlying mechanism of natural antioxidants to protect against atherosclerosis.

Real-world bleeding in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and prescribed different combinations of dual antiplatelet therapy (DAPT) in England: a population-based cohort study emulating a 'target trial'.

OBJECTIVE: To estimate the incidence and HRs for bleeding for different dual antiplatelet therapies (DAPT) in a real-world population with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in England. DESIGN: A retrospective, population-based cohort study emulating a target randomised controlled trial (tRCT). DATA SOURCES: Linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). SETTING: Primary and secondary care. PARTICIPANTS: Patients ≥18 years old with ACS undergoing emergency PCI. INTERVENTIONS: Aspirin and clopidogrel (AC, reference) versus aspirin and prasugrel (AP) or aspirin and ticagrelor (AT); AP evaluated only in patients with ST-elevation myocardial infarction (STEMI). MAIN OUTCOME MEASURES: Primary: any bleeding up to 12 months after the index event (HES- or CPRD- recorded). Secondary: HES-recorded bleeding, CPRD-recorded bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: In ACS, the rates of any bleeding for AC and AT were 89 per 1000 person years and 134 per 1000 person years, respectively. In STEMI, rates for AC, AP and AT were 93 per 1000 person years, 138 per 1000 person years and 143 per 100 person years, respectively. In ACS, compared with AC, AT increased the hazard of any bleeding (HR: 1.47, 95% CI 1.19 to 1.82) but did not reduce MACCE (HR: 1.06, 95% CI 0.89 to 1.27). In STEMI, compared with AC, AP and AT increased the hazard of any bleeding (HR: 1.77, 95% CI 1.21 to 2.59 and HR: 1.50, 95% CI 1.10 to 2.05, respectively) but did not reduce MACCE (HR: 1.10, 95% CI 0.80 to 1.51 and HR: 1.21, 95% CI 0.94 to 1.51, respectively). Non-adherence to the prescribed DAPT regimen was 28% in AC (29% in STEMI only), 31% in AP (STEMI only) and 33% in AT (32% in STEMI only). CONCLUSIONS: In a real-world population with ACS, DAPT with ticagrelor or prasugrel are associated with increased bleeding compared with DAPT with clopidogrel. TRIAL REGISTRATION NUMBER: ISRCTN76607611.

Hybrid coronary revascularization versus coronary artery bypass grafting for multivessel coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Hybrid coronary revascularization (HCR) combines the benefits of a left internal mammary artery to left anterior descending artery anastomosis, via a mini thoracotomy, with percutaneous coronary intervention (PCI) for other diseased coronaries. AIMS: The aim of this meta-analysis is to compare the short- and long-term outcomes of HCR with those of coronary artery bypass grafting (CABG) for multi-vessel coronary artery disease (MCAD). METHODS: We performed a meta-analysis with a primary outcome of short-term mortality and secondary outcomes of mid-term survival, length of hospital stay, stroke, renal failure and mid-term MACE rate. RESULTS: 3399 patients (HCR = 1164, CABG = 2235) were included, with no significant difference in short-term mortality between groups (OR = 1.50, 95% CI = [0.90,2.49], p = 0.11), although a higher mortality rate was seen in the HCR group (0.73% vs 0.64%). The average length of stay in intensive care unit was significantly shorter following HCR than CABG (mean difference = -15.52 h, CI = [-22.47,-8.59], p˂0.001) and overall hospital stay was also shorter in this group, although not statistically significant (mean difference = -3.15 days, 95% CI = [-6.55, 0.25], p = 0.07). HCR was associated with a reduced odds of blood transfusion (OR = 0.34, 95% CI = [0.22,0.54], p < 0.001). There was not a significant difference in mid-term survival (OR = 0.86, 95% CI = [0.62,1.21], p = 0.39) or MACE rate (OR = 0.82, 95% CI = [0.55,1.23], p = 0.34). No differences were found between HCR and CABG for post-operative stroke (OR = 1.36, 95% CI = [0.87, 2.13], p = 0.16) or renal failure (OR = 0.71, 95% CI = [0.43,1.16], p = 0.14). CONCLUSIONS: HCR has a higher incidence of short-term mortality compared to CABG in patients with MCAD, although this difference is not statistically significant. Similar rates of mid-term survival and other short term post-operative complications were found between the two groups. HCR has a shorter ICU stays and reduced requirement for blood transfusion.

Confounders and co-interventions identified in non-randomized studies of interventions.

OBJECTIVES: To identify potential confounders and co-interventions systematically to optimise control of confounding for three non-randomized studies of interventions (NRSI) designed to quantify bleeding in populations exposed to different dual antiplatelet therapy (DAPT). STUDY DESIGN AND SETTING: Systematic review, interviews, and surveys with clinicians. We searched Ovid Medline, Ovid Embase, and the Cochrane Library to identify randomized-controlled trials and cohort studies of DAPT interventions. Two researchers independently screened citations, identified eligible studies and extracted data. We conducted individual semi-structured interviews with six cardiologists and six cardiac surgeons to elicit factors clinicians consider when they prescribe DAPT. We administered two online surveys for members of professional cardiology and cardiac surgery organisations. RESULTS: We screened 2,544 records, identified 322 eligible studies, and extracted data from 47. We identified 10 co-interventions and 70 potential confounders: review 31 (91%); interviews 19 (56%); surveys 31 (91%). 16/34 (47%) were identified by all three methods while, 3/34 (9%) were picked up by one method only. CONCLUSION: The review identified the majority of factors, but the interviews identified hard-to-measure factors such as perceived patient adherence and local prescribing culture. The methods could, in principle, be widely applied when designing or reviewing non-randomized studies of interventions (NRSI).

Prevalence and prognostic significance of DNMT3A- and TET2- clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction.

BACKGROUND: Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1ß, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. FINDINGS: Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4-3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103-3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154-2.912, P = 0.010). Concentrations of plasma IL-1ß (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group. INTERPRETATION: DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers. FUNDING: National Natural Science Foundation of China; National Key R&D Program of China.

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.

"My son was castrated as a result of a medical error. Is it OK to raise him as a eunuch?"

A 12-year-old boy lost both testes after testicular torsion. He is now 14, and his father wants to know if the boy should immediately start supplemental testosterone or if he might reasonably choose to live as a eunuch. The boy does not yet express any strong opinion except that he is embarrassed about his weight gain. We advised the father that there is no need to rush the decision as the boy could at least delay testosterone therapy until his teens or early 20s and still go through male puberty with little risk of adverse health effects. We seek to know if others endorse our endocrinological advice. The boy's father wants to be honest with his son about the social challenges the boy may face if he elects to delay or avoid puberty altogether and chooses to openly identify as a eunuch.

Pharmacodynamic Comparison of Ticagrelor Monotherapy Versus Ticagrelor and Aspirin in Patients After Percutaneous Coronary Intervention: The TEMPLATE (Ticagrelor Monotherapy and Platelet Reactivity) Randomized Controlled Trial.

Background To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. Methods and Results In a single-center parallel group, open label, randomized controlled trial, 110 participants were randomized to receive either TIC (n=55) or TIC+ASP (n=55) for 4 weeks. The primary outcome was the platelet aggregation response with 10 µmol/L thrombin receptor activation peptide-6 (TRAP-6). The secondary outcomes were platelet aggregation responses and binding of surface activation markers with a panel of other activators. The mean percentage aggregation for 10 µmol/L TRAP-6 was similar for the TIC and TIC+ASP groups (mean difference+4.29; 95% CI, -0.87 to +9.46). Aggregation was higher in the TIC group compared with the TIC+ASP group with 1 µg/mL (+6.47; +2.04 to +10.90) and 0.5 µg/mL (+14.00; +7.63 to +20.39) collagen related peptide. Aggregation responses with 5 µmol/L TRAP-6, 5 µmol/L or 2.5 µmol/L thromboxane A2 receptor agonist and surface activation marker binding with 5 µmol/L TRAP-6 or 0.5 µg/mL collagen related peptide were the same between the treatment groups. Conclusions Patients with PCI show similar levels of inhibition of most platelet activation pathways with TIC compared with dual therapy with TIC + ASP. However, the greater aggregation response with collagen related peptide during TIC indicates incomplete inhibition of glycoprotein VI (collagen) receptor-mediated platelet activation. This difference in pharmacodynamic response to anti-platelet medication may contribute to the lower bleeding rates observed with TIC compared with dual antiplatelet therapy in recent clinical trials. Registration Information URL: https://www.isrctn.com; Unique Identifier ISRCTN84335288.

Patient perspectives of nuisance bleeding and adherence to dual antiplatelet therapy: a qualitative study.

OBJECTIVE: To understand the experiences of patients with dual antiplatelet therapy (DAPT) and nuisance bleeding, and their perspectives of the impact of nuisance bleeding on medication adherence and information seeking. METHODS: We conducted focus groups with patients who had undergone percutaneous coronary intervention, coronary artery bypass graft and conservatively managed acute coronary syndrome patients. Two focus groups were with patients at the early stages of treatment (0-3 months), and two with patients coming to the end of treatment (9-12 months). Group discussions were audio recorded, and recordings were transcribed verbatim, anonymised and analysed using framework analysis. FINDINGS: Nine patients taking DAPT for up to 3 months, and 12 taking DAPT between 9 and 12 months participated in the focus groups. We found that: (1) participants adhered to treatment when they believed DAPT was important to health outcomes; (2) those who experienced nuisance bleeding reported symptoms to be mild and manageable; (3) participants' and their family's understanding of DAPT risks and benefits, and their ability to manage symptoms, influenced perspectives of and experiences with adherence. Factors influencing DAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from hospital. CONCLUSIONS: Positive attitudes towards adherence were facilitated by knowledge and understanding of DAPT and confidence in dealing with symptoms caused by DAPT, but hindered by lack of opportunities to access relevant, timely and appropriate medication counselling. Education interventions should aim to support medication literacy through family-centred approaches and involve patients and families at all stages of intervention design and evaluation.

Clinical Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusion in Native Coronary Arteries vs Saphenous Vein Grafts.

BACKGROUND: There are limited data comparing outcomes of patients with previous coronary artery bypass grafting (CABG) presenting with stable angina who undergo percutaneous coronary intervention (PCI) to either a saphenous vein grafts (SVG) or a chronic total occlusion (CTO) in the native coronary arteries. We compared clinical characteristics and outcomes of these two groups in a national cohort. METHODS AND RESULTS: We formed a longitudinal cohort (2007-2014; n = 11,132) of patients who underwent SVG-PCI (group 1; n = 8619) or CTO-PCI in native arteries (group 2; n = 2513) in the British Cardiovascular Intervention Society (BCIS) database. Median age was 68 years in both groups, but patients in group 2 were less likely to be female, had a higher prevalence of diabetes mellitus, hypertension, hypercholesterolemia, and previous myocardial infarction, as well as worsened angina and breathlessness, but history of prior stroke, renal diseases, and the presence of left ventricular systolic dysfunction were similar to group 1. Following multivariable analysis, no significant difference in mortality was observed during index hospital admission (odds ratio [OR], 1.70; 95% confidence interval [CI], 0.63-4.58; P=.29), at 30 days (OR, 1.81; 95% CI, 0.99-3.3; P=.05), and 1 year (OR, 1.11; 95% CI, 0.85-1.44; P=.43), nor was a significant difference found in in-hospital MACE rates (OR, 1.36; 95% CI, 0.85-2.19; P=.19). However, CTO-PCI was associated with more procedural complications (OR, 2.88; 95% CI, 2.38-3.47; P<.01) and vessel perforation (OR, 4.82; 95% CI, 2.80-8.28; P<.01) as compared with the SVG-PCI group. Risk of target-vessel revascularization at 1 year was similar (SVG-PCI 5.6% vs CTO-PCI 6.9%; P=.08). CONCLUSION: In this national cohort, CTO-PCI was performed in higher-risk patients, and was associated with more procedural complications but similar short-term or long-term mortality and in-hospital MACE.

Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT) in the UK: study protocol for three population-based cohort studies emulating 'target trials' (the ADAPTT Study).

INTRODUCTION: 'Real world' bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified. METHODS AND ANALYSIS: We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three 'target trials' in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study's main limitation-that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD. ETHICS AND DISSEMINATION: This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders. TRIAL REGISTRATION NUMBER: 76607611; Pre-results.

The role of optical coherence tomography in the setting of acute myocardial infarction.

In recent years, intravascular imaging-guided percutaneous coronary intervention (PCI) has been increasing in patients with acute myocardial infarction (AMI). However, the role of optical coherence tomography (OCT) has not been established in the setting of AMI despite OCT providing superior resolution (10µm axial resolution) and facilitating assessment of baseline lesion characteristics and post-intervention evaluation of the acute result of stent implantation, including visualization of procedural dissections, malapposition, tissue prolapse, and thrombus. We provide an overview of the potential benefits of OCT-guidance in various situations of AMI.

Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study.

OBJECTIVES: This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy. BACKGROUND: TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding. METHODS: Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy. RESULTS: A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39). CONCLUSIONS: Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Coronary Perforation Complicating Percutaneous Coronary Intervention in Patients With a History of Coronary Artery Bypass Surgery: An Analysis of 309 Perforation Cases From the British Cardiovascular Intervention Society Database.

BACKGROUND: The evidence base for coronary perforation (CP) occurring during percutaneous coronary intervention in patients with a history of coronary artery bypass surgery (PCI-CABG) is limited and the long-term effects unclear. Using a national PCI database, the incidence, predictors, and outcomes of CP during PCI-CABG were defined. METHODS AND RESULTS: Data were analyzed on all PCI-CABG procedures performed in England and Wales between 2005 and 2013. Multivariate logistic regressions and propensity scores were used to identify predictors of CP and its association with outcomes. During the study period, 309 CPs were recorded during 59 644 PCI-CABG procedures with the incidence rising from 0.32% in 2005 to 0.68% in 2013 (P<0.001 for trend). Independent associates of perforation in native vessels included age, chronic occlusive disease intervention, rotational atherectomy use, number of stents, hypertension, and female sex. In graft PCI, predictors of perforation were history of stroke, New York Heart Association class, and number of stents used. In-hospital clinical complications including Q-wave myocardial infarction (2.9% versus 0.2%; P<0.001), major bleeding (14.0% versus 0.9%; P<0.001), blood transfusion (3.7% versus 0.2%; P<0.001), and death (10.0% versus 1.1%; P<0.001) were more frequent in patients with CP. A continued excess mortality occurred after perforation, with an odds ratio for 12-month mortality of 1.35 for perforation survivors compared with matched nonperforation survivors without a CP (P<0.0001). CONCLUSIONS: CP is an infrequent event during PCI-CABG but is closely associated with adverse clinical outcomes. A legacy effect of perforation on 12-month mortality was observed.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

AIMS: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. METHODS AND RESULTS: We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). CONCLUSION: A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Infertility, impotence, and emasculation--psychosocial contexts for abandoning reproduction.

From a Darwinian perspective we live to reproduce, but in various situations genetic males elect not to reproduce by choosing medical treatments leading to infertility, impotence, and, in the extreme, emasculation. For many men, infertility can be psychologically distressing. However, for certain genetic males, being infertile may improve their quality of life. Examples include (1) men who seek vasectomy, (2) individuals with Gender Dysphoria (e.g., transwomen, and modern day voluntary eunuchs), (3) most gay men, and (4) men treated for testicular and prostate cancer. Men who desire vasectomy typically have a Darwinian fitness W >1 at the time of their vasectomies; i.e., after they have their desired number of offspring or consider themselves past an age for parenting newborns. In contrast, prostate and testicular cancer patients, along with individuals with extreme Gender Dysphoria, do not necessarily seek to be sterile, but accept it as an unavoidable consequence of the treatment for their condition undertaken for survival (in case of cancer patients) or to achieve a better quality of life (for those with Gender Dysphoria). Most gay men do not father children, but they may play an avuncular role, providing for their siblings' offspring's welfare, thus improving their inclusive fitness through kin selection. In a strictly Darwinian model, the primary motivation for all individuals is to reproduce, but there are many situations for men to remove themselves from the breeding populations because they have achieved a fitness W ≥1, or have stronger medical or psychological needs that preclude remaining fertile.

Endothelial erosion of plaques as a substrate for coronary thrombosis.

Myocardial infarction is a prevalent, life-threatening consequence of athero-thrombosis. Post-mortem histology and intravascular imaging in live patients have shown that approximately one third of myocardial infarctions are caused by a thrombus overlying an intact, non-ruptured atherosclerotic plaque. Histology identifies erosion of luminal endothelial cells from smooth muscle and proteoglycan-rich, thick fibrous cap atheromas as the underlying pathology. Unlike plaque ruptures, endothelial erosions tend to occur on thick-capped atherosclerotic plaques and may or may not be associated with inflammation. Smoking and female gender are strong risk factors for erosion. Multiple mechanisms may contribute to endothelial erosion, including endothelial dysfunction, TLR signalling, leukocyte activation and modification of sub-endothelial matrix by endothelial or smooth muscle cells, which may trigger loss of adhesion to the extracellular matrix or endothelial apoptosis. Diagnosis of endothelial erosion by intravascular imaging, especially high resolution optical coherence tomography, may influence treatment strategies, offering prognostic value and utility as an endpoint in trials of agents designed to preserve an intact coronary endothelium.