RESUMEN
OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.
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Microbioma Gastrointestinal , Esclerosis Múltiple , Animales , Ácidos y Sales Biliares , Sistema Nervioso Central , Trasplante de Microbiota Fecal , HumanosRESUMEN
INTRODUCTION: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited. METHODS: We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated. RESULTS: The analysis included 66 stage I-III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval [CI]: 0.16-0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17-0.81, p: 0.013) for multivariate analysis. CONCLUSIONS: Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I-III SCLCs and warrants further investigation.
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Antígeno B7-H1/inmunología , Factores de Transcripción Forkhead/inmunología , Neoplasias Pulmonares/inmunología , Carcinoma Pulmonar de Células Pequeñas/inmunología , Microambiente Tumoral/inmunología , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/biosíntesis , Femenino , Factores de Transcripción Forkhead/biosíntesis , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/terapiaRESUMEN
BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management. METHODS: The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS). RESULTS: In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66-3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08-1.93, P=0.014), advanced (III-IV) stage (HR 1.47; 95% CI 1.09-1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02-1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28-0.56, P<0.001). CONCLUSIONS: Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.
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Neoplasias Pulmonares/mortalidad , Mesotelioma/mortalidad , Neoplasias Pleurales/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Humanos , Italia/epidemiología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Mesotelioma/patología , Mesotelioma/terapia , Mesotelioma Maligno , Neoplasias Pleurales/patología , Neoplasias Pleurales/terapia , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). METHODS: Eligible patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(-1), administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated. RESULTS: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. CONCLUSION: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Masculino , Mesotelioma/sangre , Persona de Mediana Edad , Pemetrexed , Neoplasias Pleurales/sangre , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangreAsunto(s)
Proteína BRCA1/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas Portadoras/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos como Asunto , Proteínas de Unión al ADN , Supervivencia sin Enfermedad , Quimioterapia , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Chaperonas de Histonas , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Platino (Metal)/administración & dosificación , ARN Mensajero/genéticaRESUMEN
Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Humanos , Mesotelioma/radioterapia , Mesotelioma/cirugía , Terapia Neoadyuvante , Neoplasias Pleurales/radioterapia , Neoplasias Pleurales/cirugíaRESUMEN
OBJECTIVE: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients (n = 165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44 mcg three times weekly), intramuscular (im) IFN beta-1a (30 mcg weekly) or glatiramer acetate (GA; 20 mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months. RESULTS: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed ≥ 1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p = 0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p = 0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p < 0.001). After 24 months, ≥ 1 new CL was observed in 41/50 (82%) of untreated (mean 3.0), 34/47 (72%) of im IFN beta-1a-treated (mean 1.6, p < 0.001), 30/48 (62%) of GA-treated (mean 1.3, p < 0.001) and 24/46 (52%) of sc IFN beta-1a-treated patients (mean 0.8, p < 0.001). Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients (p = 0.023). CONCLUSIONS: Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients, with faster and more pronounced effects seen with sc IFN beta-1a than with im IFN beta-1a or GA.
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Corteza Cerebelosa/patología , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/patología , Péptidos/uso terapéutico , Adolescente , Adulto , Atrofia/tratamiento farmacológico , Corteza Cerebelosa/efectos de los fármacos , Progresión de la Enfermedad , Femenino , Acetato de Glatiramer , Humanos , Inyecciones Intramusculares , Inyecciones Subcutáneas , Interferón beta-1a , Interferón beta/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: The cause of epilepsy in multiple sclerosis (MS) has not yet been elucidated. The relevance of cortical pathology (cortical lesions and thickness) in MS patients with and without epilepsy was evaluated in a longitudinal study. METHODS: 32 relapsing-remitting MS patients with epilepsy (RRMS/E) and 60 matched RRMS patients without epilepsy were included in a 3 year longitudinal study. The following clinical and MR parameters were analysed: Expanded Disability Status Scale (EDSS), cognitive score (CS), cortical lesion (CL) number and volume, grey matter fraction (GMf), global cortical thickness (CTh), T2 white matter lesion volume (T2WMLV), new CLs and new WM lesions. RESULTS: At baseline (T0), CLs were observed in 27/32 (84.4%) RRMS/E and in 26/60 (43.3%) RRMS (p<0.001) patients, and the RRMS/E group had a higher number (10.2 ± 8.9 vs 4.5 ± 2.4; p<0.001) and total volume (2.0 ± 1.3 vs 0.7 ± 0.8 cm(3); p<0.001) of CLs compared with the RRMS group. No significant difference in T2WMLV was observed. Global CTh was lower in RRMS/E (2.12 ± 0.19 vs 2.35 ± 0.14 mm; p<0.001), and this group also showed a decline in cognition (CS 10.9 ± 6.3 vs 6.2 ± 3.5; p<0.001). After 3 years (T1), the RRMS/E group had a higher accumulation of new CLs (3.4 ± 3.2 vs 1.2 ± 1.1; p<0.001) and faster reduction of GMf (p=0.022) while the two groups did not differ in the number of new WM and new Gad+ lesions. DISCUSSION: RRMS/E had a more severe and rapidly evolving cortical pathology (CLs and atrophy) compared with RRMS without epilepsy. The RRMS/E group was also characterised by more pronounced cognitive decline, higher EDSS and higher prevalence of men.
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Corteza Cerebral/parasitología , Epilepsia/complicaciones , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Adolescente , Adulto , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Progresión de la Enfermedad , Electroencefalografía , Epilepsia/patología , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
BACKGROUND: Although gray matter (GM) atrophy is recognized as a common feature of multiple sclerosis (MS), conflicting results have been obtained in patients with clinically isolated syndromes (CIS). Methodologic and clinical constraints may take account for literature discrepancies. METHODS: A total of 105 patients presenting with CIS and 42 normal controls (NC) were studied. At baseline, 65/105 patients with CIS met the criterion of dissemination in space of lesions (DIS+). All patients were clinically assessed by means of the Expanded Disability Status Scale every 6 months and underwent MRI evaluation at study entry and then annually for 4 years. Global and regional cortical thickness and deep GM atrophy were assessed using Freesurfer. RESULTS: No significant reduction in GM atrophy was observed between the entire CIS group and the NC, excepting for the cerebellum cortical volume. When the 59 patients with CIS (46 DIS+, 13 DIS-) who converted to MS during the follow-up were compared to the NC, a significant atrophy in the precentral gyrus, superior frontal gyrus, thalamus, and putamen was observed (p ranging from 0.05 to 0.001). The multivariate analysis identified the atrophy of superior frontal gyrus, thalamus, and cerebellum as independent predictors of conversion to MS. CIS with atrophy of such areas had a double risk of conversion compared to DIS+ (odds ratio 9.6 vs 5.0). CONCLUSION: Selective GM atrophy is relevant in patients with CIS who convert early to MS. The inclusion of GM analysis in the MS diagnostic workup is worthy of further investigation.
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Encéfalo/patología , Enfermedades Desmielinizantes/diagnóstico , Fibras Nerviosas Mielínicas/patología , Adolescente , Adulto , Análisis de Varianza , Atrofia/patología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
BACKGROUND: Sorafenib is a small-molecule multitargeted kinase inhibitor that blocks the activation of C-RAF, B-RAF, c-KIT, FLT-3, RET, vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3 and platelet-derived growth factor receptor ß. The aim of this multicenter, randomized phase II study was to evaluate clinical activity and safety of sorafenib in combination with erlotinib or gemcitabine in unselected untreated elderly patients with non-small-cell lung cancer (NSCLC). METHODS: The trial was designed to select the most promising sorafenib-containing combination in previously untreated elderly (≥70 years) stage IIIB or IV NSCLC patients, with performance status of zero to two. Patients were randomly assigned to one of the following combinations: gemcitabine, 1200 mg/m(2) days 1 and 8, every 21 days, for a maximum of six cycles, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 1); or erlotinib, 150 mg/day, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 2). A selection design was applied with 1-year survival rate as the primary end point of the study, requiring 58 patients. RESULTS: Sixty patients were randomly allocated to the study (31 patients in arm 1 and 29 patients in arm 2). After a median follow-up of 15 months, 10 patients [32%, 95% confidence interval (CI) 16% to 49%] in arm 1 and 13 patients (45%, 95% CI 27% to 63%) in arm 2 were alive at 1 year. Median overall survival was 6.6 and 12.6 months in arm 1 and arm 2, respectively. Observed toxic effects were consistent with the expected drug profiles. CONCLUSIONS: The combination of erlotinib and sorafenib was feasible in elderly patients with advanced NSCLC and was associated with a higher 1-year survival rate than the other arm. According to the selection design, this combination warrants further investigation in phase III trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma Bronquioloalveolar/tratamiento farmacológico , Adenocarcinoma Bronquioloalveolar/mortalidad , Anciano , Anciano de 80 o más Años , Bencenosulfonatos/administración & dosificación , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Clorhidrato de Erlotinib , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/administración & dosificación , Quinazolinas/administración & dosificación , Sorafenib , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes. METHODS: A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer. RESULTS: Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment. CONCLUSIONS: A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.
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Corteza Cerebral/patología , Trastornos del Conocimiento/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Fibras Nerviosas Amielínicas/patología , Adolescente , Adulto , Análisis de Varianza , Atrofia/patología , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Análisis Multivariante , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS. OBJECTIVE: This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability. METHODS: Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up. RESULTS: At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period. CONCLUSIONS: Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.
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Corteza Cerebral/patología , Esclerosis Múltiple Crónica Progresiva/patología , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Adulto JovenRESUMEN
BACKGROUND: Using double inversion recovery (DIR) MRI, cortical lesions can be seen in the brain of patients with multiple sclerosis (MS). The burden of such lesions seems to be well correlated with the severity of MS-related disability. OBJECTIVE: To investigate whether the extent of cortical damage in patients with benign MS (BMS) might contribute to explain their favorable clinical status. METHODS: Forty-eight patients with BMS (Expanded Disability Status Scale [EDSS] score < or =3.0 and disease duration > or =15 years) and 96 patients with non-disabling, early relapsing-remitting (RR) MS (EDSS score < or =3.0 and disease duration < or =5 years) were studied. Brain MRI, including a DIR and a fluid-attenuated inversion recovery (FLAIR) sequence, was acquired at baseline and after 12 months. On DIR images, intracortical (ICL) and cortical-subcortical lesions (CSL) were identified and their number and volume calculated. Total white matter (WM) lesion volume was quantified on FLAIR images. RESULTS: Compared with early RRMS, patients with BMS had lower number of ICL at both study time points (P < or = 0.001 for both comparisons). At one-year follow-up, a significant increase of ICL and CSL number and total volume was observed only in early patients with RRMS. The number and volume of cortical lesions was not correlated with WM lesion volume. Total ICL number at baseline, total cortical lesion volume at baseline, and total cortical lesion volume change were independent predictors of MS phenotype. CONCLUSION: In patients with BMS, the selective sparing of the cortex from disease-related focal pathology might be one of the factors associated to their favorable clinical status, independently of the (possible) accrual of WM lesions.
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Corteza Cerebral/patología , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Índice de Severidad de la Enfermedad , Adulto , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. In this study, pooled data from two phase II trials of pemetrexed and carboplatin (PC) as first-line therapy were retrospectively analysed for comparisons between age groups. Patients received pemetrexed 500 mg m(-2) and carboplatin AUC 5 mg ml(-1) min(-1) intravenously every 21 days with standard vitamin supplementation. Elderly patients were defined as those >or=70 years old. A total of 178 patients with an ECOG performance status of
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Glutamatos/administración & dosificación , Guanina/análogos & derivados , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Ensayos Clínicos Fase II como Asunto , Femenino , Guanina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Pemetrexed , Estudios RetrospectivosRESUMEN
BACKGROUND: Metastatic renal cell carcinoma (RCC) has a poor prognosis and conventional treatments such as chemoradiotherapy show little efficacy. Surgical resection of pulmonary metastases from RCC is a widely accepted treatment, even if selection criteria based on prognostic factors have still not been defined. The aim of this study was to determine the long-term survival, clinical outcome and prognostic factors after surgery. METHODS: Between 1988 and 2004, 59 patients underwent resection of pulmonary metastases from RCC. Univariate and multivariate analysis of prognostic factors was carried out. RESULTS: Complete resection was achieved in 54 (91.5 %) patients. No intra- or postoperative mortality occurred, 5 (8.5 %) patients experienced postoperative complications. Overall, the 1-, 3-, and 5-year survival rates were 86.5 %, 63 % and 53 %, respectively. Age at the time of pulmonary resection was found to be the only independent factor influencing prognosis. CONCLUSION: Pulmonary resection of metastases from RCC is a safe and effective treatment associated with a low morbidity and mortality and with high long-term survival. The lack of other effective therapies suggests use of the surgical approach whenever possible.
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Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Adulto , Anciano , Carcinoma de Células Renales/terapia , Quimioterapia Adyuvante , Femenino , Humanos , Inmunoterapia , Neoplasias Renales/cirugía , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrectomía , Pronóstico , Radioterapia Adyuvante , Toracotomía , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ensayos Clínicos Fase III como Asunto , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Docetaxel , Humanos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Compuestos de Platino/administración & dosificación , Compuestos de Platino/efectos adversos , Taxoides/administración & dosificación , Taxoides/efectos adversos , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/análogos & derivados , Vinorelbina , GemcitabinaRESUMEN
A strict collaboration is necessary between the oncologist and the surgeon, both must know the respective problematic and competences and must contribute together to all phases of clinical management of patients affected by NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/terapia , Comunicación Interdisciplinaria , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Oncología Médica/métodos , Rol del Médico , Cirugía Torácica/métodos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia Combinada/métodos , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Modelos Biológicos , Estadificación de NeoplasiasRESUMEN
The survey, realized in 2002-03 in the North-East of Italy, describes renal care in dialysis services. A questionnaire, structured at European level, was sent to all dialysis centres by mail. The questionnaire was returned from 21 centres (61.8%) and related satellite units. Results show nonhomogeneity in renal care. Some important results were: low use of peritoneal dialysis (18%), compared to the rest of Europe, elevated presence of older people on haemodialysis, reduced percentage of patients on transplantation waiting list, diffused use of isolation for HCV positive patients, high use of AV fistulae (84%), low employment of renal technicians, absence of renal dieticians and social workers and nurses performing prevalently direct care. Data can be used for different goals: benchmarking activities, selection of deeper research topics and development of more oriented continuous education activities.
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Pautas de la Práctica en Medicina/organización & administración , Terapia de Reemplazo Renal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Dietética/organización & administración , Femenino , Investigación sobre Servicios de Salud , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Italia/epidemiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Personal de Enfermería/organización & administración , Ciencias de la Nutrición/educación , Grupo de Atención al Paciente/organización & administración , Educación del Paciente como Asunto/organización & administración , Proyectos Piloto , Terapia de Reemplazo Renal/instrumentación , Terapia de Reemplazo Renal/métodos , Terapia de Reemplazo Renal/estadística & datos numéricos , Servicio Social/organización & administración , Encuestas y Cuestionarios , Listas de EsperaRESUMEN
BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study. METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Anciano , Análisis de Varianza , Carboplatino/administración & dosificación , Distribución de Chi-Cuadrado , Cisplatino/administración & dosificación , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificaciónRESUMEN
We investigated the effects of adenosine on prolactin (PRL) secretion from rat anterior pituitaries incubated in vitro. The administration of 5-N-methylcarboxamidoadenosine (MECA), an analog agonist that preferentially activates A2 receptors, induced a dose-dependent (1 nM to 1 microM) increase in the levels of PRL released, an effect abolished by 1,3-dipropyl-7-methylxanthine, an antagonist of A2 adenosine receptors. In addition, the basal levels of PRL secretion were decreased by the blockade of cyclooxygenase or lipoxygenase pathways, with indomethacin and nordihydroguaiaretic acid (NDGA), respectively. The stimulatory effects of MECA on PRL secretion persisted even after the addition of indomethacin, but not of NDGA, to the medium. MECA was unable to stimulate PRL secretion in the presence of dopamine, the strongest inhibitor of PRL release that works by inducing a decrease in adenylyl cyclase activity. Furthermore, the addition of adenosine (10 nM) mimicked the effects of MECA on PRL secretion, an effect that persisted regardless of the presence of LiCl (5 mM). The basal secretion of PRL was significatively reduced by LiCl, and restored by the concomitant addition of both LiCl and myo-inositol. These results indicate that PRL secretion is under a multifactorial regulatory mechanism, with the participation of different enzymes, including adenylyl cyclase, inositol-1-phosphatase, cyclooxygenase, and lipoxygenase. However, the increase in PRL secretion observed in the lactotroph in response to A2 adenosine receptor activation probably was mediated by mechanisms involving regulation of adenylyl cyclase, independent of membrane phosphoinositide synthesis or cyclooxygenase activity and partially dependent on lipoxygenase arachidonic acid-derived substances.