RESUMEN
BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.
Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Hepatitis B/tratamiento farmacológico , Hepatitis B/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Asia/epidemiología , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Abuso de Medicamentos/estadística & datos numéricos , Femenino , Mal Uso de los Servicios de Salud/estadística & datos numéricos , Hepatitis B/complicaciones , Virus de la Hepatitis B/fisiología , Humanos , Prescripción Inadecuada/estadística & datos numéricos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/mortalidad , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
The presence of lysozyme in human epidermis was determined in extracts from the surface of human skin and in sonicates of human epidermal cell preparations with the use of a bacteriolytic assay employing Micrococcus lysodeikticus cell walls as substrate. Preincubation of the extracts with the Fab portion of the IgG fraction of an antiserum to human lysozyme abolished the lytic activity of the extracts showing the specificity of the assay. De novo synthesis of lysozyme by human epidermal cells was demonstrated by radiolabeling studies. Human epidermal cells cultured in serum-free medium and pulsed with [3H]leucine for 24 h were sonicated and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A major band at Mr 14,500 exhibited both immunoreactivity with a rabbit antihuman lysozyme antibody and radioactivity. Gel filtration of the cell sonicate revealed bacteriolytic activity in the fractions containing radioactive and immunoreactive proteins. These findings suggest that lysozyme is newly synthesized by human epidermal cells.
Asunto(s)
Epidermis/enzimología , Muramidasa/biosíntesis , Células Cultivadas , Humanos , Peso MolecularRESUMEN
The nature of elastotic material in sun-damaged human skin was investigated by indirect immunofluorescence. Antibodies were used against the following components of the dermis: type I and type VI collagens, aminopropeptide of type I and type III procollagens, fibronectin, elastin, microfibrillar proteins, and basement membrane represented by the 7S domain of type IV collagen, laminin, and nidogen. The elastotic material exhibited marked fluorescence for elastin and microfibrillar proteins which codistributed with fibronectin. The presence of type I and VI collagens and procollagen type III were demonstrated to a lesser extent within the elastotic material. These results suggest that solar elastosis is primarily derived from elastic fibers and not from preexisting or newly synthesized collagens.
Asunto(s)
Trastornos de la Pigmentación/etiología , Rayos Ultravioleta/efectos adversos , Anticuerpos/análisis , Colágeno/inmunología , Tejido Elástico/inmunología , Elastina/inmunología , Fibronectinas/inmunología , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoquímica , Microscopía Fluorescente , Pigmentación de la PielRESUMEN
The densities of T6 antigen-bearing Langerhans cells in 112 biopsies of human skin from sixteen surgical out-patients and four cadavers were determined for eight anatomical regions. The regional mean densities (+/- s.e.m.) of epidermal Langerhans cells per mm2 were: head and neck, 489 +/- 27; chest, 466 +/- 22; back, 466 +/- 11; upper extremities, 458 +/- 25; lower extremities, 431 +/- 30; buttocks, 411 +/- 11; genitalia, 298 +/- 45; soles, 58 +/- 12. No statistically significant differences were found between any of these Langerhans cell densities except for that of the soles which was lower than those of all other regions (P less than 0.002). No significant differences were detected between the mean densities of patients and cadavers, Caucasians and Hispanics or males and females.
Asunto(s)
Células Epidérmicas , Células de Langerhans/citología , Adulto , Anciano , Dorso , Nalgas , Recuento de Células , Femenino , Pie , Genitales , Mano , Cabeza , Humanos , Masculino , Persona de Mediana Edad , Cuello , TóraxRESUMEN
Three electrolyte solutions were used as priming perfusates for 1 hour of cardiopulmonary bypass in 9 dogs. Arterial blood pressure was maintained at a satisfactory level during perfusion and returned to the original ranges shortly after bypass. Measurement of various blood constituents indicated that they were constantly maintained in the normal range during the procedure. The PVC decreased sharply until the 3rd postperfusion day, then returned to the base-line values. Similar patterns were obtained for each solution, with no additional infusion being administered after bypass. All dogs recovered without complications and evidence of cerebral abnormalities was not seen. The dogs were euthanatized and necropsied 14 days after surgery and all major organs appeared normal on gross examination.