Hereditary Amyloidosis: Insights Into a Fibrinogen A Variant Protein.

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a ß-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.

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.

Capacidad pronóstica del dímero D en la predicción de mortalidad en pacientes con el diagnóstico de COVID-19 / Pronostic capacity of D-dimer in predicting mortality in patients diagnosed with COVID-19

RESUMEN Introducción: La infección por SARS-CoV-2 puede aumentar el riesgo de trombosis. Estudios asocian niveles de dímero D con mortalidad por COVID-19. Objetivo: Determinar la capacidad pronostica del dimero D en la predicción de mortalidad por COVID-19 en pacientes hospitalizados en la Unidad de Cuidados Intensivos. Métodos: Se realizó un estudio de cohorte retrospectiva en el Centro Médico Naval durante enero-julio de 2021. Se incluyeron 324 pacientes adultos con COVID-19 confirmada por RT-PCR. Se midieron niveles de dímero D al ingreso utilizando turbidimetría de coagulación (Sysmex CS-5100). Se analizaron variables sociodemográficas, comorbilidades y datos clínicos. El análisis estadístico se realizó con SPSS versión 26, empleando pruebas Chi cuadrado, exacta de Fisher, U de Mann Whitney, COR y regresión de Cox. Resultados: Se determinó un punto de corte de 1,40 µg/mL para los valores de dimero D con una sensibilidad de 80,9%, una especificidad de 86,4% y área bajo la curva (AUC) de 0,916 (IC 95%: 0,884 - 0,947; p =0,016) para predecir mortalidad por COVID-19. Asimismo, se encontró que pacientes con valores de dimero D mayores o iguales a 1,40 µg/mL tenian un riesgo incrementado de fallecimiento en pacientes con COVID-19 (HRa = 6,545; IC 95%: 3,867 - 11,077; p<0,001), independientemente de las variables edad, diabetes mellitus, hipertensión arterial, cardiopatía isquémica, enfermedad cerebrovascular, fibrilación auricular, enfermedad pulmonar obstructiva crónica, asma, cáncer y trombocitopenia. Conclusión: El presente estudio mostró que los niveles de dimero D al ingreso representan un biomarcador fiable en la evaluación del pronostico de pacientes con COVID-19.

ABSTRACT Introduction: SARS-CoV-2 infection can increase the risk of thrombosis. Studies associate D-dimer levels with COVID-19 mortality. Objective: To determine the prognostic capacity of D-dimer in predicting COVID-19 mortality in patients hospitalized in the Intensive Care Unit. Methods: A retrospective cohort study was conducted at the Naval Medical Center from January to July 2021. A total of 324 adult patients with RT-PCR confirmed COVID-19 were included. D-dimer levels were measured upon admission using coagulation turbidimetry (Sysmex CS-5100). Sociodemographic variables, comorbidities, and clinical data were analyzed. Statistical analysis was performed using SPSS version 26, employing Chi-square tests, Fisher's exact test, Mann-Whitney U test, ROC, and Cox regression. Results: A cut-off point of 1.40 µg/mL for D-dimer values was determined, with a sensitivity of 80.9%, specificity of 86.4%, and an area under the curve (AUC) of 0.916 (95% CI: 0.884 - 0.947; p=0.016) for predicting COVID-19 mortality. Additionally, patients with D-dimer values greater than or equal to 1.40 µg/mL had an increased risk of death (adjusted HR = 6.545; 95% CI: 3.867 - 11.077; p<0.001), independent of age, diabetes mellitus, arterial hypertension, ischemic heart disease, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, asthma, cancer, and thrombocytopenia. Conclusion: This study showed that admission D-dimer levels represent a reliable biomarker in evaluating the prognosis of COVID-19 patients. Keywords: COVID-19; SARS-CoV-2; Mortality; Fibrin-Fibrinogen Degradation Products (Source: MeSH NLM).

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.

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.

The Welfare of Horses Competing in Three-Barrel Race Events Is Shown to Be Not Inhibited by Short Intervals between Starts.

Equestrian sports require precise animal welfare and health evaluations. To test the hypothesis that horses maintain their welfare when subjected to two three-barrel (3TB) races with 2 min intervals, an experiment was designed to evaluate their surface temperature using infrared thermography (IRT) in regions of interest (barrel, flank, neck, jaw, corner of the mouth, and ocular caruncle) and also measure blood biomarkers (hemogram, total plasma protein, fibrinogen, urea, creatinine, GGT, CK, cortisol, IL-6, and IL-1ß). Ten Quarter Horses were monitored through thermography (pre-race, +1, +4, and +24 h post-race) and blood sampling (pre-race, +1, +4, and +24 h post-race). ANOVA and Tukey test at 5% were used. IRT in six regions of interest (Left/Right-barrel, flank, neck muscles) increased at +, with no differences between values recorded at +1 and +4 when compared to those measured pre-race (p > 0.05). Plasma protein, RBC count, hemoglobin, hematocrit, WBC count, neutrophils, and lymphocytes (p < 0.05) increased immediately after the races, with recovery at +1 h. Other biomarkers did not change, including cortisol, IL-6, and IL-1ß (p > 0.05). Results indicate that well-conditioned 3TB horses subjected to two races at short intervals do not show changes that could be related to impaired health or welfare.

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

ABSTRACT 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.

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

ABSTRACT 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.

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

Abstract 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. Level of Evidence: 4.

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.

Plasma Fibrinogen as a Predictor of Perioperative-Blood-Component Transfusion in Major-Nontraumatic-Orthopedic-Surgery Patients: A Cohort Study.

There is a trend towards increased perioperative bleeding in patients with plasma fibrinogen levels < 200 mg/dL-1. This study aimed to assess whether there is an association between preoperative fibrinogen levels and perioperative blood-product transfusion up to 48 h after major orthopedic surgery. This cohort study included 195 patients who underwent primary or revision hip arthroplasty for nontraumatic etiologies. Plasma fibrinogen, blood count, coagulation tests, and platelet count were measured preoperatively. A plasma fibrinogen level of 200 mg/dL-1 was the cutoff value used to predict blood transfusion. The mean (SD) plasma fibrinogen level was 325 (83) mg/dL-1. Only thirteen patients had levels < 200 mg/dL-1, and only one of them received a blood transfusion, with an absolute risk of 7.69% (1/13; 95%CI: 1.37-33.31%). Preoperative plasma fibrinogen levels were not associated with the need for blood transfusion (p = 0.745). The sensitivity and the positive predictive value of plasma fibrinogen < 200 mg/dL-1 as a predictor of blood transfusion were 4.17% (95%CI: 0.11-21.12%) and 7.69% (95%CI: 1.12-37.99%), respectively. Test accuracy was 82.05% (95%CI: 75.93-87.17%), but positive and negative likelihood ratios were poor. Therefore, preoperative plasma fibrinogen level in hip-arthroplasty patients was not associated with the need for blood-product transfusion.

Determining the relationship between serum acute phase reactants and cervical premalignant lesions: a cohort study

Abstract BACKGROUND: Acute phase reactants play a role in the progression and prognosis of many malignant and premalignant tumors. This study investigated the diagnostic value of certain reactants as markers for cervical premalignant lesions. OBJECTIVES: Despite advanced screening and vaccination programs, cervical cancer remains a serious health problem worldwide. We aimed to determine the possible relationship between premalignant cervical disease and serum acute phase reactant levels. DESIGN AND SETTING: This study included 124 volunteers who underwent cervical cancer screening. We divided the patients into three groups according to cervical cytology and histopathological findings as follows: no cervical lesion, low-grade neoplasia, or high-grade neoplasia. METHODS: We included women aged 25-65 years with benign smear or colposcopy results, low- and high-grade squamous intraepithelial lesions. The benign group was based only on cytology findings, whereas the other groups were based on histopathology findings. Demographic data and serum albumin, fibrinogen, ferritin, and procalcitonin levels were evaluated in the three groups. RESULTS: We found significant differences among the three groups in terms of age, albumin level, albumin/fibrinogen ratio, and procalcitonin level. The regression analysis revealed lower serum albumin levels in the low- and high-grade squamous intraepithelial lesion groups compared with the benign group. CONCLUSION: This is the first study to evaluate the importance of serum inflammatory markers in cervical intraepithelial lesions. Our results indicate that serum albumin level, albumin/fibrinogen ratio, procalcitonin level, and neutrophil values differ among cervical intraepithelial lesions.

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.

The impact of gender and peripheral blood parameters on the characteristics of L-PRF membranes.

Aim: The purpose of this study was to evaluate the impact of gender and peripheral blood parameters on the characteristics of Leucocyte-and Platelet-Rich Fibrin (L-PRF) membranes and to describe histologically three different zones of L-PRF membranes. Methods: Blood was collected from twenty healthy donors (10 men and 10 women). Peripheral blood parameters including leucocyte and platelet counts, and fibrinogen levels were recorded. L-PRF membranes were prepared to quantify the release of growth factors (PDGF, VEGF, BMP-2, and BMP-9) at 1, 2, 3 and 7 days and for histological examination. Three zones within each L-PRF membrane (face, body, and tail) were analysed separately, quantifying the area of leucocytes, platelets, and fibrin in percentage. The Young's modulus of the membranes was also considered (during tensile and compression tests). Results: Women had significantly higher fibrinogen levels in their peripheral blood, and a higher release of BMP-9, whereas men showed a significantly higher Young's modulus in compression tests. The histology revealed significant differences in cellular content and fibrin concentration between the 3 areas, with the face being biologically the richest. Conclusion: Several factors influenced the final characteristics of L-PRF membranes. These need to be taken into consideration when interpreting the results of research, but especially in clinical practice.

Fibrinogen-to-Albumin Ratio and Blood Urea Nitrogen-to-Albumin Ratio in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Fibrinogen-to-albumin ratio (FAR) and blood urea nitrogen-to-albumin ratio (BAR) are inflammatory biomarkers that have been associated with clinical outcomes of multiple diseases. The objective of this study is to evaluate the association of these biomarkers with the severity and mortality of COVID-19 patients. A systematic search was performed in five databases. Observational studies that reported the association between FAR and BAR values with the severity and mortality of COVID-19 patients were included. Random-effects models were used for meta-analyses, and effects were expressed as Odds Ratio (OR) and their 95% confidence intervals (CI). Publication bias was assessed using the Begg test, while the quality assessment was assessed using the Newcastle Ottawa Scale. A total of 21 studies (n = 7949) were included. High FAR values were associated with a higher risk of severity (OR: 2.41; 95% CI 1.41−4.12; p < 0.001) and mortality (OR: 2.05; 95% CI 1.66−2.54; p < 0.001). High BAR values were associated with higher risk of mortality (OR: 4.63; 95% CI 2.11−10.15; p < 0.001). However, no statistically significant association was found between BAR values and the risk of severity (OR: 1.16; 95% CI 0.83−1.63; p = 0.38). High FAR and BAR values were associated with poor clinical outcomes.

Experimental Evaluation of Chitosan Membrane and Collagen Sponge (TachoSil®) as Sealants in Cardiovascular Surgery.

INTRODUCTION: The objectives of this study are to experimentally evaluate the haemostatic effects of two organic substances, a membrane of chitosan and a collagen sponge coated with thrombin and human fibrinogen (TachoSil®), in sealing 7-0 needle stitches holes on the femoral arteries of rats as well as to evaluate local histological reactions. METHODS: Twenty-four rats were included, and four holes were made in each common femoral artery. In the control group, haemostasis was achieved only by compression with gauze sponge; and in the two other groups, haemostasis was achieved with application of one of these two substances. RESULTS: Membrane of chitosan and TachoSil® showed a power to reduce the time to achieve haemostasis compared with the control group (P=0.001), and the haemostatic effects of these two substances were comparable. There was lower blood loss in the groups where these two substances were used when compared with the control group, but no difference was found comparing the two substances. CONCLUSION: The use of these sealants did not promote more adhesion or local histological reactions when compared to the control group. Since chitosan is easy to find in nature, has a positive effect to promote haemostasis, and did not bring considerable local reactions, it might be used as a sealant in cardiovascular surgery.

Role of fibrinogen in the attenuation of ischemia reperfusion and remote ischemic preconditioning / El papel del fibrinógeno en la atenuación de la isquemia-reperfusión y el preacondicionamiento isquémico remoto

Abstract Background: Ischemic reperfusion injury (IRI) is a common hazard involved in many human diseases, such as cerebral stroke, myocardial infarction, solid organ transplant dysfunction or failure, and vascular diseases. Understanding the molecular bases of this injury is essential for the prevention and control of these life-threatening conditions. Ischemic and remote ischemic preconditioning techniques (IPC and RIPC, respectively) have gained increasing importance in the clinical practice to protect against the IRI; however, the exact mechanisms of these techniques are not fully understood, which renders their clinical application query. Possible effectors: Nitric oxide (NO) has been reported by multiple studies to be an important mediator of the protective effects of those techniques. While the physiological concentrations of NO and fibrinogen (FB) are known to antagonize each other, the circulating levels of both effectors increase in response to RIPC. Hypothesis: While NO has potential anti-inflammatory effects, non-soluble fibrinogen (sFB) shows pro- inflammatory effects. However, the sFB may have the potential to act synergistically rather than antagonistically with NO toward the attenuation of the IRI. Conclusion: While increased FB is considered a risk factor for cardiovascular and inflammatory conditions that is also able to decrease the efflux of NO, and increase the NO oxidative metabolits and S- nitroglutathione, the increased sFB during the acute phase reaction might have other protective aspects that should be carefully investigated.

Resumen Antecedentes: La lesión por isquemia-reperfusión (LIR) es un riesgo común involucrado en muchas enfermedades humanas tales como derrame cerebral, infarto del miocardio, disfunción o falla de trasplante de órgano sólido, y enfermedades vasculares. Una comprensión de la base molecular de esta lesión es fundamental para la prevención y el control de estas enfermedades potencialmente mortales. Las técnicas de preacondicionamiento isquémico y preacondicionamiento isquémico remoto (PIR) han cobrado una creciente importancia en la práctica clínica para la protección contra la LIR, sin embargo, los mecanismos precisos de estas técnicas no se entienden plenamente, lo cual pone en duda su aplicación clínica. Posibles efectores: El óxido nítrico (ON) ha sido reportado por varios estudios como un importante mediador de los efectos protectores de estas técnicas. Si bien se sabe que las concentraciones fisiológicas del ON y fibrinógeno son antagónicas, los niveles circulantes de ambos efectores aumentan en respuesta al PIR. Hipótesis: Aunque el ON tiene posibles efectos anti-inflamatorios, el fibrinógeno insoluble muestra efectos proinflamatorios. Sin embargo, el fibrinógeno soluble puede tener el potencial de actuar de manera sinérgica en lugar de antagónica con el ON hacia la atenuación de la LIR. Conclusión: Aunque el fibrinógeno elevado se considera un factor de riesgo para las enfermedades cardiovasculares e inflamatorias, que también puede disminuir la descarga de ON y aumentar los niveles de metabolitos oxidantes del ON y de S-nitrosoglutatión, el aumento de fibrinógeno soluble durante la reacción de fase aguda puede tener otros aspectos protectores que deben ser cuidadosamente investigados.

Experimental Evaluation of Chitosan Membrane and Collagen Sponge (TachoSil®) as Sealants in Cardiovascular Surgery

ABSTRACT Introduction: The objectives of this study are to experimentally evaluate the haemostatic effects of two organic substances, a membrane of chitosan and a collagen sponge coated with thrombin and human fibrinogen (TachoSil®), in sealing 7-0 needle stitches holes on the femoral arteries of rats as well as to evaluate local histological reactions. Methods: Twenty-four rats were included, and four holes were made in each common femoral artery. In the control group, haemostasis was achieved only by compression with gauze sponge; and in the two other groups, haemostasis was achieved with application of one of these two substances. Results: Membrane of chitosan and TachoSil® showed a power to reduce the time to achieve haemostasis compared with the control group (P=0.001), and the haemostatic effects of these two substances were comparable. There was lower blood loss in the groups where these two substances were used when compared with the control group, but no difference was found comparing the two substances. Conclusion: The use of these sealants did not promote more adhesion or local histological reactions when compared to the control group. Since chitosan is easy to find in nature, has a positive effect to promote haemostasis, and did not bring considerable local reactions, it might be used as a sealant in cardiovascular surgery.

Cryofibrinogenemia: What Rheumatologists Should Know.

Cryofibrinogenemia refers to the presence of cryofibrinogen in plasma. This protein has the property of precipitating at lower temperatures. Cryofibrinogenemia is a rare disorder, clinically characterized by skin lesions, such as ulcers, necrosis, livedo reticularis, arthralgia, thrombosis, and limb ischemia. These features are most often observed in rheumatological practice and consist of differential diagnoses of antiphospholipid syndrome, primary vasculitis, thrombotic thrombocytopenic purpura, and cryoglobulinemia. Classical histopathological findings include the presence of thrombi within the lumen of blood vessels of the skin without vasculitis. To date, there are no validated classification criteria. Management includes corticosteroids, immunosuppressive therapy, anticoagulants, and fibrinolytic agents. This narrative review aims to make physicians, particularly rheumatologists, aware of the existence of this underdiagnosed condition. There are no epidemiological studies evaluating the prevalence of cryofibrinogenemia in different rheumatological disorders. Studies are also required to investigate if certain features of rheumatological diseases are related to the presence of cryofibrinogenemia.

Computational Characterization of Mechanical, Hemodynamic, and Surface Interaction Conditions: Role of Protein Adsorption on the Regenerative Response of TEVGs.

Currently available small diameter vascular grafts (<6 mm) present several long-term limitations, which has prevented their full clinical implementation. Computational modeling and simulation emerge as tools to study and optimize the rational design of small diameter tissue engineered vascular grafts (TEVG). This study aims to model the correlation between mechanical-hemodynamic-biochemical variables on protein adsorption over TEVG and their regenerative potential. To understand mechanical-hemodynamic variables, two-way Fluid-Structure Interaction (FSI) computational models of novel TEVGs were developed in ANSYS Fluent 2019R3® and ANSYS Transient Structural® software. Experimental pulsatile pressure was included as an UDF into the models. TEVG mechanical properties were obtained from tensile strength tests, under the ISO7198:2016, for novel TEVGs. Subsequently, a kinetic model, linked to previously obtained velocity profiles, of the protein-surface interaction between albumin and fibrinogen, and the intima layer of the TEVGs, was implemented in COMSOL Multiphysics 5.3®. TEVG wall properties appear critical to understand flow and protein adsorption under hemodynamic stimuli. In addition, the kinetic model under flow conditions revealed that size and concentration are the main parameters to trigger protein adsorption on TEVGs. The computational models provide a robust platform to study multiparametrically the performance of TEVGs in terms of protein adsorption and their regenerative potential.