Abstract
Background
The characteristics of patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) differ from those with Myocardial Infarction with Obstructive Coronary ...Artery Disease (MI-CAD). Thus, the mechanisms involved, such as inflammation, may be different. The objective of this study is to analyze the relationship between pro-inflammatory conditions and MINOCA, as well as the impact on their prognosis.
Methods
An analytical and observational study, including all patients admitted to our hospital with myocardial infarction and who underwent coronary angiography in the last four years (2016–2020; n=712). According to the definitions of the 2019 AHA Scientific Statement on Diagnosis and Management of MINOCA and ESC 2020 guidelines on Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation, we classified the patients into two groups: MI-CAD (n=643) and MINOCA (n=69). Besides general data, we recorded specific information about pro-inflammatory conditions (prevalence of autoimmune diseases, connective tissue disorders, and active infections and neoplasms). We also assessed C-reactive protein (C-RP) at admission, peak CK-MB and troponin levels. Follow-up analysis included death from any cause, major adverse cardiac events (MACE: cardiac death, MI, stroke), readmissions due to cardiovascular causes, and in-hospital mortality.
Results
The composite of pro-inflammatory conditions (autoimmune pathologies, connective tissue diseases and active cancer and infections) was significantly higher in the MINOCA group (30.4% vs 14.6%, p<0.001). Patients with MINOCA had higher rates of connective tissue disorders (5.8% vs 1.4%, p 0.01), and autoimmune diseases (14.5% vs 7.8%, p 0.058) tended to be more frequent in these patients. However, MINOCA patients had lower C-RP levels (180 vs 206mg/L, p<0.001), probably because they have smaller infarcts (peak CK-MB: 228 vs 325 U/L, p<0.001; high-sensitivity cardiac troponin T levels: 111 vs 176ng/L, p<0.001). In the follow-up of MINOCA patients, MACE did not occur more frequently in those patients with inflammatory conditions (4.8% vs 13%, p 0.3) than those without them. Moreover, pro-inflammatory disorders were not related to significantly higher mortality from any cause (8.7% vs 10%, p 0.86) nor readmissions due to cardiovascular causes (19.6% vs 23.8%, p 0.6). Our median follow-up was 29 months. There were no differences in in-hospital mortality.
Conclusion
This study suggests that pro-inflammatory disorders may be a risk factor for developing MINOCA without resulting in an unfavourable short- and long-term prognosis. Further research is needed to confirm this finding and identify its optimal management.
Funding Acknowledgement
Type of funding sources: None.
Abstract
Background
MINOCA's physiopathology, treatment and prognosis are yet to be completely understood. The aim of this study is to compare baseline characteristics and prognosis of MINOCA ...patients and those of patients with myocardial infarction (MI) and obstructive coronary arteries.
Methods
We analysed all consecutive patients with MI who underwent coronary angiography admitted in a University Hospital covering a population of 220.000 people during a period of 60 months. The database and the all the patient's angiographies were revised by a group of experts in order to adequate MINOCA to 2020 ESC Guidelines definition and the American Heart Association position paper.
Results
680 patients, 68 of whom were MINOCA (10%) with a median of follow up of 31±16 months were analysed (see table 1). We found no differences in both groups' age. Female gender was more prevalent among MINOCA patients. The underlying mechanism in MINOCA was coronary spasm (17.6%), plaque rupture (13.2%), coronary embolism (7.4%), coronary dissection (2.9%), type II infarction (19.1%) or unknown (39.7%). Coronary arteries in MINOCA patients had no obstructions at all in 57.4%, and 30–50% obstruction in 42.6% of the cases. MINOCA patients didn't have higher prevalence of cancer, autoimmune or psychiatric diseases, dyslipidaemia, hypertension or inflammatory analytical parameters. However, we found significant differences in atrial fibrillation, migraine, connective tissue diseases, tobacco use and diabetes. We found no effect of stress in the development of MINOCA (measured with validated STAI and DS-14 scales). Symptoms at admission didn't differ between the two groups, but those with MINOCA had normal ECG more frequently. Prognosis showed relevant differences, as MINOCA patients had less major cardiovascular complications, such as inotropic requirements (0% Vs 4.8%, p=0.04), shock (0% vs 6.6%, p=0.013) and left ventricular dysfunction (11.8 vs 30.2, p=0.015). Furthermore, myocardial injury biomarkers' levels were, significantly lower in MINOCA patients. Death rates tend to be lower both in hospital (0% vs 3.1%, p=0.131) and during follow up (9.1% vs 11.5%, p=0.369).
Conclusion
Analysing MINOCA patients' clinical profile might help us understanding the underlying physiopathology, prognosis and treatment targets. In these patients, classic cardiovascular risk factors don't appear to be as important as in obstructive patients. At admission, we found no clinical differences that could help making an early diagnosis, even if those with normal ECG and lower levels of myocardial injury biomarkers are more likely to have non-obstructive coronary arteries. These patients seem to have better prognosis and lower myocardial injury than those with obstructive coronary arteries. Further research is needed to provide more evidence on the accurate treatment of these patients.
Funding Acknowledgement
Type of funding sources: None.
Due to the absence of specific instruments to study the psychosocial sphere of patients undergoing extracorporeal shock wave lithotripsy (SWL), the objective of this study is to develop a ...satisfaction questionnaire regarding the SWL treatment from a health questionnaire which was already designed and had been previously validated.
The design of the satisfaction questionnaire was carried out in 5 phases, based on a previously validated health scale in patients treated with SWL (ESPTL), including a total cohort of 135 patients treated at our center who received a phone interview. Phase 1: descriptive analysis of the series and scores of the 8 items of ESPTL. Phase 2: U-Mann Whitney comparison of ESPTL based on the patients’ sex. Phase 3: study of ESPTL correlation with age using Spearman’s Rho. Phase 4: grouping by factors of ESPTL, comparison by sex and correlation with age, as performed in phases 2 and 3 with the global score. Phase 5: obtaining the satisfaction subscale -SATISLIT-, descriptive analysis, comparison according to sex, correlation with age and linear regression model of SATISLIT with respect to ESPTL.
135 patients, 85(63%) men, 50(37%) women. Median (minimum-maximum) age 56 (27–79) and ESPTL score 31 (8–39).
Differences in global ESPTL score between men and women (p<.001), as well as in items 1 (p=.029), 3 (p=.002), 6 (p=.006), 7 (p=.005) and 8 (p=.025).
Non-significant correlation of ESPTL regarding age. Significant correlation in items 2, 4, 5 and 8 but, very weak (<0.2).
4 factors, each one with 2 items, with statistically significant differences regarding sex in F2 (p=.001), F3 (p=.007) and F4 (p=.001). Significant correlation with age only in F1 and F3, but very weak (<0.2).
Median (minimum-maximum) SATISLIT 18 (4–20). Statistically significant differences regarding patients’ sex (p=.001). Non-significant correlation with age (p=.836). Significant linear regression of SATISLIT with respect to ESPTL (p<.001).
Based on validated health questionnaire, the present work has provided a new instrument called SATISLIT for assessing patients’ satisfaction after treatment with SWL. Future studies with external and temporal validation will be necessary to contrast its real clinical usefulness.
Debido a la ausencia de instrumentos específicos para estudiar la esfera psicosocial de los pacientes que reciben litotricia extracorpórea por ondas de choque (LEOC), el objetivo es desarrollar un cuestionario de satisfacción respecto al tratamiento recibido con LEOC a partir de un cuestionario de salud ya diseñado y validado previamente.
El diseño del cuestionario de satisfacción se realizó en 5 fases a partir de una escala de salud en pacientes tratados con LEOC (ESPTL) ya validada previamente, utilizando una muestra total de 135 pacientes tratados en nuestro centro a los que se entrevistó por vía telefónica.
En la fase 1 se realizó análisis descriptivo de la serie y de las puntuaciones de los 8 ítems de ESPTL. En la fase 2 se compararon las puntuaciones de ESPTL según sexo con U-Mann Whitney, estudiando la correlación con la edad mediante Rho de Spearman en la fase 3. En la fase 3 se compararon las puntuaciones de los factores de ESPTL según el sexo y se analizó la correlación con la edad al igual que en las fases 2 y 3 con la puntuación global. En la fase 5 se obtuvo la subescala de satisfacción–SATISLIT- y se realizó análisis descriptivo, comparación según sexo, correlación con la edad y modelo de regresión lineal con respecto a ESPTL.
Ciento treinta y cinco pacientes, 85(63%) hombres, 50(37%) mujeres. Mediana (mínimo-máximo) de edad 56 (27-79) y puntuación ESPTL 31 (8-39).
Diferencias en puntuación global ESPTL entre hombres y mujeres p<0,001, así como en los ítems 1 p=0,029, 3p=0,002, 6 p=0,006, 7 p=0,005 y 8 p=0,025.
Correlación no significativa de ESPTL con la edad. Significativa en ítems 2, 4, 5 y 8 pero correlación muy débil (<0,2).
Cuatrofactores con 2 ítems cada uno, con diferencias estadísticamente significativas según sexo en F2 p=0,001, F3 p=0,007 y F4 p=0,001. Correlación significativa con la edad únicamente en F1 y F3 pero muy débil <0,2.
Mediana (mínimo-máximo) SATISLIT 18 (4-20). Diferencias estadísticamente significativas según sexo p=0,001. Correlación no significativa con la edad p=0,836. Regresión lineal de SATISLIT con respecto a ESPTL significativa p<0,001.
El trabajo realizado a partir de un cuestionario validado de salud ha proporcionado un nuevo instrumento de evaluación de la satisfacción tras tratamiento con LEOC llamado SATISLIT. Serán necesarios futuros estudios de validación externa y validación temporal para contrastar su verdadera utilidad clínica.
The aim of this paper is to assess co-registration errors in remote imagery through the AUGEO system, which consists of geo-referenced coloured tarps acting as terrestrial targets (TT), captured in ...the imagery and semi-automatically recognised by AUGEO2.0® software. This works as an add-on of ENVI® for image co-registration. To validate AUGEO, TT were placed in the ground, and remote images from satellite Quick Bird (QB), airplanes and unmanned aerial vehicles (UAV) were taken at several locations in Andalusia (southern Spain) in 2008 and 2009. Any geo-referencing system tested showed some error in comparison with the Differential Global Positioning System (DGPS)-geo-referenced verification targets. Generally, the AUGEO system provided higher geo-referencing accuracy than the other systems tried. The root mean square errors (RMSE) from the panchromatic and multi-spectral QB images were around 8 and 9 m, respectively and, once co-registered by AUGEO, they were about 1.5 and 2.5 m, for the same images. Overlapping the QB-AUGEO-geo-referenced image and the National Geographic Information System (NGIS) produced a RMSE of 6.5 m, which is hardly acceptable for precision agriculture. The AUGEO system efficiently geo-referenced farm airborne images with a mean accuracy of about 0.5–1.5 m, and the UAV images showed a mean accuracy of 1.0–4.0 m. The geo-referencing accuracy of an image refers to its consistency despite changes in its spatial resolution. A higher number of TT used in the geo-referencing process leads to a lower obtained RMSE. For example, for an image of 80 ha, about 10 and 17 TT were needed to get a RMSE less than about 2 and 1 m. Similarly, with the same number of TT, accuracy was higher for smaller plots as compared to larger plots. Precision agriculture requires high spatial resolution images (i.e., <1.5 m pixel−1), accurately geo-referenced (errors <1–2 m). With the current DGPS technology, satellite and airplane images hardly meet this geo-referencing requirement; consequently, additional co-registration effort is needed. This can be achieved using geo-referenced TT and AUGEO, mainly in areas where no notable hard points are available.
In this work, we report the experimental results on the formation of porous silicon (PSi) monolayers by electrochemical etching using a formaldehyde based electrolyte. The results were compared with ...PSi monolayers obtained with the traditional electrolyte (HF:ethanol). Both electrolytes facilitate the removal of H
2
generated as a subproduct during the electrochemical etching process in the surface of the c-Si substrate. Formaldehyde presents a good affinity to surfaces and interfaces and the excess of water in the electrolyte reduces the pore sizes of PSi samples. The porosity and etching rate values are similar than those obtained using HF:et solutions. The refractive index values are the same in both cases at the same porosity in the visible range. The results have shown that the chemical characteristics of the ethanol and formaldehyde can give some different advantages to the PSi process and its applications.
Abstract
Background: Palbociclib (PAL) is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor that is under investigation in multiple oncologic clinical trials and is currently approved for use in ...combination with aromatase inhibitors (AIs) or fulvestrant (FUL) in patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer (BC).
The PEARL Study is an ongoing international, open label, controlled, randomized Phase 3 study comparing the efficacy and safety of PAL in combination with endocrine therapy (exemestane EXE or FUL) versus capecitabine in postmenopausal women with HR+/ HER2– metastatic BC whose disease progressed on AIs. A secondary objective of the study was to evaluate the pharmacokinetics (PK) of PAL (125mg QD, 3 weeks on/1 week off) and EXE (25mg QD, continuously) when coadministered. This is the first study to investigate the drug-drug interaction (DDI) potential of the combination of PAL and the AI EXE.
Methods: Patients (pts) randomized to the PAL+EXE arm of the PEARL Study in seven selected sites had the option of participating in the PK sub-study. Those who enrolled in the PK sub-study received EXE alone in a 7-day lead-in period immediately prior to Cycle 1 Day 1, when both drugs were coadministered on their standard dosing regimens. Sub-study pts were to have 2 pre-dose plasma PK samples drawn at steady-state (ss) during the lead-in period ("EXE Alone") for EXE determination, and 2 ss PK samples drawn for EXE and PAL determination (2 per analyte) during coadministration ("PAL+EXE"). Plasma concentrations of PAL and EXE were measured using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The withinpatient mean concentration of the PK samples which met ss acceptance criteria (WPM-Ctrough) for each analyte were generated for each treatment period as the input for DDI analyses.
To assess the effect of coadministration of PAL on EXE PK, the WPM-Ctrough of EXE was compared within patients between the "PAL+EXE" (Test) and "EXE Alone" (Reference) treatment periods using a one-way analysis of variance (ANOVA) model with treatment as a fixed effect and patient as a random effect. To assess the effect of coadministration of EXE on PAL PK, the WPM-Ctrough of PAL was compared between the "PAL+EXE" period (Test) and historical data (Reference) using an ANOVA model. Analysis of covariance (ANCOVA) models were used to assess the impact of demographic differences between analysis populations in covariates known to impact PAL PK on the ANOVA model conclusions.
Results: A total of 26 pts randomized to the PAL+EXE arm were enrolled in the PK sub-study and had PK samples analysed, of which 23 meet ss acceptance criteria. The ratio of the adjusted geometric means for EXE WPM-Ctrough was 106.9% (90%CI: 82.4-138.8), when EXE was administered with PAL, compared with its administration alone. Likewise, the models to assess potential for EXE to perpetrate DDI on PAL PK showed ratios of adjusted geometric means of 102.4% (90%CI: 82.0-127.9) and 111.6% (90%CI: 90.3137.8), when adjusted for covariates.
Conclusion: The PK data indicate a lack of a clinically meaningful DDI between PAL and EXE when the 2 drugs are coadministered.
Sponsor: GEICAM
Citation Format: Martín M, Hoffman J, Ruiz-Borrego M, Muñoz M, Calvo L, Crownover P, García-Sáenz JA, Alba E, Wang D, Thallinger C, Stradella A, Montaño Á, Adamo B, Antolín S, Moreno-Antón F, Falo C, Ruiz V, Martín N, Caballero R, Carrasco E, Gil-Gil M. Evaluation of the drug interaction potential of palbociclib and exemestane – Results from the PEARL pharmacokinetic sub-Study abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-23.
The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to ...appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with (90)Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of (90)Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with (90)Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy.
clinical.gov identifier: NCT2005-004400-37.
Infection of ewes by Toxoplasma gondii may induce abortions, thus it has consequences for sheep production. Colima, Western State of Mexico, has favourable climatic conditions for transmission and ...both domestic and wild cats live there. The aim of this study was to determine the frequency of specific antibodies in sheep from the coast, a mountain, and a hill of Colima. Serum samples from 351 sheep were tested by a previously standardized indirect ELISA. The frequency of infection was estimated and the farm location and flock size, as well as the animals' age and sex were analysed as risk factors for toxoplasmosis. The frequency of antibodies depended on the altitude, being higher at sea level than at 1200 metres above sea level (OR=3·77, 95% CI=1·79-7·94, P<0·0001), and the size of the flock, being higher in the large ones (OR=2·23, 95% CI=1·35-3·71, P=0·002). Older animals were more frequently positive and with a stronger response than young ones (OR=1·77, 95% CI=1·07-2·93, P=0·016). No differences were observed between male and female sheep. In conclusion, toxoplasmosis is present in sheep of Colima with variations related to altitude, flock size and age.
A model of a stepwise malignant transformation has been proposed for the pathogenesis of monoclonal gammopathies. In this model, cell cycle regulators play a central role as a source of genetic ...events; particularly, p16/INK4a gene acts as a tumoral suppressor gene and, recently, inactivation of this gene through a methylation mechanism, has been observed in multiple myeloma patients. Under the diagnosis of monoclonal gammopathies there is a broad spectrum of disorders with very different outcomes, ranging from indolent courses, such as those of monoclonal gammopathy of undetermined significance, Waldeströn macroglobulinemia and smoldering multiple myeloma, to aggressive diseases such as symptomatic MM and primary plasma cell leukemia. To the best of our knowledge, the activity of p16 gene has not been evaluated and compared in these different subtypes of monoclonal gammopathies.
The methylation status of the p16 gene was analysed in a group of 159 patients with monoclonal gammopathies (40 monoclonal gammopathy of uncertain significance, eight Waldenström Macroglobulinemia, eight smoldering multiple myeloma, 98 symptomatic multiple myeloma and five primary plasma cell leukemia) using three different assays (restriction enzymes and PCR or S-B and modification by sodium bisulphite).
Forty-one of 98 MM patients (41.8%) as well as four of the five (80%) primary PCL patients showed methylation of the p16 gene, while none of the patients with monoclonal gammopathy of undetermined significance, Waldenström Macroglobulinemia or smoldering multiple myeloma displayed a methylation status.
These findings suggest that the methylation of the p16 gene could be a relevant oncogenic event in the monoclonal gammopathies evolution being associated with the most aggressive forms.
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