RESUMEN
This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery. Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19. Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses. At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk. Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy(mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness. We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.
RESUMEN
The comparative absorption of zinc after oral administration of three different complexed forms was studied in 15 healthy human volunteers in a double-blind four-period crossover trial. The individuals were randomly divided into four groups. Each group rotated for four week periods through a random sequence of oral supplementation including: zinc picolinate, zinc citrate, and zinc gluconate (equivalent to 50 mg elemental zinc per day) and placebo. Zinc was measured in hair, urine, erythrocyte and serum before and after each period. At the end of four weeks hair, urine and erythrocyte zinc levels rose significantly (p less than 0.005, p less than 0.001, and p less than 0.001) during zinc picolinate administration. There was no significant change in any of these parameters from zinc gluconate, zinc citrate or placebo administration. There was a small, insignificant rise in serum zinc during zinc picolinate, zinc citrate and placebo supplementation. The results of this study suggest that zinc absorption in humans can be improved by complexing zinc with picolinic acid.
Asunto(s)
Citratos/metabolismo , Gluconatos/metabolismo , Ácidos Picolínicos/metabolismo , Zinc/metabolismo , Administración Oral , Adulto , Citratos/administración & dosificación , Ácido Cítrico , Método Doble Ciego , Eritrocitos/análisis , Gluconatos/administración & dosificación , Cabello/análisis , Humanos , Absorción Intestinal , Ácidos Picolínicos/administración & dosificación , Distribución Aleatoria , Distribución Tisular , Orina/análisis , Zinc/administración & dosificaciónRESUMEN
Thrombophlebitis leading to pulmonary embolism has been stated to cause as many as 9% of hospital deaths. Its diagnosis, sites of common occurrence, treatment and immediate sequelae have long been controversial subjects. A prospective study of thrombophlebitis was set up to evaluate these problems. One hundred and sixty-six patients diagnosed clinically as having thrombophlebitis or pulnmonary embolus were studied with the ultrasonic flow detector (doppler). To assess the stated accuracy of this instrument, venograms were done when possible. The doppler proved in this series to be 93% accurate as compared to venography which is comparable to other series. Pulmonary scans and angiograms were obtained from patients suspected of having pulmonary emboli. Results were as follows: 1) Of 113 patients suspected of having thrombophlebitis clinically, only 26 (23%) of the cases were confirmed by doppler; 2) Of 53 patients suspected of having pulmonary embolus clinically, only 18 (34%) had confirmation by scan, angiogram or doppler; 3) Of 39 patients in this series who had thrombophlebitis, 11 (23%) were not suspected of having lower extremity venous disease until pulmonary embolus occurred, 4) Calf vein thrombosis without additional proximal occlusion was present in only 10% of cases; and 5) Thirty per cent of doppler or venographically proven cases of thrombophlebitis occurred after orthopedic injuries or operations. It was concluded that physical examination alone was grossly inaccurate in determining the recurrence of lower extremity thrombosis. In fact physical examination alone appeared to select out for treatment large numbers of patients without venous disease while a significant number of patients with thrombophlebitis remained clinically asymptomatic until pulmonary embolism occurred. Most deep venous disease was found in the larger veins above the knee, explaining the paucity of diagnostic symptoms in these individuals. The ultrasonic flow detector was found to be an extremely accurate, simple and rapid bedside test that could be applied daily to the high risk groups. The appearance of thrombosis could then be treated with heparin with excellent prospects of preventing occurrence of pulmonary embolus.