Incidencia, predictores e impacto pronóstico de una clase funcional disminuida inmediatamente después de un implante percutáneo de válvula aórtica / Incidence, predictors, and prognostic significance of impaired functional status early after transcatheter aortic valve replacement

Introducción y objetivos: Existen pocos datos acerca del impacto pronóstico de una clase funcional NYHA III-IV después del implante percutáneo de válvula aórtica (TAVI). El objetivo del estudio fue determinar la incidencia, los predictores y las implicaciones pronósticas de una clase NYHA III-IV al mes del TAVI.MétodosEstudio multicéntrico que incluyó a 3.462 pacientes sometidos a TAVI que recibieron dispositivos de nueva generación. Se compararon pacientes en clase funcional NYHA I-II frente a pacientes en clase NYHA III-IV al mes de seguimiento. Los predictores de clase NYHA III-IV a un mes se identificaron mediante regresión logística multivariante. La supervivencia se evaluó con el método de Kaplan-Meier y los factores asociados a peor pronóstico se identificaron mediante la regresión de Cox.ResultadosLa edad media de la población de estudio era de 80,3±7,3 años, con el 47% de mujeres y un valor mediano en la escala de la Society of Thoracic Surgeons del 3,8% [IQR, 2,5-5,8]). Un total de 208 pacientes (6%) presentaron NYHA III-IV al mes del TAVI. Los predictores de NYHA III-IV al mes fueron: NYHA basal III-IV (OR=1,76; IC95%, 1,08-2,89; p=0,02), enfermedad pulmonar obstructiva crónica (OR=1,80; IC95%, 1,13-2,83; p=0,01) e insuficiencia mitral severa post-TAVI (OR=2,00; IC95%, 1,21-3,31; p<0,01). Los pacientes en NYHA III-IV al mes del TAVI tenían un mayor riesgo de muerte (HR=3,68; IC95%, 2,39-5,70; p<0,01) y hospitalización por insuficiencia cardiaca (HR=6,00; IC95%, 3,76-9,60; p<0,01) durante el año que siguió al TAVI. (AU)

Introduction and objectives: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR.MethodsThis multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis.ResultsThe mean age of the study population was 80.3±7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P=.02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P=.01), and post-TAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P<.01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P<.01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P<.01) at 1-year follow-up. (AU)

Patients' Preferences for Sphingosine-1-Phosphate Receptor Modulators in Multiple Sclerosis Based on Clinical Management Considerations: A Choice Experiment.

BACKGROUND: Several sphingosine-1-phosphate receptor (S1PR) modulators are available in the US for treating relapsing forms of multiple sclerosis (RMS). Given that these S1PR modulators have similar efficacy and safety, patients may consider the clinical management characteristics of the S1PR modulators when deciding among treatments. However, none of the S1PR modulators is clearly superior in every aspect of clinical management, and for some treatments, clinical management varies based on a patient's comorbid health conditions (e.g., heart conditions [HC]). OBJECTIVES: This study aimed to determine which S1PR modulator patients with relapsing-remitting multiple sclerosis (RRMS) would prefer based on clinical management considerations, and to estimate how different clinical management considerations might drive these preferences. Preferences were explored separately for patients with and without comorbid HC. METHODS: A multicriteria decision analysis was conducted on S1PR modulators approved to treat RMS: fingolimod, ozanimod, siponimod, and ponesimod. Clinical management preferences of patients with RRMS were elicited in a discrete choice experiment (DCE) in which participants repeatedly chose between hypothetical S1PR modulator profiles based on their clinical management attributes. Attributes included first-dose observations, genotyping, liver function tests, eye examinations, drug-drug interactions, interactions with antidepressants, interactions with foods high in tyramine, and immune system recovery time. Preferences were estimated separately for patients with HC and without HC (noHC). Marginal utilities were calculated from the DCE data for each attribute and level using a mixed logit model. In the multicriteria decision analysis, partial value scores were created by applying the marginal utilities for each attribute and level to the real-world profiles of S1PR modulators. Partial value scores were summed to determine an overall clinical management value score for each S1PR modulator. RESULTS: Four hundred patients with RRMS completed the DCE. Ponesimod had the highest overall value score for patients both without (n = 341) and with (n = 59) HC (noHC: 5.1; HC: 4.0), followed by siponimod (noHC: 4.9; HC: 3.3), fingolimod (noHC: 3.4; HC: 2.8), and ozanimod (noHC: 0.9; HC: 0.8). Overall, immune system recovery time contributed the highest partial value scores (noHC: up to 1.9 points; HC: up to 1.2 points), followed by the number of drug-drug interactions (noHC: up to 1.2 points; HC: up to 1.7 points). CONCLUSIONS: When considering the clinical management of S1PR modulators, the average patient with RRMS is expected to choose a treatment with shorter immune system recovery time and fewer interactions with other drugs. Patients both with and without heart conditions are likely to prefer the clinical management profile of ponesimod over those of siponimod, fingolimod, and ozanimod. This information can help inform recommendations for treating RRMS and facilitate shared decision making between patients and their doctors.

Botánicas Function as Health Care Safety Nets Among Hispanic American Immigrants: A Brief Report.

As the U.S. population becomes more racially/ethnically diverse, the Hispanic American immigrant population has slowly grown in recent years. In the face of anti-immigrant policies, limited access to care, fear of deportation, discrimination, stigmatization, poverty, and other stressors, Hispanic American immigrants seek services from botánicas for religious, spiritual, medical, and psychosocial health reasons, including the accessibility and affordability of services from folk practitioners in these herbal dispensaries. Hispanics are the primary consumers of herbal remedies and complementary and alternative medicines in the United States. The purpose of this article is to emphasize the critical role of botánicas in the health and wellness of Hispanic American immigrants. Recommendations for health professionals are provided in the care of Hispanic Americans who utilize folk, traditional, and herbal medicines for health and healing.

Measurement of cerebrospinal fluid lactate levels in pediatric patients with suspected ventriculoperitoneal shunt infection: A retrospective cohort study.

INTRODUCTION: Ventriculoperitoneal shunt (VPS) infection is a severe complication. Early diagnosis could help to decrease morbidity and treatment costs. Lactate has been used for the diagnosis of other central nervous system infections. The aim of this study is to determine the usefulness of lactate for the diagnosis of VPS infection. METHODOLOGY: Retrospective cohort study. Lactate was measured in patients who consulted with VPS dysfunction between May 2019 and May 2022. Mean were compared according to culture results. A Receiver Operating Characteristic (ROC) curve was performed to determine the appropriate cut-off point. RESULT: Lactate has a high negative predictive value but a low positive predictive value for the diagnosis of ventriculitis.

Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally.

Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal ß-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI both in vitro and in vivo. In human monocytes, this effect represents a truly trained process, as HKMtb confers boosted inflammatory responses against various heterologous challenges, such as lipopolysaccharide (Toll-like receptor [TLR] 4 ligand) and R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced TI relies on epigenetic mechanisms in a Syk/HIF-1α-dependent manner. In vivo, HKMtb induced TI when administered both systemically and intranasally, with the latter generating a more robust TI response. Summarizing, our research has demonstrated that HKMtb has the potential to act as a mucosal immunotherapy that can successfully induce trained responses.

Preferences of Patients with Amyotrophic Lateral Sclerosis for Intrathecal Drug Delivery: Choosing between an Implanted Drug-Delivery Device and Therapeutic Lumbar Puncture.

BACKGROUND: Novel intrathecal treatments for amyotrophic lateral sclerosis (ALS) may require delivery using lumbar puncture (LP). Implanted drug-delivery devices (IDDDs) could be an alternative but little is known about patients' preferences for intrathecal drug-delivery methods. OBJECTIVE: We aimed to elicit preferences of patients with ALS for routine LP and IDDD use. METHODS: A discrete choice experiment (DCE) and a threshold technique (TT) exercise were conducted online among patients with ALS in the US and Europe. In the DCE, patients made trade-offs between administration attributes. Attributes were identified from qualitative interviews. The TT elicited maximum acceptable risks (MARs) of complications from device implantation surgery. DCE data were analyzed using mixed logit to quantify relative attribute importance (RAI) as the maximum contribution of each attribute to a preference, and to estimate MARs of device failure. TT data were analyzed using interval regression. Four scenarios of LP and IDDD were compared. RESULTS: Participants (N = 295) had a mean age of 57.7 years; most (74.2%) were diagnosed < 3 years ago. Preferences were affected by device failure risk (RAI 28.6%), administration frequency (26.4%), administration risk (19.7%), overall duration (17.8%), and appointment location (7.5%). Patients accepted a 5.6% device failure risk to reduce overall duration from 2 h to 30 min and a 3.6% risk for administration in a local clinic instead of a hospital. The average MAR of complications from implantation surgery was 29%. Patients preferred IDDD over LP in three of four scenarios. CONCLUSION: Patients considered an IDDD as a valuable alternative to LP in multiple clinical settings.

Combined Vertebral Augmentation for Vertebral Body Fracture With Contraindications for Traditional Techniques.

INTRODUCTION AND OBJECTIVE: A vertebral compression fracture (VCF) can be found in trauma, osteoporosis, and tumor pathology. The most frequent is the pathological fracture in osteoporotic vertebrae in the elderly. Percutaneous techniques of vertebral cementation allow treatment of A1-A2 AO spine fractures, improving pain control and spine stabilization and decreasing mobility and mortality. Traditionally, the selection of patients is fundamental for spine surgery success, with an absolute contraindication being posterior wall involvement (A3-A4 AO spine fractures) or VCF with a loss of height greater than 50%. In this report, we present a variant surgical technique combining percutaneous spine surgery with cementoplasty for patients with classical spine surgery contraindications. METHODS: Five patients with complex symptomatic VCF or A3-A4 AO spine fractures in pathologic bone with MRI short tau inversion recovery (STIR) sequence (+) were operated on with a combined technique (percutaneous kyphoplasty (KP) and vesselplasty). The visual analog scale (VAS) was used to measure postoperative pain. RESULTS: The procedure was performed within 60 days of the fracture in all patients. The mean hospital stay was two days. No patient developed major complications. All the patients had a satisfactory clinical (improvement in pain control) and radiological response at the perioperative period and at a 30-day follow-up. CONCLUSIONS: The combined percutaneous technique allows surgical resolution of cases previously considered contraindicated, especially in elderly patients and those with comorbidities, without involving higher cost, complications, surgical time, and hospital stay. We suggest a novel, safe, and effective variation of the vertebral cementoplasty technique.

First description and validation of a new method for estimating aortic stenosis burden and predicting the functional response to TAVI.

Background: Up to one-fifth of patients continue to have poor quality of life after transcatheter aortic valve implantation (TAVI), with an additional similar proportion not surviving 1 year after the procedure. We aimed to assess the value of a new method based on an integrated analysis of left ventricular outflow tract flow velocity and aortic pressure to predict objective functional improvement and prognosis after TAVI. Methods: In a cohort of consecutive patients undergoing TAVI, flow velocity-pressure integrated analysis was obtained from simultaneous pressure recordings in the ascending aorta and flow velocity recordings in the left ventricular outflow tract by echocardiography. Objective functional improvement 6 months after TAVI was assessed through changes in a 6-min walk test and NT-proBNP levels. A clinical follow-up was conducted at 2 years. Results: Of the 102 patients studied, 82 (80.4%) showed objective functional improvement. The 2-year mortality of these patients was significantly lower (9% vs. 44%, p = 0.001). In multivariate analysis, parameter "(Pressure at Vmax - Pressure at Vo)/Vmax" was found to be an independent predictor for objective improvement. The C-statistic was 0.70 in the overall population and 0.78 in the low-gradient subgroup. All echocardiographic parameters and the valvuloarterial impedance showed a C-statistic of <0.6 for the overall and low-gradient patients. In a validation cohort of 119 patients, the C-statistic was 0.67 for the total cohort and 0.76 for the low-gradient subgroup. Conclusion: This new method allows predicting objective functional improvement after TAVI more precisely than the conventional parameters used to assess the severity of aortic stenosis, particularly in low-gradient patients.

Incidence, predictors, and prognostic significance of impaired functional status early after transcatheter aortic valve replacement.

INTRODUCTION AND OBJECTIVES: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR. METHODS: This multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis. RESULTS: The mean age of the study population was 80.3±7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P=.02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P=.01), and post-TAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P<.01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P<.01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P<.01) at 1-year follow-up. CONCLUSIONS: Up to 6% of contemporary TAVR patients exhibited an impaired functional status following TAVR. Worse baseline NYHA class, chronic pulmonary obstructive disease, and severe mitral regurgitation predicted 30-day NYHA class III/IV, and this determined a higher risk of mortality and heart failure hospitalization at 1-year follow-up. Further studies on the prevention and treatment optimization of patients with impaired functional status after TAVR are needed.

Surgical vs. transcatheter aortic valve replacement in patients over 75 years with aortic stenosis: sociodemographic profile, clinical characteristics, quality of life and functionality.

Background: Aortic valve stenosis (AVS) affects 25% of the population over 65 years. At present, there is no curative medical treatment for AVS and therefore the surgical approach, consisting of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), is the treatment of choice. Methodology: The aim of this study was to analyze the sociodemographic and clinical characteristics, quality of life and functionality of a sample of patients with AVS over 75 years of age, who underwent TAVR or SAVR, applying standard clinical practice. A prospective multicenter observational study was conducted in two hospitals of the Spanish National Health System. Data were collected at baseline, 1, 6 months and 1 year. Results: In total, 227 participants were included, with a mean age of 80.6 [SD 4.1]. Statistically significant differences were found in terms of quality of life, which was higher at 1 year in patients who underwent SAVR. In terms of functionality, SAVR patients obtained a better score (p < 0.01). However, patients who underwent TAVR began with a worse baseline situation and managed to increase their quality of life and functionality after 1 year of follow-up. Conclusion: The individualized choice of TAVR or SAVR in patients with AVS improves patients' quality of life and function. Moreover, the TAVR procedure in patients with a worse baseline situation and a high surgical risk achieved a similar increase in quality of life and functionality compared to patients undergoing SAVR with a better baseline situation.

Cardiac Death After Transcatheter Aortic Valve Replacement With Contemporary Devices.

BACKGROUND: The burden of cardiac death after transcatheter aortic valve replacement (TAVR), particularly from advanced heart failure (HF) and sudden cardiac death (SCD), remains largely unknown. OBJECTIVES: This study sought to evaluate the incidence and predictors of SCD and HF-related death in TAVR recipients treated with newer-generation devices. METHODS: This study included a total of 5,421 consecutive patients who underwent TAVR with newer-generation devices using balloon (75.7%) or self-expandable (24.3%) valves. RESULTS: After a median follow-up of 2 (IQR: 1-3) years, 976 (18.0%) patients had died, 50.8% from cardiovascular causes. Advanced HF and SCD accounted for 11.6% and 7.5% of deaths, respectively. Independent predictors of HF-related death were atrial fibrillation (HR: 2.17; 95% CI: 1.47-3.22; P < 0.001), prior pacemaker (HR: 1.79; 95% CI: 1.10-2.92; P = 0.01), reduced left ventricular ejection fraction (HR: 1.08 per 5% decrease; 95% CI: 1.01-1.14; P = 0.02), transthoracic approach (HR: 2.50; 95% CI: 1.37-4.55; P = 0.003), and new-onset persistent left bundle branch block (HR: 1.85; 95% CI: 1.14-3.02; P = 0.01). Two baseline characteristics (diabetes, HR: 1.81; 95% CI: 1.13-2.89; P = 0.01; and chronic kidney disease, HR: 1.72; 95% CI: 1.02-2.90; P = 0.04) and 3 procedural findings (valve in valve, HR: 2.17; 95% CI: 1.01-4.64; P = 0.04; transarterial nontransfemoral approach, HR: 2.23; 95% CI: 1.23-4.48; P = 0.01; and periprocedural ventricular arrhythmia, HR: 7.19; 95% CI: 2.61-19.76; P < 0.001) were associated with an increased risk of SCD after TAVR. CONCLUSIONS: Advanced HF and SCD accounted for a fifth of deaths after TAVR in contemporary practice. Potentially treatable factors leading to increased risk of HF deaths and SCD were identified, such as arrhythmia/dyssynchrony factors for HF and valve-in-valve TAVR or periprocedural ventricular arrhythmias for SCD.

Epidemiology, patterns of care and prognosis of acute kidney injury in critically ill patients: A multicenter study in Argentina (The EPIRA study).

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality rates in the intensive care unit (ICU). In low- and middle-income countries (LMICs), epidemiological information about this condition is still scarce. Our main objective was to characterize its epidemiology, prognosis, and its treatment. METHODS: This multicenter prospective cohort study included 1466 patients from 35 ICUs during 6 months in Argentina in 2018. Risk factors and outcomes in patients with and without AKI, and between AKI on admission (AKIadm) and that developed during hospitalization (AKIhosp) were analyzed. RESULTS: AKI occurred in 61.3% of patients (900/1466); 72.6% were AKIadm and 27.3% AKIhosp. Risk factors were age, BMI, arterial hypertension, cardiovascular diseases, diabetes, SOFA, APACHE II, dehydration, sepsis, vasopressor use, radiocontrast, diuresis/h and mechanical ventilation. Independent predictors for AKI were sepsis, diabetes, dehydration, vasopressors on admission, APACHE II and radiocontrast use. Renal replacement therapies (RRT) requirement in AKI patients was 14.8%. Hospital mortality in AKI vs. non-AKI was 38.7% and 23.3% (p < 0.001); and in AKIadm vs. AKIhosp, 41.2% and 37.8% (p = 0.53). CONCLUSIONS: ICU-acquired AKI has high incidence, complications and mortality. Risk factors for AKI and RRT utilization were similar to those described in other epidemiological studies. AKIadm was more frequent than AKIhosp, but had equal prognosis.

Intraprocedural delayed reassessment of paravalvular regurgitation in TAVR significantly reduces the use of postdilatation.

OBJECTIVES: We sought to investigate the effect of a 15-min delayed intraprocedural reassessment of paravalvular aortic regurgitation (PVR) after an immediate evaluation of posttranscatheter aortic valve replacement (TAVR) on the regurgitation grading and usage of postdilatation. BACKGROUND: PVR after TAVR is associated with poor prognosis, but postdilatation may increase the risk of other complications. METHODS: In a prospective cohort of consecutive patients treated with balloon-expandable valve ES-3 ultra, the degree of PVR was assessed immediately and 15 min after that first evaluation (excluded severe cases), with the indication of postdilatation based on the delayed assessment. As a control group, the previous consecutive series of patients also treated with the same model of valve prosthesis was used. RESULTS: A total of 180 patients were included in the prospective study cohort and 152 in the retrospective control group. In the study group, the immediate PVR assessment showed none-trace 27.5%, mild 52%, moderate 19%, and severe 1.5%, and the delayed re-evaluation graded PVR as none-trace 83%, mild 15.6%, and moderate 1.2% (p < 0.001 as compared to immediate). In the control group, the immediate PVR assessment showed none-trace 33.5%, mild 52%, moderate 13%, and severe 1.5%. The rate of postdilatation was 2.8% in the study group versus 10.5% in the control group (p = 0.006). At discharge, no differences were observed between groups in PVR echocardiographic grading. CONCLUSIONS: A post-TAVR delayed intraprocedural reassessment of the PVR shows a clearly lower degree of regurgitation as compared to immediate evaluation, which significantly decreased the indication of postdilatation.

EFFECTS OF BACTERIAL LIPOPOLYSACCHARIDE AND SHIGA TOXIN ON INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS.

ABSTRACT: Background : Mesenchymal stem cells (MSCs) can be activated by different bacterial toxins. Lipopolysaccharides and Shiga Toxin (Stx) are the main toxins necessary for hemolytic uremic syndrome development. The main etiological event in this disease is endothelial damage that causes glomerular destruction. Considering the repairing properties of MSC, we aimed to study the response of MSC derived from induced pluripotent stem cells (iPSC-MSC) to LPS and/or Stx and its effect on the restoration of injured endothelial cells. Methods : iPSC-MSC were treated with LPS and or/Stx for 24 h and secretion of cytokines, adhesion, and migration were measured in response to these toxins. In addition, conditioned media from treated iPSC-MSC were collected and used for proteomics analysis and evaluation of endothelial cell healing and tubulogenesis using human microvascular endothelial cells 1 as a source of endothelial cells. Results : The results obtained showed that LPS induced a proinflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb 3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of conditioned media of iPSC-MSC treated with LPS + Stx, decreased the capacity of human microvascular endothelial cells 1 to close a wound, and did not favor tubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support the functional results described. Conclusions : iPSC-MSC activated by LPS acquired a proinflammatory profile that induces migration and adhesion to extracellular matrix proteins but the addition of Stx did not activate any repair program to ameliorate endothelial damage, indicating that the use of iPSC-MSC to regenerate endothelial injury caused by LPS and/or Stx in hemolytic uremic syndrome could not be the best option to consider to regenerate a tissue injury.

A new integrative approach to assess aortic stenosis burden and predict objective functional improvement after TAVR.

Background: A non-negligible rate of patients undergoing transcatheter aortic valve replacement (TAVR) do not report symptomatic improvement or even die in the short-midterm. We sought to assess the degree of objective functional recovery after TAVR and its prognostic implications and to develop a predictive model. Methods: In a cohort of patients undergoing TAVR, a prospective evaluation of clinical, anatomical, and physiological parameters was conducted before and after the procedure. These parameters were derived from echocardiography, non-invasive analysis of arterial pulse waves, and cardiac tomography. Objective functional improvement 6 months after TAVR was assessed using a 6-min walk test and nitro-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The derived predictive model was prospectively validated in a different cohort. A clinical follow-up was conducted at 2 years. Results: Among the 212 patients included, objective functional improvement was observed in 169 patients (80%) and subjective improvement in 187 (88%). Patients with objective functional improvement showed a much lower death rate at 2 years (9% vs. 31% p = 0.0002). Independent predictors of improvement were as follows: mean aortic gradient of ≥40 mmHg, augmentation index75 of ≥45%, the posterior wall thickness of ≤12 mm, and absence of atrial fibrillation. A simple integer-based point score was developed (GAPA score), which showed an area under the curve of 0.81 for the overall cohort and 0.78 for the low-gradient subgroup. In a validation cohort of 216 patients, these values were 0.75 and 0.76, respectively. Conclusion: A total of 80% of patients experienced objective functional improvement after TAVR, showing a significantly lower 2-year mortality rate. A predictive score was built that showed a good discriminative performance in overall and low-gradient populations.

The Impact of Substantial Improvements in HbA1c and Weight Loss on the Medication Preferences of People with Type 2 Diabetes.

Purpose: To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile. Patients and Methods: Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients' preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited. Results: Participants (N=620) in the US (N=301) and UK (N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants' preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg). Conclusion: HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles.

Lung Function Decline in Cystic Fibrosis: Impact of Data Availability and Modeling Strategies on Clinical Interpretations.

Rationale: Studies estimating the rate of lung function decline in cystic fibrosis have been inconsistent regarding the methods used. How the methodology used impacts the validity of the results and comparability between studies is unknown. Objectives: The Cystic Fibrosis Foundation established a work group whose tasks were to examine the impact of differing approaches to estimating the rate of decline in lung function and to provide analysis guidelines. Methods: We used a natural history cohort of 35,252 individuals with cystic fibrosis aged ⩾6 years in the Cystic Fibrosis Foundation Patient Registry (CFFPR), 2003-2016. Modeling strategies using linear and nonlinear forms of marginal and mixed-effects models, which have previously quantified the rate of forced expiratory volume in 1 second (FEV1) decline (percent predicted per year), were evaluated under clinically relevant scenarios of available lung function data. Scenarios varied by sample size (overall CFFPR, medium-sized cohort of 3,000 subjects, and small-sized cohort of 150), data collection/reporting frequency (encounter, quarterly, and annual), inclusion of FEV1 during pulmonary exacerbation, and follow-up length (<2 yr, 2-5 yr, entire duration). Results: Rate of FEV1 decline estimates (percent predicted per year) differed between linear marginal and mixed-effects models; overall cohort estimates (95% confidence interval) were 1.26 (1.24-1.29) and 1.40 (1.38-1.42), respectively. Marginal models consistently estimated less rapid lung function decline than mixed-effects models across scenarios, except for short-term follow-up (both were ∼1.4). Rate of decline estimates from nonlinear models diverged by age 30. Among mixed-effects models, nonlinear and stochastic terms fit best, except for short-term follow-up (<2 yr). Overall CFFPR analysis from a joint longitudinal-survival model implied that an increase in rate of decline of 1% predicted per year in FEV1 was associated with a 1.52-fold (52%) increase in the hazard of death/lung transplant, but the results exhibited immortal cohort bias. Conclusions: Differences were as high as 0.5% predicted per year between rate of decline estimates, but we found estimates were robust to lung function data availability scenarios, except short-term follow-up and older age ranges. Inconsistencies among previous study results may be attributable to inherent differences in study design, inclusion criteria, or covariate adjustment. Results-based decision points reported herein will support researchers in selecting a strategy to model lung function decline most reflective of nuanced, study-specific goals.

Optimal Degree of Balloon-Expandable Transcatheter Valve Oversizing in Patients With Borderline Aortic Annulus Measurements: Insights From a Multicenter Real-World Experience.

BACKGROUND: The potential benefit of using larger or smaller transcatheter heart valves (THV) in patients with borderline aortic annulus measurement (BAM) remains uncertain. The objective of this study was to evaluate the clinical outcomes associated with the selection of larger or smaller THV in the context of BAM. METHODS: This was a multicenter observational study including patients who underwent transcatheter aortic valve replacement with the SAPIEN 3 or SAPIEN 3 Ultra-valve systems (Edwards Lifesciences, Irvine, CA) from April 2014 to June 2021. BAM was defined according to the manufacturer sizing chart and included the following annulus areas: 314 to 346, 400 to 430, 500 to 546 mm2. A 1:1 propensity score matching was used to compare outcomes of patients with larger or smaller THV. RESULTS: From a total of 2467 patients, BAM was identified in 852 patients (34.5%). A larger and smaller THV was selected in 338 (39.7%) and 514 patients (60.3%) patients, respectively. The choice of a larger THV was associated (before and after propensity matching) with a higher risk of new-onset left bundle branch block (HR, 2.25 [95% CI, 1.39-3.65; P=0.001) and permanent pacemaker implantation (HR, 1.86 [95% CI, 1.11-3.09]; P=0.016) without any impact on gradients or the risk of moderate or severe paravalvular regurgitation at discharge (HR, 0.78 [95% CI, 0.41-1.45]; P=0.427). The risk of periprocedural complications such as aortic rupture and tamponade was low (<1%) and similar between groups. CONCLUSIONS: In patient with BAM, selecting a larger SAPIEN 3/Ultra THV increased the risk of conduction disturbances without any benefit on valve hemodynamics and clinical outcomes.

Multivariate data analysis: Validation of an instrument for the evaluation of teaching digital competence.

Background: Technology plays a fundamental role to achieve higher education key learning objectives. Digital competence (DC) is defined as a set of skills, knowledge, abilities, and attitudes in technological aspects. It is necessary to employ an effective training action plan in higher education institutions to advance towards a level of teaching digital competence (TDC). The objective of this study was to validate the COMDID A instrument to assess Teaching Digital Competence (TDC) of active teachers, through a confirmatory factor and internal reliability analysis. Methods: The research was developed within a descriptive-correlational scope and a non-experimental-cross-sectional design to validate the dimensionality and reliability of the COMDID A instrument and evaluate the self-perceived digital competence of active teachers. The population was made up of 690 professors who were part of the teaching staff of the National University of Chimborazo, Ecuador, in the first academic period of the year 2021. The sample was probabilistic, in a simple random scheme, the percentage of potential error admitted was 3%. The representativeness of the sample was 50%, and the confidence level was 97%. A total of 511 teachers completed the questionnaire compared to the 452 individuals needed. Results: The instrument was robust, and it was reliable for the calculated sample. There were correlations between the variables, and the statistical calculation ensured the development of the multivariate analysis to validate the dimensionality of the instrument. Moreover, the correct dimensionality was determined through a confirmatory analysis and high reliability of the instrument. Conclusions: The calculated factorial scores were defined in order for further studies to be carried out. It is important to apply confirmatory factor analysis in educational technology research to validate the dimensionality of data collection instruments.