Paraspecificity of Mexican antivipmyn TRI antivenom in envenomation by Chinese Protobothrops mangshanensis (Mangshan pit viper) in France: A case report and experimental neutralization of venom procoagulant effect.

This case report presents an exotic envenomation by a Chinese snake, Protobothrops mangshanensis. Its venom exhibited potent activity against plasma and fibrinogen, among other enzymatic activities. The patient initially presented with edema of the right upper limb, without tissue necrosis. There were no signs of bleeding; however, severe hypofibrinogenemia was observed (nadir value at 0.4 g/L), with a marked increase in fibrinogen degradation products and D-dimers, without any other coagulation disturbances. In the absence of a specific antivenom available against Asian Crotalinae venoms, the patient was treated at the 29th hour after bite with six vials of Antivipmyn™ TRI (Instituto Bioclon, Mexico, Mexico), a Mexican antivenom initially intended for American Crotalinae venoms, i.e., Bothrops asper, Lachesis muta and Crotalus durissus. Fibrinogen began to rise 6 hours after the antivenom infusion and was within the normal range 38 hours later. The report also underscores the utility of ClotPro® (Haemonetics ®USA), a viscoelastic test, for real-time monitoring of the snakebite-related coagulopathy. The clotting time was extended to 188 seconds on the EX-test while the MCF was decreased to 31 mm on the EX-test and the AP-test and was not measurable on the FIB-test, confirming severe hypofibrinogenemia. In order to confirm the paraspecificity of antivenom on the venom of P. mangshanensis, we studied the experimental neutralization of the venom procoagulant effect by Antivipmyn TRI and Green Pit Viper antivenom, which has been used in previous published clinical cases of P. mangshanensis envenomation. Both Antivipmyn™ TRI and Green Pit Viper antivenom corrected the procoagulant effect induced by P. mangshanensis venom. These findings suggest that Antivipmyn™ TRI cross-reacts with Protobothrops mangshanensis venom. In the absence of antivenom covering Asian Crotalinae, Antivipmyn TRI should be considered to treat an envenomation by Protobothrops spp.

Isolation and characterization of a Mannheimiahaemolytica secreted serine protease that degrades sheep and bovine fibrinogen.

Mannheimiahaemolytica is an opportunistic agent of the respiratory tract of bovines, a member of the Pasteurellaceae family, and the causal agent of fibrinous pleuropneumonia. This bacterium possesses different virulence factors, allowing it to colonize and infect its host. The present work describes the isolation and characterization of a serine protease secreted by M. haemolytica serotype 1. This protease was isolated from M. haemolytica cultured media by precipitation with 50 % methanol and ion exchange chromatography on DEAE-cellulose. It is a 70-kDa protease able to degrade sheep and bovine fibrinogen or porcine gelatin but not bovine IgG, hemoglobin, or casein. Mass spectrometric analysis indicates its identity with protease IV of M. haemolytica. The proteolytic activity was active between pH 5 and 9, with an optimal pH of 8. It was stable at 50 °C for 10 min but inactivated at 60 °C. The sera of bovines with chronic or acute pneumonia recognized this protease. Still, it showed no cross-reactivity with rabbit hyperimmune serum against the secreted metalloprotease from Actinobacilluspleuropneumoniae, another member of the Pasteurellaceae family. M. haemolytica secreted proteases could contribute to the pathogenesis of this bacterium through fibrinogen degradation, a characteristic of this fibrinous pleuropneumonia.

Fibrinógeno humano liofilizado para solución inyectable / Lyophilized human fibrinogen for solution for injection

INTRODUCCIÓN: Algunas consideraciones quirúrgicas en pacientes con enfermedades oncológicas se asocian con hemorragias graves. Aunque la causa suele ser multifactorial, la hipofibrinogenemia (nivel de fibrinógeno plasmático <150 a 200 mg/dl) es común. El fibrinógeno es el principal componente estructural en la formación de coágulos y es esencial para una hemostasia eficaz, pero el fibrinógeno es el primer factor que cae a y sangrado quirúrgico2 . Las causas de hipofibrinogenemia incluyen el consumo de factores de coagulación, exacerbado por niveles críticamente bajos en situaciones como hemorragia importante durante cirugías, así como la hemodilución y la hiperfibrinólisis3, 4 Existe una estrecha asociación entre los niveles bajos de fibrinógeno y el sangrado posoperatorio grave5 . Además, la transfusión de componentes sanguíneos después de una cirugía cardíaca se asocia fuertemente con una mayor morbilidad, mortalidad y costos hospitalarios6 . El manejo eficaz de la coagulación es esencial para ayudar a lograr resultados exitosos. La principal coagulopatía observada durante esta cirugía abdominal extensa es la rápida caída de la concentración de fibrinógeno plasmático y, en consecuencia, la disminución de la calidad del coágulo7 . Las directrices recientes de la Asociación Europea de Cirugía Cardiotorácica y la Asociación Europea de Anestesiología Cardiotorácica recomiendan el uso de crioprecipitado o concentrado de fibrinógeno (FC) para el tratamiento de la hipofibrinogenemia adquirida durante la cirugía cardíaca. ACERCA DE LA TECNOLOGÍA SANITARIA: Hay varias fuentes de fibrinógeno disponibles, siendo el crioprecipitado y el concentrado de fibrinógeno humano (HFC) las opciones preferidas en términos de concentración de fibrinógeno. Ambos tipos de productos han demostrado capacidad para aumentar los niveles de fibrinógeno plasmático en pacientes hemorrágicos10,11. El crioprecipitado tiene un contenido variable de fibrinógeno, requiere compatibilidad con el tipo de sangre, tiempo para descongelarse y conlleva riesgos de lesión pulmonar aguda relacionada con transfusiones y transmisión de patógenos, y se ha retirado en algunos países europeos12,13 . El HFC es una preparación altamente purificada que contiene una concentración definida de fibrinógeno, no requiere coincidencia del tipo de sangre y ofrece una mayor seguridad contra patógenos debido a los pasos de inactivación del virus utilizados en la producción. El crioprecipitado se precipita descongelando plasma fresco congelado de donantes, desprovisto de leucocitos, que se centrifuga y se re-suspende en plasma; mientras que FC es una preparación inactivada por virus, altamente purificada y derivada de plasma. Existe un alto grado de variabilidad en la concentración de fibrinógeno en el crioprecipitado, que según se informa contiene entre 3 y 30 g/l de unidades de fibrinógeno. Un estudio encontró que 2 unidades de crioprecipitado por cada 10 kg de peso corporal aumentaban la concentración de fibrinógeno plasmático en 1 g/l18; sin embargo, el contenido de fibrinógeno del crioprecipitado no está estandarizado. Por el contrario, el FC reconstituido contiene un contenido estandarizado de 200 mg/dL de fibrinógeno. METODOLOGÍA: Primero se realizó una revisión de los documentos que fueron enviados a la unidad y se conversó con la Unidad funcional de Banco de Sangre y Medicina Transfusional (Unidad solicitante) del Instituto Nacional de Enfermedades Neoplásicas (INEN). La segunda parte estuvo enfocada en un análisis de la revisión de la literatura para respaldar la decisión basada en evidencia científica. Se priorizaron estudios por ensayos clínicos aleatorizados (ECA) o revisiones sistemáticas (RS), en caso de haber nuevos estudios observacionales que no fueron incluidos en RS se evaluaron su inclusión. ANALISIS DE EVIDENCIA: En Astana, Kazajstán24 se realizó un estudio prospectivo y aleatorizado realizado en pacientes que se sometieron a cirugía cardíaca y desarrollaron hemorragia e hipofibrinogenemia clínicamente significativas después de la cirugía cardiaca con circulación extracorpórea; el crioprecipitado y el fibrinógeno concentrado (FC) eran el estándar de atención en la institución. El estudio incluyó a todos los pacientes adultos de ≥18 años sometidos a cirugía cardíaca con hemorragia significativa e hipofibrinogenemia, definida como un nivel plasmático de fibrinógeno <200 mg/dL confirmado por el método Clauss. Después de la inscripción se aleatorizó en dos grupos, FC calculado como: [nivel de fibrinógeno objetivo (mg/dL) ­ nivel de fibrinógeno medido (mg/dL)] / 1,8 (mg/dL por mg/kg de peso corporal); y crioprecipitado 1 unidad/5-10kg. Además, estimaron costos directos. Ochenta y ocho pacientes adultos con hipofibrinogenemia adquirida (<2,0 g/l) distribuido en crioprecipitado (N = 40) o FC (N = 48), con datos demográficos y laboratoriales similares entre los grupos. En general, se administró una media 9,33±0,94 unidades (rango, 8-10) de crioprecipitado y 1,40±0,49 g (rango 1-2) de FC. Cabe mencionar que antes de la cirugía, los niveles de fibrinógeno plasmático eran ligeramente más bajos en el grupo FC. Después de la administración de crioprecipitado o FC, los niveles medios de fibrinógeno aumentaron en ambos grupos. Desde antes de la administración hasta 24 horas después de la administración, el nivel medio de fibrinógeno plasmático aumentó en una media de 125 ± 65 mg/dL en el grupo de crioprecipitado y 96 ± 65 mg/dL en el grupo de FC (entre grupos, p = 0,4409 para varianzas iguales. 48 horas después de la administración del fármaco del estudio, los niveles de fibrinógeno habían aumentado aún más en ambos grupos y no hubo diferencias significativas en los niveles de fibrinógeno entre los pacientes de los grupos de crioprecipitado y FC. Los autores concluyen que en el estudio mostraron que tanto el FC como el crioprecipitado fueron eficaces para aumentar los niveles de fibrinógeno plasmático en pacientes que requirieron cirugía cardíaca, que sufrieron hemorragia significativa e hipofibrinogenemia. No se informaron problemas de seguridad para ninguno de los medicamentos. Se describió que el concentrado de fibrinógeno era significativamente más barato que el crioprecipitado y ventajoso debido a la velocidad y facilidad de preparación. Debido a la necesidad de cumplir con los protocolos establecidos en el centro hospitalario, las dosis no fueron equivalentes de fibrinógeno. CONCLUSIONES: INFORME N° 000098-2024-UFBSMT- DP-DISAD/INEN remitido por la Dra. Evelyn Norabuena Mautino, Coordinador de la Unidad Funcional de Banco de Sangre y Medicina Transfusional(e) del INEN al Jefe de la Unidad Funcional de Evaluación de Tecnologías Sanitarias del INEN. Existe una estrecha asociación entre los niveles bajos de fibrinógeno y el sangrado posoperatorio grave5. Además, la transfusión de componentes sanguíneos después de una cirugía cardíaca se asocia fuertemente con una mayor morbilidad, mortalidad y costos hospitalarios6. El fibrinógeno se puede complementar mediante la administración de plasma fresco congelado (PFC), crioprecipitado o concentrado de fibrinógeno. El PFC y el crioprecipitado son productos sanguíneos alogénicos que requieren pruebas cruzadas y descongelación antes de su administración y también están relacionados con un mayor riesgo de transmisión de patógenos y reacciones inmunológicas17,18. Alternativamente, el concentrado de fibrinógeno es un derivado del plasma sometido a pasteurización que minimiza el riesgo de reacciones inmunológicas y alérgicas18,19. Se realizó una estrategia de búsqueda en PubMed encontrando un total, de 102 artículos, donde finalmente se seleccionaron 4 estudios. La evidencia científica indica que el análisis de la concentración de fibrinógeno plasmático mostró que el crioprecipitado y el FC tenían una eficacia comparable. Sin embargo, el FC tiene ventajas sobre el crioprecipitado debido a su facilidad de manipulación, menor reacción cruzada y alta pureza. Se puede considerar el uso de concentrado de fibrinógeno para el tratamiento de hemorragias en pacientes con hipofibrinogenemia adquirida en cirugías. El beneficio económico del FC es incierto, teniendo evidencias contradictorias, pero un estudio indica que puede ser competitivo con la crioterapia, si el costo del FC disminuye en un 44% o demostrar que ahorra entre 025 y 066 días de UCI, mientras que otro estudio indica el beneficio neto incremental del concentrado de fibrinógeno frente al crioprecipitado fue positivo (probabilidad de ser rentable 86% y 97% a $0 y USD $1489 disposición a pagar, respectivamente. El beneficio neto fue muy incierto para los pacientes no selectivos y con enfermedades críticas del estudio FIBERS.

The association of fibrinogen-albumin ratio and neutrophil-lymphocyte ratio with the severity of respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections. It is responsible for more than half of lower respiratory tract infections in infants requiring hospitalization. This study aimed to investigate the correlation between the fibrinogen-albumin ratio (FAR) and the severity of RSV infection and to compare its effectiveness with the neutrophil-lymphocyte ratio (NLR). This was a retrospective cohort study with patients aged from 29 days to two years who had been admitted to the pediatric clinic of our hospital. Patients were divided into four groups: group 1 (mild disease), group 2 (moderate disease), group 3 (severe disease), and group 4 (control). FAR and NLR were measured in all groups. FAR was significantly higher in group 3 than in the other groups, in group 2 than in groups 1 and 4, and in group 1 than in group 4 (p<0.001 for all). NLR was significantly higher in group 4 than in the other groups and in group 3 than in groups 1 and 2 (p<0.001 for all). FAR totaled 0.078 ± 0.013 in patients with bronchiolitis; 0.099 ± 0.028, in patients with bronchopneumonia; and 0.126 ± 0.036, in patients with lobar pneumonia, all with statistically significant differences (p<0.001). NLR showed no significant statistical differences. This study found a statistically significant increase in FAR in the group receiving invasive support when compared to that receiving non-invasive support (0.189 ± 0.046 vs. 0.112 ± 0.030; p=0.003). Mechanical ventilation groups showed no differences for NLR. FAR was used to identify severe RSV-positive patients, with a sensitivity of 84.4%, a specificity of 82.2%, and a cutoff value of >0.068. This study determined a cutoff value of ≤1.49 for NLR, with a sensitivity of 62.2% and a specificity of 62.2% to find severe RSV-positive patients. Also, statistically significant associations were found between FAR and hospitalization and treatment length and time up to clinical improvement (p<0.001 for all). NLR and hospitalization and treatment length showed a weak association (p<0.001). In children with RSV infection, FAR could serve to determine disease severity and prognosis and average lengths of hospitalization, treatment, and clinical improvement. Additionally, FAR predicted disease severity more efficiently than NLR.

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery.

INTRODUCTION: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. METHODS: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. RESULTS: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. CONCLUSION: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Ascorbic acid prevents stress-induced hypercoagulability in overweight and obese individuals.

Ascorbic acid (AA) may contribute to restoring hemostatic balance after mental stress (MS) in overweight/obese adults. We aimed to determine the effects of AA administration on hemostatic responses to MS in overweight/obese men. Fourteen overweight/obesity men (27 ± 7 years; BMI: 29.7 ± 2.6 kg m-2) performed the Stroop color-word stress task for 5 min after non-simultaneous infusion of placebo (PL, 0.9% NaCl) and AA (3 g). Blood was collected at baseline, during MS, and 60 min after MS to measure: activated partial thromboplastin time, prothrombin time, and fibrinogen concentration, by coagulometer; platelet-derived microvesicles (PMV, mv/µL), by flow cytometry; nitrite (µM), by chemiluminescence. In PL session, MS led to decreases in PTs (stress, p = 0.03; 60 min, p < 0.001), PT-INR (stress, p < 0.001; 60 min, p < 0.01), aPTTs (60 min, p = 0.03), aPTT ratio (60 min, p = 0.04) and fibrinogen (60 min, p = 0.04), while increased PT activity (60 min, p = 0.01) when compared to baseline. Furthermore, AA increased PTs (60 min, p < 0.001), PT-INR (60 min, p = 0.03) and decreased PT activity (60 min, p < 0.001) and fibrinogen (stress, p = 0.04) when compared to PL. Nitrite was increased in response to stress during AA session (p < 0.001 vs PL). There was no difference in PMV. Ascorbic acid prevented the impaired hemostatic profile and improved nitrite response to stress in the overweight and obese adults.

Development and application of novel ELISA-based analytical tools for assessing nitroxidative distress biomarkers in ischemic stroke: implications for improved diagnosis and clinical management.

Ischemic cerebrovascular accident (iCVA) is a public health issue, whose subjacent events involve the development of nitroxidative distress. Identifying biomarkers that assist in the diagnosis of this disease has clinically relevant implications. The aim of this study was to develop an analytic tool for measuring nitroxidative distress biomarkers, intended for application in clinical practice to enhance patient healthcare. Three enzyme linked immunosorbent assays (ELISA) were developed, with different detection objectives. One of them, in a sandwich format, quantifies the amount of fibrinogen in human plasma, an important glycoprotein involved in the blood coagulation process, contributing to thrombus formation and thereby participating in the mechanism of ischemic stroke. Another ELISA, also in a sandwich format, detects the presence of nitrotyrosine residues in fibrinogen from human plasma, a nitroxidative posttranslational modification resulting from the attack of peroxynitrite by-products on tyrosine residues present in proteins. The third one, in inhibition format, determines human plasma nitrotyrosine total content and was used to analyze human plasma samples from control and iCVA patients. Those two groups of plasma samples were analyzed using inhibition ELISA, revealing statistically significant differences in their nitrotyrosine content and molar ratios of nitrotyrosine to fibrinogen, which were higher in the iCVA group. This study provides evidence that nitroxidative distress occurs in ischemic stroke, as indicated by the detection of the biomarker nitrotyrosine. This finding supports other studies that also identified nitrotyrosine in ischemic stroke, through several different methods. This specific ELISA method is applicable for the rapid analysis of clinical samples, making it a potential clinical tool for assessing iCVA patients.

Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3).

The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bß3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bß3 preventing the interaction between α2bß3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.

The TIGIT+ T regulatory cells subset associates with nosocomial infection and fatal outcome in COVID-19 patients under mechanical ventilation.

The TIGIT+FOXP3+Treg subset (TIGIT+Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT+Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT+Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT+Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT+Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT+Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT+Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome.

The prognostic value of peripheral blood parameters on all-frequency sudden sensorineural hearing loss.

OBJECTIVE: To determine whether peripheral blood parameters have any predictive value for all-frequency Sudden Sensorineural Hearing Loss (SSNHL). METHODS: We chose 78 individuals with all-frequency SSNHL who had been admitted to our department. They were divided into two groups: the effective group and the ineffective group. In patients with all-frequency SSNHL, the prognostic variables, including peripheral blood tests and clinical traits, were examined by a logistic regression analysis. In addition, the predictive value was carried out. RESULTS: The effective rate of all-frequency SSNHL was 61.5%. Pre-treatment hearing level and the proportion of patients with diabetes were both significantly lower in the effective group than in the ineffective group (p = 0.024 and 0.000, respectively). The levels of fibrinogen and C-reactive protein were also significantly different between the two groups (p = 0.001 and 0.025, respectively). Pre-treatment hearing level and fibrinogen level both significantly impacted the prognosis of all-frequency SSNHL (p = 0.032 and 0.002, respectively), according to a logistic regression analysis. Furthermore, the prognosis was significantly predicted by both fibrinogen level and pre-treatment hearing level (p = 0.001 and 0.0002, respectively). The receiver operating characteristic curve showed that the fibrinogen level had a sensitivity of 85.4% and a specificity of 60.0% for predicting the prognosis of all-frequency SSNHL. CONCLUSION: For the prognosis of all-frequency SSNHL, the fibrinogen level can be regarded as a useful predictor. The level of C-reactive protein, however, does not have a significant prognostic effect on predicting all-frequency SSNHL. Therefore, more attention should be devoted to the level of fibrinogen in the acute period of all-frequency SSNHL.

The rs16969968 Tobacco Smoking-Related Single-Nucleotide Variant Is Associated with Clinical Markers in Patients with Severe COVID-19.

Tobacco smoking is the leading risk factor for many respiratory diseases. Several genes are associated with nicotine addiction, such as CHRNA5 and ADAM33. This research aims to evaluate the association of the polymorphisms rs16969968 (CHRNA5) and rs3918396 (ADAM33) in patients who developed severe COVID-19. We included 917 COVID-19 patients hospitalized with critical disease and oxygenation impairment. They were divided into two groups, tobacco-smoking (n = 257) and non-smoker (n = 660) patients. The genotype and allele frequencies of two single nucleotide variants, the rs16969968 (CHRNA5) and rs3918396 (ADAM33), were evaluated. The rs3918396 in ADAM33 does not show a significative association. We analyzed the study population according to the rs16969968 genotype (GA + AA, n = 180, and GG, n = 737). The erythrocyte sedimentation rate (ESR) shows statistical differences; the GA + AA group had higher values than the GG group (p = 0.038, 32 vs. 26 mm/h, respectively). The smoking patients and GA or AA genotype carriers had a high positive correlation (p < 0.001, rho = 0.753) between fibrinogen and C-reactive protein. COVID-19 patients and smokers carriers of one or two copies of the risk allele (rs16969968/A) have high ESR and a positive correlation between fibrinogen and C-reactive protein.

Effect of the time to antivenom administration on recovery from snakebite envenoming-related coagulopathy in French Guiana.

BACKGROUND: Snakebite (SB) envenoming is an acute emergency requiring an early care delivery. We aimed to search for the time to reach healthcare facilities in various regions of French Guiana (FG) and to assess the impact of time to antivenom (AV) on the correction of coagulation parameters in these patients. METHODOLOGY: This is a prospective observational study conducted in Cayenne General Hospital between January 1st, 2016, and July 31st, 2022. We included all patients hospitalized for SB envenoming less than 48h after the bite, and receiving antivenom (AV). We assessed the time lapse between SB and medical attention and the time needed to return of the coagulation parameters to normal. PRINCIPAL FINDINGS: Overall, 119 patients were investigated, and 48.7% were from remote areas. The median time from SB to AV therapy was 09:15 h (05:32-17:47). The time was longer in patients from remote rural locations. AV was dispensed within the first six hours after the SB in 45 cases (37.8%). Time from SB to reaching normal plasma fibrinogen concentration was 23:27 h (20:00-27:10) in patients receiving AV≤6h vs. 31:23 h (24:00-45:05) in those receiving AV>6h (p<0.001). Whereas, the time from AV administration to reach normal fibrinogen dosage was similar in the two groups. CONCLUSIONS: Patients from rural settings in FG suffer from a delay in AV administration after SB envenoming leading to an extended time in which patients are coagulopathic. Once AV is administered, clotting parameters recover at a similar rate. Supplying remote healthcare facilities with AV and with medical teams trained on its use should be planned.

Acute Phase Protein Response in Native and Imported Horses After Routine Combination Vaccination Protocol.

Fibrinogen and serum amyloid A (SAA) are commonly measured equine acute phase proteins. Limited data exist on SAA and fibrinogen responses to combination vaccination protocols in horses. A prospective cohort study evaluating SAA, fibrinogen, and rectal temperature following a standard combination vaccination. Blood for measurement of SAA and serum fibrinogen and rectal temperatures were obtained before (0 hour) and after vaccination (24, 48, 72, 96, 168 hours). After vaccination, SAA and fibrinogen increased in all horses. Imports had elevated SAA from 24-168 hours, whereas native horses returned to baseline by 168 hours. Compared to native horses, SAA was significantly higher in imports (coefficient 24-168 hours 358, 95%CI: 46-671 mg/L; P = .03). Fibrinogen increased significantly from 24 to 168 hours postvaccination, but groups did not differ (coefficient -16; 95%CI: -69 to 37 mg/dL; P = .5). Absolute rectal temperatures were significantly higher in imports throughout, including 0 hour (median 37.8; IQR 37.7-38.0 vs. 37.3; 37.1-37.3; P = .002). At 24 hours postvaccination when temperatures significantly increased above baseline in both groups, there was a small but significant difference in the percent change relative to baseline (coefficient 1.9; 95%CI 0.8%-2.9%; P = .002). A standard combination vaccination protocol elicited an acute phase response in all horses. Compared to native previously vaccinated horses, imports had a stronger SAA response. The observed response is worthy of consideration when examining recently vaccinated imported horses.

Relationship between the Fibrinogen/Albumin Ratio and Microvascular Perfusion in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction: A Prospective Study. / Relação entre a Relação Fibrinogênio/Albumina e a Perfusão Microvascular em Pacientes Submetidos à Intervenção Coronária Percutânea Primária para Infarto do Miocárdio com Elevação do Segmento ST: Um Estudo Prospectivo.

BACKGROUND: Correct TIMI frame count (CTFC), myocardial blush grade (MBG), and ST-segment resolution (STR) are parameters used to evaluate reperfusion at the microvascular level in patients that have undergone primary percutaneous coronary intervention (pPCI). Fibrinogen-to-albumin ratio (FAR) has been associated with thrombotic events in patients with ST-elevation myocardial infarction (STEMI) and chronic venous insufficiency. OBJECTIVES: To investigate the relationship of FAR with CTFC, MBG, and STR. Methods: The study included 167 consecutive patients who underwent successful pPCI for STEMI and achieved TIMI-3 flow. The cases were divided into two groups, high (>0.0765) and low FAR (≤0.0765), according to the cut-off value of this parameter in the receiver operator characteristic analysis (ROC). STR, CTFC, and MBG were used to evaluate myocardial reperfusion. P values<0.05 were considered statistically significant. RESULTS: CTFC value, SYNTAX score, neutrophil/lymphocyte ratio, low-density lipoprotein, glucose, and peak cTnT were significantly higher, whereas STR, MBG, and LVEF were lower in the high FAR group. Spearman's correlation analysis revealed a significant relationship between the FAR and STR (r=-0.666, p<0.001), MBG (-0.523, p<0.001), and CTFC (r=0.731, p≤0.001). According to the logistic regression analysis, FAR, glucose, peak cTnT, and pain to balloon time were the most important independent predictors of MBG 0/1, CTFC>28, and STR<50%).ROC analysis revealed that the cut-off value of FAR≥0.0765 was a predictor of incomplete STR with a sensitivity of 71.9 % and a specificity of 69.8 %, MBG0/1 with a sensitivity of 72.6 % and a specificity of 68.6 %, and CTFC >28 with a sensitivity of 76 % and a specificity of 65.8 %. CONCLUSIONS: FAR is an important independent predictor of microvascular perfusion in patients undergoing pPCI for STEMI.

FUNDAMENTO: A contagem corrigida de quadros TIMI (CTFC), o grau de blush miocárdico (MBG) e a resolução do segmento ST (STR) são parâmetros utilizados para avaliar a reperfusão em nível microvascular em pacientes submetidos à intervenção coronária percutânea primária (ICPp). A relação fibrinogênio/albumina (FAR) tem sido associada a eventos trombóticos em pacientes com infarto do miocárdio com elevação do segmento ST (IAMCSST) e insuficiência venosa crônica. OBJETIVOS: Investigar a relação do FAR com CTFC, MBG e STR.Métodos: O estudo incluiu 167 pacientes consecutivos que foram submetidos a ICPp com sucesso para IAMCSST e alcançaram fluxo TIMI-3. Os casos foram divididos em dois grupos, FAR alto (> 0,0765) e FAR baixo (≤ 0,0765), de acordo com o valor de corte desse parâmetro na análise característica do operador do receptor (ROC).  STR, CTFC e MBG foram utilizados para avaliar a reperfusão miocárdica. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: O valor CTFC, escore SYNTAX, relação neutrófilos/linfócitos, lipoproteína de baixa densidade, glicose e pico de cTnT foram significativamente maiores, enquanto STR, MBG e FEVE foram menores no grupo FAR alto. A análise de correlação de Spearman revelou relação significativa entre FAR e STR (r=-0,666, p<0,001), MBG (-0,523, p<0,001) e CTFC (r=0,731, p≤0,001). De acordo com a análise de regressão logística, FAR, glicose, pico de cTnT e dor até o tempo de Balão foram os preditores independentes mais importantes de MBG 0/1, CTFC>28 e STR<50%). A análise ROC revelou que o ponto de corte o valor de FAR≥0,0765 foi preditor de STR incompleto com sensibilidade de 71,9% e especificidade de 69,8%, MBG0/1 com sensibilidade de 72,6% e especificidade de 68,6%, e CTFC>28 com sensibilidade de 76% e uma especificidade de 65,8%. CONCLUSÕES: A FAR é um importante preditor independente de perfusão microvascular em pacientes submetidos a ICPp por IAMCSST.

Resilience and the reduction of occupational stress in Nursing.

OBJECTIVE: to analyze the association between resilience and occupational stress of Nursing professionals from a general hospital. METHOD: an observational, cross-sectional study involving 321 Nursing professionals. The data collected were: socio-demographic and labour variables, stress and resilience, analyzed with descriptive and inferential statistics. RESULTS: 54.5% of the participants presented moderate resilience and 36.4%, high; 73.5% were at risk of exposure to occupational stress; the relationship between psychological demands and professional category (p=0.009), between control over work and age (p=0.04), professional category (p<0.001), having a management position (p=0.009), being a specialist (p=0.006) and between social support and professional category (p<0.001), having a management position (p=0.03), daily working hours (p=0.03), being a specialist (p<0.001) were verified. There was an association between resilience Factor I - resolutions of actions and values and control over work (p=0.04) and social support (p=0.002). CONCLUSION: the Nursing professionals of a general hospital have moderate to high resilience which, associated with high control over their work and high social support, may contribute to the reduction of exposure to occupational stress.

A fibrinogen-related Lectin from Echinometra lucunter represents a new FReP family in Echinodermata phylum.

Fibrinogen-related proteins (FREPs) have been identified in several animals. They are involved in the body's defense, acting as mediators of phagocytosis. Ficolins and intelectins are some of the most studied Fibrinogen-related Domain (FReD)-containing lectins. In this work, we have isolated a singular FReD-containing lectin, which cannot be classified as ficolin or intelectin. ELL (Echinometra lucunter lectin) was isolated from coelomic plasma by affinity chromatography on xanthan gum. Primary structure was determined by tandem mass spectrometry. Moreover, antimicrobial activity of ELL was evaluated against planktonic cells and biofilm of Escherichia coli, Staphylococcus aureus and S. epidermidis. ELL showed hemagglutinating activity in Ca2+ presence, which was inhibited by glycoprotein mucin and thyroglobulin. Complete amino acid sequence consisted of 229 residues, including a FReD in the N-terminal. Searches for similarity found that ELL was very close to putative proteins from Strongylocentrotus purpuratus. ELL showed moderate similarity with uncharacterized sea stars proteins and protochordate intelectins. ELL was able to inhibit the planktonic growth of the Gram-positive bacteria and significantly reduce the biofilm formation of all bacteria tested. In conclusion, we identified a new type of FReP-containing lectin with some structural and functional conservation towards intelectins.

Mannheimia haemolytica OmpH binds fibrinogen and fibronectin and participates in biofilm formation.

Mannheimia haemolytica is the causal agent of the shipping fever in bovines and produces high economic losses worldwide. This bacterium possesses different virulence attributes to achieve a successful infection. One of the main virulence factors expressed by a pathogen is through adhesion molecules; however, the components participating in this process are not totally known. The present work identified a M. haemolytica 41 kDa outer membrane protein (Omp) that participates in bacterial adhesion. This protein showed 100% identity with the OmpH from M. haemolytica as determined by mass spectrometry and it interacts with sheep fibrinogen. The 41 kDa M. haemolytica OmpH interacts with bovine monocytes; a previous incubation of M. haemolytica with a rabbit hyperimmune serum against this Omp diminished 45% cell adhesion. The OmpH was recognized by serum from bovines affected by acute or chronic pneumonia, indicating its in vivo expression; moreover, it showed immune cross-reaction with the serum of rabbit infected with Pasteurella multocida. The OmpH is present in biofilms and previous incubation of M. haemolytca with rabbit serum against this protein diminished biofilm, indicating this protein's participation in biofilm formation. M. haemolytica OmpH is proposed as a relevant immunogen in bovine pneumonia protection.