Comparison of the prognostic value of platelet-based prognostic models in patients with malignant hepatic tumors after TACE therapy

Abstract Purpose: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. Methods: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. Results: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. Conclusion: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.

Transplante hepático na hepatite delta: experiência da América do Sul / Liver transplantation in hepatitis delta: south america experience

ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5%) compared to Group D (58.6%). The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034). Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent episodes of upper gastrointestinal bleeding. Patients with hepatitis by delta virus had lower mortality and higher survival than patients with hepatitis B virus.

RESUMO CONTEXTO: A região Amazônica é uma das principais áreas endêmicas da hepatite delta no mundo e a única relacionada com a presença do genótipo 3 do vírus delta. OBJETIVO: Analisar o perfil, mortalidade e sobrevida dos pacientes cirróticos submetidos a transplante hepático por hepatite crônica pelo vírus delta e comparar com os transplantados pela monoinfecção do vírus da hepatite B. MÉTODOS: Estudo retrospectivo, observacional e descritivo. Entre maio de 2002 a dezembro de 2011, foram realizados 629 transplantes de fígado no Hospital Universitário Walter Cantídio, dos quais 29 pacientes foram transplantados por cirrose causada pela infecção crônica do vírus delta e 40 pela monoinfecção crônica da hepatite B. As variáveis analisadas foram: origem, idade, sexo, escore de MELD, classificação de Child-Pugh, ocorrência de hemorragia digestiva alta e carcinoma hepatocelular antes do transplante, número de plaquetas perioperatória, mortalidade e sobrevida. RESULTADOS: O Grupo Delta foi mais jovem e todos oriundos da região Amazônica Brasileira. O Grupo B apresentou maior proporção de pacientes do sexo masculino (92,5%) em relação ao Grupo D (58,6%). A ocorrência de hemorragia digestiva alta antes do transplante, escore de MELD e classificação de Child-Pugh não obtiveram diferenças estatísticas entre os grupos. A ocorrência de carcinoma hepatocelular e a mortalidade foram maiores no grupo com hepatite B. A sobrevida em 4 anos foi de 95% no Grupo delta e 75% no Grupo B com diferença estatisticamente significante (P=0,034). Pacientes com hepatite delta, apresentaram mais acentuada plaquetopenia no pré-transplante e no pós-operatório imediato. CONCLUSÃO: Os pacientes com hepatite por vírus delta submetidos ao transplante hepático eram predominantemente homens, vindos da região da Amazônia brasileira e com função hepática semelhante a dos pacientes com vírus da hepatite B. Apresentavam menor incidência de carcinoma hepatocelular, níveis de trombocitopenia perioperatória mais acentuados e episódios frequentes de hemorragia digestiva alta. Os pacientes com hepatite por vírus delta apresentaram menor mortalidade e maior sobrevida que os pacientes com vírus da hepatite B.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Abstract: INTRODUCTION: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

The putative catalytic role of higher serotonin bioavailability in the clinical response to exposure and response prevention in obsessive-compulsive disorder

Objective: Exposure and response prevention (ERP) is effective to treat obsessive-compulsive disorder (OCD), but the lack of tolerance to the aversion nature of exposure techniques results in a high drop-out rate. There have been reports of a generic stress endurance effect of serotonin (5-HT) in the central nervous system (CNS) which might be explained by suppression of defensive fixed action patterns. Previous studies have proposed that higher baseline 5-HT concentration and slow decrease in concentration during drug treatment of OCD were predictors of good clinical response to 5-HT reuptake inhibitors. The objective of this study was to investigate whether pre-treatment platelet rich plasma (PRP) 5-HT concentration is associated with latency of treatment response and final response to an ERP protocol for obsessive-compulsive disorder (OCD). Methods: Thirty adult and treatment-free OCD patients were included in an 8-week, 16-session ERP protocol. 5-HT concentration was determined at baseline and after treatment. Patients with a reduction ≥30% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of ERP were defined as responders. Results: A positive correlation between baseline 5-HT concentration and reduction of symptoms on the Y-BOCS was observed after 4 weeks. Baseline 5-HT concentration was not correlated with clinical response after 8 weeks of ERP, possibly due to the similar though delayed clinical response of patients with lower (compared to those with higher) baseline 5-HT concentration. Patients with higher 5-HT baseline concentration also showed more improvement in depressive symptoms with treatment. Conclusion: The present results partially support the hypothesis of a stress endurance effect of 5-HT in OCD patients. According to the literature, fast onset responders possibly have more or larger 5-HT containing neurons, higher endogenous 5-HT synthesis or lower monoamine oxidase activity; all these hypotheses remain to be investigated.

Reconhecimento materno na Unidade de Cuidado Intensivo Neonatal / Reconocimiento materno en la Unidad de Cuidado Intensivo Neonatal / Mother recognition in the Neonatal Intensive Care Unit

RESUMO Objetivo: analisar experiências maternas em Unidade de Cuidado Intensivo Neonatal, com foco nas relações de reconhecimento. Método: estudo qualitativo, desenvolvido na perspectiva da hermenêutica gadameriana, fundamentado no conceito honnethiano de reconhecimento. Foram entrevistadas, em profundidade, dez mães de crianças internadas em Unidade de Cuidado Intensivo Neonatal. Resultados: há comprometimentos no processo de reconhecimento materno na unidade e, como desdobramento, surgem sentimentos de obrigação e insegurança para o cuidado do filho e fragilidades na autoestima. Conclusão: as interações com os profissionais de saúde e as normas e protocolos ali existentes promovem vulnerabilidades e comprometem o reconhecimento e a autonomia materna. .

RESUMEN Objetivo: analizar la experiencia derivada de la maternidad en la Unidad de Cuidados Intensivos Neonatales, centrándose en las relaciones de reconocimiento. Método: estudio cualitativo, desarrollado desde la perspectiva de la hermenéutica de Gadamer, basado en el concepto honnethiano de reconocimiento. Fueron entrevistados en profundidad diez madres de niños ingresados en una Unidad de Cuidados Intensivos Neonatales. Resultados: existen deficiencias en el proceso de reconocimiento materno en la UCIN y, por consiguiente, surgen sentimientos de inseguridad y obligación de cuidar de su hijo resultando en debilidades en su autoestima. Conclusión: las interacciones con profesionales de la salud en la unidad y las normas y protocolos allí existentes llevan a vulnerabilidades y comprometen el reconocimiento y autonomía materna. .

ABSTRACT Objective: analyze the maternal experience in a neonatal intensive care unit, focusing on relations of recognition. Method: a qualitative study, built on the perspective of Gadamer’s hermeneutics, based on Honneth’s concept of recognition. In-depth interviews were conducted with 10 mothers of children admitted to a neonatal intensive care unit. Results: failures were reported in the process of mother recognition in the unit, with consequent feelings of insecurity and obligation to child care, resulting in fragility of self-esteem. Conclusion: interactions with health professionals in the NICU and its standards and protocols cause vulnerabilities and affect maternal recognition and autonomy. .

Effects of Platelet Lysate Preparations on the Proliferation of HaCaT Cells

BACKGROUND: Standard protocols are lacking for the preparation of platelet lysates (PL) as an alternative to using fetal bovine serum as a cell culture supplement. This study aimed to establish optimum conditions for preparing PL for use in cell cultures. METHODS: Cell density in three pooled platelet concentrates (PC) were adjusted to 1x10(12)/L and 2x10(12)/L. PL was prepared from PC by 1 to 3 freeze-thaw (FT) cycles. HaCaT cells were cultured in media supplemented with 5% or 10% PL. Cell numbers were estimated using a Cell Counting Kit-8 (CCK-8; Dojindo Laboratories, Japan). Growth factors were quantified by using the Luminex 200 system (Luminex Corporation, USA). RESULTS: Cell proliferation rates in the presence of PLs were similar when prepared from PCs of both cell densities. The rates were higher in media containing 5% PL than 10% PL when prepared by two FT cycles. Concentrations of vascular endothelial growth factor (VEGF), platelet-derived growth factor-AB/BB (PDGF-AB/BB), PDGF-AA, and epidermal growth factor (EGF) were significantly higher in PL prepared from PC with a cell density of 2x10(12)/L than 1x10(12)/L PC. However, only VEGF and PDGF-AA concentrations in PLs were correlated with HaCaT cell counts. CONCLUSIONS: The 5% PL from PC with a cell density of 1x10(12)/L prepared by two FT cycles treatment was the most effective condition that supported steady HaCaT cell proliferation. Our finding may be useful for preparing PL-supplemented cell culture media.

Preliminary comparative analysis of antibacterial effects of activated and non-activated of expired platelet concentrate by disc diffusion method.

Background: Platelets release more than 30 cytokines to provide primary hemostatic function. In addition, platelets are also known to release antimicrobial peptides upon activation by thrombin. Materials and Methods: In this study, comparative analysis of antibacterial activity of activated and non-activated expired platelet concentrate was determined against Gram-positive and Gram-negative bacteria by Kirby-Bauer disk diffusion method. Thrombin was used to prepare activated platelet concentrate. Gram-positive bacteria tested in this study were S.aureus and S.pyogenes and Gram-negative bacteria were E.coli and K.oxytoca. All the bacteria used in this study were sensitive strains from clinical isolates. Activated and non-activated platelet showed no zone of inhibition against S.pyogenes and E.coli. Results: Activated platelet showed antibacterial activity against S.aureus and K.oxytoca with the zone of inhibition of 8.3 ± 0.6 mm and 7.7 ± 0.2 mm, respectively. Zone of inhibition observed in non-activated platelet against S.aureus and K.oxytoca were 7.8 ± 0.4 mm and 7.5 ± 0.3 mm, respectively. Conclusions: These findings showed that no significant differences in antibacterial activity produced by activated and non-activated platelet. However, zone of inhibition observed in activated and non-activated platelet indicate the presence of antibacterial property in expired platelet.

Implementación de una técnica in house para la producción de geles de plaquetas a partir de hemocomponentes de donantes voluntarios / Implementation of an in house technique to produce platelets gel from blood components from volunteer blood donors

Se implementó una técnica para producir geles de fibrina y geles de plaquetas a partir de hemocomponentes de banco de sangre, en el Hospital Nacional de Niños de Costa Rica. Se aplicaron nueve combinaciones de, tres volúmenes de gluconato de calcio al 10% y tres volúmenes del sobrenadante de trombina obtenido a partir de plasma fresco congelado (PFC), con un volumen definido de PFC (plasma pobre en plaquetas) o, el mismo volumen de concentrado de plaquetas (CP). Se midieron los tiempos de gelificación in vitro, obteniéndose que la combinación 6 mL PRP/PPP más 0.5 mL de gluconato de calcio al 10% más 1.5 mL trombina, parece ser la más adecuada. Las pruebas de tamizaje de la coagulación son útiles para explicar tiempos de gelificación tardíos.

Protein Profile Changes in Platelet Concentrates According to Storage and Leukoreduction- Analysis Using Proteomics Technology / 대한진단검사의학회지

BACKGROUND: Knowing how the protein profile of platelet products changes with storage or leukoreduction may give us greater insight into cell physiology and the cause of transfusion reactions other than cytokines and chemokines. METHODS: We filtered four packs of platelet concentrates (PC) within 24 hr of blood collection and after 120 hrs of storage. Four aliquots of each supernatant in PC were obtained: pre-storage+prefiltration, pre-storage+post-filtration, post-storage+pre-filtration and post-storage+post-filtration. Routine chemistry tests and a two-dimensional electrophoresis (2-DE) were performed. The stained images were analyzed and the significant spots were identified using a peptide mass finger printing (PMF) with matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis after trypsin digestion. RESULTS: The protein spots increased with storage and decreased after filtration (P<0.05, prestorage+post-filtration). The spot density of various proteins, including macrophage inflammatory protein-2 alpha, megakaryocyte colony stimulating factor and interleukin-22 changed with storage and leukoreduction. CONCLUSIONS: The database of identified protein spots and their changes produced in this study is a useful basic tool for future studies on the mechanism of transfusion reactions. Further studies should validate the significance of each protein spot.

Brain ischemia alters platelet ATP diphosphohydrolase and 5'-nucleotidase activities in naive and preconditioned rats

The effects of transient forebrain ischemia, reperfusion and ischemic preconditioning on rat blood platelet ATP diphosphohydrolase and 5'-nucleotidase activities were evaluated. Adult Wistar rats were submitted to 2 or 10 min of single ischemic episodes, or to 10 min of ischemia 1 day after a 2-min ischemic episode (ischemic preconditioning) by the four-vessel occlusion method. Rats submitted to single ischemic insults were reperfused for 60 min and for 1, 2, 5, 10 and 30 days after ischemia; preconditioned rats were reperfused for 60 min 1 and 2 days after the long ischemic episode. Brain ischemia (2 or 10 min) inhibited ATP and ADP hydrolysis by platelet ATP diphosphohydrolase. On the other hand, AMP hydrolysis by 5'-nucleotidase was increased after 2, but not 10, min of ischemia. Ischemic preconditioning followed by 10 min of ischemia caused activation of both enzymes. Variable periods of reperfusion distinctly affected each experimental group. Enzyme activities returned to control levels in the 2-min group. However, the decrease in ATP diphosphohydrolase activity was maintained up to 30 days of reperfusion after 10-min ischemia. 5'-Nucleotidase activity was decreased 60 min and 1 day following 10-min ischemia; interestingly, enzymatic activity was increased after 2 and 5 days of reperfusion, and returned to control levels after 10 days. Ischemic preconditioning cancelled the effects of 10-min ischemia on the enzymatic activities. These results indicate that brain ischemia and ischemic preconditioning induce peripheral effects on ecto-enzymes from rat platelets involved in nucleotide metabolism. Thus, ATP, ADP and AMP degradation and probably the generation of adenosine in the circulation may be altered, leading to regulation of microthrombus formation since ADP aggregates platelets and adenosine is an inhibitor of platelet aggregation

Carbohydrate induced modulation of cell membrane. IV: Interaction with mucin and fucoidan totally immobilizes the human platelet membrane.

P selectins and E selectins are cell adhesion molecules that mediate the interaction of platelets and endothelial cells with neutrophils and monocytes. The proposed ligands for these receptors contain the Le(x) core, sialic acid and sulfated fucose. In this paper we report that binding of sialic acid markedly restricts the mobility of membrane proteins and lipids as studied by EPR spectroscopy using spin probes. Binding of mucin and fucoidan totally restricts the mobility probably due to cross-linking of the surface lectins. Binding of these ligands also resulted in an increase in the cytoplasmic viscosity.

Physiology and function of platelets from patients with Alzheimer's disease.

The discovery that intact Alzheimer amyloid precursor protein is present in platelet granules, has created a great interest in the biochemistry, physiology and function of platelets of patients with Alzheimer disease (AD). In this study we monitored various biochemical and physiological parameters, such as serotonin and adenine nucleotide levels, membrane fluidity, agonist-mediated release of arachidonic acid, thromboxane formation, calcium mobilization, as well as irreversible aggregation and secretion of granule contents. Platelets of patients with AD responded poorly when stirred with weak or potent agonists on a platelet aggregometer. Although capable of agonist-mediated calcium mobilization and synthesis of thromboxanes, the aggregation response of platelets of patients with AD to thrombin and archidonate was considerably compromised. In view of the normal biochemistry and signal transduction capabilities, the compromised response of these cells to potent agonists like thrombin suggested an extrinsic defect. The present study has shown that a plasmatic factor is at least in part responsible for the functional abnormalities of AD platelets.

Elevated levels of plasma and platelet PAI-1 in type II diabetes: relationships with plasma insulin and lipoproteins

This study aimed to measure both plasma and platelet PAI-1 in type II diabetes and to investigate the relationship between PAI-1 levels and plasma insulin and lipoproteins. The data obtained suggested that higher level of platelet PAI-1 may contribute to impaired fibrinolysis seen in type II diabetes. Concordant increase of platelet PAI-1 and plasma insulin suggested that hyperinsulinemia presents in type II diabetes may have direct effects on the synthesis of platelet PAI-1

The kinetics of chondroitin 4-sulfate release from stimulated platelets and its relation to thromboxane A2 formation and granule secretion

1. In platelet rich plasma (PRP), chondroitin 4-sulfate release from platelets occurred after stimulation with ADP (5µM), collagen (5-10µM). Release started within 60 s and maximum release (0.7-2.0 mg/l) was reached within 180 s. TXA2 formation and dense granule release reached a maximum within 90 s after stimulation. 2. Using washed platelets (1.5 x 10**8 cells/ml), the platelet responses were faster. Release of chondroitin 4-sulfate and TXA2 started within 20-30 s after thrombin addition (100 mU/ml). Maximum release was reached within 60 s in both cases. Dense granule release started in the first 5 s of stimulation (34.6 ñ 12.4 por cento) reaching maximum secretion (74.4 ñ 8.7 por cento) within 60 s. 3. Our results demonstrate that maximal chondroitin 4-sulfate release occurs after the dense granule release reaction in both PRP and washed platelets. This observation suggests that chondroitin 4-sulfates is unlikely to be stored in the dense granules but may be stored in the alfagranules

Phosphoinositides of sheep platelets plasma membranes.

Phospholipid composition of sheep blood platelets and its various plasma membrane fractions have been analyzed. Based on their flotation rates in discontinuous sucrose density gradient centrifugation, three membrane fractions were isolated. 5'-Nucelotidase and alkaline phosphatase were distributed nearly equally in all the three membrane fractions. However these membrane fractions showed differences in the distribution of phosphatidyl ethanolamine, phosphatidyl choline and phosphoinositides. Phosphatidyl ethanolamine was predominant in fraction I (11.05 micrograms PLP/mg protein) while phosphatidyl choline was predominant in fractions II and III (110.10 and 68.30 micrograms PLP/mg protein respectively). Phosphatidyl inositol (Ptd-InsP) was equally distributed in all three membrane fractions. However, both Ptd-InsP and phosphatidyl inositol 4,5-bisphosphate were about 4-fold higher in fraction II (73.55 and 89.89 micrograms PLP/mg protein respectively).

Platelet antibodies in bilharzial Hepatosplenomegaly

This study was conducted on forty subjects, thirty male patients with bilharzial hepatosplenomegaly and ten healthy control subjects matched for age and sex. Platelets were studied quantitatively and platelet functions were assessed by bleeding time, clot retraction, platelet adhesion and aggregation. Immunological investigations including determination of serum immunoglobulins [IgG, IgM, and IgA], serum complement [C3c and C4], circulating immune complexes [CICs], as well as clot retraction test for detection of platelet antibodies. There was a significant reduction of platelet count and a negative correlation between the platelet count and the platelet antibodies in patients group. Diminished platelet functions were demonstrated by decreased platelet adhesion, decreased clot retraction, and impaired adenosine diphosphate [ADP] aggregation. No statistical correlation was found between the impairment of aggregation and the degree of inhibition of clot retraction. On the contrary, and inverse correlation was demonstrated between clot retraction and platelet antibodies. Significant higher levels of IgG and IgM in patients' group were detected whereas serum IgA levels showed no statistical difference. Significantly increased levels of serum C3c were demonstrated and there was an inverse correlation between C3c levels and platelet count, however, there was no correlation between serum C3c and platelet antibodies. Serum levels of C4 were not significantly deviated from normal levels. Serum levels of CICs were higher in patients' group and a significant positive correlation was found between these complexes and serum IgG levels. In conclusion, the present study proved the presence of platelet antibodies in patients with bilharzial hepatosplenomegaly. The observed quantitative and qualitative platelet defects in those patients had been correlated to the presence of platelet antibodies and the concomitant immunological disturbances