Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Bicarbonate Values for Healthy Residents Living in Cities Above 1500 Meters of Altitude: A Theoretical Model and Systematic Review.

Ramirez-Sandoval, Juan C., Maria F. Castilla-Peón, José Gotés-Palazuelos, Juan C. Vázquez-García, Michael P. Wagner, Carlos A. Merelo-Arias, Olynka Vega-Vega, Rodolfo Rincón-Pedrero, and Ricardo Correa-Rotter. Bicarbonate values for healthy residents living in cities above 1500 m of altitude: a theoretical model and systematic review. High Alt Med Biol. 17:85-92, 2016.-Plasma bicarbonate (HCO3(-)) concentration is the main value used to assess the metabolic component of the acid-base status. There is limited information regarding plasma HCO3(-) values adjusted for altitude for people living in cities at high altitude defined as 1500 m (4921 ft) or more above sea level. Our aim was to estimate the plasma HCO3(-) concentration in residents of cities at these altitudes using a theoretical model and compare these values with HCO3(-) values found on a systematic review, and with those venous CO2 values obtained in a sample of 633 healthy individuals living at an altitude of 2240 m (7350 ft). We calculated the PCO2 using linear regression models and calculated plasma HCO3(-) according to the Henderson-Hasselbalch equation. Results show that HCO3(-) concentration falls as the altitude of the cities increase. For each 1000 m of altitude above sea level, HCO3(-) decreases to 0.55 and 1.5 mEq/L in subjects living at sea level with acute exposure to altitude and in subjects acclimatized to altitude, respectively. Estimated HCO3(-) values from the theoretical model were not different to HCO3(-) values found in publications of a systematic review or with venous total CO2 measurements in our sample. Altitude has to be taken into consideration in the calculation of HCO3(-) concentrations in cities above 1500 m to avoid an overdiagnosis of acid-base disorders in a given individual.

Embolia grasa: un síndrome clínico complejo / Fat embolism: a complex clinic syndrome

La embolia grasa describe la presencia de grasa en la circulación sanguínea asociada o no, al desarrollo de un síndrome de severidad variable e identificable por sus signos y síntomas. Puede ser secundaria a traumatismos, incluyendo cirugía ortopédica y estética, y a causas no traumáticas. Se han descrito diversas teorías para explicar el origen del émbolo y las manifestaciones sistémicas como la intravasación, la lipasay los ácidos grasos libres, la embolia grasa de origen no traumático, la del choque y la coagulación. Las manifestaciones clínicas dependen del órgano o sistema afectado, habitualmente del aparato respiratorio, sistema nervioso central y hematológico. El diagnóstico se puede hacer mediante los criterios clínicos de Gurd y/o Lindeque. La determinación de grasa en sangre y orina carecen de sensibilidad, y la identificación de macrófagos alveolares con grasa depende de una muestra adecuada de lavado broncoalveolar; la tomografía de alta resolución y la resonancia magnética nuclear son promisorias para demostrar la entidad. El tratamiento es de soporte y no específico. El uso de esteroides ha producido disminución de la mortalidad en la mayoría de estudios, pero si se requiere de ventilación mecánica, la mortalidad en la mayoría se incrementa. En cirugía ortopédica y traumatología es posible prevenir el evento, y en general, evitando la hipoxemia, hipotnesión y la deshidratación perioperatoria y postraumática.

Fat embolism (FE) describes the presence of fat globules in the circulation. It may be associated with a clinical syndrome (FES) that can be readily identified by its signs and symptoms. It may follow traumatic events such as orthopedic or cosmetic surgery, or non-traumatic events. Diverse theories try to explain the origin of FE and the FES, such as intravasation, Upase and free fatty acids, FE of non-traumatic origin, and one of shock and coagulation. The clinical manifestations vary from mild to severe and include the respiratory, central nervous, dermatologic and hematologic systems. Diagnosis may be established following Gurd and/or Lindeque's clinical criteria. Fat determination in blood and urine lacks sensitivity; bronchoalveolar lavage to determine the presence of fat depends on an adequate sample of alveolar macrophages. High resolution thoracic tomography and nuclear magnetic resonance of the brain can be helpful. Treatment is only palliative and non-specific. In most studies, steroids have decreased mortality, but if ventilatory support is needed, the mortality rate increases. Prevention is possible during orthopedic and trauma surgery; hypoxemia, hypotension, and perioperative and post-traumatic dehydration should be avoided.