The association of sleep duration with the risk of chronic kidney disease: a systematic review and meta-analysis.

Background and hypothesis: Published literature suggests that sleep duration and quality may be affected in adults with chronic kidney disease. However, the relationship between these two entities remains a matter of debate. The objective of this systematic review and meta-analysis is to assess the effect of sleep duration and quality on chronic kidney disease. Methods: A systematic review of the Medline/PubMed, Embase, Cochrane Library, and CINAHL databases was conducted for articles pertaining to the association between sleep duration and quality on chronic kidney disease. The main outcome was the hazard/risk ratio of chronic kidney disease in patients of varying sleep durations and quality. Results: In total, 42 studies (2 613 971 patients) with a mean age of 43.55 ± 14.01 years were included in the meta-analysis. Compared with a reference range of 7 to 8 hours of sleep, short sleep durations of ≤4 hours (RR 1.41, 95% CI: 1.16 to 1.71, P < 0.01), ≤5 hours (RR 1.46, 95% CI: 1.22 to 1.76, P < 0.01), ≤6 hours (RR 1.18, 95% CI: 1.09 to 1.29, P < 0.01), and ≤7 hours (RR 1.19, 95% CI: 1.12 to 1.28, P < 0.01) were significantly associated with an increased risk of incident chronic kidney disease. Long sleep durations of ≥8 hours (RR 1.15, 95% CI: 1.03 to 1.28, P < 0.01) and ≥9 hours (RR 1.46, 95% CI: 1.28 to 1.68, P < 0.01) were also significantly associated with an increased risk of incident chronic kidney disease. Meta-regression did not find any significant effect of age, gender, geographical region, and BMI and an association with sleep duration and risk of incident chronic kidney disease. Conclusion: Both short and long sleep durations were significantly associated with a higher risk of chronic kidney disease. Interventions targeted toward achieving an optimal duration of sleep may reduce the risk of incident chronic kidney disease.

Drug-Coated Balloon Angioplasty in Patients Undergoing Complex Percutaneous Coronary Intervention.

Background: There are limited clinical data on drug-coated balloon (DCB)-based percutaneous coronary intervention (PCI) compared with drug-eluting stent (DES)-only PCI in patients with complex coronary artery lesions. Objectives: The goal of the current study was to investigate the efficacy of DCB in patients undergoing PCI for complex coronary artery lesions. Methods: From an institutional registry of patients with de novo complex coronary artery lesions, 126 patients treated with DCB-based PCI were compared with 234 propensity score-matched patients treated with DES-only PCI. Complex coronary artery lesions were defined as the presence of at least 1 of the following: bifurcation, chronic total occlusion, unprotected left main disease, long lesion ≥38 mm, multivessel disease, lesion requiring ≥3 devices, or severe calcification. The primary endpoint was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Results: Baseline characteristics were comparable between the 2 groups. DCB-based PCI showed a comparable risk of TVF vs DES-based PCI (7.6% vs 8.1%; HR: 0.81; 95% CI: 0.33-1.99; P = 0.638). The risks of cardiac death (5.0% vs 5.7%; HR: 0.78; 95% CI: 0.24-2.49), target vessel-related myocardial infarction (0.9% vs 1.3%; HR: 2.65; 95% CI: 0.26-27.06), and target vessel revascularization (3.5% vs 2.0%; HR: 1.30; 95% CI: 0.30-5.67) were also comparable between the 2 groups. Conclusions: DCB-based PCI showed comparable risks of TVF vs those of DES-only PCI in patients with complex coronary artery lesions. DCB might be considered as a suitable alternative device to DES in patients undergoing complex PCI. (Long-term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815).

The association between sleep quantity, insomnia and lung cancer risk - A systematic review and meta-analysis.

PURPOSE: The effect of various sleep traits on the risk of lung cancer differs among pre-existing studies. This study aims to systematically review and synthesise the association between sleep duration and insomnia with the incidence of lung cancer. METHODS: PubMed, Embase and The Cochrane Library were searched from inception to 23 April 2023 for observational studies examining the effect of sleep quantity or insomnia on lung cancer incidence. We pooled maximally-adjusted hazard ratios and odds ratios separately using random effects inverse variance weighted models. The risk of bias of observational studies was assessed using the Newcastle-Ottawa Scale. RESULTS: We included 11 observational studies with a pooled cohort of 5,049,141 patients. The mean age of the patients was 49.5 ± 17.7 years, and 51.4% were males. The risk of bias ranged from low-moderate. Individuals who slept for a shorter or longer duration than the reference range of sleep per night showed an increased risk of lung cancer by 11% (HR:1.11; 95%CI:1.00-1.23) and 16% (HR:1.16; 95%CI:1.06-1.27) respectively. Furthermore, individuals with insomnia symptoms had a 9% greater risk of lung cancer than those without symptoms (HR:1.09; 95%CI:1.05-1.13). CONCLUSION: This study suggests that insufficient sleep, excessive sleep and insomnia may be associated with an increased risk of lung cancer. Physicians should be mindful of this association and encourage healthy sleep practises among patients. Given the observed heterogeneity among some pre-existing studies, future research with longer periods of follow-up, greater control for covariates and objective testing of sleep parameters may add value to this topic.

Paratenon preserving repair of the midsubstance acute Achilles tendon rupture: a systematic review and meta-analysis with best- and worst-case analyses for rerupture rates.

INTRODUCTION: Paratenon preserving techniques to facilitate acute Achilles tendon rupture repair (AATR) functions by maintaining vascularity and biology for optimal healing response. Therefore, the purpose is to evaluate the outcomes following paratenon preserving repair of the midsubstance AATR. The hypothesis was that paratenon-preserving techniques demonstrate high return to play rates and low complication rates for the repair of the midsubstance AATR. MATERIALS AND METHODS: A systematic review of the PubMed, Embase, and the Cochrane Library databases was performed by two authors using specific search terms and eligibility criteria. The assessment of the evidence was two-fold: level and quality of evidence. A meta-analysis of proportions for the various complication rates was performed using the restricted maximum likelihood method following the Freeman-Tukey double-arcsine transformation. Fixed effects models were employed if I2 < 25% (low heterogeneity), and random effects models were employed if I2 ≥ 25% (moderate to high heterogeneity). RESULTS: The pooled return to play rate was 90.3%. The pooled rerupture rate as reported was 0.9% (best-case scenario 0.8% and worst-case scenario 6.8%). No meaningful subgroup analysis for rerupture rates could be performed based on the meta-regression. The pooled complication rate other than reruptures was 4.8%. The pooled infection rates were 0.3%, DVT rates were 1.6%, and sural nerve injury rates were 0.3%. CONCLUSIONS: Paratenon preserving techniques that are minimally invasive in nature demonstrated safe and favorable outcomes with high return to play rates and low complication rates for the repair of the midsubstance AATR.

Realization of higher-order topological lattices on a quantum computer.

Programmable quantum simulators may one day outperform classical computers at certain tasks. But at present, the range of viable applications with noisy intermediate-scale quantum (NISQ) devices remains limited by gate errors and the number of high-quality qubits. Here, we develop an approach that places digital NISQ hardware as a versatile platform for simulating multi-dimensional condensed matter systems. Our method encodes a high-dimensional lattice in terms of many-body interactions on a reduced-dimension model, thereby taking full advantage of the exponentially large Hilbert space of the host quantum system. With circuit optimization and error mitigation techniques, we measured on IBM superconducting quantum processors the topological state dynamics and protected mid-gap spectra of higher-order topological lattices, in up to four dimensions, with high accuracy. Our projected resource requirements scale favorably with system size and lattice dimensionality compared to classical computation, suggesting a possible route to useful quantum advantage in the longer term.

Lactate promotes fatty acid oxidation by the tricarboxylic acid cycle and mitochondrial respiration in muscles of obese mice.

Lower oxidative capacity in skeletal muscles (SKMs) is a prevailing cause of metabolic diseases. Exercise not only enhances the fatty acid oxidation (FAO) capacity of SKMs but also increases lactate levels. Given that lactate may contribute to tricarboxylic acid cycle (TCA) flux and impact monocarboxylate transporter 1 in the SKMs, we hypothesize that lactate can influence glucose and fatty acid (FA) metabolism. To test this hypothesis, we investigated the mechanism underlying lactate-driven FAO regulation in the SKM of mice with diet-induced obesity (DIO). Lactate was administered to DIO mice immediately after exercise for over 3 wk. We found that increased lactate levels enhanced energy expenditure mediated by fat metabolism during exercise recovery and decreased triglyceride levels in DIO mice SKMs. To determine the lactate-specific effects without exercise, we administered lactate to mice on a high-fat diet (HFD) for 8 wk. Similar to our exercise conditions, lactate increased FAO, TCA cycle activity, and mitochondrial respiration in the SKMs of HFD-fed mice. In addition, under sufficient FA conditions, lactate increased uncoupling protein-3 abundance via the NADH-NAD+ shuttle. Conversely, ATP synthase abundance decreased in the SKMs of HFD mice. Taken together, our results suggest that lactate amplifies the adaptive increase in FAO capacity mediated by the TCA cycle and mitochondrial respiration in SKMs under sufficient FA abundance.NEW & NOTEWORTHY Lactate administration post-exercise promotes triglyceride content loss in skeletal muscles (SKMs) and reduced body weight. Lactate enhances fatty acid oxidation in the SKMs of high-fat diet (HFD)-fed mice due to enhanced mitochondrial oxygen consumption. In addition, lactate restores the malate-aspartate shuttle, which is reduced by a HFD, and activates the tricarboxylic acid cycle (TCA) cycle in SKMs. Interestingly, supraphysiological lactate facilitates uncoupling protein-3 expression through NADH/NAD+, which is enhanced under high-fat levels in SKMs.

Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor.

Background: In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. Objectives: To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. Results: One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). Conclusion: In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. Clinical trial registration: NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Free essential amino acid feeding improves endurance during resistance training via DRP1-dependent mitochondrial remodelling.

BACKGROUND: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET. METHODS: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp. RESULTS: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05). CONCLUSIONS: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.

Very early vs delayed invasive strategy in high-risk NSTEMI patients without hemodynamic instability: Insight from the KAMIR-NIH.

BACKGROUND: High-risk non-ST-elevation myocardial infarction (NSTEMI) patients' optimal timing for percutaneous coronary intervention (PCI) is debated despite the recommendation for early invasive revascularization. This study aimed to compare outcomes of NSTEMI patients without hemodynamic instability undergoing very early invasive strategy (VEIS, ≤ 12 hours) versus delayed invasive strategy (DIS, >12 hours). METHODS: Excluding urgent indications for PCI including initial systolic blood pressure under 90 mmHg, ventricular arrhythmia, or Killip class IV, 4,733 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Patients were divided into low and high- global registry of acute coronary events risk score risk score (GRS) groups based on 140. Both groups were then categorized into VEIS and DIS. Clinical outcomes, including all-cause death (ACD), cardiac death (CD), recurrent MI, and cerebrovascular accident at 12 months, were evaluated. RESULTS: Among 4,733 NSTEMI patients, 62% had low GRS, and 38% had high GRS. The proportions of VEIS and DIS were 43% vs. 57% in the low GRS group and 47% vs. 53% in the high GRS group. In the low GRS group, VEIS and DIS demonstrated similar outcomes; however, in the high GRS group, VEIS exhibited worse ACD outcomes compared to DIS (HR = 1.46, P = 0.003). The adverse effect of VEIS was consistent with propensity score matched analysis (HR = 1.34, P = 0.042). CONCLUSION: VEIS yielded worse outcomes than DIS in high-risk NSTEMI patients without hemodynamic instability in real-world practice.

Long-term prognostic implications of brachial-ankle pulse wave velocity in patients undergoing percutaneous coronary intervention.

Objective: The long-term clinical effect of arterial stiffness in high-risk disease entities remains unclear. The prognostic implications of brachial-ankle pulse wave velocity (baPWV) were assessed using a real-world registry that included patients who underwent percutaneous coronary intervention (PCI). Methods: Arterial stiffness was measured using baPWV before discharge. The primary outcome was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or major bleeding. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE: a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke), and major bleeding. The outcomes were assessed over a 4-year period. Results: Patients (n = 3,930) were stratified into high- and low-baPWV groups based on a baPWV cut-off of 1891 cm/s determined through time-dependent receiver operating characteristic curve analysis. baPWV was linearly correlated with 4-year post-PCI clinical events. The high baPWV group had a greater cumulative incidence of NACE, MACCE, and major bleeding. According to multivariable analysis, the high baPWV groups had a significantly greater risk of 4-year NACE (adjusted hazard ratio [HRadj]: 1.44; 95% confidence interval [CI]: 1.12-1.85; p = 0.004), MACCE (HRadj: 1.40; 95% CI: 1.07-1.83; p = 0.015), and major bleeding (HRadj: 1.94; 95% CI: 1.15-3.25; p = 0.012). Conclusion: In PCI-treated patients, baPWV was significantly associated with long-term clinical outcomes, including ischemic and bleeding events, indicating its value for identifying high-risk phenotypes.

Prevalence and Association of Sarcopenia with Mortality in Patients with Head and Neck Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to assess the association of sarcopenia defined on computed tomography (CT) head and neck with survival in head and neck cancer patients. METHODS: Following a PROSPERO-registered protocol, two blinded reviewers extracted data and evaluated the quality of the included studies using the Quality In Prognostic Studies (QUIPS) tool, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. A meta-analysis was conducted using maximally adjusted hazard ratios (HRs) with the random-effects model. Heterogeneity was measured using the I2 statistic and was investigated using meta-regression and subgroup analyses where appropriate. RESULTS: From 37 studies (11,181 participants), sarcopenia was associated with poorer overall survival (HR 2.11, 95% confidence interval [CI] 1.81-2.45; p < 0.01), disease-free survival (HR 1.76, 95% CI 1.38-2.24; p < 0.01), disease-specific survival (HR 2.65, 95% CI 1.80-3.90; p < 0.01), progression-free survival (HR 2.24, 95% CI 1.21-4.13; p < 0.01) and increased chemotherapy or radiotherapy toxicity (risk ratio 2.28, 95% CI 1.31-3.95; p < 0.01). The observed association between sarcopenia and overall survival remained significant across different locations of cancer, treatment modality, tumor stages and geographical region, and did not differ between univariate and multivariate HRs. Statistically significant correlations were observed between the C3 and L3 cross-sectional area, skeletal muscle mass, and skeletal muscle index. CONCLUSIONS: Among patients with head and neck cancers, CT-defined sarcopenia was consistently associated with poorer survival and greater toxicity.

Association of head and neck CT-derived sarcopenia with mortality and adverse outcomes: A systematic review.

BACKGROUND: There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings. PURPOSE: The aim of this systematic review is to summarize existing literature on the prognostic implications of CT-assessed sarcopenia in non-oncological patients. MATERIALS AND METHODS: Three independent authors searched Medline/PubMed, Embase and Cochrane Library up to 30 December 2023 for observational studies that reported the presence of sarcopenia defined on CT head and neck in association with mortality estimates and other adverse outcomes, in non-oncological patients. The quality of included studies were assessed using the Quality of Prognostic Studies tool. RESULTS: Overall, 15 studies (3829 participants) were included. Nine studies were at low risk of bias, and six were at moderate risk of bias. Patient populations included those admitted for trauma or treatment of intracranial aneurysms, ischemic stroke, transient ischemic attack, and intracranial stenosis. Sarcopenia was associated with increased 30-day to 2-year mortality in inpatients and patients undergoing carotid endarterectomy or mechanical thrombectomy for acute ischemic stroke. Sarcopenia was also associated with poorer neurological and functional outcomes, increased likelihood of admission to long-term care facilities, and longer duration of hospital stays. The observed associations of sarcopenia with adverse outcomes remained similar across different imaging modalities and methods for quantifying sarcopenia. CONCLUSION: CT-assessed sarcopenia was associated with increased mortality and poorer outcomes across diverse patient populations. Measurement and early identification of sarcopenia in vulnerable patients allows for enhanced prognostication, and focused allocation of resources to mitigate adverse outcomes.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.

BACKGROUND AND AIMS: Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). METHODS: In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. RESULTS: High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). CONCLUSIONS: In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Impact of Intravascular Imaging-Guided Stent Optimization According to Clinical Presentation in Patients Undergoing Complex PCI.

BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).

Polyrhodanine-based nanomaterials for biomedical applications: A review.

Rhodanine is a heterocyclic organic compound that has been investigated for its potential biomedical applications, particularly in drug discovery. Rhodanine derivatives have been examined as the medication options for numerous illnesses, including cancer, inflammation, and infectious diseases. Some rhodanine derivatives have also shown promising activity against drug-resistant strains of bacteria and viruses. One of these derivatives is polyrhodanine (PR), a conducting polymer that has gained attention for its biomedical properties. This review article summarises the latest advancements in creating biomaterials based on PR for biosensing, antimicrobial treatments, and anticancer therapies. The distinctive characteristics of PR, such as biocompatibility, biodegradability, and good conductivity, render it an attractive candidate for these applications. The article also explores obstacles and potential future paths for advancing biomaterials made with PR, including synthesis modifications, characterisation techniques, and in vivo evaluation of biocompatibility and efficacy. Overall, as an emerging research topic, this review emphasises the potential of PR as a promising biomaterial for various biomedical applications and provides insights into the contemporary state of research and prospective directions for investigation.

Inhibitory Regulation of FOXO1 in PPARδ Expression Drives Mitochondrial Dysfunction and Insulin Resistance.

Forkhead box O1 (FOXO1) regulates muscle growth, but the metabolic role of FOXO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FOXO1 in skeletal muscle, we generated skeletal muscle-specific Foxo1 inducible knockout (mFOXO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFOXO1 iKO mice and assessed the correlation between FOXO1 and mitochondria-related protein in the skeletal muscle of patients with diabetes. Obese mFOXO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FOXO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle, and deletion of PPARδ abolished the beneficial effects of FOXO1 deficiency. FOXO1 protein levels were higher in the skeletal muscle of patients with diabetes and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FOXO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FOXO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.