RESUMEN
Chondrosarcoma of the hand is a rare disease, but is one of the more common malignancies of the hand. Biopsies and imaging are a fundamental step in determining correct diagnosis, grading and selection for best treatment. We describe the case of a 77-year-old male complaining of a painless swelling in the proximal phalanx of the third ray of left hand. A biopsy was performed and the histology revealed a G2 chondrosarcoma. The patient underwent III ray amputation with metacarpal bone disarticulation and sacrifice of the radial digit nerve of the fourth ray. Definitive histology revealed grade 3 CS. Eighteen months after surgery, the patient is apparently disease-free with a good functional and aesthetic outcome although with persistent paresthesia of the fourth ray. Although there is no agreement in the literature for the treatment of low-grade chondrosarcomas, wide resection or amputation can be considered the mainstay treatment for high-grade tumors. Key words: chondrosarcoma, proximal phalanx, ray amputation, surgical treatment, tumor hand.
Asunto(s)
Neoplasias Óseas , Condrosarcoma , Masculino , Humanos , Anciano , Neoplasias Óseas/cirugía , Huesos/patología , Mano , Amputación Quirúrgica , Condrosarcoma/diagnóstico , Condrosarcoma/patología , Condrosarcoma/cirugíaRESUMEN
The Giant Cell tumor (GCT) is a benign, locally aggressive lesion that cause bone destruction and shows a malignant potential. It is a relatively common skeletal tumor that is therefore typically seen in young adults. Few cases are described in literature of GCT in the immature skeleton, and the metatarsal is an unusual location for a primary bone GCT, especially in pediatric age. Therefore, there are very few data reported regarding the management protocol of GCT in metatarsal bones. We report a case about the use of no vascularized fibular graft for an original Y-shaped reconstruction of the metatarsal bone after Giant Cell Tumor resection in a 9 years-old patient, and performed a literature review about metatarsal bone reconstruction in skeletally immature patient.
RESUMEN
Giant-cell tumor (GCT) is often more aggressive when located in the distal radius, and wide resection is then the gold-standard. No single reconstruction protocol is recommended, and the technique depends upon the surgeon's preferences. The aim of the present review was to determine the recurrence rate of GTC of the distal radius after intralesional treatment, to assess the results, advantages and complications of the various surgical techniques, and to draw up a decision-tree for surgical indications. The review of literature was performed in the main healthcare databases, searching for studies that reported results of wide resection and reconstruction of distal radius GCT. Local recurrence rates, metastasis rates, reconstruction techniques and respective results and complications were evaluated and analyzed. Sixteen studies were selected, for a total population of 226 patients; 6.0% and 0.9% experienced local recurrence and lung metastasis, respectively. Arthroplasty with non-vascularized or vascularized ipsilateral fibula were the most common techniques and were associated with the highest satisfaction rates: 86.4% and 88.0%, respectively. Arthroplasty with allograft presented a MusculoSkeletal Tumor Society (MSTS) score of 79.2% and arthroplasty with custom-made prosthesis presented an MSTS score of 81.8%. Arthrodesis was performed in 46 cases, with an MSTS score of 82.7%. Arthroplasty techniques are the most common in literature; they are used in patients who wish to conserve joint motion. Reconstruction with non-vascularized fibula seems to provide the best results, with lower morbidity. Arthrodesis is usually reserved for heavy manual workers or in case of arthroplasty failure.
Asunto(s)
Neoplasias Óseas , Tumor Óseo de Células Gigantes , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Trasplante Óseo/métodos , Tumor Óseo de Células Gigantes/cirugía , Humanos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Radio (Anatomía)/patología , Radio (Anatomía)/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Reconstruction is very important to ensure good function and quality of life after bone tumor resection. For metacarpals and phalanges, amputation and toe transfer are the gold-standard indications; nevertheless, allograft reconstruction must also be taken into account. Unfortunately, because of its inert biological behavior, it undergoes progressive resorption, with frequent fracture. Several attempts have been made to induce new vascularization in massive bone allograft, with poor results. However, neo-angiogenesis was reported with vascular loops, and we therefore hypothesized that heterologous graft integration could be enhanced by creating a vascular loop through the graft. A 50-year-old male with chondrosarcoma of the ring finger of the left hand underwent wide resection. An allogenic middle phalanx of comparable size was then prepared to fill the defect. Two small windows were performed proximally and distally on the radial surface of the allogenic phalanx, and a 4 cm-long vein graft was inserted inside the medullary canal. Metacarpophalangeal joint stability was achieved by collateral ligament reconstruction with micro-anchors. The distal part of the allograft was then stabilized to the middle phalanx with a 1.5 mm-thick micro-plate and screws. The radial proper palmar digital artery was proximally and distally sutured end-to-end to the vein graft, under microscopy. At 12-month follow-up, the allograft was fused, and histology performed at plate removal at 18 months revealed viable spindle cells with osteoblastic differentiation, without evidence of atypia, in a dense fibrous stroma. At 22 months' follow-up, the patient was apparently disease-free, and satisfied with his manual function.
Asunto(s)
Falanges de los Dedos de la Mano , Procedimientos de Cirugía Plástica , Aloinjertos/cirugía , Trasplante Óseo/métodos , Falanges de los Dedos de la Mano/cirugía , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Procedimientos de Cirugía Plástica/métodosRESUMEN
Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Enfermedades Renales/etiología , Trasplante de Riñón/efectos adversos , Riñón/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Vimentina/metabolismo , Adulto , Biomarcadores/metabolismo , Biopsia , Transición Epitelial-Mesenquimal , Femenino , Fibrosis , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Riñón/patología , Riñón/fisiopatología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of this study is to verify the effectiveness and complications occurrence of radiofrequency ablation (RFA) in the treatment of osteoid osteoma (OO) in non-operating room anesthesia (N.O.R.A.). PATIENTS AND METHODS: From 2014 to 2017, 61 patients affected by OO (40 men and 21 women) with an age of 20.7 years on average (range, 4-51 years; 12 patients aged 20 years or younger) underwent computed tomography-guided percutaneous radiofrequency ablation (RFA) in N.O.R.A. (Non-Operating Room Anesthesia). Lesion sites treated were: femur (27), tibia (22), pelvis (2), talar bone (3), distal radius (1), and humerus (6). Mean follow-up time was 36 months. In each case, anesthesiologic support followed a new protocol (N.O.R.A. protocol), approved by our Institute. Primary success rate, complications, symptom-free intervals, and follow-up results were evaluated. RESULTS: Pain relief (evaluated with Visual Analogue Scale - VAS) was significant in 97% of patients; it disappeared within 24 hours of the procedure in 44 patients, within 3 days in 10 patients, and within 7 days in 7 patients. After 6 months of observation time, 60 of 61 patients were successfully treated and had no more complaints. In 2 patients, two major complications were found: infection of the site treated, healed with antibiotics, and a nerve lesion, healed with steroid therapy. No other complications were observed. CONCLUSIONS: RFA is a highly effective, efficient, minimally invasive and safe method for the treatment of OO following N.O.R.A.
Asunto(s)
Anestesia Local/métodos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/cirugía , Ablación por Radiofrecuencia/métodos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Core biopsy is today recognized as the gold standard for the diagnosis of bone lesions; unfortunately, when the bone is too solid it can be very difficult to penetrate it; in case of failure, open biopsy is indicated but it is associated with greater contamination and complications. A possible solution is to connect a common orthopedic drill to the core biopsy needle. The aim of the presenting study was to present a technique useful for performing biopsies in case of very strong bone lesions and to evaluate the adequacy and quality of the obtained specimen. MATERIALS AND METHODS: A standard bone biopsy set was connected to a commercial drill to perform bone biopsies. Data was collected over a 2-year period (2015-2016). Information regarding technical success, diagnostic data and complication rates was all collated to assess the technical feasibility of this technique. RESULTS: Out of 357 bone biopsies, 34 patients underwent the procedure using a common orthopedic drill connected to a core biopsy needle. Diagnostic material was obtained in each patient and the artifacts were considered irrelevant. No major complications occurred in any patient. DISCUSSION: The use of a core biopsy needle connected to a common orthopedic drill facilitates the penetration of thick cortical bone by simply applying continuous speed and pressure; nevertheless, the biopsy needle we use is not designed for a drilling procedure and for this reason it can be damaged, but if the biopsy is performed with particular attention, the mechanical failure can be avoided CONCLUSIONS: Bone biopsy using a commercial hand drill has a technically high success rate with minimal complications. Further studies with more cases are necessary to verify our results.
Asunto(s)
Biopsia con Aguja Gruesa , Neoplasias Óseas/patología , Huesos/patología , Equipo Ortopédico , Adolescente , Adulto , Artefactos , Biopsia con Aguja Gruesa/instrumentación , Neoplasias Óseas/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND AND AIMS: The nature of the link (causal vs non-causal) between low 1,25-OH vitamin D and insulin resistance (IR) in patients with chronic kidney disease (CKD) remains elusive. We have now made a post hoc analysis of the effect of vitamin D receptor activation by paricalcitol on IR in the complete dataset of a double-blind, randomized, placebo controlled trial, the Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY). METHODS AND RESULTS: Eighty-eight patients with stage 3-4 CKD were randomized (1:1) to receive 2 µg/day paricalcitol or matching placebo for 12 weeks. IR was measured by five IR indices: the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the McAuley index, the HOMA corrected for adiponectin (HOMA-AD) and the Leptin-adiponectin ratio (LAR). As compared to placebo, paricalcitol produced the expected small rise in serum calcium (+0.07 mmol/L, P = 0.01) and phosphate (+0.08 mmol/L, P = 0.034) and the expected parathyroid hormone suppression (-96 pg/ml, P < 0.001). However, the drug largely failed to affect the five indices of IR which remained unchanged both in the active and the placebo arm (paricalcitol vs placebo, P ranging from 0.25 to 0.62) and no effect modification of paricalcitol on IR by vitamin D or other parameters was registered. CONCLUSION: Paricalcitol treatment for 12 weeks does not improve IR in patients with stage 3-4 CKD. Low vitamin D receptor activation is not a causal factor for IR in the CKD population.
Asunto(s)
Ergocalciferoles/uso terapéutico , Resistencia a la Insulina , Receptores de Calcitriol/agonistas , Insuficiencia Renal Crónica/tratamiento farmacológico , Adiponectina/sangre , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Método Doble Ciego , Ergocalciferoles/efectos adversos , Femenino , Humanos , Insulina/sangre , Italia , Leptina/sangre , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle, and health policy measures that makes preventive behaviors an affordable option.
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Epidemias , Enfermedades Renales/epidemiología , Obesidad/epidemiología , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Humanos , Incidencia , Enfermedades Renales/diagnóstico , Enfermedades Renales/prevención & control , Obesidad/diagnóstico , Obesidad/terapia , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Obesidad Infantil/terapia , Prevalencia , Pronóstico , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.
Asunto(s)
Obesidad/complicaciones , Insuficiencia Renal Crónica/etiología , Adulto , Índice de Masa Corporal , Niño , Progresión de la Enfermedad , Humanos , Obesidad/epidemiología , Insuficiencia Renal Crónica/prevención & control , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: 1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. METHODS AND RESULTS: Eighty-eight stage G3-4 CKD patients randomly received 2 µg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks. Sclerostin, a major AGE compound like pentosidine, and bone mineral disorder biomarkers were measured at baseline, at 12 weeks and 2 weeks after stopping the treatments. At baseline, in the whole study population sclerostin correlated with male gender (P = 0.002), BMI (P < 0.001), waist circumference (P < 0.001), serum pentosidine (P = 0.002) and to a weaker extent, with diabetes (P = 0.04), 1,25(OH)2Vitamin D (r = 0.22, P = 0.04) and serum phosphate (r = -0.26, P = 0.01). Sclerostin increased during PCT treatment (average + 15.7 pg/ml, 95% CI: -3.0 to +34.3) but not during placebo (P = 0.03) and the PCT effect was abolished 2 weeks after stopping this drug. The increase in sclerostin levels induced by PCT was modified by prevailing pentosidine levels (P = 0.01) and was abolished by statistical adjustment for simultaneous changes in PTH but not by FGF23 changes. CONCLUSIONS: VDRA by paricalcitol causes a moderate increase in serum sclerostin in CKD patients. Such an effect is abolished by adjustment for PTH, suggesting that it may serve to counter PTH suppression. The sclerostin rise by PCT is attenuated by pentosidine, an observation in keeping with in vitro studies showing that AGEs alter the functioning of the VDRA.
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Arginina/análogos & derivados , Proteínas Morfogenéticas Óseas/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/tratamiento farmacológico , Ergocalciferoles/administración & dosificación , Lisina/análogos & derivados , Insuficiencia Renal Crónica/tratamiento farmacológico , Vitaminas/administración & dosificación , Proteínas Adaptadoras Transductoras de Señales , Anciano , Arginina/sangre , Biomarcadores/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Método Doble Ciego , Ergocalciferoles/efectos adversos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Marcadores Genéticos , Humanos , Italia , Lisina/sangre , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Vitaminas/efectos adversosRESUMEN
Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.
Asunto(s)
Humanos , Adulto , Obesidad/complicaciones , Insuficiencia Renal Crónica/etiología , Índice de Masa Corporal , Progresión de la Enfermedad , Obesidad/epidemiología , Insuficiencia Renal Crónica/prevención & control , Medición de Riesgo , Factores de RiesgoRESUMEN
Background. Oxidative stress is a hallmark of CKD and this alteration is strongly implicated in LV hypertrophy and in LV dysfunction. Methods and Patients. We resorted to the strongest genetic biomarker of paraoxonase-1 (PON1) activity, the Q192R variant in the PON1 gene, to unbiasedly assess (Mendelian randomization) the cross-sectional and longitudinal association of this gene-variant with LV mass and function in 206 CKD patients with a 3-year follow-up. Results. The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoPGF2α (P = 0.03) and was dose-dependently related in a direct fashion to LVMI (QQ: 131.4 ± 42.6 g/m(2); RQ: 147.7 ± 51.1 g/m(2); RR: 167.3 ± 41.9 g/m(2); P = 0.001) and in an inverse fashion to systolic function (LV Ejection Fraction) (QQ: 79 ± 12%; RQ: 69 ± 9%; RR: 65 ± 10% P = 0.002). On longitudinal observation, this gene variant associated with the evolution of the same echocardiographic indicators [LVMI: 13.40 g/m(2) per risk allele, P = 0.005; LVEF: -2.96% per risk allele, P = 0.001]. Multivariate analyses did not modify these associations. Conclusion. In CKD patients, the R allele of the Q192R variant in the PON1 gene is dose-dependently related to the severity of LVH and LV dysfunction and associates with the longitudinal evolution of these cardiac alterations. These results are compatible with the hypothesis that oxidative stress is implicated in cardiomyopathy in CKD patients.
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Arildialquilfosfatasa/genética , Cardiomiopatías/etiología , Estrés Oxidativo , Insuficiencia Renal Crónica/genética , Anciano , Alelos , Estudios Transversales , Ecocardiografía , Femenino , Genotipo , Tasa de Filtración Glomerular , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Insuficiencia Renal Crónica/complicaciones , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND AND AIMS: Vitamin D receptor activation (VDRA) ameliorates endothelial dysfunction in CKD patients but also increases phosphate and FGF-23, which may attenuate the beneficial effect of VDRA on endothelial function. METHODS AND RESULTS: This is a pre-specified secondary analysis of the PENNY trial (NCT01680198) testing the effect of phosphate and FGF-23 on the flow mediated vasodilatory (FMD) response to paricalcitol (PCT, 2 µg/day) and placebo over a 12-weeks treatment period. Eighty-eight stage G3-4 CKD patients were randomized to PCT (n = 44) and Placebo (n = 44). Endothelial function was assessed by measuring endothelium dependent forearm blood flow (FBF) response to ischemia. The FMD response was by the 61% higher in PCT treated patients than in those on placebo (P = 0.01). Phosphate (+11%, P = 0.039), calcium (+3%, P = 0.01) and, particularly so, FGF23 (+164%, P < 0.001) increased in PCT treated patients. Changes in FMD by PCT associated inversely with phosphate (r = -0.37, P = 0.01) but were independent of FGF-23, calcium and PTH changes. The response to PCT was maximal in patients with no changes in phosphate (1st tertile), attenuated in those with mild-to-moderate rise in phosphate (2nd tertile) and abolished in those with the most pronounced phosphate increase (3rd tertile) (effect modification P = 0.009). No effect modification by FGF-23 and other variables was observed. CONCLUSIONS: The beneficial effect of PCT on endothelial function in CKD is maximal in patients with no or minimal changes in phosphate and it is abolished in patients with a pronounced phosphate rise. These findings generate the hypothesis that the endothelium protective effect by VDRA may be potentiated by phosphate lowering interventions.
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Arteria Braquial/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Ergocalciferoles/uso terapéutico , Antebrazo/irrigación sanguínea , Fosfatos/sangre , Receptores de Calcitriol/agonistas , Insuficiencia Renal Crónica/tratamiento farmacológico , Vasodilatación/efectos de los fármacos , Vasodilatadores/uso terapéutico , Anciano , Biomarcadores/sangre , Arteria Braquial/metabolismo , Arteria Braquial/fisiopatología , Método Doble Ciego , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Ergocalciferoles/efectos adversos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/metabolismo , Flujo Sanguíneo Regional , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Resultado del Tratamiento , Vasodilatadores/efectos adversosRESUMEN
BACKGROUND AND AIMS: Recent data demonstrated that serum phosphorus, within the normal range, is an independent predictor of atherosclerotic cardiovascular disease, independently of renal function. Traditional cardiovascular risk factors are important mediators of endothelial dysfunction, the early step of atherosclerosis. We designed this study to evaluate a possible correlation between serum phosphorus and endothelium-dependent vasodilation, evaluated by the strain-gauge plethysmography, in naïve hypertensives. METHODS AND RESULTS: We investigated by strain-gauge plethysmography, the relationship between forearm blood flow (FBF) response to acetylcholine (ACh) and serum phosphorus in 500 patients with uncomplicated, never-treated, essential hypertension, divided by phosphorus tertiles. There were no significant differences among tertiles with the exclusion of forearm blood flow (FBF). Phosphorus (ß = -0.454; P = 0.0001), estimated-glomerular filtration rate (e-GFR, by CKD-EPI formula) (ß = 0.261; P = 0.0001), gender (ß = 0.215; P = 0.0001), BMI (ß = -0.086; P = 0.018), HDL-cholesterol (ß = 0.077; P = 0.036) were significantly related to endothelium-dependent vasodilation. In an additional analysis including serum high sensitivity C-reactive protein (hs-CRP) (measured in 400 patients) in the same model, the link between serum phosphorus and ACh-stimulated FBF did not change (ß = -0.422; P = 0.0001). Clinically relevant, 0.1 mg of phosphorus increase is associated with a reduction of 22% of ACh-stimulated FBF. On multiple logistic regression analysis, the risk of endothelial dysfunction was about twice higher in patients in the second (OR = 1.754, 95% CI = 1.055-2.915; P = 0.030) and three-fold higher in the third tertile (OR = 2.939, 95% CI = 1.598-5.408; P = 0.0001) in comparison with those in the first tertile of phosphorus. CONCLUSION: An impaired ACh-stimulated FBF is associated with serum phosphorus levels, within the normal range, in hypertensives.
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Endotelio Vascular/fisiopatología , Antebrazo/irrigación sanguínea , Hipertensión/sangre , Hipertensión/fisiopatología , Fósforo/sangre , Vasodilatación , Acetilcolina/administración & dosificación , Adulto , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Estudios Transversales , Diagnóstico Precoz , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Hipertensión/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pletismografía , Valor Predictivo de las Pruebas , Factores de Riesgo , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificaciónAsunto(s)
Arginina/análogos & derivados , Factores de Crecimiento de Fibroblastos/sangre , Inflamación/sangre , Insuficiencia Renal Crónica/sangre , Sepsis/sangre , Arginina/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Factor-23 de Crecimiento de Fibroblastos , Tasa de Filtración Glomerular , Estudio Históricamente Controlado , Hospitalización , Humanos , Inflamación/diagnóstico , Inflamación/terapia , Mediadores de Inflamación/sangre , Riñón/fisiopatología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Sepsis/diagnóstico , Sepsis/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: The strongest genetic marker of uric acid levels, the rs734553 SNP in the GLUT9 urate transporter gene, predicts progression to kidney failure in CKD patients and associates with systolic BP and carotid intima media thickness in family-based studies. METHODS: Since genes are transmitted randomly (Mendelian randomization) we used this gene polymorphism as an unconfounded research instrument to further explore the link between uric acid and cardiovascular disease (cardiovascular death, and non-fatal myocardial infarction and stroke) in a meta-analysis of three cohort studies formed by high risk patients (MAURO: 755 CKD patients; GHS: 353 type 2 diabetics and coronary artery disease and the TVAS: 119 patients with myocardial infarction). RESULTS: In separate analyses of the three cohorts, the incidence rate of CV events was higher in patients with the rs734553 risk (T) allele (TT/GT) than in those without (GG patients) and the HR in TT/GT patients in the three cohorts (range 1.72-2.14) coherently signaled an excessive cardiovascular risk with no heterogeneity (I2 = 0.01). The meta-analytical estimate (total number of patients, n = 1227; total CV events, n = 222) of the HR for the combined end-point in TT/GT patients was twice higher (pooled HR: 2.04, 95% CI: 1.11-3.75, P = 0.02) than in GG homozygotes. CONCLUSIONS: The T allele of the rs734553 polymorphism in the GLUT9 gene predicts a doubling in the risk for incident cardiovascular events in patients at high cardiovascular risk. Findings in this study are compatible with the hypothesis of a causal role of hyperuricemia in cardiovascular disease in high risk conditions.