Fatty Acids Regulate Germline Sex Determination through ACS-4-Dependent Myristoylation.

Fat metabolism has been linked to fertility and reproductive adaptation in animals and humans, and environmental sex determination potentially plays a role in the process. To investigate the impact of fatty acids (FA) on sex determination and reproductive development, we examined and observed an impact of FA synthesis and mobilization by lipolysis in somatic tissues on oocyte fate in Caenorhabditis elegans. The subsequent genetic analysis identified ACS-4, an acyl-CoA synthetase and its FA-CoA product, as key germline factors that mediate the role of FA in promoting oocyte fate through protein myristoylation. Further tests indicated that ACS-4-dependent protein myristoylation perceives and translates the FA level into regulatory cues that modulate the activities of MPK-1/MAPK and key factors in the germline sex-determination pathway. These findings, including a similar role of ACS-4 in a male/female species, uncover a likely conserved mechanism by which FA, an environmental factor, regulates sex determination and reproductive development.

The optimized Fenton-like activity of Fe single-atom sites by Fe atomic clusters-mediated electronic configuration modulation.

The performance optimization of isolated atomically dispersed metal active sites is critical but challenging. Here, TiO2@Fe species-N-C catalysts with Fe atomic clusters (ACs) and satellite Fe-N4 active sites were fabricated to initiate peroxymonosulfate (PMS) oxidation reaction. The AC-induced charge redistribution of single atoms (SAs) was verified, thus strengthening the interaction between SAs and PMS. In detail, the incorporation of ACs optimized the HSO5- oxidation and SO5·- desorption steps, accelerating the reaction progress. As a result, the Vis/TiFeAS/PMS system rapidly eliminated 90.81% of 45 mg/L tetracycline (TC) in 10 min. The reaction process characterization suggested that PMS as an electron donor would transfer electron to Fe species in TiFeAS, generating 1O2. Subsequently, the hVB+ can induce the generation of electron-deficient Fe species, promoting the reaction circulation. This work provides a strategy to construct catalysts with multiple atom assembly-enabled composite active sites for high-efficiency PMS-based advanced oxidation processes (AOPs).

Coronary bypass surgery for multivessel disease after percutaneous coronary intervention in acute coronary syndromes: why, for whom, how early?

Multivessel coronary artery disease is present in ∼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.

Casein kinase 1 AELs promote senescence by enhancing ethylene biosynthesis through phosphorylating WRKY22 transcription factor.

Leaf senescence is a complex process regulated by developmental and environmental factors, and plays a pivotal role in the development and life cycle of higher plants. Casein kinase 1 (CK1) is a highly conserved serine/threonine protein kinase in eukaryotes and functions in various cellular processes including cell proliferation, light signaling and hormone effects of plants. However, the biological function of CK1 in plant senescence remains unclear. Through systemic genetic and biochemical studies, we here characterized the function of Arabidopsis EL1-like (AEL), a CK1, in promoting leaf senescence by stimulating ethylene biosynthesis through phosphorylating transcription factor WRKY22. Seedlings lacking or overexpressing AELs presented delayed or accelerated leaf senescence, respectively. AELs interact with and phosphorylate WRKY22 at Thr57, Thr60 and Ser69 residues to enhance whose transactivation activity. Being consistent, increased or suppressed phosphorylation of WRKY22 resulted in the promoted or delayed leaf senescence. WRKY22 directly binds to promoter region and stimulates the transcription of 1-amino-cyclopropane-1-carboxylate synthase 7 gene to promote ethylene level and hence leaf senescence. Our studies demonstrated the crucial role of AEL-mediated phosphorylation in regulating ethylene biosynthesis and promoting leaf senescence by enhancing WRKY22 transactivation activity, which helps to elucidate the fine-controlled ethylene biosynthesis and regulatory network of leaf senescence.

Is there a role for autologous conditioned serum injections in osteoarthritis? A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess whether patient reported outcome measures (PROMs) improve after autologous conditioned serum (ACS) administration in patients with osteoarthritis. METHODS: Databases and clinical trial registers were searched to March 2024 for randomised controlled trial (RCTs) comparing ACS vs comparators/controls. Primary outcomes were pain, function and stiffness measured with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS). Secondary outcome was complications. Risk of bias (RoB) and certainty of evidence were assessed using RoB 2 and the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) respectively. Meta-analysis was undertaken using RevMan v5.4. Results are presented as standardised mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI). Sensitivity analysis compared all comparators and saline control. RESULTS: Five RCTs were identified (n = 741 participants); two (n = 529 participants) compared ACS against saline (placebo). Three studies were "some concern" and two studies "high risk" for bias. Analysis comparing ACS with all comparators significantly favoured ACS at 6 months for WOMAC: SMD -0.61 (95% CI -1.01 to -0.21; p = 0.003); and VAS: SMD -1.24 (95% CI -2.11 to -0.38; p = 0.005); with high heterogeneity. Comparing ACS with saline, there was no significant difference in WOMAC or VAS at 6 months: SMD -0.40 (95% CI -0.93 to 0.12; p = 0.13) and MD -9.87 (95% CI -27.73 to 7.98, p = 0.28). Complications were similar: ACS (24.8%) vs saline (24.4%), with serious complications rare. CONCLUSION: There is currently insufficient data to support the use of ACS in osteoarthritis with conflicting results when compared to alternative therapies and saline control, with high heterogeneity. Before consideration as a potential treatment, a high-quality multicentre RCT is required to assess the efficacy of ACS.

The association between the AIP and undiagnosed diabetes in ACS patients with different body mass indexes and LDL-C levels: findings from the CCC-ACS project.

BACKGROUND: The atherogenic index of plasma (AIP) has been demonstrated to be significantly associated with the incidence of prediabetes and diabetes. This study aimed to investigate the association between the AIP and undiagnosed diabetes in acute coronary syndrome (ACS) patients. METHODS: Among 113,650 ACS patients treated with coronary angiography at 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS Project from 2014 to 2019, 11,221 patients with available clinical and surgical information were included. We analyzed these patients' clinical characteristics after stratification according to AIP tertiles, body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: The AIP was independently associated with a greater incidence of undiagnosed diabetes. The undiagnosed diabetes was significantly greater in the T3 group than in the T1 group after adjustment for confounders [T3 OR 1.533 (1.199-1.959) p < 0.001]. This relationship was consistent within normal weight patients and patients with an LDL-C level ≥ 1.8 mmol/L. In overweight and obese patients, the AIP was significantly associated with the incidence of undiagnosed diabetes as a continuous variable after adjustment for age, sex, and BMI but not as a categorical variable. The area under the receiver operating characteristic curve (AUC) of the AIP score, triglyceride (TG) concentration, and HDL-C concentration was 0.601 (0.581-0.622; p < 0.001), 0.624 (0.603-0.645; p < 0.001), and 0.493 (0.472-0.514; p = 0.524), respectively. A nonlinear association was found between the AIP and the incidence of undiagnosed diabetes in ACS patients (p for nonlinearity < 0.001), and this trend remained consistent between males and females. The AIP may be a negative biomarker associated with undiagnosed diabetes ranging from 0.176 to 0.738. CONCLUSION: The AIP was significantly associated with the incidence of undiagnosed diabetes in ACS patients, especially in those with normal weight or an LDL-C level ≥ 1.8 mmol/L. A nonlinear relationship was found between the AIP and the incidence of undiagnosed diabetes, and this trend was consistent between male and female patients. The AIP may be a negative biomarker associated with undiagnosed diabetes and ranges from 0.176 to 0.738.

First time ACS in patients with on-target lipid levels: Inflammation at admission and re-event rate at follow-up.

BACKGROUND: Dyslipidaemia, inflammation and elevated Lp(a) levels are associated with the progression of atherosclerosis. This study investigates whether patients with a first-time presentation of chest pain and on-target LDL-C levels and intermediate FRS/ESC-Score risks, display a high inflammatory burden linked to myocardial injury and whether inflammation at admission affects the re-event rate up to 6 years follow-up. METHODS: Blind assessments of novel inflammatory markers such as Glycoprotein A and B via nuclear magnetic resonance (NMR), cytokines, hsCRP, Neutrophil-to-Lymphocyte ratio (NLR) and Lipoprotein(a) levels were examined. Out of 198 chest pain patients screened, 97 met the inclusion criteria at admission. RESULTS: cTnI(+) patients (>61 ng/L) with elevated Lipoprotein(a), showed significantly increased levels of Glycoprotein A and B, hsCRP, IL-6, a high NLR and a reduced left ventricular ejection fraction (%) compared to cTnI(-) individuals. Those patients, with a higher inflammatory burden at hospital admission (hsCRP, IL-6, Glycoprotein A and B, and Lipoprotein(a)) had a higher re-event rate at follow-up. CONCLUSIONS: Inflammation and Lipoprotein(a) levels were particularly prominent in patients presenting with reduced left ventricular ejection fraction. Notably, Glycoproteins A/B emerge as novel markers of inflammation in these patients. Our study highlights the significantly higher impact of inflammatory burden in patients with chest pain and high level of myocardial damage than in those with lower myocardial affectation, even when they all had lipid levels well controlled. Inflammation at the time of admission influenced the re-event rate over a follow-up period of up to 6 years.

Ten-year clinical outcomes after drug-eluting stents implantation according to clinical presentation-Insights from the DECADE cooperation.

BACKGROUND: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation. METHODS: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR). RESULTS: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up. CONCLUSIONS: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

BACKGROUND: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. METHODS: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. RESULTS: Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. CONCLUSIONS: In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. REGISTRATION: ClinicalTrials.gov Identifier: NCT01000701.

In-Hospital Methadone Enrollment: a Novel Program to Facilitate Linkage from the Hospital to the Opioid Treatment Program for Vulnerable Patients with Opioid Use Disorder.

INTRODUCTION: Methadone ameliorates opioid withdrawal among hospitalized patients with opioid use disorder (OUD). To continue methadone after hospital discharge, patients must enroll in an opioid treatment program (OTP) per federal regulations. Uncontrolled opioid withdrawal is a barrier to linkage from hospital to OTP. AIM: Describe a federally compliant In-Hospital Methadone Enrollment Team (IN-MEET) that enrolls hospitalized patients with OUD into an OTP with facilitated hospital to OTP linkage. SETTING: Seven hundred-bed university hospital in Aurora, CO. PROGRAM DESCRIPTION: A physician dually affiliated with a hospital's addiction consultation service and a community OTP completes an in-hospital, face-to-face medical assessment required by federal law and titrates methadone to comfort. An OTP-affiliated nurse with hospital privileges completes a psychosocial evaluation and provides case management by arranging transportation and providing weekly telephone check-ins. PROGRAM EVALUATION METRICS: IN-MEET enrollments completed, hospital to OTP linkage, and descriptive characteristics of patients who completed IN-MEET enrollments compared to patients who completed community OTP enrollments. RESULTS: Between April 2019 and April 2023, our team completed 165 IN-MEET enrollments. Among a subset of 73 IN-MEET patients, 56 (76.7%) presented to the OTP following hospital discharge. Compared to community OTP enrolled patients (n = 1687), a higher percentage of IN-MEET patients were older (39.7 years, standard deviation [SD] 11.2 years vs. 36.1 years, SD 10.6 years) and were unhoused (n = 43, 58.9% vs. n = 199, 11.8%). Compared to community OTP enrolled patients, a higher percentage of IN-MEET patients reported heroin or fentanyl as their primary substance (n = 53, 72.6% vs. n = 677, 40.1%), reported methamphetamine as their secondary substance (n = 27, 37.0% vs. n = 380, 22.5%), and reported they injected their primary substance (n = 46, 63.0% vs. n = 478, 28.3%). CONCLUSION: IN-MEET facilitates hospital to OTP linkage among a vulnerable population. This model has the potential to improve methadone access for hospitalized patients who may not otherwise seek out treatment.

Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period.

Retinal vasoactive intestinal peptide amacrine cells (VIP-ACs) play an important role in various retinal light-mediated pathological processes related to different developmental ocular diseases and even mental disorders. It is important to characterize the developmental changes in VIP-ACs to further elucidate their mechanisms of circuit function. We bred VIP-Cre mice with Ai14 and Ai32 to specifically label retinal VIP-ACs. The VIP-AC soma and spine density generally increased, from postnatal day (P)0 to P35, reaching adult levels at P14 and P28, respectively. The VIP-AC soma density curve was different with the VIP-AC spine density curve. The total retinal VIP content reached a high level plateau at P14 but was decreased in adults. From P14 to P16, the resting membrane potential (RMP) became more negative, and the input resistance decreased. Cell membrane capacitance (MC) showed three peaks at P7, P12 and P16. The RMP and MC reached a stable level similar to the adult level at P18, whereas input resistance reached a stable level at P21. The percentage of sustained voltage-dependent potassium currents peaked at P16 and remained stable thereafter. The spontaneous excitatory postsynaptic current and spontaneous inhibitory postsynaptic current frequencies and amplitudes, as well as charge transfer, peaked at P12 to P16; however, there were also secondary peaks at different time points. In conclusion, we found that the second, third and fourth weeks after birth were important periods of VIP-AC development. Many developmental changes occurred around eye opening. The development of soma, dendrite and electrophysiological properties showed uneven dynamics of progression. Cell differentiation may contribute to soma development whereas the changes of different ion channels may play important role for spine development.

Continuous thermodilution and microvascular resistance reserve during the index procedure in acute coronary syndrome without obstructive coronary artery disease: A pilot study.

BACKGROUND: In 5%-25% of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients, coronary angiography reveals no obstructive coronary arteries (MINOCA). Coronary microvascular disease (CMD) is a potential causal pathophysiological mechanism in these patients and can be diagnosed by continuous thermodilution assessment. Recently, the microvascular resistance reserve (MRR) has been introduced as a novel index to assess the vasodilatory capacity of the microcirculation. However, continuous thermodilution and MRR have never been investigated in the acute setting in MINOCA patients and invasive assessment of the microcirculation in these patients are currently lacking. AIMS: The objectives of the study were to investigate the incidence of CMD (MRR ≤ 2.7) in patients with MINOCA and to evaluate the feasibility and safety of continuous thermodilution-based assessment during index coronary angiography in the acute setting. METHODS: This study was a prospective, observational, pilot study investigating coronary physiology in the acute setting in MINOCA patients. Patients admitted with a diagnosis of NSTE-ACS were eligible for inclusion. RESULTS: In total, 19 MINOCA patients were included in this analysis; the mean age was 70 ± 9 years, and 79% were females. CMD was present in 6 patients (32%). Qrest was significantly higher in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (0.076 [0.057-0.100] vs. 0.049 [0.044-0.071] L/min, p = 0.03). Rµ,rest was significantly lower in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (1083 [710-1510] vs. 1563 [1298-1970] WU, p = 0.04). No periprocedural complications or hemodynamic instability have occurred during continuous thermodilution assessment during the index coronary angiography. CONCLUSION: In patients admitted for MINOCA undergoing immediate coronary angiography, continuous thermodilution assessment and MRR are feasible and safe in the acute setting, and evidence of functional CMD could be observed in one-third of the MINOCA patients.

Circumflex distortion following mitral valve repair.

Mitral valve repair or replacement poses a potential risk of injury to the left circumflex coronary artery (LCx). Such injuries can arise from either direct LCx injury caused by encircling or transfixing stitches, or indirect occlusion resulting from the distortion of adjacent tissues. We provide and illustrate a representative image depicting LCx distortion. Additionally, we offer guidance to aid angiographers in comprehending the angiographic appearance and the underlying mechanism of occlusion.

Mechanical circulatory support versus vasopressors alone in patients with acute myocardial infarction and cardiogenic shock undergoing percutaneous coronary intervention.

BACKGROUND: Previous studies have compared Impella use to intra-aortic balloon pump (IABP) use in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI). Our objective was to compare clinical outcomes in patients with AMI-CS undergoing PCI who received Impella (percutaneous left ventricular assist device) without vasopressors, IABP without vasopressors, and vasopressors without mechanical circulatory support (MCS). METHODS: We queried the National Inpatient Sample (NIS) using ICD-10 codes (2015-2018) to identify patients with AMI-CS undergoing PCI. We created three propensity-matched cohorts to examine clinical outcomes in patients receiving Impella versus IABP, Impella versus vasopressors without MCS, and IABP versus vasopressors without MCS. RESULTS: Among 17,762 patients, Impella use was associated with significantly higher in-hospital major bleeding (31.4% vs. 13.6%; p < 0.001) and hospital charges (p < 0.001) compared to IABP use, with no benefit in mortality (34.1% vs. 26.9%; p = 0.06). Impella use was associated with significantly higher mortality (42.3% vs. 35.7%; p = 0.02), major bleeding (33.9% vs. 22.7%; p = 0.001), and hospital charges (p < 0.001), when compared to the use of vasopressors without MCS. There were no significant differences in clinical outcomes between IABP use and the use of vasopressor without MCS. CONCLUSIONS: In this analysis of retrospective data of patients with AMI-CS undergoing PCI, Impella use was associated with higher mortality, major bleeding, and in-hospital charges when compared to vasopressor therapy without MCS. When compared to IABP use, Impella was associated with no mortality benefit, along with higher major bleeding events and in-hospital charges. A vasopressor-only strategy suggested no difference in clinical outcomes when compared to IABP. This study uses the NIS for the first time to highlight outcomes in AMI-CS patients undergoing PCI when treated with vasopressor support without MCS, compared to Impella and IABP use.

P2Y12 adenosine receptor inhibitors preloading among patients with non-ST-elevation acute coronary syndromes; insights from a nationwide multicenter registry.

BACKGROUND: The safety and efficacy of treatment with P2Y12 adenosine-diphosphate receptor inhibitors (P2Y12-RI) before coronary angiography among patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) are questionable. AIMS: To assess the pretreatment rate with P2Y12-RI and its association with ischemic and bleeding risks among patients with NSTEACS. METHODS: The study comprised patients with NSTEACS referred for coronary angiography and included in the Acute Coronary Syndrome Israeli Surveys between 2013 and 2021. Patients were divided into two groups according to the timing of P2Y12-RI loading concerning coronary angiography: pretreatment and posttreatment. The primary endpoints were 30-day major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and 1-year all-cause mortality. RESULTS: Of 3076 patients, 2423 (78.8%) received pretreatment with a P2Y12-RI, and 653 (21.2%) received P2Y12-RI posttreatment. Prasugrel and ticagrelor were used more in the posttreatment group compared to the pretreatment group (16% vs. 6% and 38% vs. 25%, respectively, p < 0.001 for both). No difference was observed in the rate of 30-day MACE comparing pretreatment and posttreatment (5.3% vs. 2.2%, respectively, p = 0.62). A sensitivity analysis of 30-day MACE among patients from the 2021 survey demonstrated similar results (2.5% in the posttreatment group vs. 8.0% in the pretreatment group, p = 0.13). There were no differences in 1-year all-cause mortality rates between the pretreatment and posttreatment groups (4.8% vs. 3.8%, p = 0.31). CONCLUSIONS: Among patients with NSTEACS referred for an invasive strategy, the P2Y12-RI posttreatment strategy was associated with similar 30-day and 1-year MACE as the pretreatment strategy. These large-scale, multicenter, real-world data provide reassurance on the safety and efficacy of delaying P2Y12-IR until after coronary stratification to improve clinical decision-making.

Outcomes among patients with non-ST-elevation myocardial infarction on chronic anticoagulation: Insights from the National Inpatient Sample.

BACKGROUND: Chronic systemic anticoagulation use is prevalent for various thromboembolic conditions. Anticoagulation (usually through heparin products) is also recommended for the initial management of non-ST-elevation myocardial infarction (NSTEMI). AIMS: To evaluate the in-hospital outcomes of patients with NSTEMI who have been on chronic anticoagulation. METHODS: Using the National Inpatient Sample (NIS) years 2016-2020, NSTEMI patients and patients with chronic anticoagulation were identified using the appropriate International Classification of Diseases, 10th version (ICD-10) appropriate codes. The primary outcome was all-cause in-hospital mortality while the secondary outcomes included major bleeding, ischemic cerebrovascular accident (CVA), early percutaneous coronary intervention (PCI) (i.e., within 24 h of admission), coronary artery bypass graft (CABG) during hospitalization, length of stay (LOS), and total charges. Multivariate logistic or linear regression analyses were performed after adjusting for patient-level and hospital-level factors. RESULTS: Among 2,251,914 adult patients with NSTEMI, 190,540 (8.5%) were on chronic anticoagulation. Chronic anticoagulation use was associated with a lower incidence of in-hospital mortality (adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.65-0.73, p < 0.001). There was no significant difference in major bleeding (aOR: 0.95, 95% CI: 0.88-1.0, p = 0.15) or ischemic CVA (aOR: 0.23, 95% CI: 0.03-1.69, p = 0.15). Chronic anticoagulation use was associated with a lower incidence of early PCI (aOR: 0.78, 95% CI: 0.76-0.80, p < 0.001) and CABG (aOR: 0.43, 95% CI: 0.41-0.45, p < 0.001). Chronic anticoagulation was also associated with decreased LOS and total charges (adjusted mean difference [aMD]: -0.8 days, 95% CI: -0.86 to -0.75, p < 0.001) and (aMD: $-19,340, 95% CI: -20,692 to -17,988, p < 0.001). CONCLUSIONS: Among patients admitted with NSTEMI, chronic anticoagulation use was associated with lower in-hospital mortality, LOS, and total charges, with no difference in the incidence of major bleeding.

Should We Keep or Transfer Our Severely Injured Geriatric Patients to Higher Levels of Care?

INTRODUCTION: Interfacility transfer to higher levels of care is becoming increasingly common. This study aims to evaluate the association between transfer to higher levels of care and prolonged transfer times with outcomes of severely injured geriatric trauma patients compared to those who are managed definitively at lower-level trauma centers. METHODS: Severely injured (Injury Severity Score >15) geriatric (≥60 y) trauma patients in the 2017-2018 American College of Surgeons Trauma Quality Improvement Program database managing at an American College of Surgeons/State Level III trauma center or transferring to a level I or II trauma center were included. Outcome measures were 24-h and in-hospital mortality and major complications. RESULTS: Forty thousand seven hundred nineteen patients were identified. Mean age was 75 ± 8 y, 54% were male, 98% had a blunt mechanism of injury, and the median Injury Severity Score was 17 [16-21]. Median transfer time was 112 [79-154] min, and the most common transport mode was ground ambulance (82.3%). Transfer to higher levels of care within 90 min was associated with lower 24-h mortality (adjusted odds ratio [aOR]: 0.493, P < 0.001) and similar odds of in-hospital mortality as those managed at level III centers. However, every 30-min delay in transfer time beyond 90 min was progressively associated with increased odds of 24-h (aOR: 1.058, P < 0.001) and in-hospital (aOR: 1.114, P < 0.001) mortality and major complications (aOR: 1.127, P < 0.001). CONCLUSIONS: Every 30-min delay in interfacility transfer time beyond 90 min is associated with 6% and 11% higher risk-adjusted odds of 24-h and in-hospital mortality, respectively. Estimated interfacility transfer time should be considered while deciding about transferring severely injured geriatric trauma patients to a higher level of care.

The 5-Factor Modified Frailty Index is a Concise and Effective Predictor of 30-Day Adverse Outcomes in Carotid Endarterectomy.

INTRODUCTION: Frailty is a clinically identifiable condition characterized by heightened vulnerability. The 5-item Modified Frailty Index provides a concise calculation of frailty that has proven effective in predicting adverse perioperative outcomes across a variety of surgical disciplines. However, there is a paucity of research examining the validity of 11-item Modified Frailty Index (mFI-5) in carotid endarterectomy (CEA). This study aimed to investigate the association between mFI-5 and 30-day outcomes of CEA. METHODS: Patients underwent CEA were identified from American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2021. Patients with age<18 were excluded. Patients were stratified into four cohorts based on their mFI-5 scores: 0, 1, 2, or 3+. Multivariable logistic regression was used to compare 30-day perioperative outcomes adjusting for preoperative variables with P value<0.1. RESULTS: Compared to controls (mFI-5 = 0), patients mFI-5 = 1 had higher risk of stroke (adjusted odds ratio [aOR] = 1.333, P = 0.02), unplanned operation (aOR = 1.38, P < 0.01), and length of stay (LOS) > 7 days (aOR = 0.814, P < 0.01). Patients with mFI-5 = 2 had higher stroke (aOR = 1.719, P < 0.01), major adverse cardiovascular events (MACE) (aOR = 1.315, P = 0.01), sepsis (aOR = 2.243, P = 0.01), discharge not to home (aOR = 1.200, P < 0.01), 30-day readmission (aOR = 1.405, P < 0.01). Compared with controls, patients with mFI-5≥3 had higher mortality (aOR = 1.997 P = 0.02), MACE (aOR = 1.445, P = 0.03), cardiac complications (aOR = 1.901, P < 0.01), pulmonary events (aOR = 2.196, P < 0.01), sepsis (aOR = 3.65, P < 0.01), restenosis (aOR = 2.606, P = 0.02), unplanned operation (aOR = 1.69, P < 0.01), LOS>7 days (aOR = 1.425, P < 0.01), discharge not to home (aOR = 2.127, P < 0.01), and 30-day readmission (aOR = 2.427, P < 0.01). CONCLUSIONS: The mFI-5 is associated with 30-day mortality and complications including stroke, MACE, cardiac complications, pulmonary complications, sepsis, and restenosis. Additionally, elevated mFI-5 scores correlate with an increased likelihood of unplanned operations, extended LOS, discharge to facilities other than home, and 30-day readmissions, all of which could negatively impact long-term prognosis. Therefore, mFI-5 can serve as a concise yet effective metric of frailty in patients undergoing CEA.

To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline.

OBJECTIVES: To accurately evaluate non-ST-elevated acute cardiac syndrome (NSTE-ACS), the quality of high-sensitive cardiac troponin (hs-cTn) assays is of vital importance. The 2020 revision of the NSTE-ACS guideline includes clinical decision-limits (CDL's) to both rule-in and rule-out NSTE-ACS for most commercially available platforms, providing both 0/1 h and 0/2 h delta limits. Our study evaluated whether laboratories are able to meet the analytical performance specifications for imprecision (APS) for hs-cTnT. METHODS: Results from external quality assurance (EQA) in commutable samples were used to evaluate the current and historic performance of analyzers. The performance of analyzers that either passed or failed to comply with 0/1 h-APS were used on a real-world dataset of first hs-cTnT-values to simulate 10.000 samples of t=0, t=1 and t=2 h values with multiple delta's for all relevant CDL's. We compared the simulated values to the input values to obtain the percentage of aberrant results simulated. RESULTS: The majority of analyzers complies with APS for rule-in in 2022 (0/1 h: 90.4 % and 0/2 h: 100 %), compliance for the 0/1 h rule-out is still far from optimal (0/1 h: 30.7 %, 0/2 h: 75.4 %), with improving compliance over the past years (rule-in p=<0.0001, rule-out p=0.011, χ2). Whilst 0/1 h-APS-passing analyzers have a minute risk to falsely rule-out patients whom should be ruled-in (0.0001 %), failing performance increases this risk to 2.1 % upon using 0/1 h CDL's. Here, adopting 0/2 h CDL's is favorable (0.01 %). CONCLUSIONS: Laboratories that fail to meet hs-cTnT 0/1 h-APS should improve their performance to the required and achievable level. Until performance is reached clinics should adopt the 0/2 h CDL's.

Evaluation of the efficacy and safety of rivaroxaban compared to warfarin in patients with left ventricular apical thrombus: a randomized clinical trial.

INTRODUCTION: This research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS). MATERIALS AND METHODS: This is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE). RESULTS: The study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups. CONCLUSION: The trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.