RESUMEN
BACKGROUND: Diabetes mellitus (DM) significantly impacts cardiovascular outcomes, particularly in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). The presence of polyvascular disease further complicates the prognosis due to the increased burden of atherosclerosis and comorbidities. This study was designed to investigate the combined impact of DM and polyvascular disease on outcomes in patients with AMI and CS. METHOD: Using the National Inpatient Sample database, we analyzed 39,140 patients with AMI complicated by CS and known polyvascular disease. The patients were stratified by diabetes status. The study assessed in-hospital major adverse cardiovascular and cerebrovascular events (MACCE), mortality, cerebrovascular accident (CVA) and major bleeding. Multivariable logistic regression models were used to examine the association between in-hospital outcomes and diabetes, adjusting for baseline differences. RESULTS: Of the study population, 54% had DM. The patients with DM were younger (69.5 vs. 72.1 years, p < 0.001) and more likely to be female (36.7% vs. 34.2%, p < 0.001). After adjustment, the patients with DM showed a 17% increased mortality risk (aOR 1.17, 95% CI: 1.11-1.23, p < 0.001) and a higher risk of major adverse cardiovascular and cerebrovascular events (aOR 1.05, 95% CI: 1.01-1.10, p = 0.020). CONCLUSIONS: DM significantly impacts outcomes in patients with AMI complicated by CS and polyvascular disease, leading to increased mortality risk, longer hospital stays, and higher healthcare costs. These findings underscore the need for targeted interventions and specialized care strategies for this high-risk population.
RESUMEN
Background: During the first months of the COVID-19 outbreak, an increase was observed in atrial fibrillation (AF)-related mortality in the United States (U.S). We aimed to investigate AF-related mortality trends in the U.S. before, during, and after the COVID-19 pandemic peak, stratified by sociodemographic factors. Methods: using the Wide-Ranging Online Data for Epidemiologic Research database of the Centers for Disease Control and Prevention, we compared the AF-related age-adjusted mortality rate (AAMR) among different subgroups in the two years preceding, during, and following the pandemic peak (2018-2019, 2020-2021, 2022-2023). Result: By analyzing a total of 1,267,758 AF-related death cases, a significant increase of 24.8% was observed in AF-related mortality during the pandemic outbreak, followed by a modest significant decrease of 1.4% during the decline phase of the pandemic. The most prominent increase in AF-related mortality was observed among males, among individuals younger than 65 years, and among individuals of African American and Hispanic descent, while males, African American individuals, and multiracial individuals experienced a non-statistically significant decrease in AF-related mortality during the pandemic decline period. Conclusions: Our findings suggest that in future healthcare crises, targeted healthcare policies and interventions to identify AF, given its impact on patients' outcomes, should be developed while addressing disparities among different patient populations.
RESUMEN
Background: Inflammation plays a central role in atherogenesis. The major neutrophilic peptide alpha-defensin is a promising evolving risk factor for atherosclerosis. The aim of the present study was to examine the role of alpha-defensin in predicting future major adverse cardiovascular events (MACE) occurrence in fully revascularized patients with stable CAD under optimal medical therapy. Methods and results: We retrospectively examined the prognostic value of baseline plasma alpha-defensin levels in predicting MACE occurrence in 174 fully revascularized patients for stable CAD between March 2016 and January 2017. Alpha-defensin levels were found 20 % higher among demised patients (10,859 pg/ml, IQR [6,920 to 23,320] vs. 9,020 pg/ml, IQR [5,540 to 16,180] pg/ml, P = 0.15). The absolute increase in mortality risk in patients with alpha-defensin levels greater than the median values was 72.5 % (P = 0.33). Log-rank analysis proved both recurrent PCI for de novo lesions (14.9 % and 2.3 %) and the composite of mortality and recurrent PCI for de novo lesions (27.6 % vs. 9.2 %) were significantly related to alpha-defensin values greater than the median (>9200 pg/ml). Conclusion: Baseline plasma alpha-defensin is an independent predictor of mortality and recurrent PCI among patients with stable CAD. Alpha-defensin may evolve as a promising factor in cardiovascular risk assessment beyond traditional risk factors. Targeting alpha-defensin to ameliorate MACE occurrence should be addressed in future studies.
RESUMEN
While the vast majority of Alzheimer's disease (AD) is non-familial, the animal models of AD that are commonly used for studying disease pathogenesis and development of therapy are mostly of a familial form. We aimed to generate a model reminiscent of the etiologies related to the common late-onset Alzheimer's disease (LOAD) sporadic disease that will recapitulate AD/dementia features. Naïve female mice underwent ovariectomy (OVX) to accelerate aging/menopause and were fed a high fat-sugar-salt diet to expose them to factors associated with increased risk of development of dementia/AD. The OVX mice fed a high fat-sugar-salt diet responded by dysregulation of glucose/insulin, lipid, and liver function homeostasis and increased body weight with slightly increased blood pressure. These mice developed AD-brain pathology (amyloid and tangle pathologies), gliosis (increased burden of astrocytes and activated microglia), impaied blood vessel density and neoangiogenesis, with cognitive impairment. Thus, OVX mice fed on a high fat-sugar-salt diet imitate a non-familial sporadic/environmental form of AD/dementia with vascular damage. This model is reminiscent of the etiologies related to the LOAD sporadic disease that represents a high portion of AD patients, with an added value of presenting concomitantly AD and vascular pathology, which is a common condition in dementia. Our model can, thereby, provide a valuable tool for studying disease pathogenesis and for the development of therapeutic approaches.
Asunto(s)
Enfermedad de Alzheimer , Demencia Vascular , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Ovariectomía , Animales , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Femenino , Ratones , Demencia Vascular/etiología , Demencia Vascular/patología , Ovariectomía/efectos adversos , Dieta Alta en Grasa/efectos adversos , Cloruro de Sodio Dietético/efectos adversos , Gliosis/patología , Encéfalo/patología , Encéfalo/metabolismoRESUMEN
Aims: A substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. Methods: Patients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3-4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. Results: The prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3-4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32-1.93, p < 0.01) for patients with 3-4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05-1.53, p < 0.01). Conclusion: The incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.
RESUMEN
Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol's adverse effects. Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18-11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84-9.28), and 3.25 (95% CI 1.78-5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.
RESUMEN
(1) Introduction: A significant proportion of patients undergoing coronary angiography (CAG) have normal (NCA) or non-obstructive coronary artery disease (NOCAD). This study retrospectively tested the incidence of re-catheterization, and long-term outcomes of this population in patients aged over 50 years. (2) Methods: We identified all patients above 50 years of age with NOCAD who underwent their first CAG at our center between January 2008 and December 2019. Patients were evaluated for their baseline characteristics, risk factors profile, and indication for CAG. Patients undergoing repeat CAG after the index procedure were assessed for the above, including the primary preventive pharmacotherapy prescribed. (3) Results: A total of 1939 patients were reported to have NOCAD. Of these, 1756 (90%) patients (62% males, median age 66 (56-75) years) had no repeat angiography (group 1). Repeat angiography was performed in 10%: 136 (7%) proved futile (median time for repeat angiography 5 (3-8) years) (group 3), and 47 (3%) ended with angioplasty (median time for repeat angiography 4 (3-6) years) (group 2). Male gender, BMI above 30 (23% vs. 13%), hypertension (68% vs. 57%), diabetes (28% vs. 17%) and smoking (36% vs. 19%) were significantly higher in the interventional group. Regression analysis showed both paroxysmal atrial fibrillation and hyperlipidemia were significantly associated with repeat CAG. The indication for the first CAG was mainly symptoms related. In the interventional repeat angiography (n = 47) the incidence of troponin positive cases increased from 8.2% before intervention to 57.5%, 50% being ST elevation cases. The symptoms-related cases went from 36.7% to 18.4%. Intriguingly, 85% of the interventional group were not prescribed statin and/or aspirin on a regular basis, and/or did not adhere to treatment. (4) Conclusions: NOCAD is a frequent occurrence. The threshold for repeat angiography must be higher, better reserved to troponin positive cases. Moreover, patients must be handled according to their risk profile, not being mistakenly reassured by a snapshot benign coronary angiography.
RESUMEN
INTRODUCTION: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors. METHODS: A prospective study was performed among healthy newborns in the Obstetrics and Gynecology Department at Hillel Yaffe Medical Center in Israel in January-June 2021. The sociodemographic characteristics of the participants, maternal age, gravidity, parity, Pitocin use, epidural analgesia, and neonatal anemia were obtained from the electronic medical records. Gestational age was determined by ultrasound biometric measurements. We classified second-stage labor as normal or prolonged using the WHO guidelines. Samples from umbilical cord blood were drawn using syringes rinsed with anticoagulant by a specialist in pediatrics. The remaining blood was used to determine hs-cTnT levels (ng/L), which was defined as a continuous quantitative variable with the median value and the 25th-75th percentiles. RESULTS: Overall, 184 cord blood samples were performed from healthy newborns (60.6% males) with a median hs-cTnT of 39.03 (25th-75th percentiles = 30.53-54.09) ng/L. A multivariable linear regression model showed no significant association between neonatal anemia and hs-cTnT levels (ng/L) (p = 0.8). Gestational age (B coefficient -4.24, p < 0.001) and gravidity (B coefficient -2.41, p = 0.03) were negatively associated with hs-cTnT levels (ng/L), while Pitocin use (B coefficient 6.91, p = 0.04) and prolonged second stage of labor (B coefficient 18.07, p = 0.02) were positively associated with hs-cTnT levels (ng/L). CONCLUSIONS: High hs-cTnT levels (ng/L) were documented in the cord blood of healthy newborns. Hs-cTnT levels were positively correlated with a prolonged second stage of labor and Pitocin use and negatively correlated with longer gestational age and higher gravidity. Hs-cTnT may signify labor-related fetal distress. A larger surveillance study is mandatory to establish this correlation and assess for possible prognostic significance of elevated hs-cTnT in this context.
Asunto(s)
Anemia Neonatal , Troponina T , Masculino , Embarazo , Femenino , Humanos , Recién Nacido , Niño , Estudios Prospectivos , Segundo Periodo del Trabajo de Parto , Oxitocina , BiomarcadoresRESUMEN
Background-Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs' efficacy and tolerability. Aim-The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods-In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual's metabolizing status for CYP2D6/CYP2C19. Results-With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56-0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions-We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.
RESUMEN
Background: It is prudent to develop biomarkers that enhance the differentiation between viral and bacterial infection in order to support expeditious and judicious antimicrobial implementation in emergency department admissions. Human neutrophilic peptides 1-3 (HNP1-3) are the major neutrophilic peptides with potent antimicrobial activity. Methods: We tested the performance of the plasma HNP1-3 test in a prospective observational cohort of children admitted to the emergency department for fever. We validated this test with traditionally used biomarkers and final diagnoses. An expert panel reviewed the patient's data and gave a final diagnosis. The final diagnosis was classified as definite, probable, or possible. Results: A total of 111 children (98 with fever and 13 control) were recruited: 55% male, mean age 6.3 years. Plasma HNP1-3 levels were higher with bacterial infections: 10,428 (5789-14,866) vs. 7352 (3762-10,672) pg/mL, p = 0.007. HNP1-3 were negatively correlated with age: r = -0.207, p = 0.029. Of the different categorical variables tested, only c-reactive protein (CRP) (≥42.3 mg/dL), neutrophil count (≥10.2), and age (odds ratio = 1.185, p = 0.013 and 95%CI = 1.037-1.354) had significant diagnostic capability for bacterial disease prediction. Conclusions: Due to its low diagnostic value in febrile patients, the HNP1-3 value is not currently recommended to support pathogen differentiation in children in an emergency setting. Further studies are needed to support its clinical use.
RESUMEN
Risk models to estimate percutaneous coronary intervention (PCI) mortality have limited value in complex high-risk patients. However, it was improved by a recently developed bedside model to predict in-hospital mortality using data from the American College of Cardiology CathPCI Registry that included 706,263 patients. The median risk-standardized in-hospital mortality rate was 1.9%. In an attempt to validate this model in patients admitted because of acute coronary ischemia to predict in-hospital, 30-day, and 1-year mortality, we applied the proposed risk score to the study population of the Acute Coronary Syndrome Israeli Survey (ACSIS). This study was conducted for 2 months in 2018 and included all patients admitted to 25 coronary care units and cardiology departments in Israel. The ACSIS included 1,155 patients admitted because of acute myocardial infarction and who underwent PCI. In-hospital, 30-day, and 1-year mortality were 2.3%, 3.1%, and 6.2%, respectively. The CathPCI risk score yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval [CI] 0.94 to 0.99) for in-hospital mortality; 0.96 (95% CI 0.94 to 0.98) for the 30-day mortality, and 0.88 (95% CI 0.83 to 0.93) for the 1-year mortality. The current model also included frail patients, and those with aortic stenosis, refractory shock, and after cardiac arrest. In conclusion, the CathPCI Registry risk score was validated using data from the ACSIS. Because the ACSIS population comprised patients with acute ischemia including those with high-risk features this model demonstrates a wider scope of application compared with previous ones. In addition, the model seems to be suitable to predict also the 30-day and 1-year mortality.
Asunto(s)
Síndrome Coronario Agudo , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Sistema de Registros , Síndrome Coronario Agudo/epidemiología , Mortalidad Hospitalaria , Medición de Riesgo , Resultado del TratamientoRESUMEN
Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients' characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0-2, and 26 were grade 3-4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3-4 fibrosis relative to grades 0-2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , alfa-Defensinas , Humanos , Masculino , Adulto , Persona de Mediana Edad , Hígado/patología , Estudios Retrospectivos , alfa-Defensinas/metabolismo , Neutrófilos , Cirrosis Hepática/complicaciones , Fibrosis , BiopsiaRESUMEN
OBJECTIVE AND AIM: The extent of the protection against SARS-CoV-2 conferred by natural infection is unclear. Vitamin D may have a role in the interplay between SARS-CoV-2 infection and the evolving acquired immunity against it. We tested the correlation between baseline 25(OH) D content and both the reinfection rate and the anti-spike protein antibody titer following COVID-19 infection. Methods A retrospective observational survey that included a large convalescent COVID-19 population of subjects insured by the Leumit HMO was recorded between 1 February 2020 and 30 January 2022. Inclusion criteria required at least one available 25(OH)D level prior to enlistment. The association between 25(OH)D levels, the rate of breakthrough infection, and the anti-spike protein antibody titer was evaluated. Results A total of 10,132 COVID-19 convalescent subjects were included, of whom 322 (3.3%) sustained reinfection within a one-year follow-up. In the first 8 months after recovery, the reinfected patients were characterized by a higher incidence of low 25(OH)D levels (<30 ng/mL, 92% vs. 84.8%, p < 0.05), while during the following three months, the incidence of low 25(OH)D levels was non-significantly higher among PCR-negative convalescent subjects compared to those reinfected (86% vs. 81.7, p = 0.15). By multivariate analysis, age > 44 years (OR-0.39, 95% CI: 0.173-0.87, p = 0.02) and anti-spike protein antibody titer > 50 AU/mL (0.49, 95% CI: 0.25-0.96, p = 0.04) were inversely related to reinfection. No consistent correlation with vitamin D levels was observed among the 3351 available anti-spike protein antibody titers of convalescent subjects. However, the median anti-spike protein antibody titers tended to increase over time in the vitamin D-deficient group. Conclusion Higher pre-infection 25(OH)D level correlated with protective COVID-19 immunity during the first 8 months following COVID-19 infection, which could not be explained by anti-spike protein antibody titers. This effect dissipated beyond this period, demonstrating a biphasic 25(OH)D association that warrants future studies.
RESUMEN
OBJECTIVE: The heart team approach is highly advocated for in treatment decision making in patients with multivessel disease (MVD). Nevertheless, many centers lack on-site cardiac surgical services (CSS)/formal heart team. Our local alternative is of remote surgical consultation without a structured image sharing platform. In our understanding, the incidence of anatomical complete revascularization (ACR) under this daily practice, and its clinical impact, has not been discussed before. METHODS: We analyzed 477 consecutive patients who were surgically revascularized between January 2009 and March 2018 for MVD, after remote surgical consultation. Unstable, late arrival, and ST elevation patients were excluded (n = 163). ACR was considered grafting all anatomic lesions > 50%. Syntax score (SS) calculation and ACR categorization were determined by an independent interventionalist using diagnostic angiograms and available operative reports (n = 267). Patients' outcomes were assessed in relation to multiple clinical variables including troponin result and the revascularization status. RESULTS: Three hundred and fourteen patients were included. Mean age was 64 years, and mean SS-II was 27.3 ± 11. At the 4-year follow-up, the observed mortality (11.8% and 12.9%, with troponin-positive and -negative groups, respectively), myocardial infarction (11.8%), and repeat revascularization (9.8%) were higher than those predicted using a nomogram depicting the predicted 4-year mortality as a function of the SYNTAX II Score (5.3%, 8.8%, and 3.5%, respectively, p = 0.02). ACR was reported in 33% of 267 available patients' reports. After multivariate adjustment ACR was the only variable associated with a significant increase in 4-year mortality (12.3% vs. 6.7%, p < 0.05). CONCLUSIONS: Partial revascularization in the absence of on-site CSS and a structured heart team platform is a frequent occurrence. Not surprisingly, this occurrence was associated with a higher risk for mid-term mortality. An upfront, structured, virtual, heart team interface is mandatory to particularly prioritize the completeness of revascularization when considering the optimal revascularization mode.
RESUMEN
Objective: Vaccines against COVID-19 induce specific antibodies whose titer is perceived as a reliable correlate of protection. Vitamin D confers complex regulatory effects on the innate and adaptive immunity. In this study, we explored a plausible impact of baseline vitamin D content on achieved immunity following COVID-19 vaccination. Methods: A retrospective observational study comprising 73,254 naïve subjects insured by the Leumit Health Service HMO, who were vaccinated between 1 February 2020 and 30 January 2022, with one available vitamin D level prior to vaccination, was performed. The association between 25(OH) vitamin D levels, SARS-CoV-2 antibody titer, and post-vaccination PCR results were evaluated. Results: Of the study population, 5026 (6.9%) tested positive for COVID-19. The proportion of low 25(OH)D levels (<30 ng/mL) was significantly higher in the PCR-positive group (81.5% vs. 79%, p < 0.001). Multivariate analysis showed a higher incidence of breakthrough infection among non-smokers [1.37 (95% CI 1.22−1.54, p < 0.001)] and lower incidences among subjects with sufficient 25(OH)D levels (>30 ng/mL) [0.87 (95% CI 0.79−0.95, p0.004)], hyperlipidemia [0.84 (95% CI 0.76−0.93, p < 0.001], depression [OR-0.87 (95% CI: 0.79−0.96, p < 0.005], socio-economic status >10 [0.67 (95% CI 0.61−0.73, p < 0.001)], and age >44 years. SARS-CoV-2 antibody titers were available in 3659 vaccinated individuals. The prevalence of antibody titers (<50 AU) among PCR-positive subjects was 42% compared to 28% among PCR-negative subjects (p < 0.001). Baseline 25(OH)D levels showed an inverse relation to total antibody titers. However, no association was found with an antibody titer <50 AU/mL fraction. Conclusion Baseline 25(OH)D levels correlated with the vaccination-associated protective COVID-19 immunity. Antibody titers <50 AU/mL were significantly linked to breakthrough infection but did not correlate with 25(OH)D levels.
RESUMEN
OBJECTIVE: Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1-3 (HNP1-3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1-3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes. METHODS: HNP1-3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1-3 levels. RESULTS: The risk of CAD was independently associated with age and HNP1-3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1-3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1-3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%). CONCLUSION: HNP1-3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1-3 levels may be suppressed using colchicine.
Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , alfa-Defensinas , Humanos , Estudios Prospectivos , Estudios Longitudinales , Estudios de Cohortes , Factores de Riesgo , Fenotipo , ColchicinaRESUMEN
Patients who are severely affected by coronavirus disease 2019 (COVID-19) may develop a delayed onset 'cytokine storm', which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimers. It was anticipated that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID-19. However, clinical trials with TCZ have recorded an increase in D-dimer levels. In contrast to TCZ, colchicine reduced D-dimer levels in patients with COVID-19. To understand how the two anti-inflammatory agents have diverse effects on D-dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID-19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL-6, α-Defensin (α-Def), a pro-thrombotic peptide, and D-dimers. In contrast, treatment with colchicine reduced α-Def and Di-dimer levels. In vitro studies show that IL-6 stimulated the release of α-Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL-6; raising the possibility that the increase in IL-6 in patients with COVID-19 treated with TCZ triggers the release of α-Def, which promotes pro-thrombotic events reflected in an increase in D-dimer levels.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Colchicina/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , alfa-Defensinas/inmunología , Anciano , Coagulación Sanguínea/efectos de los fármacos , COVID-19/sangre , COVID-19/inmunología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/inmunología , Humanos , Interleucina-6/sangre , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunologíaRESUMEN
The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers. Immunohistochemistry revealed intense deposition of α-defensins in lung vasculature and thrombi. IL-6 stimulated the release of α-defensins from neutrophils, thereby accelerating coagulation and inhibiting fibrinolysis in human blood, imitating the coagulation pattern in COVID-19 patients. The procoagulant effect of IL-6 was inhibited by colchicine, which blocks neutrophil degranulation. These studies describe a link between inflammation and the risk of thromboembolism, and they identify a potential new approach to mitigate this risk in patients with COVID-19 and potentially in other inflammatory prothrombotic conditions.
Asunto(s)
COVID-19/metabolismo , Inflamación/metabolismo , Tromboembolia/prevención & control , alfa-Defensinas/sangre , Adulto , Anciano , Animales , Coagulación Sanguínea/efectos de los fármacos , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/virología , Estudios de Casos y Controles , Colchicina/farmacología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Inflamación/complicaciones , Interleucina-6/sangre , Interleucina-6/farmacología , Masculino , Ratones , Persona de Mediana Edad , Modelos Animales , Neutrófilos/efectos de los fármacos , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tromboembolia/etiología , Trombosis/etiología , Trombosis/metabolismo , Moduladores de Tubulina/farmacología , alfa-Defensinas/farmacologíaRESUMEN
BACKGROUND: The treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy. METHODS: We evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients. RESULTS: Median admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p<0.001) demonstrating good differentiating capability. The Receiver-operator-curve of admission CRP/troponin ratio for diagnosis of myopericarditis against all AMI, STEMI, and NSTEMI patients yielded an area-under-the curve of 0.74, 0.73, and 0.765, respectively. CRP/troponin ratio>500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%. CONCLUSION: The CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation.
Asunto(s)
Proteína C-Reactiva/análisis , Infarto del Miocardio/diagnóstico , Miocarditis/diagnóstico , Troponina/análisis , Adulto , Anciano , Diagnóstico Diferencial , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Miocarditis/sangreRESUMEN
Background Shortening the pain-to-balloon (P2B) and door-to-balloon (D2B) intervals in patients with ST-segment-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) is essential in order to limit myocardial damage. We investigated whether direct admission of PPCI-treated patients with STEMI to the catheterization laboratory, bypassing the emergency department, expedites reperfusion and improves prognosis. Methods and Results Consecutive PPCI-treated patients with STEMI included in the ACSIS (Acute Coronary Syndrome in Israel Survey), a prospective nationwide multicenter registry, were divided into patients admitted directly or via the emergency department. The impact of the P2B and D2B intervals on mortality was compared between groups by logistic regression and propensity score matching. Of the 4839 PPCI-treated patients with STEMI, 1174 were admitted directly and 3665 via the emergency department. Respective median P2B and D2B were shorter among the directly admitted patients with STEMI (160 and 35 minutes) compared with those admitted via the emergency department (210 and 75 minutes, P<0.001). Decreased mortality was observed with direct admission at 1 and 2 years and at the end of follow-up (median 6.4 years, P<0.001). Survival advantage persisted after adjustment by logistic regression and propensity matching. P2B, but not D2B, impacted survival (P<0.001). Conclusions Direct admission of PPCI-treated patients with STEMI decreased mortality by shortening P2B and D2B intervals considerably. However, P2B, but not D2B, impacted mortality. It seems that the D2B interval has reached its limit of effect. Thus, all efforts should be extended to shorten P2B by educating the public to activate early the emergency medical services to bypass the emergency department and allow timely PPCI for the best outcome.