Definition of Polypharmacy in Heart Failure: A Scoping Review of the Literature.

Patients with heart failure (HF) have a high prevalence of polypharmacy, which can lead to drug interactions, cognitive impairment, and medication non-compliance. However, the definition of polypharmacy in these patients is still inconsistent. The aim of this scoping review was to find the most common definition of polypharmacy in HF patients. We conducted a scoping review searching Medline, Embase, CINAHL, and Cochrane using terms including polypharmacy, HF and deprescribing, which resulted in 7,949 articles. Articles without a definition of polypharmacy in HF patients and articles which included patients < 18 years of age were excluded; only 59 articles were included. Of the 59 articles, 49% (n = 29) were retrospective, 20% (n = 12) were prospective, 10% (n = 6) were cross-sectional, and 27% (n = 16) were review articles. Twenty percent (n = 12) of the articles focused on HF with reduced ejection fraction, 10% (n = 6) focused on HF with preserved ejection fraction and 69% (n = 41) articles either focused on both diagnoses or did not clarify the specific type of HF. The most common cutoff for polypharmacy in HF was five medications (59%, n = 35). There was no consensus regarding the inclusion or exclusion of over-the-counter medications, supplements, or vitamins. Some newer studies used a cutoff of 10 medications (14%, n = 8), and this may be a more practical and meaningful definition for HF patients.

Evaluation of Midodrine Utilization in Patients with Cancer and Heart Failure.

PURPOSE: The purpose of this study was to evaluate safety and cardiovascular outcomes as well as overall survival of cancer patients with concomitant heart failure (HF) treated with midodrine for hypotension. METHODS: Adult patients diagnosed with cancer and HF who were treated with midodrine at a tertiary cancer center from 03/2013 to 08/2021 were identified. Demographic and clinical parameters were collected retrospectively. RESULTS: A total of 85 patients were included with a median age of 68 years (IQR: 60, 74; 33% female and 85% White). Of those, 31% had HFpEF (EF ≥ 50%), 42% HF with mildly reduced EF (HFmrEF; EF 41-49%), and 27% HFrEF (EF ≤ 40%). The most common indication for midodrine use was orthostatic hypotension (49%). Midodrine was continued for at least one month in 57% of the patients. Supine hypertension was the only side effect reported in 6% of patients. No statistically significant changes in NYHA class, guideline-directed medical therapy, cardiac biomarkers (NT-proBNP or troponin T), echocardiographic findings or cardiovascular hospitalizations were observed between patients who continued treatment with midodrine compared to those who stopped using midodrine over a median follow-up of 38 months. In the multivariable cox regression analysis, continuation of midodrine, compared to discontinuation, and use of midodrine for orthostatic hypotension, as opposed to other causes of hypotension, were not associated with an increased risk of mortality (HR 0.41, 95% CI 0.24-0.69, p < .0001; HR 0.34, 95% CI 0.18-0.64, p < .001, respectively). In contrast, elevated creatinine (> 1.3 for males and > 1.1 for females) was associated with an increased risk of mortality (HR 1.83, 95% CI 1.07-3.14). LVEF was not significantly associated with lower or higher risk of mortality. CONCLUSIONS: In our study, midodrine use in patients with cancer and HF was not associated with significant adverse effects, worse cardiovascular outcomes, or increased risk of mortality. Larger, prospective studies are needed to confirm these findings.

The addition of evolocumab to maximal tolerated statin therapy improves walking performance in patients with peripheral arterial disease and intermittent claudication (Evol-PAD study).

OBJECTIVE: To test the hypothesis that in patients with peripheral arterial disease (PAD) and claudication, treated with maximal tolerated statin therapy, the addition of a monthly subcutaneous injection of evolocumab for 6 months improves treadmill walking performance. BACKGROUND: Lipid lowering therapy improves walking parameters in patients with PAD and claudication. Evolocumab decreases cardiac and limb adverse events in patients with PAD; however, the effect of evolocumab on walking performance is not known. METHODS: We performed a double-blind, randomized, placebo-controlled study to compare maximal walking time (MWT) and pain free walking time (PFWT) in patients with PAD and claudication treated with monthly subcutaneous injections of evolocumab 420 mg (n = 35) or placebo (n = 35). We also performed measurements of lower limb perfusion, brachial flow mediated dilatation (FMD), carotid intima media thickness (IMT), and serum biomarkers of PAD disease severity. RESULTS: After six-months of treatment with evolocumab MWT increased by 37.7 % (87.5 ± 24 s) compared to 1.4 % (-21.7 ± 22.9 s) in the placebo group, p = 0.01. PFWT increased by 55.3 % (67.3 ± 21.2 s) in the evolocumab group compared to 20.3 % (8.5 ± 20.3 s) in the placebo group, p = 0.051. There was no difference in lower extremity arterial perfusion measurements. FMD increased by 42.0 ± 73.9 % (1.01 ± 0.7 %) in the evolocumab group and decreased by 16.29 ± 20.06 % (0.99 ± 0.68 %) in the placebo group (p < 0.001). IMT decreased by 7.16 ± 4.6 % (0.06 ± 0.04 mm) in the evolocumab group and increased by 6.68 ± 4.9 % (0.05 ± 0.03 mm) in the placebo group, (p < 0.001). CONCLUSIONS: The addition of evolocumab to maximal tolerated statin therapy improves maximal walking time in patients with PAD and claudication, increases FMD, and decreases IMT. CONDENSED ABSTRACT: Peripheral arterial disease (PAD) impairs quality of life by causing lower extremity intermittent claudication, rest pain, or amputation. Evolocumab is a monthly injectable monoclonal antibody medication that reduces cholesterol. In this study, we randomly treated patients with PAD and claudication, and on background statin therapy, with evolocumab or placebo, and found that evolocumab improves walking performance on a treadmill test by increasing maximal walking time. We also found that evolocumab decreases plasma MRP-14 levels, a marker of PAD severity.

The Year in Cardio-oncology 2022.

Cardiovascular disease and cancer are the leading causes of death worldwide. With advent of novel and improved cancer therapies, a growing population of cancer patients with cardiac complications is seen. Taking this into consideration, the clinical studies have also shifted their focus from the study of a single disease to the interdisciplinary study of oncology and cardiology. This current review article provides a comprehensive review of all major articles and guidelines from the year 2021-2022 in the field of cardio-oncology.

Coronary artery calcium score on standard of care oncologic CT scans for the prediction of adverse cardiovascular events in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy.

Introduction: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT. Methods: Patients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed on NCCT scans by an expert cardiologist and a cardiac radiologist following the 2016 SCCT/STR guidelines. CVAE were graded based on the most recent Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CVAE were also grouped into (i) coronary/vascular events, (ii) arrhythmias, or (iii) heart failure. All CVAE were adjudicated by a board-certified cardiologist. Results: Out of a total of 193 patients, 45% were female and 91% Caucasian. Mean age was 64 ± 9 years and mean BMI 28 ± 6 kg/m2. Of 193 patients, 74% had CAC >0 Agatston units (AU), 49% CAC ≥100 AU and 36% CAC ≥300 AU. Twenty-nine patients (15%) developed a grade ≥2 CVAE during a median follow-up of 24.3 months (IQR: 10.9-51.7). Of those, 11 (38%) were coronary/vascular events. In the multivariate cox regression analysis, controlling for mean heart dose and pre-existing CV disease, higher CAC score was independently associated with development of a grade ≥2 CVAE [HR: 1.04 (per 100 AU), 95% CI: 1.01-1.08, p = 0.022] and with worse overall survival (OS; CAC ≥100 vs. <100 AU, HR: 1.64, 95% CI: 1.11-2.44, p = 0.013). In a sub-analysis evaluating the type of the CVAE, it was the coronary/vascular events that were significantly associated with higher baseline CAC (median: 676 AU vs. 73 AU, p = 0.035). Discussion: Cardiovascular adverse events are frequent in patients with NSCLC treated with CRT. CAC calculated on "standard of care" NCCT can predict the development of CVAEs and specifically coronary/vascular events, as well as OS, independently from other traditional risk factors and radiation mean heart dose. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT00915005], identifier [NCT00915005].

Determinants of change in code status among patients with cardiopulmonary arrest admitted to the intensive care unit.

BACKGROUND: Patients with cardiopulmonary arrest often have a poor prognosis, prompting discussion with families about code status. The impact of socioeconomic factors, demographics, medical comorbidities and medical interventions on code status changes is not well understood. METHODS: This retrospective study included adult patients presenting with cardiac arrest to the intensive care unit of a hospital group between 5/1/2010-5/1/2020. We extracted chart data on socioeconomic factors, demographics, and medical comorbidities. RESULTS: We identified 1,254 patients, of which 57.5% were males. Age was different across the groups with (61.2 ± 15.5 years) and without (61.2 ± 15.5 years) code status change (p= <0.0001). Code status was changed in 583 patients (46.5%). Among patients with code status change, the highest prevalence was White patients (34.8%), followed by African Americans (30.9%), and Hispanics (25.4%). Compared to patients who did not have a code status change, those with a change in code status were older (66.7 ± 14.8 years vs 61.2 ± 15.5 years). They were also more likely to receive vasopressor/inotropic support (74.6% vs 58.5%), and broad-spectrum antibiotics (70.3% vs 57.7%). Insurance status, ethnicity, religion, education, and salary did not lead to statistically significant changes in code status. CONCLUSIONS: In patients with cardiopulmonary arrest, code status change was more likely to be influenced by the presence of medical comorbidities and medical interventions during hospitalization rather than by socioeconomic factors.

Primary HPV-DNA screening in women under 30 years of age: health technology assessment / Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria

Background: Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed: Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy. Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods: Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results: Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions: The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Antecedentes: A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar: Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos: Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados: De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los criterios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones: El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

Pituitary Imaging Abnormalities and Related Endocrine Disorders in Erdheim-Chester Disease.

PURPOSE: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. METHODS: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans. We determined the frequency of various pituitary imaging abnormalities in ECD and assessed its relationships with age, sex, body mass index (BMI), BRAF V600E status, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), pituitary hormone deficits and number, diabetes insipidus (DI), and panhypopituitarism. RESULTS: Our cohort included 61 subjects with ECD [age (SD): 54.3 (10.9) y, 46 males/15 females]. API was present in 47.5% (29/61) of ECD subjects. Loss of the posterior pituitary bright spot (36.1%) followed by thickened pituitary stalk (24.6%), abnormal enhancement (18.0%), and pituitary atrophy (14.8%) were the most common abnormalities. DI and panhypopituitarism were more frequent in subjects with API without differences in age, sex distribution, hsCRP, ESR, and BRAF V600E status compared to normal pituitary imaging. CONCLUSIONS: We noted a high burden of API and endocrinopathies in ECD. API was highly associated with the presence of panhypopituitarism and DI. Therefore, a thorough assessment of hypothalamic-pituitary integrity should be considered in subjects with ECD.

Let's go fishing: A quantitative analysis of subsistence choices with a special focus on mixed economies among small-scale societies.

The transition to agriculture is regarded as a major turning point in human history. In the present contribution we propose to look at it through the lens of ethnographic data by means of a machine learning approach. More specifically, we analyse both the subsistence economies and the socioecological context of 1290 societies documented in the Ethnographic Atlas with a threefold purpose: (i) to better understand the variability and success of human economic choices; (ii) to assess the role of environmental settings in the configuration of the different subsistence economies; and (iii) to examine the relevance of fishing in the development of viable alternatives to cultivation. All data were extracted from the publicly available cross-cultural database D-PLACE. Our results suggest that not all subsistence combinations are viable, existing just a subset of successful economic choices that appear recurrently in specific ecological systems. The subsistence economies identified are classified as either primary or mixed economies in accordance with an information-entropy-based quantitative criterion that determines their degree of diversification. Remarkably, according to our results, mixed economies are not a marginal choice, as they constitute 25% of the cases in our data sample. In addition, fishing seems to be a key element in the configuration of mixed economies, as it is present across all of them.

Validación de la escala de convivencia con artrosis en la población española / Validation of the living with osteoarthritis in Spanish population

Objetivo: Presentar los resultados psicométricos de la escala de convivencia con artrosis (EC-Artrosis) en la población española. Diseño: Estudio observacional, multicéntrico y transversal, con retest en una fracción de la muestra. Emplazamiento: Centros públicos y privados de atención primaria y secundaria, así como asociaciones de pacientes con artrosis de Navarra, La Rioja, Madrid, Valencia y Málaga. Participantes: La muestra estuvo compuesta por un total de 291 pacientes con diagnóstico de artrosis por su médico, en cualquier estadio de la enfermedad de atención primaria o especializada, nacionalidad española, y no hospitalizados. Intervenciones: De manera adicional a la EC-Artrosis, se incluyó un cuestionario sociodemográfico y escalas para evaluar el apoyo social percibido por el paciente (DUFSS), la calidad de vida relacionada con la salud (WHOQOL-BREF) y la escala de satisfacción con la vida del paciente. Mediciones principales: Se analizaron las propiedades psicométricas de la escala EC-Artrosis, tales como viabilidad y aceptabilidad, fiabilidad (consistencia interna y estabilidad), precisión y validez de constructo (convergente, interna y para grupos conocidos). Resultados : El 100% de los datos fueron computados. La calidad de los datos y la aceptabilidad fueron excelentes. El alfa de Cronbach para el total de la escala fue de 0,87 y el índice de homogeneidad de 0,22. El ICC para el total de la escala fue de 0,88. En cuanto a la precisión, el valor del EEM fue de 5,18 (<½DE=7,47). Conclusiones: La EC-Artrosis ha mostrado ser un instrumento válido y fiable para evaluar la convivencia del paciente con artrosis a nivel nacional.(AU)

Objective: Present the psychometric results of the Living with Osteoarthritis (LW-OA) in Spanish population. Design: Observational, cross-sectional and multicenter study, with retest on a fraction of the sample. Location: Public and private centres of primary and secondary healthcare, as well as patient associations from Navarra, La Rioja, Madrid, Valencia and Malaga. Participants: The sample was composed by 291 patients with OA with a medical diagnosis in every stage of the disease from primary or secondary healthcare, Spanish nationality and not hospitalized. Interventions: In addition to LW-OA, a sociodemographic questionnaire was included, as well as scales to evaluate social support perceived from the patient (DUFSS), quality of life (WHOQOL-BREF) and satisfaction with life. Main measurements: Psychometric properties of the LW-OA were measured, as viability and acceptability, reliability (internal consistency and reproducibility), precision and construct validity (convergent, internal and known-groups). Results: 100% of the data were computable. Excellent data quality was obtained. Cronbach's alpha for the scale total was 0.87 and the homogeneity index 0.22. ICC for the scale total was 0.88. As for precision, the SEM was 5.18 (<½DE=7.47). Conclusions: The LW-OA is a valid and feasible measure to evaluate the process of living with OA in Spain.(AU)

[Validation of the living with osteoarthritis in Spanish population]. / Validación de la escala de convivencia con artrosis en la población española.

OBJECTIVE: Present the psychometric results of the Living with Osteoarthritis (LW-OA) in Spanish population. DESIGN: Observational, cross-sectional and multicenter study, with retest on a fraction of the sample. LOCATION: Public and private centres of primary and secondary healthcare, as well as patient associations from Navarra, La Rioja, Madrid, Valencia and Malaga. PARTICIPANTS: The sample was composed by 291 patients with OA with a medical diagnosis in every stage of the disease from primary or secondary healthcare, Spanish nationality and not hospitalized. INTERVENTIONS: In addition to LW-OA, a sociodemographic questionnaire was included, as well as scales to evaluate social support perceived from the patient (DUFSS), quality of life (WHOQOL-BREF) and satisfaction with life. MAIN MEASUREMENTS: Psychometric properties of the LW-OA were measured, as viability and acceptability, reliability (internal consistency and reproducibility), precision and construct validity (convergent, internal and known-groups). RESULTS: 100% of the data were computable. Excellent data quality was obtained. Cronbach's alpha for the scale total was 0.87 and the homogeneity index 0.22. ICC for the scale total was 0.88. As for precision, the SEM was 5.18 (<½DE=7.47). CONCLUSIONS: The LW-OA is a valid and feasible measure to evaluate the process of living with OA in Spain.

Enfermedad cerebrovascular en pacientes jóvenes: aspectos claves de la literatura / Cerebrovascular disease in young patients: key aspects of literature

RESUMEN La enfermedad cerebrovascular (ECV) es una patología con una alta tasa de morbimortalidad. Los adultos jóvenes, que se ubican entre las edades de 15 a 50 años, representan hasta el 15 % de los casos. Aparte de los factores de riesgo tradicionales, también se observan otros factores como: consumo de cannabis, cocaína y metanfetaminas. La ECV de origen isquémico sigue siendo el evento cerebrovascular más frecuente, sin embargo, el porcentaje del hemorrágico aumenta en comparación con el resto de la población adulta. Otras causas incluyen: malformaciones arteriovenosas, aneurismas, cardiopatía embolica, enfermedades autoinmunes, trombofilias, entre otras patologías. La clínica es muy variada, pudiendo cursar con síndrome piramidal caracterizado por hemiplejia o hemiparesia, alteraciones en la marcha, hiperreflexia, hipertonía e hipotrofia. Además, el paciente puede presentar afasia, crisis epilépticas y síndrome vestibular. Sin embargo, existen casos en los que no se evidencian factores de riesgo clásicos y el diagnóstico etiológico se vuelve un reto, haciendo necesario la realización de estudios más especializados en búsqueda de la patología de base desencadenante. El abordaje terapéutico siempre va a estar acompañado de la detección y el manejo de la causa desencadenante.

SUMMARY Cerebrovascular disease (CVD) is a pathology with a high morbidity and mortality rate. Young adults, who are between the ages of 15 and 50, account for up to 15 % of cases. Besides the traditional risk factors, other factors are also observed, such as: consumption of cannabis, cocaine and methamphetamines. CVD of ischemic origin continues to be the most frequent cerebrovascular event, however, the hemorrhagic percentage increases compared to the rest of the adult population. Other causes include: arterio-venous malformations, aneurysms, embolic heart disease, autoimmune diseases, thrombophilias, among other pathologies. The symptoms are very varied and can present with pyramidal syndrome characterized by hemiplegia or hemiparesis, gait disturbances, hyperreflexia, hypertonia and hypotrophy. In addition, the patient may present with aphasia, epileptic seizures, and vestibular syndrome. However, there are cases in which no classical risk factors and etiologic diagnosis is evident becomes a challenge, necessitating studies seeking more specialized pathology trigger base. The therapeutic approach will always be accompanied by the detection and management of the triggering cause.

Prevalence of Hypothyroidism in Patients With Erdheim-Chester Disease.

Importance: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated. Objective: To assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD. Design, Setting, and Participants: This cross-sectional study included 61 patients with ECD who were enrolled in a natural history study at a tertiary care center between January 2011 and December 2018. ECD was diagnosed on the basis of clinical, genetic, and histopathological features. Data were analyzed in March 2020. Exposure: Diagnosis of ECD. Main Outcomes and Measures: Main outcome was the prevalence of thyroid dysfunction in adults with ECD compared with community estimates. Patients underwent baseline evaluation with a thyroid function test, including thyrotropin, free thyroxine (fT4), and total thyroxine (T4), and sellar imaging with magnetic resonance imaging or computed tomography scan. The association of HPT dysfunction was assessed for differences in age, sex, body mass index, BRAF V600E status, high sensitivity C-reactive protein level, sellar imaging, and pituitary hormonal dysfunction. Results: A total of 61 patients with ECD (46 [75%] men; mean [SD] age, 54.3 [10.9] years) were evaluated. Seventeen patients (28%) had hypothyroidism requiring levothyroxine therapy. The prevalence of both central and primary hypothyroidism were higher than community estimates (central hypothyroidism: 9.8% vs 0.1%; odds ratio, 109.0; 95% CI, 37.4-260.6; P < .001; primary hypothyroidism: 18.0% vs 4.7%; OR, 4.4; 95% CI, 2.1-8.7; P < .001). Patients with hypothyroidism (both primary and central), compared with patients with euthyroidism, had higher body mass index (median [interquartile range] 31.4 [28.3-38.3] vs 26.7 [24.4-31.9]; P = .004) and a higher prevalence of panhypopituitarism (7 [47%] vs 3 [7%]; P < .001). Among patients with hypothyroidism, those with central hypothyroidism, compared with patients with primary hypothyroidism, had a lower mean (SD) body mass index (28.3 [2.6] vs 36.3 [5.9]; P = .007) and higher frequencies of abnormal sellar imaging (5 [83%] vs 3 [27%]; P = .050) and panhypopituitarism (5 [83%] vs 3 [27%]; P = .050). Conclusions and Relevance: In this cohort study, a higher prevalence of central and primary hypothyroidism was identified in patients with ECD compared with the community. There should be a low threshold for testing for hypothyroidism in patients with ECD, and treatment should follow standard guidelines.

Timpanoplastias: factores asociados al resultado anatómico y auditivo / Tympanoplasty: factors associated with anatomical and audiometric results

INTRODUCCIÓN: La timpanoplastia es una cirugía frecuente en otorrinolaringología. Su mayor indicación es la perforación timpánica, y con menor frecuencia la otitis adhesiva. Su objetivo primario o anatómico es restaurar la integridad timpánica, previniendo infecciones, y secundario o auditivo es preservar o mejorar la audición. MATERIAL Y MÉTODO: Estudio retrospectivo de los pacientes operados de timpanoplastia en nuestro hospital. Se registraron características biodemográficas, de la patología del oído, de la cirugía y se analizaron los resultados anatómicos y auditivos. RESULTADOS: Se incluyeron 182 pacientes, la mayoría de sexo femenino (57,1%), edad promedio de 36,1 años. La principal indicación fue la perforación timpánica (89,0%), seguida de otitis adhesiva (7,1%). La mayoría de las timpanoplastias correspondió a cirugía primaria (84,1%), tipo I (62,6%), por abordaje endoaural (83,5%) y técnica medial o Austin (90,1%). El injerto más utilizado fue el compuesto de cartílago-pericondrio (87,9%). El éxito anatómico fue 84,6% y el auditivo 66,8%. Los pacientes operados de miringoplastia (sin elevación de colgajo timpanomeatal) presentaron mejor resultado auditivo (p = 0,003). No se identificaron factores asociados a mejor resultado anatómico. CONCLUSIONES: Los resultados anatómicos y auditivos obtenidos son comparables a lo publicado en la literatura. Se requieren más estudios prospectivos para definir factores asociados a un mejor resultado anatómico y auditivo

INTRODUCTION: Tympanoplasty is a frequent surgery in otolaryngology. Its main indication is tympanic perforation, followed by adhesive otopathy. Its main and (or) anatomic objective is to restore the tympanic membrane's integrity, preventing infections, and its secondary or audiometric objective is to preserve or improve hearing. MATERIAL AND METHOD: Retrospective study of all patients submitted to tympanoplasty at our hospital. Biodemographic, ear pathology and surgery characteristics were registered, and anatomic and audiometric success rates were analyzed. RESULTS: A total of 182 patients were included, most female (57.1%), with average age of 36.1 years. The main surgical indication was tympanic perforation (89.0%), followed by adhesive otopathy (7.1%). Most tympanoplasties were primary surgeries (84.1%), type I (62.6%), performed by endoaural approach (83.5%) using medial or Austin technique (90.1%). Compound cartilage-perichondrium grafts were most frequently used (87.9%). The anatomic success rate was 84.6%, and the audiometric success rate was 66.8%. Patients who underwent myringoplasty (without raising of tympanomeatal flap) presented a better audiometric result (p = .003). No factors associated with better anatomical results were identified. CONCLUSIONS: Our anatomic and audiometric results are comparable to those previously published. Further prospective studies are required to define factors associated with improved anatomic and audiometric results

Tympanoplasty: factors associated with anatomical and audiometric results. / Timpanoplastias: factores asociados al resultado anatómico y auditivo.

INTRODUCTION: Tympanoplasty is a frequent surgery in otolaryngology. Its main indication is tympanic perforation, followed by adhesive otopathy. Its main and (or) anatomic objective is to restore the tympanic membrane's integrity, preventing infections, and its secondary or audiometric objective is to preserve or improve hearing. MATERIAL AND METHOD: Retrospective study of all patients submitted to tympanoplasty at our hospital. Biodemographic, ear pathology and surgery characteristics were registered, and anatomic and audiometric success rates were analyzed. RESULTS: A total of 182 patients were included, most female (57.1%), with average age of 36.1 years. The main surgical indication was tympanic perforation (89.0%), followed by adhesive otopathy (7.1%). Most tympanoplasties were primary surgeries (84.1%), type I (62.6%), performed by endoaural approach (83.5%) using medial or Austin technique (90.1%). Compound cartilage-perichondrium grafts were most frequently used (87.9%). The anatomic success rate was 84.6%, and the audiometric success rate was 66.8%. Patients who underwent myringoplasty (without raising of tympanomeatal flap) presented a better audiometric result (p=.003). No factors associated with better anatomical results were identified. CONCLUSIONS: Our anatomic and audiometric results are comparable to those previously published. Further prospective studies are required to define factors associated with improved anatomic and audiometric results.

Therapeutic Window of Clopidogrel and Ticagrelor in Patients With Critical Limb-Threatening Ischemia.

BACKGROUND: Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a "therapeutic window" (TW) of platelet inhibition. METHODS: Data from the "Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study" were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients' platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily. RESULTS: At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor (P < .0001). At steady state, 42% of patients on clopidogrel were within the TW compared to 10% of patients on ticagrelor (P < .0001). Patients on ticagrelor exhibited higher rates of LPR compared to those on clopidogrel at baseline as well as at steady state (baseline 88% vs 18%, steady state 88% vs 28%; P < .0001). CONCLUSION: Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.

Quantifying the relationship between food sharing practices and socio-ecological variables in small-scale societies: A cross-cultural multi-methodological approach.

This article presents a cross-cultural study of the relationship among the subsistence strategies, the environmental setting and the food sharing practices of 22 modern small-scale societies located in America (n = 18) and Siberia (n = 4). Ecological, geographical and economic variables of these societies were extracted from specialized literature and the publicly available D-PLACE database. The approach proposed comprises a variety of quantitative methods, ranging from exploratory techniques aimed at capturing relationships of any type between variables, to network theory and supervised-learning predictive modelling. Results provided by all techniques consistently show that the differences observed in food sharing practices across the sampled populations cannot be explained just by the differential distribution of ecological, geographical and economic variables. Food sharing has to be interpreted as a more complex cultural phenomenon, whose variation over time and space cannot be ascribed only to local adaptation.

Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2.

Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1) results in a systemic vasculitis known as deficiency of ADA2 (DADA2). Neutrophils and a subset of neutrophils known as low-density granulocytes (LDGs) have been implicated in the pathogenesis of vasculitis, at least in part, through the formation of neutrophil extracellular traps (NETs). The study objective was to determine whether neutrophils and NETs play a pathogenic role in DADA2. In vivo evidence demonstrated NETs and macrophages in affected gastrointestinal tissue from patients with DADA2. An abundance of circulating LDGs prone to spontaneous NET formation was observed during active disease in DADA2 and were significantly reduced after remission induction by anti-tumor necrosis factor (TNF) therapy. Increased circulating LDGs were identified in unaffected family members with monoallelic ADA2 mutations. Adenosine triggered NET formation, particularly in neutrophils from female patients, by engaging A1 and A3 adenosine receptors (ARs) and through reactive oxygen species- and peptidylarginine deiminase-dependent pathways. Adenosine-induced NET formation was inhibited by recombinant ADA2, A1/A3 AR antagonists, or by an A2A agonist. M1 macrophages incubated with NETs derived from patients with DADA2 released significantly greater amounts of TNF-α. Treatment with an A2AAR agonist decreased nuclear translocation of NF-κB and subsequent production of inflammatory cytokines in DADA2 monocyte-derived macrophages. These results suggest that neutrophils may play a pathogenic role in DADA2. Modulation of adenosine-mediated NET formation may contribute a novel and directed therapeutic approach in the treatment of DADA2 and potentially other inflammatory diseases.

Hunter-gatherer mobility and technological landscapes in southernmost South America: a statistical learning approach.

The present work aims to quantitatively explore and understand the relationship between mobility types (nautical versus pedestrian), specific technological traits and shared technological knowledge in pedestrian hunter-gatherer and nautical hunter-fisher-gatherer societies from the southernmost portion of South America. To that end, advanced statistical learning techniques are used: state-of-the-art classification algorithms and variable importance analyses. Results show a strong relationship between technological knowledge, traits and mobility types. Occupations can be accurately classified into nautical and pedestrian due to the existence of a non-trivial pattern between mobility and a relatively small fraction of variables from some specific technological categories. Cases where the best-fitted classification algorithm fails to generalize are found significantly interesting. These instances can unveil lack of information, not enough entries in the training set, singular features or ambiguity, the latter case being a possible indicator of the interaction between nautical and pedestrian societies.