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Frontiers in Cardiovascular Medicine 2024Previous research has demonstrated the validity of the triglyceride-glucose (TyG) index as a robust measure of insulin resistance (IR) and its association with coronary...
BACKGROUND
Previous research has demonstrated the validity of the triglyceride-glucose (TyG) index as a robust measure of insulin resistance (IR) and its association with coronary artery disease (CAD). The objective of this study is to elucidate the relationship between the TyG index and the prognosis of patients underwent percutaneous coronary intervention (PCI) through a comprehensive systematic review and meta-analysis. Our goal is to provide a thorough analysis of the available evidence to offer more clarity on this association.
METHODS
A systematic and thorough search was carried out in the PubMed, Embase, Cochrane Library, and Web of Science databases, covering studies published in English from the beginning until October 1, 2023. The focus of the search was to gather relevant studies pertaining to the occurrence of major adverse cardiovascular events (MACE). To address the variability among the included studies, random or fixed effect models were utilized to summarize the hazard ratios (HR). In cases where heterogeneity was detected, subgroup or sensitivity analyses were performed to explore potential sources. To evaluate publication bias, the Egger or Begg test was employed.
RESULTS
This study incorporated a total of 17 studies. Individuals with the highest TyG index exhibited an elevated risk of major adverse cardiovascular events (MACEs) compared to those with the lowest TyG index (HR = 1.69; 95% CI: 1.47-1.95; < 0.001). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.60 (95% CI: 1.48-1.73; < 0.001). Moreover, in patients diagnosed with acute coronary syndrome (ACS), higher TyG index levels showed a trend of increased risk of MACE (HR = 1.54; 95% CI: 1.27-1.86; < 0.001). Furthermore, an elevated TyG index was found to be associated with a higher risk of in-stent restenosis (HR = 1.62; 95% CI: 1.29-2.03; < 0.001), new-onset atrial fibrillation (HR = 2.97; 95% CI: 2.10-4.06; = 0.014), and a reduction in quantitative flow ratio (HR = 1.35; 95% CI: 1.101-1.592; = 0.005). Subgroup analysis indicated the risk of MACE was comparable between varied durations of follow-up ( = 0.11). Furthermore, regression analysis revealed that the positive association between TyG index and the risk of MACE did not differ between individuals with or without diabetes ( = 0.23).
CONCLUSION
An increase in the TyG index may lead to a higher vulnerability to major adverse cardiovascular events (MACE) in patients underwent PCI and there was no significant difference in the risk of major adverse cardiovascular events (MACE) between diabetic and non-diabetic individuals.
PubMed: 38952542
DOI: 10.3389/fcvm.2024.1396865 -
Immuno-oncology Technology Jun 2024Immune-related adverse events (IRAEs) during therapy with immune checkpoint inhibitors (ICIs) are common, and their management sometimes requires glucocorticoids (GCs)....
Effect of glucocorticoids for the management of immune-related adverse events on outcome in melanoma patients treated with immunotherapy-a retrospective and biomarker study.
BACKGROUND
Immune-related adverse events (IRAEs) during therapy with immune checkpoint inhibitors (ICIs) are common, and their management sometimes requires glucocorticoids (GCs). Predictors for development of IRAEs and data about the impact of GCs on clinical outcome are missing. We evaluated the impact of GCs to treat IRAEs on clinical outcome, and plasmatic inflammatory proteins as predictors for IRAEs.
PATIENTS AND METHODS
Patients with melanoma ( = 98) treated with ICIs at Karolinska University Hospital were included. Clinical information and data regarding prescription of systemic GCs were collected. Baseline plasma samples ( = 57) were analyzed for expression of 92 inflammatory proteins.
RESULTS
Forty-four patients developed at least one IRAE requiring systemic GCs and the most common was hypocortisolemia ( = 11). A median overall survival of 72.8 months for patients developing IRAEs requiring GCs, 17.7 months for those who did not, and 1.4 months for individuals receiving GCs at baseline was observed in Kaplan-Meier curves ( = 0.001). In immortal time bias adjusted analysis, patients receiving steroids to treat IRAE survived slightly longer, even though this time trend was not statistically significant. The median overall survival was 29 months for those treated with GCs within 60 days after ICIs start and was not reached for patients receiving GCs later. The number of ICI cycles was higher in subjects receiving GCs after 60 days ( = 0.0053). Hypocortisolemia occurred mainly in males (10/11) and correlated with favorable outcome. Male patients with hypocortisolemia had lower expression of interleukin 8, transforming growth factor-α, and fibroblast growth factor 5 and higher expression of Delta/Notch-like epidermal growth factor-related receptor.
CONCLUSIONS
GCs may be used to treat IRAEs without major concern. GCs early during ICIs may, however, impact clinical outcome negatively. The prognostic value of hypocortisolemia and inflammation proteins as biomarkers should be further investigated.
PubMed: 38952418
DOI: 10.1016/j.iotech.2024.100713 -
Heliyon Jun 2024With the development of surgical techniques and medical equipment, the mortality rate of off-pump coronary artery bypass grafting (CABG) has been declining year by year,...
BACKGROUND
With the development of surgical techniques and medical equipment, the mortality rate of off-pump coronary artery bypass grafting (CABG) has been declining year by year, but there is a lack of convenient and accurate predictive models. This study aims to use two nomograms to predict 30-day mortality after off-pump CABG.
METHODS
Patients with isolated off-pump CABG from January 2016 to January 2021 were consecutively enrolled. Potential predictive factors were first screened by lasso regression, and then predictive models were constructed by multivariate logistic regression. To earlier identify high-risk patients, two nomograms were constructed for predicting mortality risk before and after surgery.
RESULTS
A total of 1840 patients met the inclusion and exclusion criteria. The 30-day mortality was 3.97 % (73/1840) in this cohort. Multivariate logistic analysis showed that age, BMI<18.5 kg/m, surgical time, creatinine, LVEF, history of previous stroke, and major adverse intraoperative events (including conversion to cardiopulmonary bypass or implantation of intra-aortic balloon pump) were independently associated with 30-day mortality. Model 1 contained preoperative and intraoperative variables, and the AUC was 0.836 (p < 0.001). The AUC of the K-fold validation was 0.819. Model 2 was only constructed by preoperative information. The AUC was 0.745 (p < 0.001). The AUC of the K-fold validation was 0.729. The predictive power of Model 1 was significantly higher than the SinoScore (DeLong's test p < 0.001).
CONCLUSIONS
The two novel nomograms could be conveniently and accurately used to predict the risk of 30-day mortality after isolated off-pump CABG.
PubMed: 38952381
DOI: 10.1016/j.heliyon.2024.e32641 -
Journal of Medicinal Chemistry Jul 2024Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that...
Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile. In this report, we performed a structure-activity relationship study focusing on the benzoxazole scaffold in , which lead to the discovery of () as a potent inhibitor of S1P release from HeLa cells (IC: 51 ± 3 nM). Administration of to mice induced ∼50% reduction in circulating lymphocyte counts, recapitulating the lymphopenia characteristic of Spns2 null animals. Molecular modeling studies suggest that binds Spns2 in its occluded inward-facing state and forms hydrogen bonds with Asn112 and Ser211 and π stacking with Phe234. Taken together, can serve as a scaffold for future inhibitor development and represents a chemical tool to study the therapeutic implication of inhibiting Spns2.
PubMed: 38952222
DOI: 10.1021/acs.jmedchem.4c00879 -
Scandinavian Cardiovascular Journal :... Jun 2024
A reply to the letter to the editor "Common practice of underreporting and downplaying adverse events and exaggerating benefits in patients undergoing percutaneous coronary intervention of chronic total occlusions".
Topics: Humans; Percutaneous Coronary Intervention; Coronary Occlusion; Chronic Disease; Treatment Outcome; Risk Assessment; Risk Factors
PubMed: 38952217
DOI: 10.1080/14017431.2024.2373102 -
Innovations (Philadelphia, Pa.) 2024Robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) is an attractive strategy for coronary revascularization. Growing evidence supports the use... (Comparative Study)
Comparative Study
OBJECTIVE
Robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) is an attractive strategy for coronary revascularization. Growing evidence supports the use of total arterial grafting in coronary surgery. We evaluated total arterial left-sided coronary revascularization with bilateral internal thoracic artery (BITA) using RA-MIDCAB and compared it with a propensity score-matched (PSM) off-pump CAB (OPCAB) surgery population.
METHODS
We retrospectively included all isolated OPCAB and RA-MIDCAB surgery using BITA without saphenous vein graft from January 1, 2015, to October 31, 2022. We analyzed all our RA-MIDCAB patients and performed PSM to compare them with our OPCAB population. Primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE) and mortality. Secondary outcomes were surgical parameters, length of hospital stay, and learning curve.
RESULTS
We included 601 OPCAB and 77 RA-MIDCAB procedures, which resulted in 2 cohorts of 54 patients after PSM. Mortality and MACCE survival analysis showed no significant difference. There was less blood transfusion in the RA-MIDCAB (16.7%) compared with the OPCAB group (38.9%; = 0.02). We observed fewer intensive care unit (ICU) admissions (24.1% vs 96.6%), shorter ICU stay (0.78 ± 1.7 vs 1.91 ± 1.01 days), and shorter hospital stay (6.78 ± 2.4 vs 8.01 ± 2.5 days) in the RA-MIDCAB versus OPCAB group ( < 0.01). Surgery time decreased from 400.0 ± 70.8 to 325.0 ± 38.0 min with more experience in RA-MIDCAB BITA harvesting ( < 0.01).
CONCLUSIONS
This is a first publication of 77 consecutive RA-MIDCAB BITA harvesting for left coronary artery system revascularization. This technique is safe in terms of MACCE and mortality. Additional advantages are shorter length of hospital stay, fewer ICU admissions, and less blood transfusion.
Topics: Humans; Robotic Surgical Procedures; Male; Female; Retrospective Studies; Propensity Score; Coronary Artery Bypass, Off-Pump; Aged; Middle Aged; Mammary Arteries; Length of Stay; Treatment Outcome; Coronary Artery Disease; Coronary Artery Bypass; Operative Time; Minimally Invasive Surgical Procedures; Postoperative Complications
PubMed: 38952215
DOI: 10.1177/15569845241245422 -
Clinical Transplantation Jul 2024We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving... (Observational Study)
Observational Study
BACKGROUND
We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy.
METHODS
A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events.
RESULTS
Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%).
CONCLUSIONS
In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Platelet Aggregation Inhibitors; Anticoagulants; Follow-Up Studies; Heart Transplantation; Prognosis; Blood Transfusion; Risk Factors; Aged; Adult; Dabigatran; Postoperative Complications
PubMed: 38952201
DOI: 10.1111/ctr.15380 -
ESC Heart Failure Jul 2024Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in...
AIMS
Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from discharge to 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria.
METHODS AND RESULTS
First, 547 HFpEF cases were divided into two groups, Hb < 11.0 g/dL (n = 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hb at discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curve that predicts MACE. We examined the incidence rate of MACE between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb. In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR): 3.14 [95% confidence interval (CI), 1.76-5.60], P < 0.001). MACE was not significantly different between G2 with improving anaemia from Hb < 11.0 g/dL to ≥ 11.0 g/dL and G4 (adjusted HR: 1.37 [95% CI, 0.68-2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronic obstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR: 1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). In multivariate linear regression analysis, covarying factors with change in Hb were BMI (β = -0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179).
CONCLUSIONS
Change in haemoglobin after discharge using a lower cut-off value than WHO criteria has prognostic impact in patients with HFpEF.
PubMed: 38952180
DOI: 10.1002/ehf2.14927 -
Oncology Jul 2024Avelumab is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to avelumab treatment...
INTRODUCTION
Avelumab is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to avelumab treatment of mUC patients.
METHODS
A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with avelumab (Ave; n=43), because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n=29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to avelumab maintenance therapy as avelumab (Ave)-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the geriatric nutritional risk index (GNRI) for determining patients suitable for Ave, were evaluated.
RESULTS
The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by receiver operating characteristic curve. Low age and GNRI sustainability revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis.
CONCLUSION
In mUC, avelumab maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as biomarker to predict being Ave-suitable.
PubMed: 38952143
DOI: 10.1159/000539795 -
Immunology Jul 2024Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the... (Review)
Review
Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.
PubMed: 38952142
DOI: 10.1111/imm.13828