Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS. RESEARCH QUESTION: Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity? STUDY DESIGN AND METHODS: Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange. RESULTS: Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo2 increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs -40.2 ± 21.3 mL/min; P < .05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak vs rest Vo2 (25.9 ± 15.3 mL/min vs -60.8 ± 25.6 mL/min; P < .01), cardiac output (-0.2 ± 0.6 L/min vs -1.9 ± 0.6 L/min; P < .05), and right atrial pressure (1.0 ± 0.5 mm Hg vs -0.6 ± 0.5 mm Hg; P < .05) were greater in the pyridostigmine group compared with placebo. INTERPRETATION: Pyridostigmine improves peak Vo2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo2, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03674541; URL: www. CLINICALTRIALS: gov.

Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Right ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known. RESEARCH QUESTION: The goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF. STUDY DESIGN AND METHODS: This study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance. RESULTS: Both HFpEF groups experienced decreased peak VO2 (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO2 compared with female patients (58 ± 16% vs 70 ± 15%; P < .05). Male patients with HFpEF had a more pronounced increase in RV afterload, Ea (1.8 ± 0.6 mm Hg/mL/m2 vs 1.3 ± 0.4 mm Hg/mL/m2; P < .05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs 1.2 ± 0.4; P < .05) and subsequent reduced stroke volume index augmentation. In contrast, female patients with HFpEF were able to augment RV contractility in the face of increasing afterload, preserving RV-PA coupling during exercise. INTERPRETATION: Male patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO2 compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO2 compared with male patients with HFpEF.

Caracterización de infecciones por bacterias productoras de BLEE en un hospital de referencia nacional / Characterization of ESBL-producing bacteria infections on a national referral hospital

La resistencia mediante la producción de betalactamasa de espectro extendido (BLEE) es la resistencia microbiana más común y de importancia en salud pública. Objetivos: Describir las características de las infecciones por bacterias productoras de BLEE en un hospital de referencia nacional. Diseño: Estudio transversal descriptivo. Lugar: Hospital Nacional Daniel Alcides Carrión, Callao, Perú. Materiales: Registros de los cultivos de secreciones realizados en el Laboratorio de Microbiología del HNDAC en el año 2012. Métodos: Se analizó datos del paciente (edad, sexo y servicio del cual se recibió la muestra) y datos de la muestra (fecha de obtención, el tipo de muestra, el microrganismo encontrado, el antibiograma detallado y su calificación como bacteria productora de BLEE). Principales medidas de resultados: Características de las infecciones por bacterias productoras de BLEE. Resultados: Se recolectó 3 149 muestras, 70,9 por ciento (2 235) fueron de mujeres; 29,4 por ciento fueron cultivos positivos para bacterias productoras de BLEE. Los servicios críticos obtuvieron la mayor prevalencia, y los meses donde se encontró mayor presencia fueron abril (34,7 por ciento) y julio (34,7 por ciento). Tanto E. coli (72,4 por ciento) como Klebsiella sp. (20 por ciento) fueron las prevalentes. No se encontró resistencia para imipinem, tanto para E. coli como para Klebsiella sp. Conclusiones: La prevalencia fue similar a la de América Latina (34,6 por ciento). Se presenta más evidencias de una alta presencia en consulta externa y en mayores de 46 años; siendo así un problema de salud pública...

Resistance by extended-spectrum beta-lactamase (ESBL) is the most common antimicrobial resistance and of public health importance. Objectives: To describe ESBL producing bacteria characteristics in a national reference hospital. Design: Cross sectional, descriptive study. Setting: Hospital Nacional Daniel Alcides Carrión, Callao, Peru. Materials: Records of secretion cultures done in the hospital Laboratory of Microbiology during 2012. Methods: Patient data (age, sex and service from which the sample was received) and sample data (date of collection, sample type, microorganism found, sensitivity and detailed classification as ESBLproducing bacteria) were analyzed. Main outcome measures: Characteristics of infections by ESBL-producing bacterias. Results: Study included 3 149 samples, 70.9 per cent (2 235) from female patients; 29.4 per cent were cultures positive for ESBL-producing bacteria. Critical services had the highest prevalence, and months with highest occurrence were April (34.7 per cent) and July (34.7 per cent). Both, E. coli (72.4 per cent) and Klebsiella sp. (20.0 per cent) were the most prevalent. No imipinem resistance was found for E. coli or Klebsiella sp. Conclusions: The prevalence was similar to that of Latin America (34.6 per cent). More evidence of high prevalence in outpatients and patients over 46 year-old is presented, considering it a public health problem...