RESUMEN
OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.
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Isquemia Encefálica/complicaciones , Epilepsia/complicaciones , Convulsiones/complicaciones , Convulsiones/diagnóstico , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Convulsiones/fisiopatología , Resultado del TratamientoRESUMEN
Prognostic characterization in the initial assessment of patients with advanced cancer disease is an essential step to plan the most appropriate therapeutic program. Since clinical prediction of survival (CPS) may be of limited value, some authors have tried to integrate specific prognostic factors into prognostic multidimensional scores. We carried out a prospective cohort study in two palliative care units to compare the accuracy of the Palliative Prognostic (PaP) Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index (PPI). In addition, we compared the accuracy of the CPS independently estimated by different healthcare professionals and we tested the role of laboratory results, together with clinical and social factors in predicting survival. Clinical and laboratory data of 334 advanced cancer patients were prospectively collected from the time of in-hospital admission. PaP Score was the most accurate index of survival prediction, followed by PPI; CPS estimates' accuracy was similar among physicians and nurse. All healthcare professionals tended to underestimate the real survival. Integrating CPS with multidimensional indexes may further improve the patient's management. The degree of autonomy and the number of metastatic sites were independent prognostic factors for 30-days mortality and overall survival in multivariate analysis.
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Neoplasias/terapia , Cuidados Paliativos/métodos , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/patología , Pronóstico , Estudios ProspectivosRESUMEN
AIM: The aim of the present study was to define subsets of patients suffering from polymyalgia rheumatica, where methotrexate (MTX) up to 20 mg/week might be more effective. METHODS: A total of 100 patients with polymyalgia rheumatica treated with MTX were studied. The criteria for MTX introduction were: (i) relapse during the first month of therapy, when tapering glucocorticoids (GC); (ii) requiring long-term GC (i.e. >24 consecutive months); (iii) requiring ≥5 mg/day of prednisone equivalents after 4 months of GC therapy; (iv) GC-related side-effects; and (v) a high risk of GC-related side-effects. All the patients were followed for at least 12 months. A group of patients treated with GC alone in the same center was also compared with the whole MTX group. RESULTS: Follow up varied from 12 to 185 months (median 46.5 months). Remission with current prednisone dose ≤2.5 mg/day at month +12 was observed in 59 out of 100 patients; remission with GC suspension at month +12 was observed in 38 out of 100, without significant difference among groups. Approximately half of the patients showed at least one relapse (54/100) during the follow-up period. The cumulative dose of GC was 1.5 g (range 0.1-15.2 g) . New GC-related side-effects were recorded in 16 out of 100 patients at last follow up. Compared with the GC alone group, the MTX group showed younger age, higher prevalence of female sex and higher level of inflammation. CONCLUSIONS: MTX up to 20 mg/day was useful in defined subsets of polymyalgia rheumatica, also in the long term. No significant differences were noticed among the five subgroups. Geriatr Gerontol Int 2018; 18: 1410-1414.
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Antirreumáticos/uso terapéutico , Metotrexato/uso terapéutico , Dimensión del Dolor , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamiento farmacológico , Centros Médicos Académicos , Administración Oral , Anciano , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Estudios de Seguimiento , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke. METHODS: In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots. FINDINGS: Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4-5) 1 year after stroke and 8% (6-9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4-1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7-1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42-77) risk of late seizures within 1 year (83% [62-93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71-0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes. INTERPRETATION: This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis. FUNDING: None.
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Isquemia Encefálica/complicaciones , Modelos de Riesgos Proporcionales , Convulsiones/etiología , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , Austria , Estudios de Cohortes , Femenino , Alemania , Humanos , Italia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Medición de Riesgo/estadística & datos numéricosRESUMEN
Valve dystrophic calcification is a common disorder affecting normophosphatemic subjects. Here, cultured aortic valve interstitial cells (AVICs) were treated 3 to 28 days with phosphate (Pi) concentrations spanning the normal range in humans (0.8, 1.3, and 2.0 mM) alone or supplemented with proinflammatory stimuli to assess possible priming of dystrophic-like calcification. Compared with controls, spectrophotometric analyses revealed marked increases in calcium amounts and alkaline phosphatase activity for 2.0-mM-Pi-containing cultures, with enhancing by proinflammatory mediators. Ultrastructurally, AVICs treated with low/middle Pi concentrations showed an enormous endoplasmic reticulum (ER) enclosing organelle debris, so apparently executing a survival-related atypical macroautophagocytosis, consistently with ultracytochemical demonstration of ER-associated acid phosphatase activity and decreases in autophagosomes and immunodetectable MAP1LC3. In contrast, AVICs cultured at 2.0-mM Pi underwent mineralization due to intracellular release and peripheral layering of phospholipid-rich material acting as hydroxyapatite nucleator, as revealed by Cuprolinic Blue and von Kossa ultracytochemical reactions. Lack of immunoblotted caspase-3 cleaved form indicated apoptosis absence for all cultures. In conclusion, fates of cultured AVICs were crucially driven by Pi concentration, suggesting that serum Pi levels just below the upper limit of normophosphatemia in humans may represent a critical watershed between macroautophagy-associated cell restoring and procalcific cell death.
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Válvula Aórtica/citología , Válvula Aórtica/patología , Calcinosis/patología , Fosfatos/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Válvula Aórtica/metabolismo , Válvula Aórtica/ultraestructura , Autofagia , Calcinosis/metabolismo , Calcio/metabolismo , Bovinos , Supervivencia Celular , Células Cultivadas , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Retículo Endoplásmico/ultraestructuraRESUMEN
OBJECTIVE: To describe how Italian medical societies interact with pharmaceutical and medical device industries through an analysis of the information available on their websites. DESIGN: Cross sectional study. SETTING: Italy. PARTICIPANTS: 154 medical societies registered with the Italian Federation of Medical-Scientific Societies. MAIN OUTCOME MEASURES: Indicators of industry sponsorship (presence of industry sponsorship in the programme of the last medical societies' annual conference; presence of manufacturers' logos on the homepage; presence of industry sponsorship of satellite symposia during the last annual conference). RESULTS: 131 Italian medical societies were considered. Of these, 4.6% had an ethical code covering relationships with industry on their websites, while 45.6% had a statute that mentioned the issue of conflict of interest and 6.1% published the annual financial report. With regard to industry sponsorship, 64.9% received private sponsorship for their last conference, 29.0% had manufacturers' logos on their webpage, while 35.9% had industry-sponsored satellite symposia at their last conference. The presence of an ethical code on the societies' websites was associated with both an increased risk of industry sponsorship of the last conference (relative risk (RR) 1.22, 95% CIs 1.01 to 1.48 after adjustment) and of conferences and/or satellite symposia (RR 1.22, 95% CIs 1.02 to 1.48 after adjustment) but not with the presence of manufacturers' logos on the websites (RR 1.79, 95% CIs 0.66 to 4.82 after adjustment). No association was observed with the other indicators of governance and transparency. CONCLUSIONS: This survey shows that industry sponsorship of Italian medical societies' conferences is common, while the presence of a structured regulatory system is not. Disclosure of the amount of industry funding to medical societies is scarce. The level of transparency therefore needs to be improved and the whole relationship between medical societies and industry should be further disciplined in order to avoid any potential for conflict of interest.
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Conflicto de Intereses , Industria Farmacéutica/ética , Internet , Médicos/ética , Sociedades Médicas/ética , Estudios Transversales , Revelación , Apoyo Financiero , Humanos , Italia , Sociedades Médicas/economía , Encuestas y CuestionariosRESUMEN
BACKGROUND: Aripiprazole (ARP) has been shown to be effective in the treatment of bipolar disorder (BD). However, no prior investigation considered both randomized clinical trials (RCTs) and non-RCTs. We here evaluated the efficacy and safety of ARP compared with placebo (PCB) and other drugs at 3- and 12-weeks in adult and pediatric population including, for the first time, both observational and controlled studies. METHODS: All studies were systematically located by searching electronic sources (EMBASE, MEDLINE, CINHAIL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and ClinicalTrials.gov) till June 30th, 2015. The primary outcome was ARP efficacy (mean change from baseline in Young Mania Rating Scale); secondary outcomes regarded acceptability and safety. Results Sixteen RCTs and 6 non-RCTs met our inclusion criteria; 2505 and 2932 patients were included in the analyses of acute and stabilization phase, respectively. In both the acute and stabilization phases ARP efficacy was superior to PCB and comparable to other drugs. The safety profile was similar to other drugs considering in particular sedation, akathisia, weight gain, extrapyramidal and gastroenteric symptoms, with a significant lower risk of hyperprolactinemia particularly at 12-weeks. LIMITATIONS: Data on failed trials are generally limited. CONCLUSIONS: ARP resulted to be an effective treatment in children and adults with BD at 3- and 12-weeks both in a controlled experimental setting or in the real world clinical practice, being poorly associated with hyperprolactinemia. Larger studies are needed to confirm our results related to the maintenance phases and to the pediatric bipolar population.
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Antipsicóticos/uso terapéutico , Aripiprazol/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Adolescente , Adulto , Anciano , Acatisia Inducida por Medicamentos/etiología , Enfermedades de los Ganglios Basales/inducido químicamente , Niño , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Hiperprolactinemia/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Aumento de Peso , Adulto JovenRESUMEN
BACKGROUND: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. METHODS: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. RESULTS: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. CONCLUSIONS: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.
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Epilepsia/epidemiología , Convulsiones/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Epilepsia/prevención & control , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sistema de Registros , Factores de RiesgoRESUMEN
Breast cancer is one of the most common tumors in the population worldwide. Conservative breast surgery (CBS) is one of the preferred surgical options, because both the oncologic and esthetic needs of the patient can be addressed. CBS surgical outcomes tend to be more effective with reduced chances of disease recurrence when radiotherapy (RT) treatment is considered as an adjunct treatment, either applied during surgery (IORT) and/or after (EBRT). The purpose of our study was to compare surgical outcomes between IORT and EBRT after CBS. In the past 5 years, we performed CBS in 489 patients in our clinic. Of these patients, 83 underwent adjunct treatment with IORT and 109 were treated with EBRT in accordance with our university approved clinical protocol. Surgical outcomes, early complication rates, and esthetic results were compared between these two groups of CBS patients, with a mean follow-up time of 17 months. IORT allowed breast irradiation treatment to be performed without effecting overlying skin, thus cosmetic outcomes tended to be favorable. Esthetic postoperative results assessed with the Breast Cancer Conservation Treatment (BCCTcore) software showed that the differences between IORT and EBRT were not statistically significant (including those patients that underwent further oncoplastic techniques after EBRT). The disease recurrence rates between the two groups were not significantly different. IORT is a safe, fast, and feasible technique that provides effective and comparable CBS outcomes for patients with breast cancer.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Cuidados Intraoperatorios/métodos , Mastectomía Segmentaria/métodos , Adulto , Anciano , Estética , Femenino , Humanos , Cuidados Intraoperatorios/efectos adversos , Mastectomía Segmentaria/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of our study is to investigate whether stroke unit (SU) care and the utilization of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria may contribute to reduce death and disability in hospitalized patients after a first-ever ischemic stroke (IS). METHODS: Data included in the present study were derived from our previous study on the incidence and outcome of cerebrovascular diseases in the district of Udine, performed from April 1, 2007, to March 31, 2009. RESULTS: We identified 429 hospitalized first-ever IS cases, 297 of 429 (69.2%) patients were admitted to a dedicated SU and 132 of 429 (30.8%) to a general medical ward. According to the TOAST criteria, 101 of 132 first-ever ISs (76.5%) admitted to general medical wards were of undetermined (UND) etiology, whereas in only 105 of 297 (35.4%) patients admitted to the SU, the diagnosis remained UND. Multivariable analysis after propensity score matching showed that compared with general medical wards, SU care was associated with a reduced probability of being dead or highly disabled (P = .025) at the end of follow-up. Moreover, patients with an UND diagnosis had a worse 6-month case fatality (P < .0001) and also higher risk of being dead or highly disabled (P < .0001). CONCLUSIONS: Our study provides real-world evidence that accurate etiologic subtype classification of ISs according to TOAST criteria and SU care as opposed to general medical ward management are associated with reduction of the proportion of poor outcomes in first-ever IS patients.
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Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Femenino , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/clasificaciónRESUMEN
We investigated 923 cervical vertebrae belonging to late-antiquity and medieval skeletal remains and assessed the qualitative and quantitative structural characteristics of transverse foramens (TF) and additional vascular canals. We also reviewed the pertinent literature. Double TF were chiefly observed in C6 (with a right/left side prevalence of 35.7 and 44.4%, respectively) and C5 vertebrae (23.6 and 23.9%, right/left side, respectively), while unclosed TF were mainly documented in C1 vertebrae (8.4%). Retrotransverse canal and retrotransverse groove were present in 8.5 and 17.8%, respectively, of C1 vertebrae examined, while arcuate foramens and supertransverse foramens were found in 7.3 and 3.7% of specimens, respectively. TF diameter decreased from C6 to C2 vertebrae, being smallest in C7 and greatest in C1 vertebrae, with no left/right significant difference. There was a significant correlation between TF diameter and stature, but only on the right side. The mean area of the arcuate foramen was lower than the mean area of the ipsilateral TF (24.5 ± 5.7 vs 28.5 ± 7.7 mm(2), respectively; p = 0.048), possibly causing compression of the vertebral artery within the arcuate foramen. The study of human vertebrae excavated from archaeological sites is a simple and effective way to analyze the morphology and quantitative anatomy of vascular foramens.
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Variación Anatómica , Vértebras Cervicales/anatomía & histología , Adulto , Vértebras Cervicales/irrigación sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteología , Paleontología , Arteria Vertebral/anatomía & histología , Adulto JovenRESUMEN
Corticosteroids (CSs) are still the mainstay of induction, rescue, and maintenance in heart transplantation (HTx). However, their use is associated with significant and well-documented side effects usually related to the dose administered and the duration of therapy. Moreover, CSs interfere with the recipient's quality of life and with the active process of graft tolerance. Physicians have been exploring ways to avoid or reduce CSs in association with other immunosuppressive drugs, minimizing side effects and costs. The regimens are classified as steroid-free or steroid withdrawal protocols. The studies analyzed in this review come to similar conclusions as benefits and adverse consequences: steroid-free protocols should be advisable and mandatory in pediatric patients, insulin-dependent diabetes mellitus (IDDM), presence of infection, familial metabolic disorders/obesity, severe osteoporosis, and in the elderly. On the other hand, steroid withdrawal can be successfully achieved in 50-80%, with late better than early withdrawal, no increase in rejection-related mortality, no adverse impact on survival, and probably a better quality of live. Safety and efficacy can certainly be improved by an individualized approach to the transplant recipient.
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Corticoesteroides/efectos adversos , Rechazo de Injerto/prevención & control , Trasplante de Corazón/métodos , Inmunosupresores/efectos adversos , Corticoesteroides/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto , Trasplante de Corazón/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Inmunología del Trasplante , Tolerancia al Trasplante/efectos de los fármacos , Resultado del Tratamiento , Privación de TratamientoRESUMEN
The Iowa Gambling Task (IGT) analyzes the ability of participants to sacrifice immediate rewards in view of a long term gain. Anorexia Nervosa (AN) in addition to weight loss and body image disturbances is also characterized by the tendency to make decisions that may result in long-term negative outcomes. Studies that analyzed IGT performance in patients with AN were not consistent with each other. Fifteen adolescents with AN and 15 matched controls carried out IGT after being clinically and neuropsychologically evaluated. An interesting generalized estimating equation approach showed that four independent clinical variables, and not the group, explained IGT performances, such as blocks repetition, anxiety, psychogenic eating disorders and self transcendence. The impairment of decision making is not related to the diagnosis of AN, but it is driven by high levels of anxiety and self transcendence. Instead, some psychogenic eating disorders traits, related to illness severity, positively affected IGT performance in the whole sample. IGT impairment in AN found by prior studies could be related to these clinical features which are not always taken into account.
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Anorexia Nerviosa/psicología , Toma de Decisiones , Pruebas Neuropsicológicas , Personalidad , Adolescente , Ansiedad/psicología , Estudios de Casos y Controles , Cognición , Femenino , Humanos , Masculino , Proyectos Piloto , PsicopatologíaRESUMEN
BACKGROUND: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. METHODS AND FINDINGS: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. CONCLUSIONS: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma.
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Neoplasias Encefálicas/patología , Glioma/patología , Células Madre Neoplásicas/patología , Microambiente Tumoral , Adulto , Anciano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular , Proliferación Celular , Exosomas/metabolismo , Femenino , Expresión Génica , Glioma/genética , Glioma/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Estimación de Kaplan-Meier , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Microscopía de Fuerza Atómica , Microscopía Fluorescente , Persona de Mediana Edad , Análisis Multivariante , Proteína Homeótica Nanog , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
OBJECT: Although a number of recent studies on the surgical treatment of insular low-grade glioma (LGG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG. METHODS: The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor's infiltrative pattern quantified by computing the difference between the preoperative T2- and T1-weighted MR images (ΔVT2T1) in 52 patients with preoperative drug-resistant epilepsy. RESULTS: The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR ≥ 90% (p < 0.001) and ΔVT2T1 < 30 cm(3) (p < 0.001). In the final model, ΔVT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001). CONCLUSIONS: No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high ΔVT2T1 values, which consequently reflects a smaller EOR.
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Neoplasias Encefálicas/cirugía , Corteza Cerebral/cirugía , Glioma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Convulsiones/etiología , Adulto , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/patología , Corteza Cerebral/patología , Femenino , Glioma/complicaciones , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Periodo Posoperatorio , Convulsiones/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: To define the biomarkers associated with lymphoproliferation in primary Sjögren's syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV). METHODS: A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions. RESULTS: Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive. CONCLUSIONS: Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.
Asunto(s)
Linfoma/diagnóstico , Linfoma/etiología , Lesiones Precancerosas/patología , Síndrome de Sjögren/complicaciones , Adulto , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Síndrome de Sjögren/inmunologíaRESUMEN
INTRODUCTION: Several therapeutic options are available for the treatment of vitiligo; among these phototherapy and topical steroids are the most widely documented. A topical formulation of 0.05% clobetasol propionate foam (CPF) has been introduced in the market, but no data are available about the efficacy and tolerability of this new formulation in the treatment of vitiligo. The aim of this study was to investigate the efficacy and tolerability of CPF in the treatment of vitiligo, in comparison with narrowband-ultraviolet B (NB-UVB) phototherapy. METHODS: The medical records of the first 60 vitiligo patients treated with NB-UVB phototherapy or with CPF were selected. Response to the treatment was determined for each anatomic site (neck, upper and lower limbs, trunk, hands/wrists, feet/ankles). Based on the area of repigmentation, treatment outcome was calculated according to a scale ranging from 0 (absent) to 4 (excellent). The incidence of adverse effects was also noted as a secondary endpoint. Significance level was set at P = 0.05. RESULTS: For each anatomic site, statistical analyses demonstrated that the efficacy of CPF was significantly higher compared to NB-UVB. Side effects occurred in 4 patients (13.33%) in the CPF group compared to none in the NB-UVB group. DISCUSSION: Clobetasol propionate has been used in vitiligo in different vehicles, but never in foam. The data showed that CPF is effective and seems to be superior to NB-UVB phototherapy, with furthermore a good safety profile. CONCLUSION: This new foam formulation of clobetasol propionate may expand the options currently available for vitiligo therapy; however, further investigations are needed to confirm our preliminary observations.
RESUMEN
BACKGROUND: The survival impact of metastasectomy for metastatic renal cell carcinoma (mRCC) is still an active research field, particularly in the multimodal/targeted therapy era. OBJECTIVE: To determine the survival impact of clinical prognostic factors and their application to stratification of patients according to their prognosis so clinicians may be aided in their management of mRCC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, bi-institutional cohort study of 109 consecutive patients (71 male and 38 female; median age: 62 yr (range: 25-82 yr) with renal cell carcinoma (RCC) who underwent partial or radical nephrectomy and at least one metastasectomy for mRCC. INTERVENTION: Metastasis resection from various anatomic sites with the aim of completely removing detected lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression models were used to analyse the impact of clinical prognostic factors on cancer-specific survival (CSS). Kaplan-Meier analysis with the log-rank test was used to compare CSS. Receiver operating characteristic (ROC) analysis was performed to test accuracy of prognostic groups. The α error for statistical significance was set at 0.05. RESULTS AND LIMITATIONS: Multivariable analysis revealed that primary tumour T stage ≥ 3 (hazard ratio [HR]: 2.8; p<0.01), primary tumour Fuhrman grade ≥ 3 (HR: 2.3; p<0.03), nonpulmonary metastases (HR: 3.1; p<0.03), disease-free interval ≤ 12 mo (HR: 2.3; p<0.058), and multiorgan metastases (HR: 2.5; p<0.04) were independent pretreatment prognostic factors. Leuven-Udine (LU) prognostic groups based on these covariates were created and analysed with Kaplan-Meier and log-rank tests. The 2- and 5-yr CSS were significantly different; the respective group A CSS rates were 95.8% and 83.1%; group B, 89.9% and 56.4%; group C, 65.6% and 32.6%; and group D, 24.7% and 0% (p<0.0001). ROC analysis on the accuracy of prognostic grouping revealed respective areas under the curve of 0.87 and 0.88 at 2 and 5 yr. Main limitations to present study are the retrospective design and the presence of different metastasis sites. CONCLUSIONS: LU prognostic groups could be considered an accurate clinical tool to stratify patients according to prognosis and aid clinicians in the management of mRCC.