Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

Tadalafil: protective action against the development of multiple organ failure syndrome

Abstract Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

Effects of statins on the development of sepsis and organ dysfunction in hospitalized older patients in China

ABSTRACT This study aimed to evaluate the protective role of statins on the development of sepsis and infection-related organ dysfunction and mortality in a hospitalized older Chinese population with bacterial infections. In this retrospective cohort study, 257 older patients with bacterial infection were divided into two groups: a statin group, those who had received statin therapy for ≥1 month before admission and continued receiving statin during hospitalization; and a non-statin group, those who had never received statin or used statin for <1 month prior to admission. A multivariate logistic regression analysis was performed to identify risk and protective factors for severe sepsis. A significantly lower incidence of organ dysfunction was found in the statin group, as compared with the non-statin group (13.3% vs 31.1%, respectively; p = 0.002), corresponding to adjusted rates ratio of 0.32 (95% confidence interval [CI], 0.13-0.75; p = 0.009). No significant difference was found between statin and non-statin groups in 30-day sepsis-related mortality (4.4% vs 10.2%, respectively; p = 0.109), incidence of intensive care unit admission (13.3% vs 16.8%, respectively; p = 0.469), or length of hospital stay (20.5 vs 25.9 days, respectively; p = 0.61). Statins significantly reduced the development of sepsis and infection-related organ dysfunction in hospitalized older Chinese patients but did not reduce 30-day mortality, ICU admission incidence, or length of hospital stay.

Toma de medición intraabdominal a personas en estado crítico, por el profesional de enfermería / Taking measurement intraabdominal people in critical condition, by the nursing professional", "_e": "n

El aumento de la presión dentro de la cavidad abdominal se asocia a múltiples alteraciones fisiopatológicas, con una importante repercusión en aparatos y sistemas originando disfunción orgánica múltiple, lo que conlleva a un incremento en la morbimortalidad en pacientes en estado crítico, la medición de presión intraabdominal es un procedimiento que se está realizando con mayor frecuencia en las Unidades de Cuidados Intensivos, en donde los profesionales de enfermería tienen un papel muy importante en la toma e identificación de posibles complicaciones que ponen en riesgo la vida del paciente. La siguiente revisión tiene la finalidad de difundir el conocimiento y dar a conocer la importancia e intervenciones de enfermería en la medición de la presión intraabdominal.

The increase in the pressure inside the abdominal cavity is associated with multiple pathophysiological changes, with a significant impact in systems causing multiple organic dysfunction, leading to increased the morbidity and mortality in critically ill patients, the measurement of intra-abdominal pressure is a procedure that is being performed more frequently in the intensive care units, where nurses have an important role in taking and identifying possible complications that endanger the patient’s life. The following review has the purpose of disseminate knowledge and explain the importance and the nursing interventions in measuring intra-abdominal pressure.

Síndrome compartimental abdominal / Abdominal compartment syndrome

Desde el siglo XIX se conocen los efectos negativos del aumento de la presión intraabdominal, pero no se le prestó la debida atención a este trastorno hasta la última década del pasado siglo y la primera del actual. En este artículo exponemos las definiciones de los términos presión intrabdominal, hipertensión intrabdominal y síndrome compartimental abdominal, que fueron tomadas por consenso y aprobadas por la World Society of the Abdominal Compartment Syndrome. En nuestro medio, para el diagnóstico de la hipertensión intrabdominal y del síndrome compartimental abdominal se requiere medir la presión intrabdominal, secundariamente la presión de perfusión abdominal y se deben correlacionar estos datos con signos de deterioro clínico en el paciente. Las medidas terapéuticas médicas en relación con el síndrome compartimental abdominal son limitadas; cuando este es sintomático la descompresión abdominal es el tratamiento ya establecido. Enfatizamos en que el diagnóstico temprano de la hipertensión intrabdominal y del síndrome compartimental abdominal contribuyen a disminuir el desarrollo de un síndrome de disfunción múltiple de órganos y por tanto a reducir la mortalidad en estos pacientes. Con el objetivo de actualizar los conocimientos sobre hipertensión intrabdominal y síndrome compartimental abdominal, su diagnóstico y tratamiento, realizamos una minuciosa revisión actualizada de diversos artículos referentes al síndrome compartimental abdominal, tanto en el ámbito nacional como internacional(AU)

The negative effects of increased intra-abdominal pressure are known since the XIX Century, but attention was not paid to this disorder until the last decade of the last century and the first decade of the present one. In this article, we state the definitions of the terms intra-abdominal pressure, intra-abdominal hypertension, and abdominal compartment syndrome which were taken with consent and approved by the World Society of the Abdominal Compartment Syndrome. In our field, to get to a diagnosis of intra-abdominal hypertension and abdominal compartment syndrome, it is required to measure the intra-abdominal pressure and secondarily, the abdominal perfusion pressure; then, these data should be correlated with the signs of clinical deterioration of the patient. The medical therapeutic measures related to the abdominal compartment syndrome are limited, and when it is symptomatic, abdominal decompression is the established treatment. We want to make emphasis on the fact that the early diagnosis of intra-abdominal hypertension and abdominal compartment syndrome contribute to diminish the development of a multiple organ dysfunction syndrome, hence reducing mortality in these patients. With the aim of updating knowledge about intra-abdominal hypertension and abdominal compartment syndrome as well as their diagnosis and treatment, we carried out a detailed updated review of different articles regarding the abdominal compartment syndrome from both national and international scopes(AU)

Vasopressin and septic shock

Septic shock continues to be one of the leading causes of death in the Intensive Care Units. When the shock state persists after adequate fluid resuscitation, vasopressor therapy is required to improve and maintain adequate tissue/organ perfusion in an attempt to improve survival and prevent the development of multiple organ dysfunction and failure. Various studies have suggested that exogenous administration of arginine vasopressin may be an effective adjunctive therapy to traditional catecholamines for the management of hypotension during septic shock. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, gastrointestinal and thermoregulatory effects, and is an adrenocorticotropic hormone secretagogue. Vasopressin is released from the axonal terminals of magnocellular neurons in the hypothalamus. Vasopressin mediates vasoconstriction via VI-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels. Current guidelines from the Surviving Sepsis Campaign recommend arginine vasopressin 0.03 unit/minute may be added to norepinephrine with the anticipation of an effect equal to higher doses of norepinephrine alone. Clinicians must be knowledgeable about the use of vasopressin in septic shock, including controversial areas where guidelines do not always provide solid recommendations

Daño pulmonar inducido por ventilación mecánica y estrategia ventilatoria convencional protectora / Pulmonary damage produced by mechanical ventilation and conventional protective ventilatory strategy

Sólo muchos años después de la descripción inicial del Síndrome de Distress Respiratorio Agudo (SDRA), se reconoce a éste como una enfermedad profundamente heterogénea y con un volumen pulmonar pequeño, siendo este pulmón con escasa capacidad de aireación (baby lung), el que da cuenta del daño inducido por ventilación mecánica (DIVM). La evidencia disponible apunta a que la injuria mecánica es la principal responsable del DIVM, así como también, su amplificación biológica a distancia. La aplicación cíclica de presiones transpulmonares que excedan la capacidad de inflación pulmonar pueden dañar la barrera epitelio-alveolar, especialmente en ausencia de una PEEP adecuada para mantener abierta las unidades alveolares mecánicamente inestables. Mientras no se cuente con terapias que puedan interferir y modular eficientemente la cascada de eventos biológicos gatillados, la única herramienta disponible para limitar su desarrollo es la administración cautelosa de la ventilación mecánica. Este tratamiento juicioso resultará en una menor tensión (stress) y elongación (strain) del parénquima pulmonar, y un consecuente menor impacto biológico. Así entonces, el principal mensaje es que la forma en que ventilamos a nuestros pacientes es crucial para su pronóstico, tratando de minimizar el DIVM, el cual comienza al momento de ventilar al paciente. En la presente comunicación pretendemos revisar conceptos básicos, aspectos anátomo-funcionales de este fenómeno mecánico y sus consecuencias biológicas, y actualizar intervenciones clínicas que nos permitan atenuar el impacto del soporte ventilatorio.

Metanálise sobre o uso de glicocorticóides pré-operatório para redução do risco de complicações após esofagectomia por carcinoma do esôfago / Use of preoperative glucocorticoid to risk reduction of complications after esophagectomy by esophagus carcinoma: meta-analysis

JUSTIFICATIVA E OBJETIVOS: O emprego de glicocorticóides tem sido proposto para reduzir a morbidade após intervenções cirúrgicas, porém, não é largamente utilizado antes da ressecção do esôfago porque não existem conhecimentos suficientes sobre a sua eficácia. O objetivo do trabalho foi verificar os efeitos da administração pré-operatória de glicocorticóides, em pacientes submetidos à esofagectomia por carcinoma de esôfago. MÉTODO: As fontes utilizadas foram: Medline, Embase, Cancerlit, Scielo, Base de Dados de Ensaios Clínicos Controlados da Colaboração Cochrane e busca manual de referências. O término da pesquisa ocorreu em dezembro de 2005. Foram pesquisados estudos aleatórios de pacientes com carcinoma esofágico, em que se compararam glicocorticóides com placebo, administrados antes das esofagectomias. Os dados foram coletados pelos mesmos revisores e a qualidade dos estudos foi avaliada usando-se o escore de Jadad. A metanálise foi realizada utilizando-se a razão de chances - odds ratio- (intervalos de confiança - IC - de 95 por cento) entre tratamento e placebo e um modelo de risco relativo baseado no teorema de Bayes. RESULTADOS: Quatro estudos envolvendo 169 pacientes foram localizados. Não ocorreram diferenças na mortalidade pós-operatória e nas incidências de deiscência de anastomose e insuficiências renal e hepática entre glicocorticóides e placebo. Houve decréscimo na incidência de complicações respiratórias pós-operatórias (95 por cento IC = 0,09-0,46) , sepse (95 por cento IC = 0,10-0,81) e no total de complicações pós-operatórias (95 por cento IC = 0,06-0,23) no grupo tratado com glicocorticóides. CONCLUSÕES: A administração pré-operatória de glicocorticóides foi associada com um decréscimo nas complicações pós-operatórias.

BACKGROUND AND OBJECTIVES: Preoperative glucocorticoid administration has been proposed for reducing postoperative morbidity. This is not widely used before esophageal resection because of incomplete knowledge regarding its effectiveness. The aim here was to assess the effects of preoperative glucocorticoid administration in adults undergoing esophageal resection for esophageal carcinoma. METHODS: Studies were identified by searching the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CancerLit, SCIELO and Cochrane Library, and by manual searching from relevant articles. The last search for clinical trials for this systematic review was performed in December 2005. This review included randomized studies of patients with potentially resectable carcinomas of the esophagus that compared preoperative glucocorticoid administration with placebo. Data were extracted by the reviewer, and the trial quality was assessed using Jadad scoring. Odds ratio with 95 percent confidence limits and bayesian relative risk were used to assess the significance of the difference between the treatment arms. RESULTS: Four randomized trials involving 169 patients were found. There were no differences in postoperative mortality, anastomotic leakage, hepatic and renal failure between the glucocorticoid and placebo groups. There were fewer postoperative respiratory complications (95 percent CI = 0.09-0.46), sepsis (95 percent CI = 0.10-0.81), and total postoperative complications (95 percent CI = 0.06-0.23) with preoperative glucocorticoid administration. CONCLUSIONS: Prophylactic administration of glucocorticoids is associated with decreased postoperative complications.

Efficacy of species specific anti-scorpion venom serum (AScVS) against severe, serious scorpion stings (Mesobuthus tamulus concanesis Pocock)--an experience from rural hospital in western Maharashtra.

BACKGROUND: Death caused by scorpion envenoming is a common event in the tropical and subtropical countries including many regions in India. Severe scorpion envenoming causes an autonomic storm producing multi-system organ-failure (MSOF) and death. OBJECTIVES: To determine the efficacy of Anti-scorpion venom serum (AScVS) in patients stung by scorpions (Mesobuthus tamulus concanesis Pocock--earlier called Buthus tamulus); to compare it with other modalities of therapy and to detect complications, if any, arising out of AScVS treatment. METHODS: Total 48 patients of severe, serious scorpion envenoming syndrome were studied during the period from 1992 to 2002. In 17 patients AScVS was the only mode of treatment. Others had received adjunctive therapy along with AScVS. RESULTS: 47 patients out of 48 scorpion sting victims recovered completely. Recovery period in patients given AScVS (10 hours) was faster than those who received alpha blockers (16-42 hours). No anaphylactic reaction with AScVS was observed. CONCLUSIONS: AScVS is effective and safe method of therapy in severe scorpion envenoming syndrome.

Perioperative glucocorticoid administration for prevention of systemic organ failure in patients undergoing esophageal resection for esophageal carcinoma

CONTEXTO E OBJETIVO: A administração de glicocorticóides tem sido proposta para reduzir a morbidade após operações, porém, não é largamente usada antes da ressecção do esôfago devido ao fato de não haver ainda conhecimentos suficientes sobre sua eficácia. O objetivo do trabalho é verificar os efeitos da administração pré-operatória de glicocorticóides em pacientes submetidos a esofagectomia por carcinoma de esôfago. ESTRATÉGIA DE PESQUISA: As fontes utilizadas foram: Medline, Embase, Cancerlit, SciELO, Base de Dados de Ensaios Clínicos Controlados da Colaboração Cochrane e busca manual de referências. O término da pesquisa ocorreu em dezembro de 2004. CRITÉRIOS DE SELEÇÃO: Estudos randomizados de pacientes com carcinoma esofágico que compararam glicocorticóide com placebo administrados antes das esofagectomias. ANÁLISE E COLETA DE DADOS: Os dados foram coletados pelos mesmos revisores e a qualidade dos estudos foi avaliada usando-se o escore de Jadad. A metanálise foi realizada utilizando-se o risco relativo e diferença de média ponderada entre tratamento e placebo (intervalos de confiança de 95%). RESULTADOS: Quatro ensaios envolvendo 146 pacientes foram localizados. Não ocorreram diferenças na mortalidade pós-operatória e nas incidências de sepse, deiscência de anastomose e insuficiências renal e hepática entre glicocorticóide e placebo. Houve decréscimo na incidência de complicações respiratórias pós-operatórias (p = 0,005), múltiplas complicações (p = 0,004) e níveis plasmáticos de interleucina-6 (p = 0,00001) nos pacientes que receberam glicocorticóide pré-operatório. Houve incremento na relação PaO2/FiO2 pós-operatória (p = 0,0001) no grupo que recebeu glicocorticóide pré-operatório. CONCLUSÃO: A administração pré-operatória de glicocorticóide foi associada com um decréscimo nas complicações pós-operatórias.

Nutriçäo e sepse / Nutrition and sepsis

A resposta neuroendócrina ao trauma e à sepse leva a um estado de hipermetabolismo e alteraçöes metabólicas que em princípio visam a proteçäo e o restabelecimento das principais funçöes orgânicas, mas que tardiamente podem estar associadas à instalaçäo adicional da síndrome de insuficiência orgânica múltipla. O aporte nutricional tem papel importante, mas näo suficiente, na prevençäo dessa síndrome (ou restriçäo do número de órgäos e sistemas atingidos), através do fornecimento de substratos energéticos específicos, necessários à cicatrizaçäo, reparo, manutençäo das funçöes musculoesqueléticas e hepáticas e prevençäo de distúrbios gastrointestinais. Este artigo tem por objetivo fazer uma revisäo dos estudos realizados sobre o binômio nutriçäo/sepse

Síndrome de disfunción (falla) orgánica múltiple en pediatría / Multisystem organ dysfunction (failure) syndrome in childhood

El síndrome de disfunción (falla) orgánica múltiple es diagnosticado cada vez con más frecuencia en todo el espectro etario. La sobrevida lograda con los avances en las técnicas de resucitación de shock, sepsis y trauma se ha visto acompañada de una mayor incidencia de esta entidad. A pesar de casi una década de su descripción en niños y de su importancia existen muy pocas publicaciones en pediatría. Inicialmente se pensaba que el síndrome era sinónimo de complicaciones infecciosas y/o trauma. La caracterización de esta enfermedad, la importancia del "huésped" en la fisiopatología y manifestaciones clínicas del síndrome, el cuadro clínico, los principios terapéuticos, la prevención y su pronóstico son analizados en detalle en una revisión extensa de la literatura

Falla orgánica multisistémica / Multiple system organ failure

La falla multisistémica es una afección compleja pero específica, que reconoce factores predisponentes claros, como son la sepsis, el shock hipovolémico y el tiempo transcurrido entre la injuria y el inicio del tratamiento. El curso clínico de los pacientes que la presentan ha sido muy bien descrita. Las complejas alteraciones metabólicas y bioquímicas en donde parece recibir la clave de la explicación fisiopatológica del síndrome, han sido esclaresidas en parte, y continúan siendo objeto de extensa investigación.

Monitoreo intraoperatorio del metabolismo del oxígeno: ataranalgesia en la prevención del síndrome de insuficiencia múltiple de órganos y sistemas / Intraoperatory monitorized their oxygen methabolism; Preventing from ataranalgesic multiple organ failure were succeded

Se presenta una serie de 10 pacientes quirúrgicos en estado crítico o sometidos a cirugía mayor, a los que se realizó controles intraoperatorios hemodinámicos y del metabolismo del oxígeno. Como técnica anestésica se utilizó la ataranalgesia, combinando midazolam y ketamina. Se logró arribar a las metas óptimas de comportamiento intraoperatorio, y, en consecuencia actuar directamente en la disminución de la deuda de oxígeno, con una mejor posibilidad de compensación intraoperatoria, actuando de forma específica en la profilaxis del síndrome de insuficiencia múltiple de órganos y sistemas.