Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
Viruses ; 15(9)2023 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-37766248

RESUMEN

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.


Asunto(s)
COVID-19 , Epidemias , Humanos , Anciano , COVID-19/epidemiología , Estudios Retrospectivos , Hospitales , Hospitalización
2.
Lancet Gastroenterol Hepatol ; 8(3): 242-252, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36528041

RESUMEN

BACKGROUND: The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS: In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS: 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION: GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING: Junta de Andalucía and EDRF.


Asunto(s)
Deterioro Clínico , Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Adulto , Humanos , Femenino , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/cirugía , Equidad de Género , Índice de Severidad de la Enfermedad , Australia , Sodio
3.
Viruses ; 14(10)2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-36298839

RESUMEN

OBJECTIVES: This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants. METHODS: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis. RESULTS: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07-9.47). Increasing age HZ: 1.1 (1.06-1.14)) and haematological disease at admission HZ: 2.99 (1.26-7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97-0.99)) and vaccination status. CONCLUSIONS: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Estudios Retrospectivos , Hospitalización , Unidades de Cuidados Intensivos , Vacunación
4.
Hepatol Commun ; 6(6): 1392-1402, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34989164

RESUMEN

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas , Hepatitis Autoinmune , Hipertensión Portal , Várices , Várices Esofágicas y Gástricas/diagnóstico , Femenino , Hepatitis Autoinmune/complicaciones , Humanos , Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Várices/complicaciones
5.
Microbiol Resour Announc ; 10(6)2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33574107

RESUMEN

Because of its small size, Gram-negative Sphingomonas paucimobilis can pose a risk of nosocomial infection. We report the complete circular genome sequence of S. paucimobilis strain Kira, which was isolated from retinoic acid-supplemented SH-SY5Y human cell cultures, to be 3,917,410 bp (G+C content, 65.7%; 3,672 protein-coding sequences), with two plasmids (79,575 bp and 44,333 bp).

6.
Rev. senol. patol. mamar. (Ed. impr.) ; 33(3): 81-87, jul.-sept. 2020. tab
Artículo en Español | IBECS | ID: ibc-197290

RESUMEN

OBJETIVO: Analizar la incidencia de cáncer de mama y de ovario, y las características de dichos tumores en pacientes portadoras de mutaciones BRCA1-2. PACIENTES Y MÉTODOS: Estudio observacional retrospectivo que incluye un total de 111 pacientes con diagnóstico molecular de mutación en genes BRCA1 (56) o BRCA2 (55). RESULTADOS: En el 69,4% de los casos el test genético se realizó tras el diagnóstico oncológico. La incidencia objetivada de cáncer de mama y ovario fue, respectivamente, del 62,2 y el 20,7%. El tipo histológico más frecuente de cáncer de mama fue el ductal infiltrante (89,7%). El 67,7% de los tumores mamarios BRCA1 presentaron un fenotipo triple negativo y el 80% de los BRCA2 mostraron un fenotipo luminal, siendo la diferencia estadísticamente significativa. El 87% de los cánceres de ovario fueron carcinomas serosos de alto grado. El 41,4% de las pacientes se realizó mastectomía profiláctica encontrándose de forma casual lesiones patológicas en el 19,5% de las piezas quirúrgicas. El 41,4% se realizó salpingooforectomía bilateral profiláctica, en cuyas piezas quirúrgicas objetivaron un 6,5% de lesiones patológicas. CONCLUSIONES: La incidencia de cáncer de mama/ovario en las pacientes portadoras de BRCA 1-2 estudiadas es superior a la descrita en la población general, desarrollándose a edades más tempranas. No obstante, el diagnóstico genético de la mutación es, en la mayoría de los casos, secundario al del evento oncológico. Se debe incidir en el diagnóstico precoz de la mutación basado en los antecedentes familiares para instaurar precozmente medidas de cribado y de reducción de riesgo


OBJECTIVE: To analyse the incidence of breast and ovarian cancer, and the characteristics of these tumours, in patients with BRCA1-2 mutations. PATIENTS AND METHODS: Retrospective observational study that included a total of 111 patients with a molecular diagnosis of mutation in BRCA1 (56) and / or BRCA2 (55) genes. RESULTS: In 69.4% of the cases, genetic testing was performed after oncological diagnosis. The incidence of breast and ovarian cancer was 62.2% and 20.7%, respectively. The most frequent histological type of breast cancer was infiltrating ductal (89.7%). A total of 67.7% of breast tumours in BRCA1 patients had a triple negative phenotype and 80% of BRCA2 patients showed a luminal phenotype. Most (87%) ovarian cancers were high grade serous carcinomas. In 41.4% of the patients, prophylactic mastectomy was performed, with a coincidental pathological finding in 19.5% of the surgical specimens. In 41.4% of the patients, prophylactic bilateral salpingo-oophorectomy was performed, with 6.5% of surgical specimens showing pathological lesions. CONCLUSIONS: The incidence of breast/ovarian cancer in patients harbouring BRCA 1-2 mutations is higher than in the general population, and the cancer develops in younger patients. However, the genetic diagnosis of the mutation is usually secondary to that of the oncological event. The early diagnosis of the mutation based on family history should be emphasised in order to initiate early screening and risk-reduction measures


Asunto(s)
Humanos , Femenino , Genes BRCA1 , Genes BRCA2 , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de la Mama/genética , Neoplasias Ováricas/genética , Patología Molecular/métodos , Mutación/genética , Biomarcadores de Tumor/análisis , Síndromes Neoplásicos Hereditarios/genética , Estudios Retrospectivos , Epidemiología Molecular/métodos
7.
Waste Manag ; 111: 22-33, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32470724

RESUMEN

The purpose of this paper is to provide a full characterization of post-consumer plastic film recovered from mixed municipal solid waste (MSW) treatment plants in Spain. Currently, this type of plastic waste is not recycled due to technical or economic barriers and is still sent to landfill. Different types of municipal plastic waste (MPW) from manual and automated sorting were studied: i) colour plastic film recovered by ballistic separators and then manual sorting in different seasons; ii) colour plastic film recovered by automated sorting (air suction); and iii) white plastic film from primary manual sorting process. The samples were characterized by different techniques, including the ultimate and proximate analysis, Higher Heating Value (HHV) and Lower Heating Value (LHV), metal content, Thermogravimetric Analysis (TGA) and Derivative Thermogravimetry (DTG), Fourier Transform Infrared (FT-IR) analysis and Differential Scanning Calorimetry (DSC). The results were compared to those obtained for pretreated colour and white plastic film waste and contrasted with industrial recycled film granules of polyethylene (as a reference material for packaging film). Additionally, pretreated plastic film samples were also characterized by analyzing viscosity, Pressure-Volume-Temperature (PVT) diagram, specific heat capacity and halogen and sulphur contents. Characterization data from this study will contribute to identify and develop potential recycling alternatives for a more sustainable municipal plastic waste management, which is recognized as a priority in the European Circular Economy Action Plan to use resources in a more sustainable way.


Asunto(s)
Eliminación de Residuos , Administración de Residuos , Plásticos , Reciclaje , Residuos Sólidos , España , Espectroscopía Infrarroja por Transformada de Fourier
8.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32070029

RESUMEN

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and occurs mainly in patients with liver cirrhosis. The mammalian target of rapamycin (mTOR) signaling pathway is involved in many hallmarks of cancer including cell growth, metabolism re-programming, proliferation and inhibition of apoptosis. The mTOR pathway is upregulated in HCC tissue samples as compared with the surrounding liver cirrhotic tissue. In addition, the activation of mTOR is more intense in the tumor edge, thus reinforcing its role in HCC proliferation and spreading. The inhibition of the mTOR pathway by currently available pharmacological compounds (i.e., sirolimus or everolimus) is able to hamper tumor progression both in vitro and in animal models. The use of mTOR inhibitors alone or in combination with other therapies is a very attractive approach, which has been extensively investigated in humans. However, results are contradictory and there is no solid evidence suggesting a true benefit in clinical practice. As a result, neither sirolimus nor everolimus are currently approved to treat HCC or to prevent tumor recurrence after curative surgery. In the present comprehensive review, we analyzed the most recent scientific evidence while providing some insights to understand the gap between experimental and clinical studies.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Recurrencia Local de Neoplasia/genética , Serina-Treonina Quinasas TOR/genética , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Everolimus/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Transducción de Señal/efectos de los fármacos , Sirolimus/uso terapéutico
9.
Elife ; 82019 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-31868590

RESUMEN

Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is controlled by nutrients.


Asunto(s)
Axones/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Neuronas/metabolismo , Proteínas Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Axones/fisiología , Transporte Biológico/genética , Encéfalo/metabolismo , Carnitina O-Palmitoiltransferasa/metabolismo , Endosomas/genética , Endosomas/metabolismo , Glucosa/metabolismo , Células HeLa , Humanos , Cinesinas/genética , Cinesinas/metabolismo , Lisosomas/genética , Lisosomas/metabolismo , Malonil Coenzima A/metabolismo , Ratones , Nutrientes/metabolismo
10.
Transplantation ; 103(12): 2539-2548, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31107827

RESUMEN

BACKGROUND: Tacrolimus minimization is usually restricted to patients with pretransplant renal impairment, and this strategy could result into worse renal outcomes after liver transplantation (LT). METHODS: A consecutive cohort of 455 LT patients receiving tacrolimus-based immunosuppression was studied (2008-2013). Cumulative exposure to tacrolimus was calculated as the area under curve of trough concentrations (AUCtc). Patients were stratified as tacrolimus minimization, conventional, or high exposure, according to the thresholds based in the COMMIT consensus. Estimated glomerular filtration rates (eGFR) were assessed by the Modification of Diet in Renal Disease formula (MDRD-4) up to 5 years after LT. RESULTS: Seventy patients (15.4%) had pretransplant eGFR < 60 mL/min, which was associated with increased mortality rates, particularly within the first 5 years post-LT (31.4% versus 17.5%; Breslow P = 0.010). After LT, there was an abrupt eGFR decline within the first 3 months (median 18.6 mL/min; P < 0.001), further decreasing up to 12 months (additional 3 mL/min), without any improvement thereafter. According to AUCtc, 33.7% of patients received tacrolimus minimization, 44.8% conventional exposure, and 21.5% high exposure. Conventional/high exposure to tacrolimus resulted in a more pronounced eGFR decline within the first 3 months when compared with minimization (23.3 mL/min versus 9.5 mL/min; P < 0.001). This gap was even higher in patients with initially preserved renal function. Tacrolimus AUCtc was an independent predictor of eGFR decline within the first 3 months after controlling for potential confounders. CONCLUSIONS: AUCtc is a surrogate of cumulative exposure to tacrolimus and may be helpful for routine dose adjustments. Tacrolimus minimization should be universally attempted after LT to preserve renal function.


Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Tacrolimus/efectos adversos , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Enfermedad Hepática en Estado Terminal/complicaciones , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , España/epidemiología , Tasa de Supervivencia/tendencias , Tacrolimus/administración & dosificación , Reino Unido/epidemiología
11.
Int J Mol Sci ; 20(2)2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30650598

RESUMEN

(1) Background: The mammalian target of rapamycin (mTOR) pathway activation is critical for hepatocellular carcinoma (HCC) progression. We aimed to evaluate the mTOR tissue expression in liver transplant (LT) patients and to analyse its influence on post-LT outcomes. (2) Methods: Prospective study including a cohort of HCC patients who underwent LT (2012⁻2015). MTOR pathway expression was evaluated in the explanted liver by using the "PathScan Intracellular Signalling Array Kit" (Cell Signalling). Kaplan-Meier and Cox regression analyses were performed to evaluate post-LT HCC recurrence. (3) Results: Forty-nine patients were included (average age 56.4 ± 6, 14.3% females). Phospho-mTOR (Ser2448) was over-expressed in peritumoral tissue as compared with tumoral tissue (ΔSignal 22.2%; p < 0.001). The mTOR activators were also increased in peritumoral tissue (phospho-Akt (Thr308) ΔSignal 18.2%, p = 0.004; phospho-AMPKa (Thr172) ΔSignal 56.3%, p < 0.001), as they were the downstream effectors responsible for cell growth/survival (phospho-p70S6K (Thr389) ΔSignal 33.3%, p < 0.001 and phospho-S6RP (Ser235/236) ΔSignal 54.6%, p < 0.001). MTOR expression was increased in patients with multinodular HCC (tumoral p = 0.01; peritumoral p = 0.001). Increased phospho-mTOR in tumoral tissue was associated with higher HCC recurrence rates after LT (23.8% vs. 5.9% at 24 months, p = 0.04). (4) Conclusion: mTOR pathway is over-expressed in patients with multinodular HCC and is it associated with increased post-LT tumour recurrence rates.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Trasplante de Hígado , Recurrencia Local de Neoplasia/patología , Serina-Treonina Quinasas TOR/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fosforilación , Modelos de Riesgos Proporcionales , Curva ROC , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
12.
Int J Mol Sci ; 19(11)2018 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-30428543

RESUMEN

Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice. For this purpose, db/db mice aged 10 weeks were treated with one drop of bosentan (5 mg/mL, n = 6) or vehicle (n = 6) administered twice daily for 14 days. Six non-diabetic (db/+) mice matched by age were included as the control group. Glial activation was evaluated by immunofluorescence using specific antibodies against glial fibrillary acidic protein (GFAP). Apoptosis was assessed by TUNEL method. A pharmacokinetic study was performed in rabbits. We found that topical administration of bosentan resulted in a significant decrease of reactive gliosis and apoptosis. The results of the pharmacokinetic study suggested that bosentan reached the retina through the trans-scleral route. We conclude that topical administration of bosentan was effective in preventing neurodegeneration in the diabetic retina and, therefore, could be a good candidate to be tested in clinical trials.


Asunto(s)
Bosentán/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/prevención & control , Administración Tópica , Animales , Apoptosis/efectos de los fármacos , Retinopatía Diabética/metabolismo , Endotelina-1/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Técnicas In Vitro , Masculino , Conejos
13.
Transplantation ; 102(12): 2056-2064, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29757893

RESUMEN

BACKGROUND: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation. METHODS: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders. RESULTS: Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation. CONCLUSION: Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Everolimus/administración & dosificación , Inmunosupresores/administración & dosificación , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Recurrencia Local de Neoplasia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Esquema de Medicación , Everolimus/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Neuroscience ; 372: 255-265, 2018 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-29337237

RESUMEN

Schwann cells (SCs) play a key role in peripheral nerve regeneration. After damage, they respond acquiring a repair phenotype that allows them to proliferate, migrate and redirect axonal growth. Previous studies have shown that Uridine-5'-Triphosphate (UTP) and its purinergic receptors participate in several pathophysiological responses in the nervous system. Our group has previously described how UTP induces the migration of a Schwannoma cell line and promotes wound healing. These data suggest that UTP participates in the signaling involved in the regeneration process. In the present study we evaluated UTP effects in isolated rat SCs and cocultures of SCs and dorsal root ganglia neurons. UTP reduced cAMP-dependent Krox-20 induction in SCs. UTP also reduced the N-cadherin re-expression that occurs when SCs and axons make contact. In myelinating cocultures, a non-significant tendency to a lower expression of P0 and MAG proteins in presence of UTP was observed. We also demonstrated that UTP induced SC migration without affecting cell proliferation. Interestingly, UTP was found to block neuregulin-induced phosphorylation of the ErbB3 receptor, a pathway involved in the regeneration process. These results indicate that UTP could acts as a brake to the differentiation signals, promoting a more migratory state in the repair-SCs.


Asunto(s)
Fármacos del Sistema Nervioso Periférico/farmacología , Células de Schwann/efectos de los fármacos , Uridina Trifosfato/farmacología , Animales , Axones/metabolismo , Cadherinas/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , AMP Cíclico/metabolismo , Proteína 2 de la Respuesta de Crecimiento Precoz/metabolismo , Ganglios Espinales/metabolismo , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Receptor ErbB-3/metabolismo , Células de Schwann/metabolismo , Regulación hacia Arriba/efectos de los fármacos
15.
Endocrinol. nutr. (Ed. impr.) ; 60(6): 287-293, jun.-jul. 2013. tab
Artículo en Español | IBECS | ID: ibc-114607

RESUMEN

Introducción La nutrición parenteral (NP) es una parte integral del tratamiento médico de aquellos pacientes que no tienen un tracto gastrointestinal funcionante o accesible. En este trabajo se describen las características clínicas de los pacientes que han recibido NP en un hospital de 420 camas desde 2009 hasta 2011. Además, se evaluaron los parámetros nutricionales al inicio y fin de la NP, y se analizaron las complicaciones asociadas. Material y métodos Estudio observacional retrospectivo de los episodios de NP en mayores de 18 años seguidos por la Unidad de Nutrición del Hospital Universitario de Guadalajara. Se recogieron: datos epidemiológicos y clínicos, número y tipo de vías empleadas, datos antropométricos, datos analíticos, número de días con NP, causa de la retirada, aporte calórico, prevalencia de flebitis, complicaciones metabólicas (hipertrigliceridemia, alteraciones en las pruebas de función hepática, hiperglucemia y síndrome de realimentación) y prevalencia de bacteriemia asociada a catéter venoso central (BAC).Resultados Se registraron 312 episodios de NP. La indicación inmediata fue íleo posquirúrgico en el 53,8% de los episodios. Se produjo una mejoría estadísticamente significativa de todos los parámetros analíticos que se evaluaron (albúmina, prealbúmina, proteína transportadora de retinol, transferrina, colesterol y linfocitos). El aporte calórico (Kcal por kg de peso) fue de 25,1 ± 6,6. En el 16,3% de los episodios no se registró ninguna complicación (..) (AU)


Introduction Parenteral nutrition (PN) is an integral part of medical management of patients who do not have a functioning or accessible gastrointestinal tract. This paper discusses the clinical characteristics of patients receiving PN in a 420-bed hospital from 2009 to 2011. In addition, nutritional parameters were assessed at the start and end of PN and associated complications were analyzed. Material and methods retrospective, observational study of PN episodes in adults conducted at the Nutrition Unit of Hospital Universitario de Guadalajara. Variables collected included epidemiological and clinical data, number and type of routes used, anthropometric data, analytical data, number of days on PN, reason for withdrawal, caloric provision, prevalence of phlebitis, metabolic complications (hypertriglyceridemia, abnormal liver function tests, hyperglycemia, and refeeding syndrome), and prevalence of bacteremia associated with central venous catheter (BAC).Results There were 312 episodes of PN. The immediate indication was postoperative ileus in 53.8% of the episodes. There was a statistically significant improvement in all analytical parameters assessed (albumin, prealbumin, retinol binding protein, transferrin, cholesterol, and lymphocytes). Caloric provision (kcal per kg) was 25.1 ± 6.6. No metabolic complication occurred in 16.3% of the episodes, and hyperglycemia was the most common complication (79.8%). There were 10 cases of phlebitis (32.2%) and 30 episodes of BAC (8.7%). Bacteriemia rate was 8.1 per 1000 days of PN. Discussion Although PN is an effective nutritional support technique, it is associated with complications of varying severity. Use of PN should therefore comply with the instructions accepted in the main clinical practice guidelines and requires careful monitoring by experienced professionals (AU)


Asunto(s)
Humanos , Evaluación Nutricional , Nutrición Parenteral Total/métodos , Trastornos Nutricionales/dietoterapia , Bacteriemia/complicaciones , Ileus/dietoterapia , Resultado del Tratamiento , Complicaciones Posoperatorias/dietoterapia
16.
Endocrinol Nutr ; 60(6): 287-93, 2013.
Artículo en Español | MEDLINE | ID: mdl-23602764

RESUMEN

INTRODUCTION: Parenteral nutrition (PN) is an integral part of medical management of patients who do not have a functioning or accessible gastrointestinal tract. This paper discusses the clinical characteristics of patients receiving PN in a 420-bed hospital from 2009 to 2011. In addition, nutritional parameters were assessed at the start and end of PN and associated complications were analyzed. MATERIAL AND METHODS: retrospective, observational study of PN episodes in adults conducted at the Nutrition Unit of Hospital Universitario de Guadalajara. Variables collected included epidemiological and clinical data, number and type of routes used, anthropometric data, analytical data, number of days on PN, reason for withdrawal, caloric provision, prevalence of phlebitis, metabolic complications (hypertriglyceridemia, abnormal liver function tests, hyperglycemia, and refeeding syndrome), and prevalence of bacteremia associated with central venous catheter (BAC). RESULTS: There were 312 episodes of PN. The immediate indication was postoperative ileus in 53.8% of the episodes. There was a statistically significant improvement in all analytical parameters assessed (albumin, prealbumin, retinol binding protein, transferrin, cholesterol, and lymphocytes). Caloric provision (kcal per kg) was 25.1±6.6. No metabolic complication occurred in 16.3% of the episodes, and hyperglycemia was the most common complication (79.8%). There were 10 cases of phlebitis (32.2%) and 30 episodes of BAC (8.7%). Bacteriemia rate was 8.1 per 1000 days of PN. DISCUSSION: Although PN is an effective nutritional support technique, it is associated with complications of varying severity. Use of PN should therefore comply with the instructions accepted in the main clinical practice guidelines and requires careful monitoring by experienced professionals.


Asunto(s)
Nutrición Parenteral , Anciano , Femenino , Humanos , Masculino , Apoyo Nutricional , Nutrición Parenteral/efectos adversos , Estudios Retrospectivos
17.
Rev. adm. sanit. siglo XXI ; 7(4): 715-728, oct.-dic. 2009. tab
Artículo en Español | IBECS | ID: ibc-85041

RESUMEN

Fundamento. El absentismo en las consultas es uno de los principales problemas en los centros deAtención Especializada; su existencia genera ineficiencias económicas y productivas. Encontrar solucionespara mitigarlo supondrá un avance en el camino de prestar un servicio sanitario excelente.Objetivo. Definir el perfil del tipo de paciente citado que no acude a las consultas de AtenciónEspecializada, estimar la repercusión económica que este hecho supone, su influencia en las demorasasistenciales y aplicar soluciones para intentar mitigar el problema.Método. Se analizaron 35.500 citas en el periodo comprendido entre mayo y septiembre de2008 del Consorcio Aragonés Sanitario de Alta Resolución (CASAR) mediante un análisis estadísticodescriptivo-bivariado para definir una regresión logística del absentismo, y así determinar el perfil delpaciente que no acude a la citación. Se han analizado las características de edad, sexo, nacionalidad,tipo de consultas y especialidad demandada.Resultados. Se encontraron diferencias estadísticamente significativas en el tiempo de demora, elcentro de especialidades, la especialidad médica y la nacionalidad de las personas que practicabanel absentismo.Conclusiones. Fijado el perfil del paciente que no acude a su cita se han de iniciar las actuacionesen las especialidades donde existe mayor probabilidad de producirse fallos en las citas. Por otrolado, se aconseja la creación de grupos de trabajo para desarrollar los protocolos de actuación de losDepartamentos de Gestión de Pacientes (guías de consultas externas) y de Documentación(AU)


Basis. The non-attendance in outpatient appointments is one of the major problems in hospitalsbecause it generates economic and productive inefficiencies. Recommendations for improving outpatientattendance must help to reach a better health service quality. Objective. To determine the main features of the non-attenders in outpatient appointments,estimate economic costs, influence in appointment delays and offer some solutions to reduce thisproblem.Method.We analyzed 35.500 appointments at CASAR over a five months period (from May toSeptember 2008) with a statistic analysis defining a logistic regression of non-attendance and establishthe profile of non-attenders. The main social features studied are age, sex, nacionality, and firstand successive consultations.Results. The difference between the social features of attenders and non-attenders were smallbut we found a positive significance between delay, place of the appointment, speciality and nationalityand non-compliance with scheduled appointments.Conclusions.We determined the profile of non-attender in the CASAR and proposed some solutionsin those specialities where outpatients present higher likely of non-compliance. Furthermore, weadviced the creation of some groups to develop measures to improve the communication in the scheduleof appointments(AU)


Asunto(s)
Humanos , Masculino , Femenino , 50230 , Servicios de Salud/economía , Continuidad de la Atención al Paciente/organización & administración , Administración de los Servicios de Salud/legislación & jurisprudencia , Administración de los Servicios de Salud/normas , Pacientes/legislación & jurisprudencia , Atención a la Salud/economía , Atención a la Salud/organización & administración , Citas y Horarios , Pacientes Desistentes del Tratamiento/legislación & jurisprudencia , Bases de Datos de Citas , 28599
18.
Prog. obstet. ginecol. (Ed. impr.) ; 52(3): 160-165, mar. 2009. graf, tab
Artículo en Español | IBECS | ID: ibc-60881

RESUMEN

Objetivo: Analizar los casos de apendicitis en gestantes diagnosticados en nuestro centro, valorando las características clínicas, analíticas, anatomopatológicas, evolutivas y terapéuticas de éstas, comparándolas con no gestantes, así como su pronóstico perinatal. Pacientes y métodos: Estudio retrospectivo descriptivo de 13 casos de apendicitis durante la gestación diagnosticados en nuestro centro entre 2002 y 2006. Resultados: El síntoma más frecuente fue el dolor abdominal, siguiéndole en frecuencia náuseas y vómitos. La mayor parte de las pacientes no presentaron fiebre ni leucocitosis > 20.000 leucocitos/ml, pero sí desviación a la izquierda. Todos los casos diagnosticados de apendicitis gangrenosa correspondieron a pacientes con cuadros de 24 h o más de evolución y, excepto uno, todos presentaron fiebre. Conclusiones: Los signos y síntomas, así como las modificaciones analíticas, de la apendicitis aguda, durante la gestación pierden sensibilidad y especificidad, dificultando y retrasando su diagnóstico y tratamiento, aumentando el riesgo de complicaciones (AU)


Objective: To analyze cases of appendicitis during pregnancy diagnosed in our center. Clinical, laboratory, histologic and therapeutic characteristics were examined and compared with those in nonpregnant women. Perinatal outcomes were also evaluated. Patients and methods: We performed a retrospective, descriptive study of 13 cases of appendicitis during pregnancy diagnosed in our center between 2002 and 2006. Results: The most frequent symptom was abdominal pain, followed by nausea and vomiting. Fever and leukocytosis with more than 20,000 cells/ mm3 were infrequent findings but granulocytosis (left shift) was common. All patients with a diagnosis of gangrenous appendicitis had symptoms for more than 24 hours and all except one had fever. Conclusions: The clinical and laboratory signs caused by appendicitis during pregnancy lose their sensitivity and specificity, hampering and delaying diagnosis and treatment and increasing the risk of complications (AU)


Asunto(s)
Humanos , Femenino , Embarazo , Apendicitis/complicaciones , Abdomen Agudo/etiología , Estudios Retrospectivos , Complicaciones Infecciosas del Embarazo/epidemiología , Diagnóstico Diferencial
19.
Nat Clin Pract Cardiovasc Med ; 6(2): 112-9, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19104518

RESUMEN

The pharmaceutical development of a cardiovascular polypill presents several unique challenges. The selection of the type and number of active drugs to be incorporated requires important consideration of clinical, pharmaceutical and commercial issues, and the final decision with regard to the polypill's components depends on how these issues are prioritized. Once the drug combination has been chosen, developers must determine which pharmaceutical formulation should be used. The most appropriate method of drug delivery can vary markedly and depends on the characteristics of the drugs to be combined. Finally, careful consideration of how to gather the type of information required by regulatory agencies before a particular polypill can be approved for use in the general population is crucial. Although the association of multiple, active ingredients in a single dosage form would represent a major step forward in the prevention of cardiovascular conditions, a careful evaluation of all the above-mentioned variables and a well thought-out development plan is mandatory to maximize the chances of success.


Asunto(s)
Fármacos Cardiovasculares/administración & dosificación , Enfermedades Cardiovasculares/tratamiento farmacológico , Fármacos Cardiovasculares/economía , Enfermedades Cardiovasculares/prevención & control , Química Farmacéutica , Esquema de Medicación , Aprobación de Drogas , Combinación de Medicamentos , Composición de Medicamentos , Costos de los Medicamentos , Industria Farmacéutica/economía , Humanos , Propiedad Intelectual , Resultado del Tratamiento
20.
Eur Eat Disord Rev ; 17(1): 40-9, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18680209

RESUMEN

OBJECTIVE: To study the prevalence of symptoms of eating disorders and risk eating behaviours and the relationship between life at a dance school and the risk of developing an eating disorder (ED) in an adolescent population of Spanish dance students. METHODS: Questionnaires were used to assess attitudes to eating, cultural influences on the body shape model, eating disorders (DSM-IV) and risk factors for eating disorders in 76 adolescent dance students (age 12-17 years) at the Barcelona Theatre Institute. Subjects were compared with a community sample of 453 female adolescents. To study the relationship between ED and characteristics of this particular school, an original questionnaire was administered to 105 students at the school aged from 12 to 21 years. RESULTS: The prevalence of eating disorders and several risk attitudes and behaviours were similar in the dance students and the female adolescents from the general population. Students at risk of eating disorders perceived greater pressure from coaches concerning eating, appearance, weight and artistic performance; they felt less satisfied with their weight and weighed themselves more often; they avoided performing so as not to exhibit their body in public, disliked comparing their body with their peers and believed that audiences paid a great deal of attention to their bodies. In contrast, Body Mass Index (BMI) had hardly any influence on these experiences. Depressive symptoms were associated almost exclusively with experience of stressors and aversive situations. CONCLUSIONS: Dance school students do not necessarily present a greater risk of ED than other girls of the same age. The risk of ED may be associated with greater pressure from coaches, with attitudes related to the ED itself, or with depressive symptoms, rather than with the BMI.


Asunto(s)
Baile/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Adolescente , Actitud Frente a la Salud , Índice de Masa Corporal , Niño , Conducta Alimentaria/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Femenino , Humanos , Prevalencia , Psicología del Adolescente , Factores de Riesgo , Autoimagen , España , Estudiantes/psicología , Encuestas y Cuestionarios , Pérdida de Peso , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...