The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.
- MeSH
- Longevity * physiology MeSH
- Cardiovascular Diseases physiopathology epidemiology MeSH
- Humans MeSH
- Oxidative Stress physiology MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aging * physiology MeSH
- Gastrointestinal Microbiome physiology MeSH
- Healthy Aging physiology MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Left ventricular assist device (LVAD) therapy may lead to an aortic regurgitation, limiting left ventricular unloading and causing adverse events. Whether concomitant aortic valve replacement may improve outcomes in patients with preoperative mild-to-moderate aortic regurgitation remains unclear. METHODS: A retrospective propensity score-matched analysis of adult patients with preoperative mild-to-moderate aortic regurgitation undergoing durable LVAD implantation between 01/01/2011 and 30/11/2021 was performed. Patients undergoing concomitant valve surgery other than biological aortic valve replacement were excluded, resulting in 77 with concomitant biological aortic valve replacement and 385 without. RESULTS: Following 1:1 propensity score matching, two groups of 55 patients with and without biological aortic valve replacement were obtained, (mean age 59 ± 11 years, 92% male, 59.1% HeartWare). Aortic regurgitation was mild in 72.7% and 76.4% and moderate in 27.3% and 23.6% in non-replacement and replacement cohorts respectively. The 30-day survival was 89.1% vs. 85.5% (p = 0.59), 1-year survival 69.1% vs. 56.4% (p = 0.19), and 2-year survival 61.8% vs. 47.3% (p = 0.10) in the non-replacement and replacement groups, respectively. After a mean follow-up of 1.2 years, non-replacement patients had a higher incidence of pump thrombosis (11 [20%] vs. 3 [5.5%], p = 0.022) and fewer major bleedings (2 [3.6%] vs. 11 [20%], p = 0.008). CONCLUSION: Compared with those treated conservatively, patients with mild-to-moderate aortic regurgitation undergoing concomitant aortic valve replacement during LVAD implantation have a similar survival up to 2 years on support. Patients with concomitant valve replacement had a higher risk of bleeding complications but fewer pump thromboses.
- MeSH
- Aortic Valve * surgery MeSH
- Aortic Valve Insufficiency * surgery complications mortality MeSH
- Heart Valve Prosthesis Implantation * adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Heart-Assist Devices * adverse effects MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Heart Failure * complications mortality surgery therapy MeSH
- Propensity Score MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- MeSH
- Biomarkers blood MeSH
- Chemoembolization, Therapeutic * methods MeSH
- Carcinoma, Hepatocellular * therapy blood genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs * blood MeSH
- Biomarkers, Tumor * blood MeSH
- Liver Neoplasms * therapy genetics blood MeSH
- Prospective Studies MeSH
- Aged MeSH
- Vascular Endothelial Growth Factor A * blood MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Isolated injury to the superior mesenteric vein (SMV) caused by blunt abdominal trauma is rare but often lethal, especially in pediatric patients. Due to the low incidence of SMV injuries, there are no universal guidelines for its diagnosis and treatment. The diagnosis is made using either computed tomography (CT) or intraoperative exploration. Primary vascular repair is recommended. CASE REPORT: A 10-year-old girl was transferred to a trauma center after a high-energy motor vehicle collision. Under the diagnosis of acute abdomen with hemoperitoneum, the patient underwent urgent laparotomy, 34 min after admission to the hospital. A complete laceration of the SMV trunk was observed. Definitive vascular repair of the transected SMV was performed. An interposition graft from the internal jugular vein was used with a good postoperative course. CONCLUSION: This case report demonstrates that definitive vascular repair of the SMV reduces the risk of intestinal ischemia and should be performed in cases where ligation presents a real threat to small bowel viability. In cases of severe SMV injury, the internal jugular vein is a high-quality and easily accessible graft.
- MeSH
- Child MeSH
- Accidents, Traffic MeSH
- Lacerations * surgery etiology MeSH
- Laparotomy methods MeSH
- Humans MeSH
- Tomography, X-Ray Computed MeSH
- Abdominal Injuries * complications surgery diagnosis MeSH
- Vascular System Injuries * surgery etiology diagnosis MeSH
- Wounds, Nonpenetrating * complications surgery diagnosis MeSH
- Mesenteric Veins * injuries surgery diagnostic imaging MeSH
- Vascular Surgical Procedures methods MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- C-Reactive Protein * analysis MeSH
- Stroke prevention & control MeSH
- Double-Blind Method MeSH
- Myocardial Infarction * prevention & control mortality MeSH
- Kaplan-Meier Estimate MeSH
- Colchicine * therapeutic use adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Recurrence MeSH
- Secondary Prevention MeSH
- Aged MeSH
- Spironolactone therapeutic use adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- Mineralocorticoid Receptor Antagonists * therapeutic use adverse effects MeSH
- Stroke mortality MeSH
- Double-Blind Method MeSH
- Myocardial Infarction * mortality drug therapy MeSH
- Kaplan-Meier Estimate MeSH
- Cardiovascular Diseases mortality prevention & control MeSH
- Percutaneous Coronary Intervention MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Spironolactone * therapeutic use adverse effects MeSH
- Heart Failure * drug therapy mortality MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit metabolism genetics MeSH
- Matrix Metalloproteinase Inhibitors pharmacology MeSH
- Hydroxamic Acids pharmacology MeSH
- Metalloproteases metabolism genetics MeSH
- Molar embryology growth & development metabolism enzymology MeSH
- Morphogenesis MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Odontogenesis * MeSH
- Cell Proliferation * MeSH
- Gene Expression Regulation, Developmental MeSH
- Tooth Germ embryology metabolism enzymology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- Adult MeSH
- Humans MeSH
- Placental Circulation physiology MeSH
- Placenta Growth Factor * blood MeSH
- Area Under Curve MeSH
- Predictive Value of Tests MeSH
- Pre-Eclampsia * blood diagnostic imaging MeSH
- Vascular Endothelial Growth Factor Receptor-1 * blood MeSH
- Rheology * methods statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Blood Flow Velocity physiology MeSH
- Pregnancy MeSH
- Pregnancy Trimester, Third * blood physiology MeSH
- Ultrasonography, Doppler methods statistics & numerical data MeSH
- Ultrasonography, Prenatal * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
OBJECTIVE: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis, in patients with neovascular age-related macular degeneration (nAMD). DESIGN: This was a multicenter, double-masked, randomized, controlled phase III trial. PARTICIPANTS: Treatment-naive patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab. METHODS: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every 4 weeks for 48 weeks. MAIN OUTCOME MEASURES: The primary end point was change in best-corrected visual acuity (BCVA) by ETDRS letters at week 8 compared with baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49. RESULTS: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n = 308) and the reference ranibizumab group (n = 308). The mean improvement of BCVA was +6.3 ± 9.13 ETDRS letters in the QL1205 group and +7.3 ± 8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI, -2.23 to 0.13) and 95% CI (-2.46 to 0.36) of the difference between the 2 treatment groups (P = 0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups. CONCLUSIONS: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
- MeSH
- Biosimilar Pharmaceuticals * administration & dosage adverse effects MeSH
- Double-Blind Method MeSH
- Angiogenesis Inhibitors administration & dosage adverse effects MeSH
- Intravitreal Injections MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Tomography, Optical Coherence MeSH
- Ranibizumab * administration & dosage adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vascular Endothelial Growth Factor A antagonists & inhibitors MeSH
- Wet Macular Degeneration * drug therapy diagnosis MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Visual Acuity * MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
