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Apoptosis is a form of naturally occurring cell death that plays fundamental roles during embryonic developement. In adults, it neatly disposes of cells damaged by injuries provoked by external causes such as UV radiation, ionisation and heat shock. Alteration of the gravity vector may be one of the external apoptosis inducers. Neurophysiological impairment signs were seen during space flights in astronauts, but very few studies were carried out on the nervous system and none at the cellular level. In this study, we submitted cultured C6 glioma cells to microgravity (0xg) of varying duration, obtained by clinorotation in a Fokker three-dimensional clinostat for 15min, 30min, 1h, 20h or 32h. After 30min at 0xg, numerous nuclei underwent the classical morphological alterations (chromatin condensation, nuclear fragmentation, apoptotic bodies) that lead to the programmed cell death. After 30min at 0xg, immunostaining for the enzyme caspase-7 was present in the cytoplasm of many cells concurrently with DNA fragmentation identified by the TUNEL method. At 32h, the number of apoptotic nuclei was much reduced indicating the ability of glial cells to adapt to altered gravity.

Background: Valvular heart disease (VHD) is a major focus of cardiovascular medicine, but limited data are available for racial and ethnic minorities. The aim was to assess the burden and clinical correlates of VHD in a highly diverse area of the United States., Methods and Results: Individuals with echocardiographic diagnosis of native VHD between January 2010 and December 2019 at a quaternary care health system of the Bronx (New York, USA) were included. Prevalence and correlates of VHD were assessed per each racial and ethnic group. From a total of 330 570 adult echocardiograms, 80 584 individuals were diagnosed with VHD and included in the final study population. Stratified by race and ethnicity, 38.0%, 23.2%, 2.1%, and 36.7% were non-Hispanic Black, non-Hispanic White, Asian, and Hispanic, respectively. The mean age was 67.7±16.3 years, with non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals being younger and having a higher burden of comorbidities. The prevalence of VHD increased with age, irrespective of race or ethnicity. In people aged ≥75 years, tricuspid and mitral regurgitation were the most prevalent VHD (21.1% and 16.1%, respectively). Non-Hispanic White individuals more frequently had tricuspid regurgitation, mitral regurgitation, and multiple VHDs, but among those aged <65 years, these were more frequent in non-Hispanic Black individuals., Conclusions: Our Bronx-Valve Registry illustrates that the burden of VHD is high, increases with age, and varies among racial and ethnic groups. When diagnosed with VHD, non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals are younger and with a higher burden of comorbidities. Appropriate resources and strategies need to be implemented to minimize racial and ethnic disparities and promote equity in VHD diagnosis and cardiovascular risk factor management., Registration: URL: https://clinicaltrials.gov. Unique Identifier: NCT05453526.

Primary percutaneous coronary intervention (PCI) has revolutionized the management of ST-elevation myocardial infarction (STEMI), markedly improving patient outcomes. Despite technological advancements, pharmacological innovations, and refined interventional techniques, STEMI prognosis remains burdened by a persistent incidence of cardiac death and heart failure (HF), with mortality rates plateauing over the last decade. This review examines current practices in primary PCI, focusing on critical factors influencing patient outcomes. Moreover, it explores future developments, emphasizing the role of microvascular dysfunction-a critical but often under-recognized contributor to adverse outcomes, including incident HF and mortality, and has emerged as a key therapeutic frontier. Strategies aimed at preserving microvascular function, mitigating ischemia-reperfusion injury, and reducing infarct size are discussed as potential avenues for improving STEMI management. By addressing these challenges, the field can advance toward more personalized and effective interventions, potentially breaking the current deadlock in mortality rates and improving longer-term prognosis.

Paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR) is an established complication, albeit rarely associated with hemolytic anemia. This report details 3 cases of significant hemolytic anemia attributed to TAVR-induced PVL, each with distinct clinical presentations and manifestations. These cases underscore the diverse and occasionally subtle clinical presentation of aortic PVL-associated hemolytic anemia. We explore the technical nuances and challenges of percutaneous PVL closure and emphasize the successful resolution of hemolytic anemia by using percutaneous PVL plugging with occluder devices. Through this case series, we encourage the awareness of PVL-associated hemolytic anemia in the differential diagnosis of patients presenting with new onset anemia after TAVR and demonstrate the efficacy of percutaneous closure techniques in resolving this serious condition., Competing Interests: Dr Scotti has served as a consultant for NeoChord and Edwards Lifesciences. Dr Echarte Morales has received support from Spanish Society of Cardiology through a mobility grant (SEC/PRS-MOV-INT 22/001). Dr Latib has served on advisory boards or as a consultant for Medtronic, Boston Scientific, Philips, Edwards Lifesciences, Abbott, and Ancora Heart. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Background: Severe tricuspid regurgitation (TR) is an adverse prognostic factor. The presence of potential racial/ethnic disparities in patient characteristics and outcomes remain unexplored. This study aimed to investigate the impact of race/ethnicity on the clinical course of severe TR., Methods: We conducted a retrospective cohort analysis of all adults diagnosed with severe TR between January 2017 and December 2019 at a quaternary-care health system. Clinical and echocardiographic features were evaluated according to race/ethnicity. TR was categorized into four etiologies: primary, cardiac implantable electronic device-induced, ventricular secondary (V-STR), and atrial secondary TR. V-STR subgroups included left-sided cardiac disease and pulmonary hypertension. The primary endpoint was 5-year all-cause mortality, with secondary endpoints being heart failure hospitalization (HFH) and cardiovascular (CV) mortality., Results: A total of 989 patients were analyzed: 47.8 %, 35.1 %, and 17.1 % were non-Hispanic Black, Hispanic, and non-Hispanic White, respectively, over a median follow-up of 14.8 (3-42.4) months. The mean age was 71.4 ± 15.6 years (60.9 % women) with non-Hispanic Black and Hispanic patients younger yet displaying higher comorbidity burden, worse functional class, and more pronounced right ventricular remodeling. Left-sided cardiac disease was the predominant etiology (65.9 %), with a higher prevalence among non-White individuals. All-cause mortality and CV mortality occurred in 575 (58.1 %) and 196 (19.8 %) of patients with no significant differences among groups. HFH presented in 334 (33.1 %) of patients with Black patients having an increased risk compared to White individuals (HR, 1.45; 95 %CI, 1.04-2.02)., Conclusions: At the time of severe TR detection, Black and Hispanic patients, despite being younger, had higher comorbidities and more advanced disease than White patients. While 5-year mortality rates showed no significant racial/ethnic differences, Black patients had a higher risk of HFH., Competing Interests: Declaration of competing interest Dr. Echarte-Morales was supported by Sociedad Española de Cardiología through a mobility grant (SEC/PRS-MOV-INT 22/001). Dr. Scotti has served as a consultant for Edwards Lifesciences and NeoChord Inc. Dr. Ludwig has received travel compensation from Edwards LifeSciences, advisory fees from Bayer, and speaker honoraria from Abbott. Dr. Latib has served on the advisory board for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord Inc., V-dyne, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Residual transprosthetic gradient (TG) after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEV) may be due to suboptimal valve expansion., Aims: To compare hemodynamics after TAVR with small BEV according to postdilation strategy., Methods: This observational, retrospective cohort study included 184 consecutive patients from a single center treated with 23 mm Sapien 3 Ultra (Edwards Lifesciences) BEV implantation in the aortic position and enrolled between January 2020 and April 2023. Patients treated with routine postdilation (RP, n = 73) were compared to patients treated according to local standard practice (SP, n = 111). Primary endpoint was 30-day mean TG. Secondary endpoints were incidence of 30-day prosthesis-patient mismatch (PPM), technical success and device success., Results: Thirty-day mean TG was lower in RP versus SP (12.3 ± 4.6 mmHg vs. 14.1 ± 5.7 mmHg, p = 0.031), and incidence of PPM was less common with RP versus SP (47.3% vs. 71.0%, p = 0.006). Technical success (98.6% vs. 99.1%, p = 0.637) and device success (93.1% vs. 90.1%, p = 0.330) did not differ between groups. Differences in 30-day mean TG were driven by patients at normal flow (12.1 ± 4.0 mmHg vs. 15.0 ± 5.5 mmHg, p = 0.014), while no differences were evident among patients at low flow (12.5 ± 5.5 mmHg vs. 11.7 ± 5.5 mmHg, p = 0.644). RP decreased height and increased width of BEV, and a linear regression established that final BEV width could predict 30-day mean TG (r = -0.6654, p < 0.0001)., Conclusions: RP after TAVR with small BEV was associated with more favorable forward-flow hemodynamics than SP., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Funding Support and Author Disclosures Dr Scotti has served as a consultant for NeoChord Inc and Edwards Lifesciences. Dr Echarte-Morales was supported by Sociedad Española de Cardiología through a mobility grant (SEC/PRS-MOV-INT 22/001). Dr Ranard reports institutional funding to Columbia University Irving Medical Center from Boston Scientific; and has received consulting fees from Philips and 4C Medical. Dr Slipczuk has served on the Advisory Board for Brystol Myers Squibb; and has received consulting honoraria and institutional grant support from Amgen and Philips. Dr Vahl has reported consulting and proctoring fees from Abbott, JenaValve, and Philips. Dr Granada is a cofounder of Cephea Valve Technologies (Abbott Vascular). Dr Latib has served on the Advisory Board for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord Inc, V-dyne, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The performance of latest iteration transcatheter aortic valve replacement platforms in patients with small aortic anatomy remains underexplored., Objectives: The aim of this study was to evaluate effectiveness and performance between the self-expanding (SE) Evolut PRO and PRO+ and the balloon-expandable (BE) SAPIEN ULTRA in patients with small aortic annuli., Methods: Data from the OPERA-TAVI (Comparative Analysis of Evolut PRO vs. SAPIEN 3 ULTRA Valves for Transfemoral Transcatheter Aortic Valve Implantation) registry were used, with 1:1 propensity score matching. Primary endpoints included 1-year effectiveness composite (all-cause mortality, disabling stroke, or heart failure hospitalization) and 30-day device-related (hemodynamic structural valve dysfunction and nonstructural valve dysfunction) outcomes., Results: Among 3,516 patients, 251 matched pairs with aortic annular area <430 mm 2 were assessed. The 1-year primary effectiveness outcome did not differ significantly between cohorts (SE 10.8% vs BE 11.2%; P = 0.91). The 30-day device-oriented composite outcome was more favorable in the Evolut PRO group (SE 4.8% vs BE 10.4%; P = 0.027). Notably, SE valve recipients showed higher rates of disabling stroke (SE 4.0% vs BE 0.0%; P < 0.01) and paravalvular leaks (mild or greater: SE 48.5% vs BE 18.6% [P < 0.001]; moderate: SE 4.5% vs BE 1.2% [P = 0.070]). The BE group had higher rates of prosthesis-patient mismatch (moderate or greater: SE 16.0% vs BE 47.1% [P < 0.001]; severe: SE 1.3% vs BE 5.7% [P = 0.197]) and more patients with residual mean gradients >20 mm Hg (SE 1.0% vs BE 13.5%; P < 0.001)., Conclusions: In patients with small aortic annuli, transcatheter aortic valve replacement with latest iteration devices is safe. SE platforms are associated with more favorable device performance in terms of hemodynamic structural and nonstructural dysfunction. Randomized data are needed to validate these findings and guide informed device selection., Competing Interests: Funding Support and Author Disclosures Dr Scotti has served as a consultant for Edwards Lifesciences and NeoChord. Dr Pilgrim has received research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and has received speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Meier has received an institutional grant from Edwards Lifesciences. Dr Barbanti is a consultant for Boston Scientifics, Edwards Lifesciences, and Medtronic. Dr Latib has served on advisory boards for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord, VDyne, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Acute hemodynamic compromise after transcatheter aortic valve replacement (TAVR) because of dynamic left ventricle (LV) obstruction (LVO), also known as suicide LV, is an infrequent but severe complication of TAVR that is poorly defined in previous studies. Understanding this complication is essential for its prompt diagnosis and optimal treatment. We conducted a systematic literature review using PubMed, Embase, Web of Science, and Medline databases for studies describing acute hemodynamic compromise after TAVR because of dynamic LVO or suicide LV. Each study was reviewed by 2 authors individually for eligibility, and a third author resolved disagreements. From a total of 506 studies, 25 publications were considered for the final analysis. The majority of patients with this condition were women demonstrating a hypertrophic septum, a small ventricle, and hyperdynamic contractility on pre-TAVR echocardiographic assessment. An intraventricular gradient before TAVR was found in half of the cases. Acute hemodynamic compromise after TAVR because of dynamic LVO manifested mainly as significant hypotension and occurred most often immediately after valve deployment. The LV outflow tract was the most common site of obstruction. Advanced therapies were required in nearly 65% of the cases. In conclusion, acute hemodynamic compromise after TAVR because of dynamic LVO occurred almost invariably in women. Echocardiography before TAVR may offer essential information to anticipate this complication. LV outflow tract obstruction appears to carry the highest risk of developing this phenomenon. Advanced therapies should be promptly considered as a bailout strategy in patients with hemodynamic collapse refractory to medical therapy., Competing Interests: Declaration of competing interest Dr. Latib has served on the advisory board for Medtronic, Abbott Vascular Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord Inc, V-dyne, and Philips. Dr. Scotti has served as a consultant for NeoChord. The remaining authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest All authors declare no conflict of interest for this contribution.

Patients with tricuspid regurgitation are often referred late in their disease course and present with volume overload, which is a detrimental factor leading to right-sided chamber dilatation and dysfunction. Treatment of volume overload can 1) improve patient functional status; 2) avoid repeated invasive examinations; and 3) establish eligibility for transcatheter tricuspid intervention. ( Level of Difficulty: Intermediate. )., Competing Interests: Dr Scotti has served as a consultant for NeoChord. Dr Ho has served as a consultant for NeoChord and GE. Dr Latib has served on advisory boards for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, NeoChord, V-Dyne, GE, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2 0 2 3 P U B L I S H E D B Y E L S E V I E R O N B E H A L F O F T H E A M E R I C A N C O L L E G E O F.)

Introduction: Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs versus vitamin K antagonists (VKAs) in LVT treatment., Evidence Acquisition: Systematic search of studies evaluating DOACs versus VKAs use in patients with LVT was performed on May 11 th , 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, hemorrhagic stroke, and all cause death., Evidence Synthesis: Twenty studies were included in the meta-analysis: 1,391 patients were treated with DOACs and 1,534 with VKAs. A significant reduction in the risk of ischemic stroke (OR 0.67, 95% CI, 0.45-0.98, P=0.048, number needed to treat to benefit [NNTB] 22 [95% CI 15-43]) and any bleeding (OR 0.64, 95% CI 0.46-0.89, P=0.009, NNTB 26 [95% CI 16-80]) was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints., Conclusions: Compared to VKAs, DOACs are associated with a reduced risk of ischemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Background: Simultaneous ulnar and radial artery compression (SURC) has emerged as a strategy to increase radial artery flow and mitigate radial artery occlusion (RAO) while achieving adequate hemostasis after transradial access (TRA), though its technical adoption has been limited worldwide. Methods: A systematic search of studies comparing SURC versus isolated radial artery compression after TRA for coronary angiography and/or intervention was performed. Data were pooled by meta-analysis using random-effects models. Odds ratios (OR) with relative 95% confidence intervals (CI) and standardized mean difference were used as measures of effect estimates. The primary endpoint was the occurrence of overall RAO. Results: A total of 6 studies and 6793 patients were included. SURC method as compared to isolated radial artery compression was associated with a lower risk of RAO both overall (OR 0.29; 95% CI, 0.13−0.61, p < 0.001; number needed to treat to benefit [NNTB] =38) and in-hospital (OR 0.28; 95% CI: 0.10 to 0.75; p = 0.01, NNTB = 36), with a reduced risk of unsuccessful patent hemostasis (OR: 0.13; 95% CI: 0.02 to 0.85; p = 0.03, NNT = 5) and upper extremity pain (OR: 0.48; 95% CI: 0.24 to 0.95; p = 0.04, NNTB = 124). No significant difference was observed in hemostasis time and in the risk of hematoma. Conclusion: Compared to isolated radial artery compression, SURC is associated with lower risk of RAO, unsuccessful patent hemostasis, and reported upper limb pain, without any trade-off in safety outcomes. With further development of dedicated dual compression devices, the proposed technique should be freed from usage constraints.

Background: Transcatheter tricuspid valve replacement (TTVR) is rapidly emerging as a therapeutic option amongst patients with secondary tricuspid regurgitation. Historical data from surgical tricuspid valve replacement (TVR) studies may serve as a benchmark for the development of TTVR trials., Aims: The aim of the study was to investigate the early and late outcomes following isolated surgical TVR., Methods: Multiple electronic databases were searched to identify studies on isolated surgical TVR. The prespecified primary endpoint was operative mortality; secondary endpoints were early and late outcomes. Overall estimates of proportions and incidence rates with 95% confidence intervals (CI) were calculated using random-effects models. Multiple sensitivity analyses accounting for baseline characteristics, country and the operative period were applied.  Results: A total of 35 studies (5,316 patients) were included in this meta-analysis. The operative period ranged from 1974 to 2019. The overall rate of operative mortality was 12% (95% CI: 9-15), with higher mortality for patients who were operated on before 1995, who had prior cardiac surgeries, or who had liver disease. The most frequent clinical events were pacemaker implantation (10% [95% CI: 6-16]), bleeding (12% [95% CI: 8-17]), acute kidney injury (15% [95% CI: 9-24]) and respiratory complications (15% [95% CI: 12-20]). At follow-up analysis of the bioprosthetic TVR, there was an incidence rate per 100 person-years of 6 (95% CI: 2-13) for death and 8 (95% CI: 5-13) for recurrence of significant tricuspid regurgitation., Conclusions: This meta-analysis provides an overview of the historical clinical outcomes following isolated surgical TVR. These findings can support the development of future clinical trials in the tricuspid space by providing thresholds for clinical outcomes.

Introduction: Despite the technological advances and increasing operator experience, the rate of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) has not decreased over time. With a continuous downward trend in post-TAVR length of stay, prolonged home-monitoring may have a key role in detecting potentially serious conduction abnormalities after TAVR discharge., Methods: In this study, the ZioPatch-AT monitor was used to detect conduction abnormalities after TAVR discharge. The cardiac monitoring device was systematically provided to all patients having pre-existing right bundle branch block or developing intra-/peri-procedural conduction disturbances, in the absence of guideline indication for PPI at discharge., Results: From a total of 75 patients at high-risk of conduction disturbances, 8 (11%) of them underwent PPI and most of them (6/8) were detected before symptoms' occurrence. Paired analysis between baseline and discharge electrocardiograms detected a significant widening of the QRS in all patients; on the contrary, PR length was significantly increased only in the group experiencing HAVB after discharge (p < 0.01)., Conclusions: In an early post-TAVR discharge era, 30-day outpatient cardiac rhythm monitoring is potentially a safe solution to allow timely recognition of new conduction disturbances requiring PPI., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and have a worse prognosis after percutaneous coronary interventions (PCI). The BioFreedom polymer-free biolimus-A9-eluting stent (PF-BES) has shown promising results in patients at high bleeding risk; however, its performance in CKD patients has yet to be analyzed., Methods: The all-comers RUDI-FREE registry documented patients undergoing PCI with PF-BES in routine clinical practice. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR): preserved renal function, mild renal insufficiency (RI), and with moderate to severe RI (eGFR ≥ 90, between 90 and 45, and <45 ml/min/1.73 m2, respectively). The primary safety end point was a patient-oriented composite end point of cardiovascular death, myocardial infarction (MI), and definite or probable stent thrombosis (ST). The primary efficacy end point was target lesion revascularization (TLR)., Results: The registry documented 1,104 consecutive patients treated with PF-BES: 258 (23.4%) with preserved renal function, whereas 712 (64.7%) and 131 (11.9%) had mild and moderate to severe RI, respectively. At 1 year, the primary safety end point was significantly higher in patients with moderate to severe RI (3.5% vs. 2.8% vs. 11.5%; P < 0.001). Conversely, TLR proved similar among groups (0.4% vs. 1.8% vs. 0.8%; P = 0.235)., Conclusions: Patients with worse renal function had increased risk of the composite of cardiovascular deaths, MI, and definite or probable ST. However, the PF-BES showed similar efficacy despite differences in renal function. These findings need to be confirmed in large-scale randomized trials., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

(1) Shorter-duration dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy has been shown to significantly reduce bleeding events while preserving anti-ischemic effects in patients undergoing conventional percutaneous coronary interventions (PCI). Whether this strategy is also safe and effective in complex PCI remains elusive; (2) A systematic search of randomized controlled trials comparing a short course of ticagrelor-based DAPT versus standard DAPT in patients undergoing complex PCI was performed; (3) Of 10,689 studies screened, 3 were identified for a total of 4176 participants on ticagrelor monotherapy after a short course of ticagrelor-based DAPT, and 4209 on standard DAPT. The pooled analysis revealed no difference in the outcomes of major bleeding, myocardial infarction, definite or probable stent thrombosis and ischemic stroke. A significant reduction in the risk of cardiovascular death (incidence rate ratio (IRR) 0.52; 95% CI 0.28-0.96; p = 0.04), all-cause death (IRR 0.65; 95% CI 0.49-0.86; p = 0.003), and any bleeding events (IRR 0.62; 95% CI 0.47-0.81; p < 0.001) was seen in the shorter DAPT group; (4) Among patients undergoing complex PCI, ticagrelor monotherapy after a short course of ticagrelor-based DAPT significantly reduced bleeding risk without increasing ischemic risk. More data are needed to definitively explain mortality benefits.

Background: The authors examined the association between colchicine treatment and clinical outcomes in patients with coronary artery disease. Methods: They performed a meta-analysis of randomised controlled trials (RCTs) involving patients with coronary artery disease receiving addon colchicine to standard treatment compared with standard treatment. They used a mixed-effects Poisson regression model with random intervention effects to estimate the pooled incidence rate ratios (IRR) with 95% CI. Results: Ten RCTs were identified, including 12,819 participants followed up for a median of 6 months. Colchicine was associated with a lower risk of major adverse cardiovascular events (IRR 0.69; 95% CI [0.60-0.79]; number needed to treat for an additional beneficial outcome [NNTB] = 28); MI (IRR 0.77; 95% CI [0.64-0.93]; NNTB = 95) and ischaemic stroke (IRR 0.48; 95% CI [0.30-0.76]; NNTB = 155) and with a higher risk of gastrointestinal adverse events (IRR 1.69; 95% CI [1.12-2.54]; number needed to treat for an additional harmful outcome [NNTH] = 10). Colchicine did not affect all-cause death (IRR 1.09; 95% CI [0.85-1.40]), or cardiovascular death (IRR 0.75; 95% CI [0.51-1.12]), while it was associated with a higher risk of non-cardiovascular death (IRR 1.45; 95% CI [1.04-2.02]; NNTH = 396). Conclusion: The meta-analysis showed that the relative and absolute beneficial treatment effects of colchicine on cardiovascular outcomes outweigh the potential harm for non-cardiovascular mortality. Registration: PROSPERO 2021 CRD42021248874., Competing Interests: Disclosure: GF is a European Cardiology Review section editor; this did not affect peer review. All other authors have no conflicts of interest to declare., (Copyright © 2021, Radcliffe Cardiology.)

Background: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y 12 inhibitor versus aspirin for secondary prevention., Methods: In this systematic review and meta-analysis, all randomised trials comparing P2Y 12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y 12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I 2 index. This study is registered with PROSPERO (CRD42018115037)., Findings: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y 12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y 12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I 2 =10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I 2 =34·5%), all-cause death (OR 0·98 [0·89-1·08]; I 2 =0%), and vascular death (OR 0·97 [0·86-1·09]; I 2 =0%) did not differ between patients who received a P2Y 12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I 2 =3·9%) did not differ between patients who received a P2Y 12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y 12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y 12 inhibitor used., Interpretation: Compared with aspirin monotherapy, P2Y 12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y 12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality., Funding: Italian Ministry of Education., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This single-center, retrospective analysis investigated the clinical outcomes of a novel vascular closure device (VASCADE, Cardiva Medical, Santa Clara, CA) for closure of 7F femoral venotomies., Background: The VASCADE closure device has been widely used to close arteriotomy sites following femoral procedures; however, little data have been published regarding the device's utility in closure of venotomy sites after procedures such as right-heart catheterization., Methods: This was a retrospective analysis of outcomes in 102 consecutive patients who underwent venous closure using the VASCADE device following diagnostic right and left-heart catheterization between April 2016 to May 2018. Patients' age, gender, valvular disease status, comorbidities, and periprocedural use of antiplatelet/anticoagulant therapy were analyzed., Results: Closure was successful in 99% (101/102) of patients with respect to achieving the primary outcome of rapid hemostasis in ≤3 min. There was one device failure requiring manual compression, with no further complications. There were no other related adverse events or complications through 30 days of follow-up., Conclusions: The VASCADE device achieved venous hemostasis in nearly all our patients. We believe devices for venous closure can aid in improving patient experience, safety, and efficiency during these procedures., (© 2018 Wiley Periodicals, Inc.)

We investigate some apparent discrepancies between two different models for curved graphene: the one based on tight-binding and elasticity theory, and the covariant approach based on quantum field theory in curved space. We demonstrate that strained or corrugated samples will have a space-dependent Fermi velocity in either approach that can affect the interpretation of local probe experiments in graphene. We also generalize the tight-binding approach to general inhomogeneous strain and find a gauge field proportional to the derivative of the strain tensor that has the same form as the one obtained in the covariant approach.

Background: In selected cases a four zone-deep inferior epigastric artery perfortor (DIEAP) flap is needed for unilateral breast reconstruction. It may happen in patients with a midline scar of the abdomen or with minimal abdominal tissue, as well as in case the recipient site needs a big amount of tissue for the breast reconstruction. The purpose of this paper is to describe two options: to raise an unipedicle DIEAP flap including large size medially located perforator/s with an additional venous outflow, or to raise a double-pedicle DIEAP flap., Methods: Since 2000 34 cases of unilateral breast reconstruction with a four-zone unipedicle DIEAP flap (two cases) or a double-pedicle DIEAP flap (32 cases) have been performed. Preoperative examination of the superficial and deep epigastric vascular system with color doppler sonography (CDS) and/or multidetector-row CT (MDCT) were performed to assess the dominant abdominal perforator/s. If one or two large size, medially located perforators were identified and the superficial venous system showed vascular connections between right and left hemiabdomen, it was possible to use an unipedicle four-zone DIEAP flap with an additional anastomosis of the superficial vein. If this specific vascular situation did not exist, a double-pedicle DIEAP flap was raised., Results: There were no major complications, and very satisfactory results have been obtained., Conclusions: This retrospective study showed that both options of raising a large DIEAP flap for unilateral breast reconstruction, namely unipedicled flap based on large medial perforator/s plus additional venous discharge or double-pedicle flap, are safe. Preoperative examination of the dominant perforator/s with CDS and/or MDCT is mandatory in both cases., (Copyright 2009 Wiley-Liss, Inc. Microsurgery, 2010.)

The Soft Tissue Sarcomas shows consisting mortality that grazes 50%. Commonly the histologic type, the largeness of the tumor and the degree of malignity, are considered prognostic factors influencing the survival of patients affected from such tumor. The aim of our study is to characterize the new prognostic factors influencing the local recidives and metastatic dissemination. We have analysed 17 possible clinical and histologic prognostic factors in 80 patients affected of soft tissue sarcomas. The results have dimonstrated that: the compartimentality and the cellular differentiation seem to be more influent to the insurgence of local recidives and metastasis; while the low malignity degree, the wide surgical margins and the histopatological characters of benignity can influense positively the survival.

Amphibians are known to spend part of their life on land and return to water to reproduce. However, some urodeles spend their entire life in water, while others succeed in completely avoiding water even during reproduction. Osmoregulatory mechanisms must therefore be different in the diverse environmental conditions of their respective life histories. The architecture of the kidney is similar in all amphibians; as a consequence the ion-water equilibrium must be regulated in the different environmental conditions. We investigated the immunolocalisation of Na(+)/K(+)/Cl(-) cotransport proteins, sodium pump and water-channel proteins (aquaporins) in aquatic Amphiuma means means, Rana dalmatina, a species that returns to water to reproduce, and Speleomantes genei, a completely terrestrial species. The investigation was carried out with immunohistochemical methods using antibodies to Na(+)/K(+)/Cl(-) cotransport protein NKCC1 T4, Na(+)/K(+)ATPase alpha-subunit, water-channel aquaporin 3 and the inner mitochondrial membrane (AMA). Cotransport proteins and sodium pump, involved in ion reabsorption, are widely distributed in A. means and R. dalmatina and confined to the distal segment in S. genei; conversely water channels, involved in water reabsorption, are limited to the collecting duct in A. means and R. dalmatina and distributed in the proximal and collecting ducts in S. genei.

The authors reviewed 32 patients who underwent vaginal reconstruction using a modified McIndoe procedure during the past 15 years. This technique consists of the application of split-thickness skin grafts into a new cavity created between the rectum, bladder, and urethra. The grafts are placed previously on a mold of Optosil, which is a silicon-based condensation curing impression material used by dentists. The mold is kept for 3 months 24 hours each day. During the next 3 to 4 weeks it is applied 12 hours per day. Later, according to sexual activity, the mold can be removed completely. In case of no sexual activity it should be used 1 hour per week. Parameters assessed during the follow-up were mold management, grade of pseudomucinous metaplasia of the skin grafts, sensation of the neovagina, neovagina size changes, sexual satisfaction, and complications. Postoperative complications included partial take of skin grafts (N = 3), postoperative anxiety (N = 2), donor site cheloids (N = 1), and neovaginal stricture in 3 patients who used the mold for 1 month only without having any further sexual activity. Patients who managed the mold correctly or who had constant sexual activity obtained satisfactory dimensions of the neovagina in terms of length, diameter, and elasticity.

Cultured astrocytes were submitted to simulated microgravity using a Fokker clinostat under continuous rotation (60 rpm) for 15', 30', 1h, 20h and 32h. Samples processing included (i) nuclear stainings using Propidium Iodide and 4,6-diamidino-2-phenilindole, dihydro chloride, (ii) immunohistochemical identification of Caspase-7, (iii) identification of DNA fragmentation using the terminal dUTP nick end labelling and (iv) Scanning Electron Microscope analysis. After 30' at simulated microgravity the glial cells showed morphological evidence of apoptosis: cell shrinkage, chromatin condensation, nuclear blebs and fragmentation. The enzyme caspase-7 was present and DNA fragmentation was evident. After 32h the density of the cell population was much lower than that observed in controls.

During and after spaceflight astronauts experience neurophysiological alterations. To investigate if the impairment observed might be traced back to cytomorphology, we undertook a ground based research using a random positioning machine (clinostat) as a simulation method for microgravity. The outcome of the study was represented by cytoskeletal changes occurring in cultured glial cells (C(6) line) after 15 min, 30 min, 1 h, 20 h and 32 h under simulated microgravity. Glia is fundamental for brain function and it is essential for the normal health of the entire nervous system. Our data showed that after 30 min under simulated microgravity the cytoskeleton was damaged: microfilaments (F-actin) and intermediate filaments (Vimentin, Glial Fibrillary Acidic Proteins GFAP) were highly disorganised, microtubules (alpha-tubulin) lost their radial array, the overall cellular shape was deteriorated, and the nuclei showed altered chromatin condensations and DNA fragmentation. This feature got less dramatic after 20 h of simulated microgravity when glial cells appeared to reorganise their cytoskeleton and mitotic figures were present. The research was carried out by immunohistochemistry using antibodies to alpha-tubulin, vimentin and GFAP, and cytochemical labelling of F-actin (Phalloidin-TRIC). The nuclei were stained with propidium iodide or 4,6-diamidino-2-phenylindole dihydrochloride (DAPI). The cells were observed at the conventional and/or the confocal laser scanning microscope. Samples were also observed at the scanning electron microscope (SEM). Our data showed that in weightlessness alterations occur already visible at the scale of the single cell; if this may lead to the neurophysiological problems observed in flight is yet to be established.

Oncocytic tumours rarely affect the major salivary glands, accounting for less than 1% of all salivary-gland tumours. The World Health Organisation classification groups these tumours into three principal types: diffuse oncocytosis, focal adenomatous oncocytic hyperplasia and oncocytoma. Diffuse hyperplastic oncocytosis is the rarest lesion: only six cases have been previously reported in the literature. This condition of putative hyperplastic pathogenesis follows a benign course, whereas oncocytomas may recur after excision. No metastatic dissemination or recurrence of diffuse hyperplastic oncocytosis has been reported. We present and discuss a new case of diffuse hyperplastic oncocytosis of the parotid gland., (Copyright 2002 The British Association of Plastic Surgeons.)

The aim of this research was to induce, at will in the laboratory, aestivation of the Dipnoan Protopterus annectens, in order to compare the structure of organs in lungfish adapted to aquatic or aestivating conditions. The animals were placed in a glass tank containing warm water, and the bottom of the tank was filled with clay and sand. To start aestivation the water was allowed to slowly evaporate; as soon as the fish was in a dry environment, it began to excavate a hole in the mud and to burrow into it. Scanning electron microscopy and histological techniques compared the morphology of skin, gills, and lungs in aestivating and free-swimming animals. In the aestivating animals, the secondary lamellae of the gills became thick and were covered by mucus that pasted the lamellae together. The epidermis of the skin was thin and composed of layers of flattened cells. In contrast, in free-swimming animals, the secondary lamellae of the gills were widely separated and the epidermis of the skin was thick and contained numerous mucus-laden cells. The lungs, thin bloodless threads in the aquatic conditions, were, in the air-breathing animals, rich in blood and showed thick walls with ridges and pillars that protruded into the lung cavity, producing small alveolar protrusions. The features of the skin and lungs were similar to that of amphibians, testifying to the convergence of some tissue morphology in aquatic animals utilizing land as a cohabitat., (Copyright 2002 Wiley-Liss, Inc.)