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BACKGROUND: Persistent inflammation and immune activation are associated with lymph node fibrosis and end-organ diseases in treatment-suppressed people living with HIV (PLWH). We investigated the effect of switching to raltegravir and/or adding losartan on lymphoid tissue fibrosis and on the inflammatory/immune-activation mediators in treated HIV patients. METHODS: Chronic HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors (2NRTI) and one non-NRTI (NNRTI) or protease inhibitor (PI) during at least 48 weeks were randomized to four groups (n = 48): 2NRTI + efavirenz (EFV), 2NRTI + EFV + losartan, 2NRTI + raltegravir and 2NRTI + raltegravir + losartan for 48 weeks. Tonsillar biopsy and peripheral blood markers of CD4 and CD8 T-lymphocyte activation and senescence, monocyte activation and soluble markers of inflammation were determined at baseline and at week 48 and compared between groups. RESULTS: No changes in lymphoid tissue architecture were observed. Adding losartan had no impact on lymphocyte subsets. Conversely, patients who switched to raltegravir showed a higher decrease in all activated [CD4+CD38+HLA-DR+, -0.3 vs. 0.48 (P = 0.033); CD8+CD38+ HLA-DR+, -1.6 vs. 1.3 (P = 0.02)] and senescent [CD4+CD28-CD57+, -0.3 vs. 0.26 (P = 0.04); CD8+CD28-CD57+, -6.1 vs. 3.8 (P = 0.002)] T lymphocytes. In addition, the median CD4/CD8 ratio increased by 0.35 in patients in the raltegravir group vs. 0.03 in the other arms (P = 0.002). Differences between groups in monocyte subpopulations or soluble inflammation markers were not observed. CONCLUSIONS: Losartan had no effect on lymphoid fibrosis or immune activation/inflammation. Conversely, switching to a regimen with raltegravir significantly decreased activated and senescent T-lymphocyte subpopulations and increased CD4/CD8 ratio in successfully treated PLWH.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Fibrosis , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Losartán/uso terapéutico , Tejido Linfoide , Raltegravir Potásico/uso terapéutico , Carga ViralRESUMEN
OBJECTIVE: The objective of this report is to analyse retinal changes over a five-year period, assessed by spectral domain-optical coherence tomography (SD-OCT), in patients from the Lupus-Cruces cohort treated with hydroxychloroquine (HCQ). METHODS: SD-OCT screening was performed annually between 2012 and 2017. Average macular thickness (AMT), ganglion cell layer thickness (GCLT) and qualitative data of retinal pigment epithelium (RPE) and external retina (ExtR) were collected prospectively. We compared data from 2012 (first) and 2017 (second) SD-OCT. RESULTS: We studied 110 patients and 195 eyes. No cases of HCQ toxicity were detected. At the time of the second SD-OCT, 99% patients had taken a daily dose of HCQ ≤5 mg/kg/day. The median time on HCQ was 133 months. The mean AMT and GCLT were significantly lower in both eyes at the second SD-OCT; however, all the differences were clinically insignificant at less than 1%. Qualitative analysis of RPE and ExtR showed no significant changes. Similar results were found among patients with risk factors for retinopathy. The comparison of patients with and without risk factors showed no differences. CONCLUSIONS: This study shows clinically irrelevant retinal changes in an SLE cohort on HCQ treatment over a five-year follow-up. Our findings support the safety of long-term HCQ at doses ≤5 mg/kg/day.
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Antirreumáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/patología , Retina/patología , Adulto , Anciano , Antirreumáticos/administración & dosificación , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Hidroxicloroquina/administración & dosificación , Incidencia , Masculino , Persona de Mediana Edad , New Mexico/epidemiología , Estudios Prospectivos , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/patología , Estadísticas no Paramétricas , Tomografía de Coherencia Óptica , Población BlancaRESUMEN
OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
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Síndrome Antifosfolípido/complicaciones , Complicaciones Cardiovasculares del Embarazo/inmunología , Trombosis/inmunología , Adulto , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/sangre , Ensayos Clínicos como Asunto , Bases de Datos Factuales , Femenino , Humanos , Embarazo , Sistema de Registros , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.
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Antimaláricos/uso terapéutico , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Artropatías/tratamiento farmacológico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Quinacrina/uso terapéutico , Adulto , Antimaláricos/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Inmunosupresores/efectos adversos , Artropatías/diagnóstico , Artropatías/inmunología , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Quinacrina/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Fumadores , Resultado del TratamientoRESUMEN
Throughout the 20th century, a remarkable improvement in the prognosis of systemic lupus erythematosus (SLE) has been seen, mostly due to a better understanding of the disease and the advent of new therapies. However, a plateau seems to have been reached. Whilst outcomes related to active disease have greatly improved, damage accrual tends to be slowly increasing especially damage secondary to high-dose glucocorticoids, which could lead not only to increased morbidity but also to a worse long-term prognosis. Cardiovascular disease and infections still account for the majority of deaths yet both could potentially be improved, again, by the use of high-dose glucocorticoids. In addition, antimalarials have also demonstrated many beneficial effects on patients with lupus. Thus, the universal use of hydroxychloroquine, a more rational prescription of glucocorticoids and preventive strategies for cardiovascular disease can be used as measures with major impacts on the future prognosis of patients with SLE.
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Lupus Eritematoso Sistémico/diagnóstico por imagen , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.
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Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pancreatitis/tratamiento farmacológico , Prednisona/administración & dosificación , Insuficiencia Respiratoria/tratamiento farmacológico , Enfermedad Aguda , Adulto , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Hemorragia/inmunología , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Pancreatitis/inmunología , Prednisona/efectos adversos , Inducción de Remisión , Insuficiencia Respiratoria/inmunología , Rituximab , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this 1-year follow-up study was to compare functional outcome as well as clinical differences between patients with first- and multiple-episode bipolar disorder. METHOD: Bipolar disorder patients with first (n = 60) and multiple episodes (n = 59) were recruited from two hospitals in Spain. The Functioning Assessment Short Test (FAST) was used to assess functioning. The Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS) were administered to assess mood symptoms. RESULTS: As expected, patients with first episode experienced a greater functioning compared to patients with multiple episodes (11.26 ± 10.94 vs. 26.91 ± 13.96; t = 6.436, P < 0.001). There were significant demographic and clinical differences between both groups. Baseline depressive symptoms (F = 9.553, df = 4, 102; P < 0.001) and age (F = 14.145, df = 4, 103; P < 0.001) were significantly associated with poor functional recovery at 6-month and 12-month assessment, respectively, in a group of patients with multiple episodes. CONCLUSION: Our data give support to the model of staging in bipolar disorder, showing that the enduring neurotoxicity of repeated episodes may contribute to sustained impairment in multiple areas of psychosocial functioning.
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Actividades Cotidianas/psicología , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Cognición , Empleo/psicología , Relaciones Interpersonales , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Actividades Recreativas/psicología , Masculino , Persona de Mediana Edad , Recuperación de la FunciónRESUMEN
Patients with systemic lupus erythematosus are exposed to a remarkably high number of maternal-fetal complications during pregnancy. Knowledge regarding the reciprocal influence between lupus and pregnancy is the starting point to assure that these patients are correctly monitored. It is also important to carry out comprehensive preconception evaluation to individually evaluate the risk of each patient. The immunological profile, history of nephritis, presence of chronic damage and disease activity are the basic data that will determine the specific individual risk profile. Finally, correct drug management must be assured during this period, based on the safety profile of the different treatments during pregnancy and lactation.
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Antiinflamatorios/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Atención Posnatal/métodos , Complicaciones del Embarazo/tratamiento farmacológico , Atención Prenatal/métodos , Adulto , Lactancia Materna , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/prevención & controlRESUMEN
Infertility and reproductive problems have been reported in women with several neurological disorders, for example, demyelination. However, the physiology of such problems has remained unknown so far. The taiep rats are an animal neurological model that initially shows a hypomyelination followed by a progressive demyelination of the central nervous system. This animal has reproductive problems, and the aim of this work is to characterize the follicular development, secretion of ovarian hormones, and presence of noradrenaline in the ovaries of the female taiep rats in the juvenile and adult stages. The taiep rats have low body weight (approximately 19% less than that of SD rats), a delay of 4 days in the age of vaginal opening, and an irregularity in the estrous cycle by the absence or prolongation of some estral cycle stage. In the juvenile stage, we observed a decrease of approximately 44% in the total number of follicles with a 15% increase of atresia and an 80% decrease in the fluorescence intensity of catecholamines in the ovaries, with a 21% increment in plasma concentrations of testosterone. In the adult stage, we observed follicular cysts and a 50% decrease in fluorescence intensity of catecholamines in the ovaries, with changes in the secretion of ovarian hormones, an increase of 20 times in progesterone, and a decrement of a half in estradiol. The demyelination in taiep rats affects follicular development and steroidogenesis in the early stages of the animal's life, and this is maintained until adulthood.
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Central administration of oxytocin has been shown to induce yawning, penile erection, grooming and scratching. Yawning and penile erections are due to activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus. We selectively bred two sublines from Sprague-Dawley rats, one with a high-yawning frequency (HY) of 20yawns/h, and one with a low-yawning (LY) frequency of 2yawns/h. The aim of the current study was to analyze the behavioral effects of centrally-administered oxytocin [15ng-10µg; intracerebroventricularly (i.c.v.)] on yawning, penile erections, grooming and scratching in adult male rats from both sublines. Oxytocin produced a dose-dependent increase in yawning and penile erection frequencies and this effect was significantly higher in the HY, compared to the LY, subline. However, the number of oxytocin-induced scratching bouts was significantly higher in the LY, compared to the HY group. In conclusion, these sublines represent a suitable model for detailed analysis of behavior induced by oxytocin and other neuropeptides in animals with different spontaneous expression of behavioral traits.
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Aseo Animal/efectos de los fármacos , Oxitocina/administración & dosificación , Erección Peniana/efectos de los fármacos , Bostezo/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Oxitocina/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs. RESULTS: The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period. CONCLUSIONS: The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.
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BACKGROUND: Extended cervical mediastinoscopy (ECM) is a technique in the staging of bronchogenic carcinoma described first by Ginsberg in 1984. To update our experience we have prospectively evaluated our results on 106 patients who underwent the technique from 1985 to 1998. METHODS: The ECM technique is performed once the operability of the patient has been evaluated, according to the computed tomography findings. The intervention is carried out at the same time as a standard cervical mediastinoscopy through the same incision following the same technique as previously published. The ECM is considered positive when metastatic nodes or tumor involvement directly in the paraaortic or subaortic regions is detected and confirmed histologically. Negative cases of ECM and positive cases of standard cervical mediastinoscopy are excluded from this study. A false-negative ECM is defined as the presence of infiltrated adenopathies at the paraortic level detected on postoperative histologic study. RESULTS: We had performed ECM in 106 patients, and a total of 13 were subsequently excluded for the reasons stated above. Of the remaining cases, 26 were positive, 61 negative and 6 had false-negative results with no false-positive results. Sensitivity was 81.2%, specificity 100%, accuracy 93.3%, positive predictive value 100%, and negative predictive value 91%. There were no complications with the technique. CONCLUSIONS: We conclude that ECM is a useful technique for staging bronchogenic carcinoma that allows samples to be taken from paraortic and subaortic regions with minimally invasive techniques.
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Carcinoma Broncogénico/patología , Neoplasias Pulmonares/patología , Mediastinoscopía/métodos , Estadificación de Neoplasias/métodos , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Células Grandes/patología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/patología , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Reactive astrocytosis in taiep rats was shown by glial fibrillary acidic protein (GFAP) immunoreactivity measured by means of enzyme-linked immunosorbent assay and indirect immunofluorescence. Increased GFAP immunoreactivity was first observed in the brainstem of 15-day-old taiep rats and was widespread throughout all brain regions at 6 months of age. Characteristically, astrocytes were hypertrophic and displayed strong GFAP fluorescence. The pattern of these reactive cells may correlate with the process of dysmyelination in the taiep rat.
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Encéfalo/patología , Enfermedades Desmielinizantes/genética , Gliosis/genética , Animales , Astrocitos/química , Astrocitos/patología , Ataxia/genética , Biomarcadores , Enfermedades Desmielinizantes/patología , Progresión de la Enfermedad , Retículo Endoplásmico Liso/patología , Ensayo de Inmunoadsorción Enzimática , Epilepsia Refleja/genética , Técnica del Anticuerpo Fluorescente Indirecta , Proteína Ácida Fibrilar de la Glía/análisis , Gliosis/patología , Hipertrofia , Microtúbulos/patología , Ratas , Ratas Mutantes , Ratas Sprague-Dawley , Convulsiones/genética , Temblor/genéticaRESUMEN
Serotonin (5-HT) effects on physostigmine (PHY)-induced yawning were studied in LY Sprague-Dawley rats by injecting Lu 10 171 (citalopram), a specific 5-HT uptake blocker, and two antagonists--methiothepine and ritanserin--which differ slightly in the selectivity of their actions on different 5-HT receptor subtypes. Infant and young rats show significant increases in PHY-induced yawning when preinjected with citalopram (5-10 mg/kg). Two-month-old animals show this effect only with 10 mg/kg. With adult animals (3-5 months old), the effect is the opposite: Yawning decreases. The facilitory effect in infant and young rats was counteracted by methiothepine but not by ritanserin, suggesting that it is mediated through 5-HT1A or 5-HT1B receptor subtypes. The inhibitory effect of citalopram in adult rats was unmodified by the two antagonists used, leaving open the possibility that it is mediated by 5-HT3 receptors.
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Envejecimiento/psicología , Serotonina/fisiología , Bostezo/fisiología , Animales , Citalopram/farmacología , Masculino , Metiotepina/farmacología , Fisostigmina/farmacología , Ratas , Ratas Sprague-Dawley , Ritanserina/farmacología , Antagonistas de la Serotonina/farmacologíaRESUMEN
Episodes of apnea during the first year of life have been classified with the term "Apparent Life-Threatening Events" (ALTE). Gastroesophageal reflux (GER) has been accepted to be one of the factors which can favor ALTE. The aim of this work is to study the continuous 24 h gastroesophageal pH-metering (fundamentally the Reflux Index [RI] and the Area Under Curve [AUC] parameters in three different periods of time: total pH-metering, pH-metering excluding the first two post-prandial hours, and pH-metering during sleep time, for 24 infants, 14 with ALTE and 10 without it). Between these two groups (with and without ALTE) there were no significant differences in the total pH-metering concerning the RI (2 +/- 1.2 vs 5.6 +/- 7.5 p > 0.05) and concerning the AUC (24.9 +/- 14.4 vs 67.4 +/- 84 p > 0.05), but in the analysis of the sleep period, the RI (p < 0.05) and the AUC (p < 0.01) both showed significant differences in the group of infants without ALTE. These results confirm that pH-metering study during sleep is the procedure of choice for recognizing infants with ALTE.
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Determinación de la Acidez Gástrica , Reflujo Gastroesofágico/fisiopatología , Monitoreo Fisiológico , Síndromes de la Apnea del Sueño/fisiopatología , Muerte Súbita del Lactante/etiología , Ritmo Circadiano/fisiología , Unión Esofagogástrica/fisiopatología , Femenino , Reflujo Gastroesofágico/diagnóstico , Humanos , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Síndromes de la Apnea del Sueño/diagnóstico , Muerte Súbita del Lactante/prevención & controlRESUMEN
To validate our experience with standard cervical mediastinoscopy (SCM) and extended cervical mediastinoscopy (ECM) to diagnose mediastinal nodes and masses, we studied 181 patients between January 1992 and February 2001. SCM and ECM were indicated for diagnostic staging of nodes related to bronchogenic carcinoma (Group I) or of mediastinal masses (Group II). An SCM was performed in all cases to explore the paratracheal region (2R, 2L, 4R, 4L, 7, 10R and 10L); in 21 additional cases, an ECM was performed to explore the aortopulmonary window or the subaortic region (area 5) and the para-aortic region (area 6). In Group I, the sensitivity of SCM was 93.6% and specificity was 100%; the positive predictive value (PPV) was 100%, the negative predictive value (NPV) was 82.8%, and the diagnostic yield was 95.1%. The sensitivity of ECM was 91% and specificity was 100%; PPV was 100%, NPV 93.3% and yield was 96%. In Group II, the sensitivity was 93.3%, specificity 100%, PPV 100%, NPV 81.2% and diagnostic yield 94.8%. The sensitivity of ECM in this group was 80%, specificity was 100%, PPV 100%, NPV 66.7% and yield 85.7%. A 2.7% complication rate was observed, with one case of bleeding after injury to the superior vena cava, one tracheal lesion, one recurring paralysis and two cases of surgical wound infection. The mean postoperative stay was 36 hours and mortality was zero. We conclude that SCM is highly specific for the evaluation of mediastinal node involvement in bronchogenic carcinoma and it is the approach of choice when a diagnosis of lesions located in the mid-mediastinal region has not been reached. ECM is a valid, safe alternative to anterior mediastinotomy for staging nodes and masses occupying para-aortic zones or the aortopulmonary window, with good diagnostic yield, low morbidity and absence of mortality.
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Neoplasias del Mediastino/diagnóstico , Mediastinoscopía/métodos , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Broncogénico/diagnóstico , Carcinoma Broncogénico/cirugía , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Pequeñas/diagnóstico , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/cirugía , Humanos , Masculino , Neoplasias del Mediastino/cirugía , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteínas , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada de EmisiónRESUMEN
OBJECTIVE: To quantify changes in tumor-node-metastasis (TNM) staging (numerical migration) and survival (prognostic migration) that arise when certainty criteria are applied to a patient population with non-small cell lung cancer (NSCLC) treated surgically. METHODS: The population consisted of 1,844 patients with NSCLC who underwent surgery between 1993 and 1996 at hospitals participating in the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). For every patient, surgical-pathological TNM staging (p) was based on two classifications: initial staging by each participating GCCB-S center (pTNM-i) and a second classification bearing greater classificatory certainty (pTNM-cc) resulting from the application of stricter criteria. Numerical migration was said to have occurred in cases where the two classifications did not coincide, and the possible prognostic migration under the new staging was then assessed. RESULTS: The results revealed great numerical migration in the pN0 classification (from 1,091 cases to 665). The changes did not result in prognostic migration either for the group as a whole or for pT1-2N0M0 cases. However, for pT3N0M0 cases, median survival increased by 13 months. The difference in three-year survival (S3) for pT3N0M0-i without certainty confirmation [S3 = 0.30 (95%CI 0.18-0.42), n=59] and pT3N0M0-cc [S3=0.54 (95%CI = 0.44-0.64), n = 92] was significant (log-rank, p = 0.035). Such behavior was not observed for pT1-2N0M0. CONCLUSIONS: The numerical migration observed as a result of applying surgical-pathological classificatory certainty criteria is relevant but the prognostic repercussion is scarce, except in cases classified as pT3N0M0, in which a significant positive prognostic migration is observed (the "Will Rogers phenomenon").
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias/estadística & datos numéricos , Resultado del Tratamiento , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Progresión de la Enfermedad , Humanos , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/patología , PronósticoRESUMEN
Thoracic wall resections are performed to treat a wide variety of conditions. Reconstruction techniques have varied considerably since the introduction of synthetic prosthesis, the most recent of which are made of polytetrafluoroethylene (PTFE, or Gore-Tex). We describe our department's experience with PTFE prosthesis. PTFE was used in 21 patients treated for various diseases. Thirteen reconstructions were of the thoracic wall, 4 were of the diaphragm and 4 of the pericardium. Three of the 13 thoracic wall reconstructions involved bilateral myoplasty of the pectoralis major, 2 involved omentoplasty and 1 required use of a wide musculocutaneous flap. Complications included pneumonia in 2 cases and 1 seroma with chronic cutaneous fistula that required removal of the prosthesis after 9 months. Two patients died, 1 after 19 days and the other after 9 months, both as a result of causes unrelated to reconstruction. Follow-up of these patients ranged from 3 to 54 months. We recommend the prosthetic use of PTFE for thoracic wall reconstruction, along with plasty or musculocutaneous flaps when necessary.
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Materiales Biocompatibles , Politetrafluoroetileno , Toracoplastia/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Most radiological signs are of low specificity for predicting malignancy in patients with a solitary pulmonary nodule (SPN), making clinical management difficult. Only certain calcification patterns in SPN or the absence of growth over a period two years assures that the nodule is benign. The clinical and radiological characteristics of 31 patients with SPN were studied. Twenty-two were cases bronchopulmonary carcinoma and 9 were pulmonary tuberculoma. Accuracy in the prediction of malignancy was assessed using Bayes' theorem, which is based on degrees of likelihood of various radiological and clinical characteristics. Patients with carcinoma (mean age 65 +/- 9 years) were significantly older than those with tuberculoma (38 +/- 19 years) (p < 0.05). The proportion of smokers was significantly higher among patients with carcinoma (91%) than those with tuberculoma (44%) (p < 0.05). In 50% of the patients with SPN due to bronchopulmonary carcinoma (11 patients), the nodule was in the upper right lobe; in 55% of those with tuberculomas (5 patients) the nodule was found in the upper left lobe. There were no significant differences in the characteristics of the computerized tomography images for the two groups. Mean likelihood of malignancy for patients with carcinoma, by Bayes' theorem, was 83.7%, a rate that was significantly higher than that of tuberculoma patients (46%) (p < 0.05). The application of Bayes' probability theorem for a set of clinical and radiological characteristics can orient the physician as to whether an SPN is likely to be malignant or not, thereby providing guidance on the advisability of performing invasive diagnostic procedures to determine etiology.
Asunto(s)
Teorema de Bayes , Nódulo Pulmonar Solitario/diagnóstico , Adulto , Factores de Edad , Anciano , Interpretación Estadística de Datos , Diagnóstico Diferencial , Femenino , Humanos , Funciones de Verosimilitud , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía Torácica , Estudios Retrospectivos , Fumar , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tuberculoma/diagnóstico , Tuberculoma/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/diagnóstico por imagenRESUMEN
Dumbbell tumors are extremely rare. Most are neurogenic in origin. Growth is both inside and outside the spinal canal, and symptoms debut with medullary or spinal compression. References to non-neurogenic dumbbell tumors are uncommon. This report describes the case of a 56 year-old woman with a dumbbell angiolipoma having mediastinal and spinal cord portions. The tumor was successfully resected using a two-stage procedure. First, the spinal portion was resected using a posterior neurosurgical approach, with improvement of symptoms. Then, the mediastinal portion was removed thoracoscopically.