To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory ...flows in endotoxic shock.
Animal experimental study.
University translational research laboratory.
Fifteen Landrace pigs.
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
Hypotension was significantly shorter in i-NE group (7.5 min 5.5-22.0 min vs 49.3 min 29.5-60.0 min; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
Derangements of microvascular blood flow distribution might contribute to disturbing O
extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O
extraction ...ratio (Formula: see text) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg
·min
) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in Formula: see text in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas Formula: see text exhibited a corresponding significant decrease (repeated-measures ANOVA,
= 0.02 and
= 0.04 for time × group interactions and intergroup differences for villi-PPV and Formula: see text, respectively). Variations in villi-PPV were paralleled by variations in Formula: see text (
= 0.88,
< 0.001) and these, in turn, by mesenteric lactate changes (
= 0.86,
< 0.001). There were no significant differences in cardiac output and systemic O
delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O
extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O
uptake during development and resuscitation from septic shock.
Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O
extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O
uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O
consumption.
Introducción. El trauma es reconocido como una epidemia global que varía según las regiones donde se presenta. Una parte de la carga de la enfermedad está determinada por los años perdidos de vida ...potencial, la cual es una estimación de amplio uso para la vigilancia en salud pública; sin embargo, existe poca información disponible en relación a esto. El objetivo de este estudio fue determinar la tendencia de los años perdidos de vida potencial por el trauma en un período de nueve años. Métodos. La información se obtuvo del Instituto Nacional de Medicina Legal y Ciencias Forenses en un período de nueve años (2007-2015). La población de referencia se determinó con base en las proyecciones del Departamento Administrativo Nacional de Estadística, que indicaron una expectativa de vida de 75 años. Resultados. En el 2015, a las lesiones por traumatismos en Colombia les correspondieron 1.920,7 años perdidos de vida potencial por cada 100.000 personas. Durante el período de estudio, las principales causas fueron los homicidios (rango, 51 a 68 %) y los accidentes de tránsito (rango, 19 a 28 %); la relación entre hombres y mujeres fue de 7:1, y la tendencia estadística fue hacia la disminución de los años perdidos de vida potencial. Conclusiones. Los homicidios siguen aportando el mayor número de lesiones por trauma y años perdidos de vida potencial. Los hombres jóvenes continuaron siendo la población mayormente afectada. Se conceptúa la necesidad de incrementar los esfuerzos para mejorar la vigilancia en salud pública y ahondar en las intervenciones oportunas relacionadas con el trauma.
Tratamiento Conservador de Heridas de la Hipofaringe Patricia Yugueros Izquierdo; Juan Manuel Sarmiento M.; Alberto F. García Marín
Revista colombiana de cirugía,
11/2021, Letnik:
9, Številka:
3
Journal Article
Odprti dostop
Se adelantó un trabajo de observación clínica iniciado en 1990 en el Hospital Universitario del Valle, sobre el comportamiento y el subsiguiente tratamiento de las heridas de la hipofaringe, ...ocasionadas con arma de fuego y arma blanca. El propósito del estudio fue el de demostrar la conveniencia de no operar e instaurar un tratamiento conservador de tales heridas traumáticas de la hipofaringe. La investigación incluyó 68 pacientes con lesiones traumáticas comprobadas de la orohipofaringe y el esófago cervical, de los cuales 49 (72%) fueron tratados quirúrgicamente en forma obligatoria, y 19 (28%) recibieron tratamiento conservador, no quirúrgico, en cuya evolución clínica, como era obvio, hubo mucho menos morbilidad que la observada en el grupo sometido a cirugía. Mediate un completo examen clínico y paraclínico asociado a un juicioso criterio, el cirujano debe ser capaz de discernir sobre cuándo no se debe operar un paciente con este tipo de lesiones cervicales.
Generalidades. Desde diciembre de 2019 se detectó una nueva infección respiratoria, causada por el virus denominado SARS-CoV-2, decretada posteriormente como pandemia, lo cual ha exigido al personal ...de salud replantear la forma de prestar sus servicios en salud y garantizar la auto-protección con recursos que han sido insuficientes incluso en los países más desarrollados.
Dado que la transmisión del SARS-CoV-2 ocurre a través de aerosoles expulsados de la vía aérea, que pueden ser inhalados o llevados a las mucosas por contacto con las manos contaminadas, se requiere minimizar la posibilidad de contagio para los equipos de atención en salud.
Objetivos. Brindar herramientas a los cirujanos que les permitan elegir la técnica con menor probabilidad de exposición a aerosoles. Describir el paso a paso de la técnica quirúrgica de la traqueostomía percutánea, enfatizando en el control sobre la generación de aerosoles en pasos críticos.
Aspectos técnicos. La técnica completamente percutánea con kit de traqueostomía permite un mejor sello entre tejidos y dispositivos. Los escenarios más frecuentes para realizar una traqueostomía son: el paciente intubado con ventilación mecánica y el paciente con falla en la intubación que requiere una intervención de emergencia.
Conclusión. El alto contagio del COVID-19 al practicar intervenciones en la vía aérea nos obliga a hacer énfasis en las estrategias que reduzcan la formación de aerosoles y permitan la contención de los mismos durante la realización de traqueostomías.
Background and purpose
The aim of this study was to describe the frequency and distribution of SOD1 mutations in Spain, and to explore factors contributing to their phenotype and prognosis.
Methods
...Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers.
Results
In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all five exons of SOD1, including seven novel mutations. A total of 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. The frequency of this mutation varied considerably among regions, due to founder events. The most frequent mutation was p.Gly38Arg (n = 58), followed by p.Glu22Gly (n = 11), p.Asn140His (n = 10), and the novel p.Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (expEstimate = 1.03 0.01, 0.05, p = 0.001) and poorer survival (hazard ratio 1.05 1.01, 1.08, p = 0.007), regardless of the underlying mutation. Female sex was independently associated with faster disease progression (expEstimate = 2.1 1.23, 3.65, p = 0.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs. 301 months).
Conclusions
These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments.
Epithelial repair and regeneration are driven by collective cell migration and division. Both cellular functions involve tightly controlled mechanical events, but how physical forces regulate cell ...division in migrating epithelia is largely unknown. Here we show that cells dividing in the migrating zebrafish epicardium exert large cell-extracellular matrix (ECM) forces during cytokinesis. These forces point towards the division axis and are exerted through focal adhesions that connect the cytokinetic ring to the underlying ECM. When subjected to high loading rates, these cytokinetic focal adhesions prevent closure of the contractile ring, leading to multi-nucleation through cytokinetic failure. By combining a clutch model with experiments on substrates of different rigidity, ECM composition and ligand density, we show that failed cytokinesis is triggered by adhesion reinforcement downstream of increased myosin density. The mechanical interaction between the cytokinetic ring and the ECM thus provides a mechanism for the regulation of cell division and polyploidy that may have implications in regeneration and cancer.
Objectives Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk ...of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.
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