Introduction and objectives: There is great interest in the development of devices for the percutaneous management of mitral regurgitation (MR). For this reason, having an experimental model that ...reproduces the conditions of the disease is of great importance. Our objective was to validate an experimental model of MR in a porcine model.
Methods: For the model creation phase 3, 2-month-old 25 ± 3 kg large white pigs were used. An acute myocardial infarction was caused in the circumflex artery territory that hampered the perfusion of the posteromedial papillary muscle. Then, volume overload was induced in the animal by creating an arteriovenous shunt and connecting the aorta and the pulmonary artery using a Dacron tube. Echocardiography and magnetic resonance imaging were performed before the intervention and on week 8. Afterwards, the animal was euthanized to conduct the pathological study.
Results: One out of the 3 pigs died during the intervention due to ventricular fibrillation. The remaining 2 pigs survived the procedure and were euthanized as scheduled on week 8. In both cases a transmural infarction occurred, 1 at lateral level and the other one at posteroinferior level with moderate secondary mitral regurgitation. Ventricular dimensions and volumes increased and the overall contractility was maintained despite segmental alterations.
Conclusions: The experimental model of chronic MR based on the ischemic damage of the posteromedial papillary muscle associated with volume overload is feasible, safe and reproducible. Also, it can be very useful to test the safety and efficacy of future devices for the management of this condition.
Introducción y objetivos: Existe un creciente interés en el desarrollo de dispositivos para el tratamiento de la insuficiencia mitral (IM) de forma mínimamente invasiva. Para este propósito, disponer de un modelo experimental que reproduzca las condiciones de la enfermedad sería de gran utilidad. Nuestro objetivo fue validar un modelo experimental de IM en cerdos.
Métodos: Para esta fase de creación del modelo se han utilizado 3 cerdos de raza large white, de 2 meses de edad y un peso de 25 ± 3 kg. Se provocó un infarto en el territorio de la arteria circunfleja que afectó la perfusión del músculo papilar posteromedial, y posteriormente se sometió al animal a una sobrecarga de volumen mediante creación de un shunt arteriovenoso, con la conexión de la aorta y la pulmonar mediante un tubo de dacrón. Se realizó análisis mediante ecocardiografía y resonancia magnética antes de la intervención y a las 8 semanas, y posteriormente el animal fue eutanasiado para realizar el estudio anatomopatológico.
Resultados: De los 3 cerdos, 1 falleció durante la intervención por fibrilación ventricular y los otros 2 sobrevivieron al procedimiento y fueron eutanasiados como estaba previsto a las 8 semanas. En ambos se produjo un infarto transmural, uno lateral y otro posteroinferior, con IM moderada secundaria. Las dimensiones y los volúmenes ventriculares aumentaron, y la contractilidad global se mantuvo a pesar de las alteraciones segmentarias.
Conclusiones: El modelo experimental de IM crónica basado en el daño isquémico del músculo papilar posteromedial asociado a una sobrecarga de volumen es factible, seguro y reproducible, y puede ser de gran utilidad para comprobar la seguridad y la eficacia de los futuros dispositivos para el tratamiento de esta afección.
Background
The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 (“GRAVID”).
Methods
The main objective was to describe the COVID-19 fatality ...rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021.
Results
One hundred-fifty cases were registered. Median age was 68 years (range 6–95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February–May 2020, August–November 2020, and December 2020–April 2021. The first wave had the highest number of registered cases and COVID-19 mortality.
Conclusion
Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection.
Clinicaltrials.gov identifier
NCT04344002.
Background:
Plasma cell proliferative index (PCPI) is an easily available prognostic parameter as well as a reliable progression indicator in multiple myeloma (MM). Despite this, there are no data ...regarding the utility of PCPI as a routine indicator to predict the response to second‐line lenalidomide based treatments.
Aims:
Study of theprognostic value of PCPI in patients with relapsed MM treated with lenalidomide/dexamethasone (len/dex) compared to other available indicators (International Staging System disease stage, high risk cytogenetics, serum albumin, LDH, β2‐microglobulin, depth and duration of the previous response) as well as to immunophenotypic features.
Methods
Study design: Observational retrospective study in a cohort of 108 patients with relapsed MM treated with len/dex (Jun 2014‐Dec 2018). The median age was 69.7 years (range, 44 to 90) with 55 males and 53 females. Study variables: Immunophenotype, PCPI and genetics using fluorescent in situ hibridation were performed in bone marrow specimens before the start of len/dex. Responses to len/dex were evaluated after 6 cycles, also recording time to progression. The primary efficacy endpoint was the progression‐free survival (PFS), and secondary efficacy endpoints included overall response rate (ORR) and rates of very good partial response or better (CR + VGPR). Flow‐cytometry: Flow cytometer FACSCanto II, BD CA was used. Study of PCPI (percentage of plasma cells in S‐phase) was performed using a single propidium iodide/CD138 BV421 double‐staining technique (fig 1‐A). Plasma cell subclones were identified using two specifically designed 8‐color combinations as previously described. Statistical methodology: χ2
and
U Mann‐Whitney tests were used to estimate statistically significant differences. Survival curves were plotted using the Kaplan‐Meier method, and differences were assessed with the log‐rank test. For multivariate analysis, stepwise Cox proportional hazard and logistic regressions were performed with SPSS Version 15.0 software.
Results:
A cut‐off PCPI value of 8% discriminates between two different groups of patients according to the detected subclones (mean of 1.14 subclones in PCPI> 8% versus 1.96 in PCPI≤8%, p < 0.05%). PCPI value was not significantly correlated with the other studied variables such as R‐ISS or genetics. Univariate analysis demonstrated that only PCPI and R‐ISS staging system were significantly associated with ORR and PFS. Overall responses (71.9%) were lower in MM > 8% (57.2% vs 79.3%; P < .05). The rates of best responses (CR + VPGR: 29.5%) were also lower in MM > 8% group (8.3% vs 39.3%; P < .01). PFS (median 24.2 months) were shorter in MM > 8% (11.1 months, vs 38.2 months p<. 001, see figure 1). In the multivariable analysis only PCPI > 8% is associated with PFS (Hazard Ratio 8.1‐ IC95% 7.2‐9.0) and predicts the duration of the response independently from R‐ISS, genetics, number of subclones detected and the other studied variables.
Summary/Conclusion:
Plasma cell proliferation measurement using PCPI is an easy technique that provides prognostic information in relapsed MM patients independently of the other risk factors. The expansion of a single subclone seems to reflect a loss of intraclonal equilibrium and may be an important factor related to the kinetics of disease progression. The perceived impact of the PCPI in the efficacy of len/dex combination must be better studied in order to understand if subsequent modifications in lenalidomide containing regimens should be considered in selected patients.
The long-term results of cryomaze in patients with longstanding persistent atrial fibrillation during concomitant surgical procedures are still uncertain.
Between 2006 and 2011, 150 consecutive ...patients with associated long-lasting permanent atrial fibrillation and associated heart disease underwent heart surgery were treated by biatrial Cox-Maze (63 patients) or by isolated endocardial or epicardial left atrial cryoablation (83 patients) concomitantly. The results at 3 years in these groups were compared with clinical monitoring, electrocardiography, 24-hour Holter, and echocardiography with measurement of the transmitral A wave at 1, 6 and 12 months and annually thereafter in all patients.
Patients undergoing Cox-Maze IV ablation presented rates of freedom from atrial fibrillation of 97, 94, 89, 80 and 54% at 1, 6, 12, 24 and 36 months, respectively. In the 12-month follow-up, these differences were significant (p<.05). The independent risk factors of atrial fibrillation recurrence was isolated ablation of left atrium.
Atrial fibrillation by cryothermia ablation had a high success rate before 2 years postoperatively. Recurrence of atrial fibrillation increased thereafter regardless of the technique used, although it was more intense and developed earlier in cases of monoatrial ablation. For the treatment of other long-lasting permanent atrial fibrillation cardiac surgery-associated pathology, an aggressive biatrial treatment with Cox maze ablation should be performed.
Information and communication technologies are currently among the supporting elements that may contribute to improving health and changing lifestyles.
The aim of this study was to evaluate the ...long-term effectiveness of adding an app to standardized counseling in order to increase physical activity (PA) and adherence to the Mediterranean diet and to analyze the effects of app adherence in lifestyle changes.
A randomized, multicenter clinical trial with a 12 month-follow up was conducted, involving 833 participants recruited by random sampling in 6 primary Spanish care centers (415 vs 418). Counseling on PA and the Mediterranean diet was given to both groups by a research nurse; however, the counseling + app group (intervention group) received additional training in the use of an app that was designed to promote the Mediterranean diet and PA over a 3-month period. Main outcomes and measures included PA by accelerometer and the 7-day Physical Activity Recall (PAR) questionnaire and adherence to the Mediterranean diet by an adherence screener questionnaire. We considered adherence to the app to be high when it was used for more than 60 days.
The mean age was 51 years (SD 12) in the intervention group and 52.3 years (SD 12.0) in the counseling-only group; females predominated in both groups (60.0%, 249/415 and 64.1%, 268/418, respectively). PA by accelerometer declined in both groups at 12 months (P value for tendency in moderate to vigorous PA, MVPA=.15). The intervention subgroup with high app adherence had better behavior than the low adherence subgroup (P value for tendency in MVPA=.001). PA analyzed by 7-day PAR did not show changes at 12 months in any of the groups (P value for tendency=.25). In the Mediterranean diet, an increase in adherence was observed in both groups at 12 months with no differences between them (P value for tendency=.46). In these two cases, the group with high app adherence also had better behavior, although without reaching significance for the tendency (P>.05).
The participants with strongest app adherence showed better outcomes in terms of maintenance of healthy lifestyles at 12 months than those with weaker adherence. Overall, however, we found no differences between intervention group and counseling-only group in PA increase and adherence to the Mediterranean diet in the long term.