RESUMEN
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. METHODS: Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. RESULTS: Serum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. CONCLUSIONS: Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.
Asunto(s)
Estenosis Carotídea/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Lipocalina 2/metabolismo , Metformina/uso terapéutico , Anciano , Biomarcadores/sangre , Arterias Carótidas/metabolismo , Enfermedades de las Arterias Carótidas/metabolismo , Estenosis Carotídea/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/sangreRESUMEN
Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities. We investigated the association of eight different cytokines with venous thromboembolism (VTE) and prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a prospective study, includes patients with newly diagnosed tumour or disease progression. Patients with an overt infection are excluded. Study end-points are VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels were measured using the xMAP technology developed by Luminex. Among 726 included patients, no associations between IL levels and VTE were found, with the exception of a trend for IL-1ß and IL-6 in pancreatic cancer. Elevated levels of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1·07, 95% confidence interval (CI) = 1·027-1·114, P = 0·001, IL-8 (HR = 1·12, 95% CI = 1·062-1·170, P < 0·001) and IL-11 (HR = 1·37, 95% CI = 1·103-1·709, P = 0·005] were associated with worse survival. In subgroup analyses based on tumour type, colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival (HR = 2·405, 95% CI = 1·252-4·618, P = 0·008). A significant association of elevated IL-10 levels with a decrease in survival (HR = 1·824, 95% CI = 1·098-3·031, P = 0·020) was seen among patients with lung cancer. No correlation between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were associated with worse survival in cancer patients. Further, elevated IL-6 levels might be a prognostic marker in colorectal cancer and elevated IL-10 levels in lung cancer patients.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/diagnóstico , Interleucinas/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Tromboembolia Venosa/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/inmunología , Neoplasias del Colon/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/mortalidad , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Tromboembolia Venosa/inmunología , Tromboembolia Venosa/mortalidadRESUMEN
BACKGROUND AND OBJECTIVES: P-selectin is stored in the alpha granules of platelets and in the Weibel Palade bodies of endothelial cells; upon activation, it is translocated to the cell surface and released into the plasma in soluble form. One variant of the P-selectin gene, the Thr715Pro polymorphism, is strongly associated with the plasma levels of soluble P-selectin. In platelet concentrates soluble P-selectin can be regarded mainly platelet derived. MATERIALS AND METHODS: The relation of the genotype with soluble P-selectin, platelet expressed P-selectin and the sum of all forms of P-selectin - comprising soluble P-selectin, platelet surface P-selectin and P-selectin from the alpha granules - was assessed in fresh whole blood and in apheresis platelets suspended in 35% plasma/65% SSP+ obtained from 89 platelet donors. RESULTS: Levels of total P-selectin were genotype associated (P = 0·025); likewise, in fresh whole blood there was an association of soluble P-selectin with genotype (P = 0·02). In platelets suspended in additive solution, however, levels of the storage-associated or TRAP-6 agonist induced increase of platelets' P-selectin were not associated with the genotype. A correlation between levels of soluble P-selectin and surface expression of P-selectin was observed on day 3 of storage in Thr715Thr individuals (P < 0·0001), but not in heterozygotes (Thr715Pro, P = 0·2). CONCLUSION: The donors' genotype has only little influence on levels of soluble P-selectin in apheresis platelets suspended in 35% plasma/65% SSP+.
Asunto(s)
Plaquetas/metabolismo , Selectina-P/genética , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Fragmentos de Péptidos/agonistas , Plaquetoferesis , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS: We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringer's lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS: The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS: Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.
Asunto(s)
Albúminas/farmacología , Coagulación Sanguínea/efectos de los fármacos , Procedimientos Quirúrgicos Cardíacos , Derivados de Hidroxietil Almidón/farmacología , Soluciones Isotónicas/farmacología , Hemorragia Posoperatoria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Fluidoterapia/métodos , Hemodilución/métodos , Hemodilución/estadística & datos numéricos , Hemostasis/efectos de los fármacos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Sustitutos del Plasma/farmacología , Lactato de Ringer , Adulto JovenRESUMEN
UNLABELLED: Osteoporotic fracture risk depends on bone mineral density (BMD) and clinical risk factors (CRF). Five hundred and eighty-eight untreated female and male outpatient subjects were evaluated, 160 with vertebral fractures. BMD was measured both by using calcaneal dual X-ray and laser (DXL) and dual-energy X-ray absorptiometry (DXA), and CRF were evaluated. Detection frequencies for different BMD methods with or without CRF are presented. INTRODUCTION: Osteoporotic fracture risk depends on bone mineral density and clinical risk factors. DXA of the spine/hip is considered a gold standard for BMD assessment, but due to degenerative conditions, particularly among the older population, assessment of BMD at the lumbar spine has been shown to be of limited significance. Portable calcaneal dual X-ray technology and laser can be an easily obtainable alternative. METHODS: Vertebral fractures were evaluated in a baseline analysis of 588 females and males (median age 64.4, range 17.6-93.1 years), comparing BMD measurements by using DXL and DXA and CRF with/without BMD. One hundred and sixty subjects had radiological verified vertebral fractures. Area under receiver-operating characteristic curves (AUROCC) and univariate and multiple logistic regressions were calculated. RESULTS: AUROCC for detection of vertebral fractures was comparable for DXL at calcaneus and DXA at femoral neck (DXL 0.665 and DXA 0.670). Odds ratio for prevalent vertebral fracture was generally weak for DXA femoral neck (0.613) and DXL (0.521). Univariate logistic regression among CRF without BMD revealed age, prevalent fragility fracture, and body mass index significantly associated with prevalent vertebral fracture (AUROCC = 0.805). Combining BMD and CRF, a prognostic improvement in case of DXA at femoral neck (AUROCC 0.869, p = 0.02), DXL at calcaneus (AUROCC 0.869, p = 0.059), and DXA at total hip (AUROCC 0.861, p = 0.06) was observed. CONCLUSIONS: DXL was similarly sensitive compared with DXA for identification of subjects with vertebral fragility fractures, and combination of CRF with BMD by DXL or DXA further increased the discriminatory capacity for detection of patients susceptible to vertebral fracture.
Asunto(s)
Densidad Ósea/fisiología , Calcáneo/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Absorciometría de Fotón/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Cuello Femoral/fisiopatología , Humanos , Rayos Láser , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/fisiopatología , Factores de Riesgo , Sensibilidad y Especificidad , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/fisiopatología , Adulto JovenAsunto(s)
Conducción Ósea , Senos Craneales/patología , Duramadre/patología , Audífonos , Pérdida Auditiva/terapia , Implantación de Prótesis , Adolescente , Adulto , Anciano , Femenino , Pérdida Auditiva/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Recent sound coding strategies for cochlear implants (CI) have focused on the transmission of temporal fine structure to the CI recipient. To date, knowledge about the effects of fine structure coding in electrical hearing is poorly charactarized. The aim of this study was to examine whether the presence of temporal fine structure coding affects how the CI recipient perceives sound. This was done by comparing two sound coding strategies with different temporal fine structure coverage in a longitudinal cross-over setting. The more recent FS4 coding strategy provides fine structure coding on typically four apical stimulation channels compared to FSP with usually one or two fine structure channels. 34 adult CI patients with a minimum CI experience of one year were included. All subjects were fitted according to clinical routine and used both coding strategies for three months in a randomized sequence. Formant frequency discrimination thresholds (FFDT) were measured to assess the ability to resolve timbre information. Further outcome measures included a monosyllables test in quiet and the speech reception threshold of an adaptive matrix sentence test in noise (Oldenburger sentence test). In addition, the subjective sound quality was assessed using visual analogue scales and a sound quality questionnaire after each three months period. The extended fine structure range of FS4 yields FFDT similar to FSP for formants occurring in the frequency range only covered by FS4. There is a significant interaction (p = 0.048) between the extent of fine structure coverage in FSP and the improvement in FFDT in favour of FS4 for these stimuli. FS4 Speech perception in noise and quiet was similar with both coding strategies. Sound quality was rated heterogeneously showing that both strategies represent valuable options for CI fitting to allow for best possible individual optimization.
Asunto(s)
Cóclea/fisiopatología , Implantación Coclear/instrumentación , Implantes Cocleares , Pérdida Auditiva/terapia , Audición , Personas con Deficiencia Auditiva/rehabilitación , Discriminación de la Altura Tonal , Percepción del Habla , Estimulación Acústica , Adolescente , Adulto , Anciano , Comprensión , Estudios Cruzados , Estimulación Eléctrica , Femenino , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/fisiopatología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ruido/efectos adversos , Enmascaramiento Perceptual , Personas con Deficiencia Auditiva/psicología , Inteligibilidad del Habla , Adulto JovenRESUMEN
BACKGROUND: Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. METHODS: Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to <350 ms. Patients were connected to a monitoring device, obtaining SVV by APCO. Haemodynamic variables were recorded before and after fluid bolus application. Fluid responsiveness was defined as an increase in stroke volume index >10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. RESULTS: Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). CONCLUSIONS: This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.
Asunto(s)
Monitoreo Intraoperatorio/métodos , Volumen Sistólico , Abdomen/cirugía , Adulto , Anciano , Algoritmos , Ecocardiografía Transesofágica , Métodos Epidemiológicos , Femenino , Fluidoterapia/métodos , Hemodinámica , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Dual-antiplatelet therapy (DAPT) is a standard strategy in acute coronary heart disease; however, it confers a considerable bleeding risk. Single-antiplatelet therapy (SAPT) inhibits haemostatic system activation ex vivo to a similar extent as DAPT. Extracellular vesicles (EV) are procoagulant and contribute to haemostatic system activation. We aimed to investigate the effect of DAPT compared with SAPT on EV. METHODS: In a randomized, double-blind, placebo-controlled trial, 44 healthy volunteers received DAPT (clopidogrelâ¯+â¯aspirin) or SAPT (clopidogrelâ¯+â¯placebo) for 7â¯days. Blood was obtained from a standardized microvascular injury and through venipuncture at baseline (BL) and at 2â¯h, 24â¯h, and 8â¯days after treatment initiation. The number, origin, and surface expression of EV were assessed using flow cytometry. Data are given as median (quartiles). Non-parametric tests were used to evaluate the short-term (BL vs 2â¯h) and long-term differences (2â¯h to 8â¯days), as well as the differences between treatment groups. RESULTS: There was no difference either in the short-term effects on the number (×103â¯mL-1) of EV in microvascular blood between DAPT [BL: 1433 (653; 3184) vs 2â¯h: 862 (545; 2026), pâ¯=â¯0.39] and SAPT [(BL: 614 (552; 1402) vs 2â¯h: 1079 (781; 1538), pâ¯=â¯0.75)] or in the long-term effects. DAPT and SAPT did not exhibit differential short-term effects on the number and proportion (36% and 27% vs 55% and 36%) of platelet-derived EV. DAPT and SAPT resulted in a significant short-term increase in phosphatidylserine expression in microvascular blood. The effects of DAPT and SAPT on EV in venous blood were similar to those in microvascular blood. CONCLUSION: DAPT and SAPT have comparable effects on the amount, origin, and surface characteristics of EV.
Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Vesículas Extracelulares/efectos de los fármacos , Hemostasis/efectos de los fármacos , Microcirculación/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Adulto , Aspirina/farmacología , Clopidogrel/farmacología , Voluntarios Sanos , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/farmacologíaRESUMEN
BACKGROUND: Tumor spread to the knee joint or skip metastasis to the adjacent bones of the knee require reconstruction with combined distal femur and proximal tibia replacements. The literature on implant survival and failure modes with this type of reconstruction is sparse. The goals of this study were to determine the implant survival, the different failure modes and the functional outcome of this megaendoprosthetic reconstruction. PATIENTS AND METHODS: Thirty-nine patients with combined distal femur and proximal tibia reconstruction were retrospectively reviewed. Median follow-up was 8.8 years (quartiles 4.7-15.5 years). Twenty-one patients received combined distal femur and proximal tibia reconstruction as a primary mode of reconstruction, 18 patients as revision surgery after failed tumor prosthesis. For survival estimations, competing risk analyses were performed. RESULTS: The revision-free survival at five years was 42% (95% CI 22%-56%) and implant survival with exchange of the original implant was 54% (95% CI 35%-68%). Five-year revision-free survival for soft tissue failure was 72% (95% CI 52%-84%), for infection 67% (95% CI 48%-80%), for structural failure 82% (95% CI 63%-91%), for aseptic loosening and tumor progression 97% (95% CI 82%-99%), respectively. Patients with revision surgery had higher risk for infection (p < 0.001), structural failure (p = 0.037) and shorter revision-free- (p = 0.025) and implant-survival (p = 0.006). Limb survival at 20 years was 94%. Mean musculoskeletal Tumor Society score was 76%. CONCLUSION: Despite high failure rates with short revision-free survivals, combined distal femur and proximal tibia reconstruction achieved longtime limb survival in the majority of patients with satisfying function.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Neoplasias Óseas/cirugía , Neoplasias Femorales/cirugía , Prótesis de la Rodilla , Procedimientos de Cirugía Plástica/métodos , Tibia/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Niño , Femenino , Neoplasias Femorales/patología , Humanos , Masculino , Persona de Mediana Edad , Falla de Prótesis , Reoperación , Estudios Retrospectivos , Tibia/patología , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
AIMS: Pelvic reconstruction after the resection of a tumour around the acetabulum is a challenging procedure due to the complex anatomy and biomechanics. Several pelvic endoprostheses have been introduced, but the rates of complication remain high. Our aim was to review the use of a stemmed acetabular pedestal cup in the management of these patients. PATIENTS AND METHODS: The study involved 48 patients who underwent periacetabular reconstruction using a stemmed pedestal cup (Schoellner cup; Zimmer Biomet Inc., Warsaw, Indiana) between 2000 and 2013. The indications for treatment included a primary bone tumour in 27 patients and metastatic disease in 21 patients. The mean age of the patients at the time of surgery was 52 years (16 to 83). RESULTS: At a median follow-up of 6.6 years (95% confidence interval 4.6 to 8.2), local control was achieved in all patients; 19 patients had died (16 of disease). Complications occurred in 19 patients (40%), of which deep infection was the most common, affecting eight patients (17%). Seven patients (15%) had a dislocation of the hip. Aseptic loosening was found in three patients (6%). Two (4%) underwent hindquarter amputation for non-oncological reasons. The risk of revision, with death being treated as a competing event, was 28% at one year, 39% at five years and 48% at ten years post-operatively. The mean Musculoskeletal Tumour Society Score at final follow-up was 71% (27% to 93%). CONCLUSION: This type of reconstruction is a satisfactory option for the treatment of patients with a periacetabular tumour. There remains, however, a high rate of complication, which may be reduced by future modifications of the device such as silver coating and tripolar articulation. Cite this article: Bone Joint J 2017;99-B:841-8.
Asunto(s)
Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/métodos , Neoplasias Óseas/cirugía , Prótesis de Cadera , Acetábulo/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Neoplasias Óseas/diagnóstico por imagen , Estudios de Seguimiento , Prótesis de Cadera/efectos adversos , Humanos , Recuperación del Miembro/efectos adversos , Recuperación del Miembro/métodos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Complicaciones Posoperatorias , Diseño de Prótesis , Falla de Prótesis , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
AIMS: Few studies dealing with chondrosarcoma of the pelvis are currently available. Different data about the overall survival and prognostic factors have been published but without a detailed analysis of surgery-related complications. We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at a single institution, with particular attention to the prognostic factors. Based on a competing risk model, our objective was to identify risk factors for the development of complications. PATIENTS AND METHODS: In a retrospective single-centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years). RESULTS: A total of 26 patients (45%) were alive and 32 patients (55%) had died. Overall survival was 76%, 55% and 45% at one, five and ten years post-operatively, respectively. In a competing risk model the cumulative risk of the development of a surgery-related complication was 64% at six months and 69% at one year, post-operatively, respectively. Endoprosthetic reconstruction was a significant risk factor for the development of complications (p = 0.006). Complications were not significantly related to age or the location or grade of the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications did not have a negative effect on survival (p = 0.147). CONCLUSION: This is the first study with competing risk analysis of surgery-related complications in patients with a pelvic chondrosarcoma. The surgery in these patients remains prone to complications. Endoprosthetic reconstruction significantly increases the risk of the development of complications (p = 0.006). A competing risk model showed that the development of complications does not have a negative influence on overall survival (p = 0.147). An aggressive, surgical resection with the goal of achieving wide margins whenever possible remains the mainstay of treatment. Cite this article: Bone Joint J 2017;99-B:686-96.
Asunto(s)
Neoplasias Óseas/cirugía , Condrosarcoma/cirugía , Huesos Pélvicos/cirugía , Adulto , Anciano , Neoplasias Óseas/patología , Condrosarcoma/patología , Condrosarcoma/secundario , Femenino , Humanos , Estimación de Kaplan-Meier , Recuperación del Miembro/efectos adversos , Recuperación del Miembro/métodos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Complicaciones Posoperatorias , Pronóstico , Sistema de Registros , Reoperación/estadística & datos numéricos , Medición de Riesgo/métodos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Angiogenesis (the formation of new blood vessels) appears to be required for the growth of invasive tumors, but little information exists about its role in the development of preinvasive lesions. We examined microvessel density and expression of vascular endothelial growth factor in specimens of cervical intraepithelial neoplasia (CIN), a preinvasive lesion of the uterine cervix, to determine whether a connection could be established between these parameters of angiogenesis and the grade of dysplasia (i.e., tissue abnormality). METHODS: Sections of biopsy specimens from 83 patients with grades I-III CIN were examined retrospectively. Microvessels were localized by use of a polyclonal antibody directed against factor VIII-related antigen; vascular endothelial growth factor was detected by means of a monoclonal antibody. Reported P values are two-sided. RESULTS: Highest microvessel densities and highest expression of vascular endothelial growth factor were found in a narrow border region between CIN lesions and the underlying stroma. A significant correlation was observed between high vascular endothelial growth factor expression and high microvessel density (Kendall's tau = 0.27; 95% confidence interval [CI] = 0.03-0.50; P = .018). Mean microvessel density values +/- standard deviations for CIN I, CIN II, and CIN III lesions were 19.4 +/- 5.8, 21.9 +/- 7.0, and 34.1 +/- 14.8, respectively (Kendall's tau = 0.46; 95% CI = 0.30-0.61; P<.0001). Corresponding values for vascular endothelial growth factor expression were 8.3 +/- 3.5, 8.4 +/- 2.0, and 12.2 +/- 3.6, respectively (Kendall's tau = 0.41; 95% CI = 0.20-0.60; P<.0001). CONCLUSIONS: Our results are consistent with the idea that progression of cervical dysplasia is dependent on angiogenesis.
Asunto(s)
Factores de Crecimiento Endotelial/biosíntesis , Regulación Neoplásica de la Expresión Génica , Linfocinas/biosíntesis , Displasia del Cuello del Útero/irrigación sanguínea , Displasia del Cuello del Útero/metabolismo , Femenino , Humanos , Estudios Retrospectivos , Displasia del Cuello del Útero/patología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Factor de von Willebrand/inmunologíaRESUMEN
UNLABELLED: ESSENTIALS: In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in ß-thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy. BACKGROUND: Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor. OBJECTIVES: To compare the effects of dual and single antiplatelet therapies on hemostatic system activation. PATIENTS/METHODS: In a randomized, parallel-group, double-blind, placebo-controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d(-1) ) and aspirin (100 mg d(-1) ) or placebo for 7 days; An additional 44 volunteers received single-dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. ß-Thromboglobulin (ß-TG [IU L(-1) ]) and prothrombin fragment 1.2 (f1.2 [nmol L(-1) ]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time. RESULTS: Clopidogrel plus aspirin and clopidogrel plus placebo reduced ß-TG by a GMR of 0.51 (0.42-0.63) and 0.54 (0.46-0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased ß-TG by a GMR of 0.38 (0.26-0.57) and 0.47 (0.31-0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45-0.75) and 0.55 (0.38-0.80); clopidogrel did not. Over 24 h, no difference in ß-TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -2.9 [-9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.5 [-11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -4.2 [-10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.6 [-10.9 to 3.7]). CONCLUSIONS: P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent.
Asunto(s)
Adenosina/análogos & derivados , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Receptores Purinérgicos P2Y12/efectos de los fármacos , Ticlopidina/análogos & derivados , Adenosina/administración & dosificación , Adenosina/efectos adversos , Adolescente , Adulto , Área Bajo la Curva , Aspirina/efectos adversos , Austria , Biomarcadores/sangre , Tiempo de Sangría , Plaquetas/metabolismo , Clopidogrel , Método Doble Ciego , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Protrombina , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Curva ROC , Receptores Purinérgicos P2Y12/metabolismo , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Factores de Tiempo , Adulto Joven , beta-Tromboglobulina/metabolismoRESUMEN
UNLABELLED: ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease. BACKGROUND: Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients. OBJECTIVES: As there are almost no data on longitudinal changes, we aimed to evaluate those in the present prospective observational study during chemotherapy and the course of disease. PATIENTS/METHODS: Patients with cancer of the brain (n = 39), lung (n = 41), colon (n = 15) or pancreas (n = 17) were included before initiation of antitumor therapy. Blood samples for determination of factor VIII, thrombin peak height, D-dimer, F1 + 2 , fibrinogen and soluble P-selectin (sP-selectin) were drawn on a monthly basis. The study endpoints were death, VTE occurrence, or completion of the study period. RESULTS: Overall, 546 blood samples of 112 patients were analyzed. D-dimer and sP-selectin levels were significantly higher in patients with distant metastasis than in those without. Patients with complete remission had significantly lower levels of F1 + 2 , D-dimer and fibrinogen. Peak height thrombin levels showed a decrease over time in all tumor types. Levels of biomarkers behaved differently in the various tumor types. Patients who developed VTE (n = 14) showed increasing levels of FVIII, sP-selectin, and D-dimer. At the last blood sampling time-point before VTE occurrence, in 13 patients the D-dimer level was above the median, and in seven of these patients it was even above the 75th percentile; however, the individual course was highly variable. Regarding survival, steadily increased FVIII, sP-selectin and D-dimer levels were associated with higher mortality. CONCLUSIONS: Hemostatic parameters show an association with disease state, prognosis, and the risk of VTE, not only at diagnosis, but also during the course of antineoplastic treatment.
Asunto(s)
Antineoplásicos/uso terapéutico , Hemostasis , Neoplasias/tratamiento farmacológico , Tromboembolia Venosa/etiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Factor VIII/metabolismo , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/mortalidad , Selectina-P/sangre , Fragmentos de Péptidos/sangre , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Protrombina , Medición de Riesgo , Factores de Riesgo , Trombina/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/sangre , Tromboembolia Venosa/mortalidad , Adulto JovenRESUMEN
INTRODUCTION: Platelets play a crucial role in cancer development, progression and metastatic spread of malignancy. In vitro data show that cancer cells have the ability to activate platelets, and clinical studies found increased levels of platelet activation markers in cancer patients. Moreover, platelets are thought to be involved in the development of venous thromboembolism (VTE) in cancer patients, a frequent complication of malignant disease associated with high morbidity and mortality. AIM: In this study, we aimed to examine the activation status of platelets in cancer patients and investigate the association with risk of future venous thromboembolism (VTE) and mortality. MATERIALS AND METHODS: In a prospective observational cohort study of cancer patients we measured pre-chemotherapy platelet P-selectin and glycoprotein (GP) IIb/IIIa expression and monocyte-platelet aggregates (MPA) in vivo and in response to ex vivo stimulation of the platelet activation receptors protease-activated receptor (PAR) -1, -4, and GPVI by whole blood flow cytometry. Primary and secondary endpoints of the study were occurrence of objectively confirmed VTE and death during 2-year follow-up, respectively. RESULTS: Out of 62 patients (median age [interquartile range, IQR]: 63 [54-70] years, 48% female) with cancers of the pancreas (n=19), lung (n=18), brain (n=14), colon (n=8) and stomach (n=3), 9 (14.5%) developed VTE and 32 (51.6%) died. P-selectin, activated GPIIb/IIIa expression and MPA formation did not significantly differ between tumor sites (Kruskal Wallis test). Reduced platelet responsiveness to PAR-1 and GPVI stimulation was associated with a higher risk of VTE (hazard ratio [HR] per decile increase in %P-selectin positive platelets: 0.73 [95% confidence interval: 0.56-0.92, p=0.007] and 0.77 [0.59-0.98, p=0.034], respectively; Table 1). Further, lower platelet P-selectin and activated GPIIb/IIIa expression in vivo and in response to PAR-1, -4 and GPVI stimulation, but not MPA formation, were associated with a higher risk of death (Table 1). CONCLUSIONS: Cancer patients with a poor prognosis had degranulated platelets, presumably as a consequence of previous activation. Our data suggest that platelets' continuous activation and thus exhaustion is involved in cancer-associated VTE and cancer mortality.
RESUMEN
This retrospective, observer blinded case-control study aims to compare the prevalence of neurovascular conflicts (NVCs) of the vestibulocochlear nerve and the anterior inferior cerebellar artery (AICA) in patients presenting with clinical signs of acute vestibular neuritis with and without subsequent objective vestibular function loss (VFL). 58 acute cases of clinically suspected acute vestibular neuritis were investigated with same day cranial MRI at a tertiary referral centre and compared to 61 asymptomatic controls. The prevalence of NVCs in cases with objective VFL were also compared to cases without VFL. Radiologists described the NVC as "no contact" (Grade 0), "contact < 2 mm" (Grade 1), "contact > 2 mm" (Grade 2) and "vascular loop presence" (Grade 3) without knowledge of neurotological data. Neurotological data was collected without knowledge of MRI findings. Vestibular function was tested by bithermic caloric irrigation. 26 cases (45%) showed caloric VFL (Group A), whereas 32 (55%) exhibited no VFL (Group B). Group A included 13 cases with NVCs (50%), Group B included 26 NVC cases (82%) (p = 0.012) and the control group included 16 individuals (26%) (p < 0.001 for comparison of all 3 groups). Group B had a significantly higher NVC-Grading than Group A (p = 0.009). There was no statistically significant association between NVCs and either SNHL or tinnitus (p > 0.05). Our results suggest that patients presenting with clinical signs of acute vestibular neuritis who show symmetrical caloric vestibular function test results have a significantly higher NVC prevalence in the cerebellopontine angle.
Asunto(s)
Ángulo Pontocerebeloso , Cerebelo/irrigación sanguínea , Neuronitis Vestibular/etiología , Nervio Vestibulococlear , Arterias , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neuronitis Vestibular/diagnósticoRESUMEN
BACKGROUND: Limited data exist on the risk of pregnancy-associated venous thromboembolism (VTE) in women with a history of VTE. OBJECTIVE: To evaluate the risk of recurrent pregnancy-associated thrombosis in women with previous VTE in a large retrospective cohort study. PATIENTS AND METHODS: One hundred and fifty-nine women with at least one pregnancy (293 pregnancies in total) after a VTE were included into the study. The patients underwent a standardized interview on their history of thrombosis and pregnancy-associated complications. RESULTS: Eight recurrent events occurred during 197 pregnancies without thrombosis prophylaxis. The probability of VTE during pregnancy without thrombosis prophylaxis was 6.2% (95% confidence interval 1.6-10.9%). The risk was constant over the whole period of pregnancy. Of the eight women with VTE during pregnancy four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53 (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138 (6.5%) after live birth. CONCLUSIONS: Without thrombosis prophylaxis the risk for recurrent symptomatic VTE is substantial during the whole period of pregnancy in women with previous VTE. The majority of events occurred after delivery, reflecting the very high risk during the postpartum period. Prospective and comparative trials to ascertain efficacy and safety of prophylactic heparin are urgently needed.
Asunto(s)
Complicaciones Cardiovasculares del Embarazo , Tromboembolia/diagnóstico , Tromboembolia/prevención & control , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/prevención & control , Adolescente , Adulto , Pruebas de Coagulación Sanguínea , Estudios de Cohortes , Factor V/genética , Femenino , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Heterocigoto , Humanos , Hiperhomocisteinemia/genética , Modelos Biológicos , Embarazo , Resultado del Embarazo , Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
A higher prevalence of risk factors for venous thromboembolism (VTE) has been found in women with preeclampsia and fetal loss. We investigated whether women with a history of VTE have a higher prevalence of pregnancy-associated complications compared with control subjects. In 395 patients with a history of VTE and in 313 control women, the prevalence of complications during pregnancy and the mean birth weight of viable infants were evaluated. The prevalence of pregnancy-induced hypertension and preeclampsia was higher in patients (5.1% and 3.0%, respectively) compared with control subjects (1.3% each). The odds ratio was 4.13 for pregnancy-induced hypertension (95% CI 1.4 to 12.22, P=0.0058) and 2.43 for preeclampsia (95% CI 0.78 to 7.6, P=0.133). Stillbirth was slightly more frequent in patients (4.3%) than in control subjects (3.2%); the difference was not statistically significant. Miscarriage was equally frequent in patients (21.8%) and control subjects (21.3%). The birth weight of viable infants born to patients was, on average, 109 g lower than that of the infants born to the control subjects (P=0.014) after adjustment for the mother's body mass index. Our study demonstrates that women with a predisposition to VTE have, overall, a good chance for a successful pregnancy outcome. However, the findings from our study support the assumption that a predisposition to venous thrombosis is associated with a higher risk for complications during pregnancy and lower infant birth weight.
Asunto(s)
Muerte Fetal/epidemiología , Preeclampsia/epidemiología , Tromboembolia/complicaciones , Trombosis de la Vena/complicaciones , Adolescente , Adulto , Peso al Nacer , Femenino , Muerte Fetal/etiología , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Persona de Mediana Edad , Preeclampsia/etiología , Embarazo , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia/diagnóstico , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy