Prognostic impact of renal function trajectories in patients with STEMI and kidney dysfunction undergoing primary percutaneous coronary intervention: An analysis of ten years all-comers registry.

BACKGROUND: Renal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge. METHODS: This prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months. RESULTS: Among the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35-0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34-0.84, p = 0.007] during follow-up. CONCLUSIONS: The improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis.

Prognostic impact of left ventricular ejection fraction recovery in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: analysis of an 11-year all-comers registry.

AIMS: Left ventricular ejection fraction (LVEF) recovery after an ST-segment elevation myocardial infarction (STEMI) identifies a group of patients with a better prognosis. However, the association between long-term outcomes and LVEF recovery among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) has not yet been well investigated. Our study aims to detect differences in long-term all-cause and cardiovascular mortality between patients who recover LVEF at 1-year post-PCI and those who do not, and search for predictors of LVEF recovery. METHODS AND RESULTS: This is a retrospective, single-centre study of 2170 consecutive patients admitted for STEMI in which primary PCI is performed. LVEF was determined at admission and at 1-year follow-up. The primary outcomes were long-term all-cause and cardiovascular mortality. Among the 2168 patients with baseline LVEF data, 822 (38%) had a LVEF < 50% and 1346 (62%) ≥ 50%. Among those with LVEF < 50%, LVEF data at 1-year were available in 554, and 299 (54.0%) presented with complete recovery (LVEF ≥ 50%). LVEF recovery was associated with a reduction in long-term all-cause and cardiovascular mortality (P < 0.0001). Female sex, treatment with ACEIs, lower creatinine levels, infarct-related artery different from the left main or left anterior descendent artery, and absence of prior ischaemic heart disease were independently associated with LVEF recovery. CONCLUSIONS: Nearly 40% of patients with STEMI undergoing primary PCI presented with LVEF depression at hospital admission. Among them, LVEF recovery at 1-year occurred in more than 50% and was independently associated with a significant decrease in long-term all-cause and cardiovascular mortality.

Multicenter and all-comers validation of a score to select patients for manual thrombectomy, the DDTA score.

BACKGROUND: Routine manual thrombectomy (MT) is not recommended in primary percutaneous coronary intervention (P-PCI) but it is performed in many procedures. The objective of our study was validating the DDTA score, designed for selecting patients who benefit most from MT. METHODS: Observational and multicenter study of all consecutive patients undergoing P-PCI in five institutions. Results were compared with the design cohort and the performance of the DDTA was analyzed in all patients. Primary end-point of the analyses was TIMI 3 after MT; secondary endpoints were final TIMI 3, no-reflow incidence, in-hospital mortality and in-hospital major cardiovascular events (MACE). In-hospital prognosis was assessed by the Zwolle risk score. RESULTS: Three hundred forty patients were included in the validation cohort and no differences were observed as compared to the design cohort (618 patients) except for lower use of MT and higher IIb/IIIa inhibitors or drug-eluting stents. The probability of TIMI 3 after MT decreased as delay to P-PCI was higher. If DDTA score, MT was associated to TIMI 3 after MT (OR: 4.11) and final TIMI 3 (OR: 2.44). There was a linear and continuous relationship between DDTA score and all endpoints. DDTA score ≥ 4 was independently associated to lower no-reflow, in-hospital MACE or mortality. The lowest incidence of in-hospital mortality or MACE was in patients who had DDTA score ≥ 4 and Zwolle risk score 0-3. CONCLUSIONS: MT is associated to higher rate of final TIMI3 in patients with the DDTA score ≥ 4. Patients with DDTA score ≥ 4 had lower no-reflow and in-hospital complications.

Impact of significant paravalvular leaks after transcatheter aortic valve implantation on anaemia and mortality.

OBJECTIVE: The aim of this work is to assess the relationship between significant paravalvular leak (SPL) after transcatheter aortic valve implantation (TAVI) on anaemia and their impact on prognosis. METHODS: Observational analytic study developed at two university hospitals, including all consecutive patients who underwent TAVI during a 10-year period (2009 to 2018). A logistic regression model was created to determine independent predictors of anaemia at 3 months. Time to event outcomes were analysed with Cox regression. Median follow-up was 21.3±21.9 months. RESULTS: 788 patients were included. 5.3% had SPL. SPL was an independent predictor of anaemia 3 months after TAVI (OR: 8.31, 95% CI: 2.06 to 33.50). SPL and anaemia at 3 months were independently associated with long-term mortality (HR: 1.82, 95% CI: 1.16 to 2.85; HR: 2.07, 95% CI: 1.39 to 3.08). CONCLUSION: SPL is an independent predictor of anaemia at 3 months after TAVI, a condition that doubles long-term mortality. Our findings could explain in part the worse prognosis of SPL after TAVI. Further pathophysiological studies are necessary to explain this association.

Allopathic and Naturopathic Medicine and Their Objective Consideration of Congruent Pursuit.

In recent years, allopathy (ALP) and naturopathy (NAP) have become a favorite topic, source of argument, and the subject discussed when it comes to choosing treatment modality. Various attempts have been made to elucidate this issue, yet limited advancement has been achieved. To this day, the dispute remains active, and the debate over what to do about it continues to damnify us. The presented qualitative analysis aims to identify existing views or else expand on or uncover already known differences. Ourexamination or position is not about the conflict, finding a superior method (ALP vs. NAP), but aims at inductive reasoning, making broader generalizations from scientific observations. Subjects and Methods. We explore the philosophical and psychological foundation of the prevailing ideologies and perspectives in the contemporary society using the Straussian grounded theory approach. The study had no subjects. Results. We outline the path for the future direction. Conclusion. Our examination concludes that it is essential to acknowledge not only the difference between ALP and NAP but also how they both act on our health. We emphasize that, by identifying our perspective, our inner reflection, and our view on this topic, we can undertake a new paradigm, new road to improve our health, and perhaps the well-being throughout our culture and society.

Prevalencia e incidencia tras el alta hospitalaria de neoplasias en pacientes con síndrome coronario agudo / Prevalence and postdischarge incidence of malignancies in patients with acute coronary syndrome

Introducción y objetivos. Las neoplasias malignas son la segunda causa de muerte en los países desarrollados, por detrás de las enfermedades cardiovasculares, y ambas entidades tienen factores en común. Métodos. Estudio prospectivo de todos los pacientes ingresados por un síndrome coronario agudo en el que se evaluó la prevalencia de neoplasias y la incidencia tras el alta. Resultados. La prevalencia de neoplasias en los 1.819 pacientes incluidos fue del 3,4% y el 41,9% de los casos se consideraron libres de enfermedad. Entre los 1.731 pacientes dados de alta, la incidencia fue 3,1% (53 casos) y las localizaciones más frecuentes fueron colon, pulmón, vejiga y páncreas. Los pacientes con neoplasias prevalentes presentaron más edad, comorbilidades y complicaciones. No se observaron diferencias en el porcentaje de revascularización, pero sí menor uso de stents farmacoactivos en los pacientes con neoplasias prevalentes. Durante el seguimiento, la mediana de tiempo hasta el diagnóstico de nuevas neoplasias fue de 25 meses y el análisis multivariante identificó como factores independientes la edad y el ser fumador o exfumador. La mortalidad por cualquier causa tras el alta fue muy superior en los pacientes con neoplasias incidentes (64,2%) o prevalentes (40,0%). El análisis multivariante mostró que en las neoplasias prevalentes e incidentes se multiplicaba por 4 el riesgo de mortalidad por cualquier causa. Conclusiones. El 3,8% de los pacientes tuvieron neoplasias prevalentes y menos del 50% se consideraban curadas en el momento del ingreso. La incidencia de nuevas neoplasias fue del 3,4% y ambas formas de neoplasias empeoraron mucho el pronóstico a largo plazo (AU)

Introduction and objectives. Malignancies are the second cause of death in developed countries after cardiovascular disease and both share common risk factors. Methods. This prospective study assessed the prevalence and postdischarge incidence of malignancies in all consecutive patients admitted for an acute coronary syndrome. Results. A total of 1819 patients were included. On admission, the prevalence of malignancies was 3.4%, and 41.9% of the patients were considered disease-free; of the 1731 discharged patients, the incidence was 3.1% (53 cases) and the most common locations were the colon, lung, bladder, and pancreas. Patients with prevalent malignancies were older and had more comorbidities and complications. There were no differences in the revascularization rate, but implantation of drug-eluting stents was less frequent in patients with prevalent malignancies. During follow-up, the median time to diagnosis of incident malignancies was 25 months. On multivariate analysis, independent risk factors were age and current or former smoking. All-cause mortality was much higher in patients with incident (64.2%) or prevalent (40.0%) malignancies. Multivariate analysis showed that prevalent and incident malignancies increased the risk of all-cause mortality by 4-fold. Conclusions. Among patients admitted for an acute coronary syndrome, 3.8% had a history of malignancy, with less than 50% considered cured. The incidence of new malignancies was 3.4% and both types of malignancies substantially impaired the long-term prognosis (AU)

Prevalence and Postdischarge Incidence of Malignancies in Patients With Acute Coronary Syndrome.

INTRODUCTION AND OBJECTIVES: Malignancies are the second cause of death in developed countries after cardiovascular disease and both share common risk factors. METHODS: This prospective study assessed the prevalence and postdischarge incidence of malignancies in all consecutive patients admitted for an acute coronary syndrome. RESULTS: A total of 1819 patients were included. On admission, the prevalence of malignancies was 3.4%, and 41.9% of the patients were considered disease-free; of the 1731 discharged patients, the incidence was 3.1% (53 cases) and the most common locations were the colon, lung, bladder, and pancreas. Patients with prevalent malignancies were older and had more comorbidities and complications. There were no differences in the revascularization rate, but implantation of drug-eluting stents was less frequent in patients with prevalent malignancies. During follow-up, the median time to diagnosis of incident malignancies was 25 months. On multivariate analysis, independent risk factors were age and current or former smoking. All-cause mortality was much higher in patients with incident (64.2%) or prevalent (40.0%) malignancies. Multivariate analysis showed that prevalent and incident malignancies increased the risk of all-cause mortality by 4-fold. CONCLUSIONS: Among patients admitted for an acute coronary syndrome, 3.8% had a history of malignancy, with less than 50% considered cured. The incidence of new malignancies was 3.4% and both types of malignancies substantially impaired the long-term prognosis.

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship.

Although multiple biochemical pathways are likely to be responsible for the pathogenesis of diabetic complications, substantial evidence suggests a key role for the polyol pathway and oxidative stress initiated by hyperglycemia. Thus aldose reductase, the first enzyme of the polyol pathway, has been identified as a potential target of pharmacological intervention to prevent diabetic complications. Aldose reductase inhibitors endowed with antioxidant activity would be dually beneficial. The aim of the study was to evaluate the structure-activity relationship of commercially available indole derivatives supported by the molecular modeling of their interaction with the enzyme aldose reductase from the viewpoint of the inhibitory effect on the enzyme and their antioxidant activity. The partially purified aldose reductase was prepared from rabbit eye lenses. In vitro inhibiton of the aldose reductase was determined by a conventional method. Antioxidant action of the compounds was documented in a DPPH test. Marked differences were recorded in the aldose reductase inhibition activities of 1- and 3-indole acetic acid derivatives. The interaction energies of the inhibitor vs. enzyme-NADP(+) complexes, calculated by computer aided molecular modeling, were in agreement with the higher inhibitory efficacy of 1-indole acetic acid in contrast with 3-indole acetic acid. The more efficient 1-indole acetic acid was proved to create stronger electrostatic interaction with NADP(+). However, the order of the antioxidant activities of the compounds studied was not in agreement with that of the inhibitory efficacies.

(2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: an aldose reductase inhibitor and antioxidant of zwitterionic nature.

Novel carboxymethylated pyridoindoles, characterized by antioxidant activity combined with the ability to inhibit aldose reductase, represent an example of a multitarget approach to the treatment of diabetic complications - severe diabetes-related health disorders of multifunctional nature. One of the novel carboxymethylated pyridoindoles, (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid (compound 1), was found to inhibit aldose reductase with the IC(50) value 18.2 ± 1.2 µM. Owing to aldose reductase pharmacophore requirements for an acidic proton, most aldose reductase inhibitors contain an acetic acid moiety, ionized at physiological pH, resulting in poor bioavailability of the drugs. The presence of a basicity center at the tertiary nitrogen of the carboxymethylated pyridoindoles, in addition to the acidic carboxylic function, predisposes these compounds to form double-charged zwitterionic species. The zwitterionic nature of compound 1 may remarkably affect its pH-lipophilicity profile allowing for increased membrane penetration in the pH region around its isoelectric point, which lies close to the physiological pH 7.4. In the first part of this study, the presence of zwitterionic species was experimentally proved by the concentration-dependent effect of sodium 1-hexanesulphonate on the distribution profile of compound 1. Then a series of experiments was performed in the cellular system of isolated erythrocytes in vitro. Isolated rat erythrocytes exposed to peroxyl radicals, generated in the solution by decomposition of the hydrophilic azoinitiator AAPH or intracellularly by decay of lipophilic t-BuOOH, underwent progressive hemolysis. The onset of the hemolysis was shifted from the starting zero point by the time interval assigned as a lag period. In the presence of compound 1 the lag period was significantly prolonged. Finally, under conditions of a short-term experiment in STZ-diabetic rats in vivo, increase in sorbitol levels in erythrocytes was recorded. Compound 1 administered in the dose 50mg/kg/day (i.g.) significantly decreased the sorbitol level in the erythrocytes. To conclude, the physico-chemical proof of the zwitterionic nature of compound 1 was established and the results obtained in isolated red blood cells indicated good cellular availability of the compound. In addition, in diabetic rats, sorbitol accumulation in red blood cells was significantly inhibited by compound 1 administered intra-gastrically, suggesting its ready uptake into the central compartment. The zwitterionic principle thus may have significant consequences for increased bioavailability of drugs bearing an acidic function.

Structure-activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity.

Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b-c and 5a-c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order to verify the optimum position of the phenol-moiety. Compound 5b emerged as the most potent and selective inhibitor. Moreover, further assays proved 5b as a potent antioxidant and an inhibitor of sorbitol accumulation in isolated rat lenses. Combining the above attributes, 5b could serve as a lead compound targeted at long-term diabetes complications.

Effect of carboxymethylated pyridoindoles on free radical-induced haemolysis of rat erythrocytes in vitro.

Recently novel carboxymethylated pyridoindoles, analogues of the efficient chain-breaking antioxidant stobadine, have been designed, synthesised and characterised as bifunctional compounds with joint antioxidant/aldose reductase inhibitory activities with the potential of preventing diabetic complications. The critical property for the efficacy of the novel aldose reductase inhibitors in vivo is their ability to penetrate into target tissues. In this study, the issue was addressed by measuring the antioxidant activity of compounds 1 [(2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid] and 2 [(+/-)-2-benzyl-(4a,9b)-cis-1,2,3,4,4a,9b-hexahydro-1H-pyrido[4,3-b] indole-8-yl acetic acid] in the cellular system of intact erythrocytes exposed to peroxyl radicals generated by thermal degradation of the azoinitiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) in vitro. Isolated washed rat erythrocytes were incubated in the presence of the azoinitiator AAPH and the compounds tested for increasing periods of time up to 4 h at 37 degrees C. The degree of haemolysis was determined by absorbance of the haemoglobin released. The onset of AAPH-induced haemolysis was found to be shifted from the starting zero point by the time interval assigned as a lag period. In the presence of the compounds studied the lag period was prolonged significantly. The free radical-initiated haemolysis was retarded by the compounds studied with decreasing efficiency: stobadine > compound 1 ~ Trolox > compound 2. The results have demonstrated an antioxidant activity of the novel carboxymethylated pyridoindoles developed as potential agents for multitarget pharmacology of diabetic complications.

Carboxymethylated tetrahydropyridoindoles as aldose reductase inhibitors: in vitro selectivity study in intact rat erythrocytes in relation to glycolytic pathway.

Oxidative stress and polyol pathway hypotheses are generally accepted in the etiology of diabetic complications. Recently, novel carboxymethylated pyridoindoles, structural analogues of the efficient chain-breaking antioxidant stobadine, were designed, synthesised and characterised as prospective aldose reductase inhibitors endowed with antioxidant activity. Of them (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid (compound 1) and (2-phenethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid (compound 2) were found to be the most efficient inhibitors of aldose reductase with the corresponding IC50 values in a micromolar region. The aim of this work was to study cellular uptake of the novel pyridoindole derivatives and their effect on the complex metabolism of glucose in isolated rat erythrocytes under euglycaemic conditions. Glycolysis was shown to be the sole process responsible for the observed clearance of glucose. The compounds studied were avidly taken up by the cells, yet they did not significantly affect glucose consumption and lactate production nor did they affect osmotic fragility of the erythrocytes. On balance, the present experimental findings indicate that compounds 1 and 2, efficient inhibitors of aldose reductase, are selective in relation to the glycolytic pathway of glucose elimination. This conclusion supports current preclinical development of novel carboxymethylated tetrahydropyridoindoles as promising aldose reductase inhibitors for pharmacological prevention and treatment of diabetic complications.