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OBJECTIVE: A non-interventional, longitudinal, retrospective follow-up study to assess CsA-induced nephrotoxicity (IN) and its reversibility after withdrawal in patients exhibiting a bilateral chronic posterior uveitis (CPU) associated with cystoid macular oedema (CMO) in at least one eye. Data from medical records between 1986 and 2013. METHODS: Primary outcome was the renal tolerance during and after CsA treatment assessed by plasma creatinine concentration and glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology (CKD-Epi) formula. Secondary outcomes were CsA through concentration, occurrence of cancers and ophthalmologic efficacy assessed by three parameters including CMO, vitreous inflammation, and best-corrected visual acuity BVCA changes. RESULTS: One hundred forty-three patients were followed for renal tolerance. Underlying diseases were Birdshot retinochoroiditis (n = 67), Behçet disease (n = 9), probable sarcoidosis (n = 23), sympathetic ophthalmia (n = 3), idiopathic (n = 41). After CsA discontinuation in 115 patients (mean treatment duration of 5.9 ± 3.8 years) mean plasma creatinine concentration was 82.2 ± 14.2 µmol/L versus 82.1 ± 14.1 µmol/L at baseline, mean GFR was 79.4 ± 13.9 mL/min versus 82.5 ± 14.3 mL/min at baseline, with no significant difference (respectively p = 0.91 and p = 0.09). Blood pressure did not significantly change during follow-up. CMO was completely resorbed in at least one eye, in 70.8% patients (n = 72) at 6 months, in 71.4% patients (n = 49) at 10 years and in 54.2% patients (n = 24) at 20 years. BCVA did not statistically change over time. CONCLUSION: Early and long-term monitoring of renal tolerance and dual adjustment of CsA doses in inflammatory stages of CPU were associated with reversible CsA IN. CsA could be effective in the treatment of CMO in CPU patients.
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Edema Macular , Uveítis Posterior , Uveítis , Humanos , Edema Macular/tratamiento farmacológico , Ciclosporina/efectos adversos , Estudios Retrospectivos , Creatinina/uso terapéutico , Estudios de Seguimiento , Uveítis/tratamiento farmacológico , Uveítis/complicaciones , Uveítis Posterior/tratamiento farmacológico , Uveítis Posterior/complicacionesRESUMEN
OBJECTIVE: To explore mortality risk factors for patients hospitalised with COVID-19 in a critical care unit (CCU) or a hospital care unit (HCU). DESIGN: Retrospective cohort analysis using the French national (Programme de médicalisation des systèmes d'information) database. SETTING: Any public or private hospital in France. PARTICIPANTS: 98 366 patients admitted with COVID-19 for more than 1 day during the first semester of 2020 were included. The underlying conditions were retrieved for all contiguous stays. MAIN OUTCOME MEASURES: In-hospital mortality and associated risk factors were assessed using frailty Cox models. RESULTS: Among the 98 366 patients included, 25 765 (26%) were admitted to a CCU. The median age was 66 (IQR: 55-76) years in CCUs and 74 (IQR: 57-85) years in HCUs. Age was the main risk factor of death in both CCUs and HCUs, with adjusted HRs (aHRs) in CCUs increasing from 1.60 (95% CI 1.35 to 1.88) for 46 to 65 years to 8.17 (95% CI 6.86 to 9.72) for ≥85 years. In HCUs, the aHR associated with age was more than two times higher. The gender was not significantly associated with death, aHR 1.03 (95% CI 0.98 to 1.09, p=0.2693) in CCUs. Most of the underlying chronic conditions were risk factors for death, including malignant neoplasm (CCU: 1.34 (95% CI 1.25 to 1.43); HCU: 1.41 (95% CI 1.35 to 1.47)), cirrhosis without transplant (1.41 (95% CI 1.22 to 1.64); 1.27 (95% CI 1.12 to 1.45)) and dementia (1.30 (95% CI 1.16 to 1.46); 1.07 (95% CI 1.03 to 1.12)). CONCLUSION: This analysis confirms the role of age as the major risk factor of death in patients with COVID-19 irrespective to admission to critical care and therefore supports the current vaccination policies targeting older individuals.
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COVID-19 , Anciano , Cuidados Críticos , Hospitales , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: The risk of postoperative compressive hematoma is the major limitation for a wide development of ambulatory thyroidectomy (AT). The aim of this study was to establish a risk score of hematoma on the basis of preoperative criteria. METHODS: All patients who underwent thyroidectomy between 2002 and 2017 were reviewed in a high-volume endocrine surgery center. Multivariate analysis of risk factors associated with hematoma was performed in lobectomy and total thyroidectomy (TT). We assigned the risk factors identified by multivariate analysis weighted points proportional to the regression coefficient values. A simple sum of all accumulated points for each patient calculated the total score. RESULTS: For lobectomy [31 hematoma among 3912 patients (0.8%)], the weighted points of Vit K antagonist (VKA) were 3 (OR 9.86), and 1 in male gender (OR 2.4). For TT [162 hematoma among 13,903 patients (1.2%)], the weighted points of VKA were 4 (OR 12.18), 1 in male gender (OR 1.89), and 1 for diabetes (OR 1.86). Other factors weighted 0 in both groups. A total score >1 was linked to a risk of hematoma > 1.3% for lobectomy or TT. AT should not be proposed to any patient under VKA, and in case of TT, to male patients with diabetes. Prospectively, patients had AT from May 2018 to February 2020, 529 patients underwent ambulatory TL (483) or TT (46) and only one patient experienced neck hematoma. CONCLUSION: We established a simple and reproducible predictive score of early discharge for lobectomy and TT that could be useful for patients' management.
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Hematoma/etiología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Ambulatorios , Femenino , Francia/epidemiología , Hematoma/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Cuidados Preoperatorios , Estudios Retrospectivos , Factores de Riesgo , Tiroidectomía/métodos , Resultado del TratamientoRESUMEN
We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV-uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006-2010 and HIV-uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH-ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV-uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50-0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52-1.10). PLHIV continue to face difficulties to access KT.
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Acceso a la Información , Infecciones por VIH/complicaciones , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Trasplante de Riñón/estadística & datos numéricos , Diálisis Renal , Listas de Espera/mortalidad , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , VIH/aislamiento & purificación , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud/normas , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The objective of this study was to assess outcomes of a hybrid technique for treatment of abdominal aortic aneurysm (AAA) associated with iliac aneurysm without distal neck by combining an AAA endovascular repair approach with open surgery for preservation of the internal iliac artery (IIA). METHODS: The files of 51 patients operated on between 1998 and 2017 in a single vascular surgery department were retrospectively analyzed. Inclusion criteria were patients with AAA associated with uni-iliac or bi-iliac aneurysm without suitable distal sealing zone. Surgery consisted of deployment of an aortouni-iliac stent graft combined with an extra-anatomic crossover prosthetic bypass. With use of a limited retroperitoneal approach, the contralateral proximal common iliac aneurysm was surgically excluded and the IIA revascularized by direct ilioiliac anastomosis or terminal common iliac suture, preserving the iliac bifurcation. RESULTS: The patients' mean age was 74 years (58-88 years), and 92% were men. The mean follow-up was 5.8 years (0.1-18 years). Twenty-nine patients (57%) had one or more high-risk criteria for open surgery. Nineteen patients (37.3%) had aortouni-iliac aneurysms, 19 (37.3%) aortobi-iliac aneurysms, 5 (10%) isolated iliac aneurysms, and 8 (15.7%) bi-iliac aneurysms without aortic location. Four patients (7.8%) also had IIA aneurysms. Surgery was successful in all cases. Two patients (4%) died during the 30 days after surgery. One surgically preserved IIA occluded within the first month, resulting in buttock claudication. The 5-year IIA primary patency rate was 96%. Type I proximal endoleaks occurred in two patients, requiring additional surgery 3 years and 13 years after the initial surgery, respectively. CONCLUSIONS: This hybrid technique, consisting of AAA endovascular exclusion combined with open IIA revascularization, is safe and effective for preservation of pelvic vascularization. It is associated with long-term patency and low morbidity rates. We have been using this technique since before the advent of branched dedicated devices, allowing preservation of the IIA with good results. This technique should continue to be proposed, especially in patients not eligible for endovascular iliac branch repair because of anatomic contraindications, to avoid pelvic ischemia if the IIA has to be sacrificed.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/métodos , Nalgas/irrigación sanguínea , Endofuga/prevención & control , Procedimientos Endovasculares/métodos , Aneurisma Ilíaco/cirugía , Arteria Ilíaca/cirugía , Claudicación Intermitente/prevención & control , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Aneurisma de la Aorta Abdominal/fisiopatología , Aortografía/métodos , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/mortalidad , Angiografía por Tomografía Computarizada , Endofuga/etiología , Endofuga/mortalidad , Endofuga/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Aneurisma Ilíaco/diagnóstico por imagen , Aneurisma Ilíaco/mortalidad , Aneurisma Ilíaco/fisiopatología , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/fisiopatología , Claudicación Intermitente/etiología , Claudicación Intermitente/mortalidad , Claudicación Intermitente/fisiopatología , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional , Estudios Retrospectivos , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del TratamientoRESUMEN
CONTEXT: Chronic kidney disease is a frequent complication in persons living with HIV/AIDS. Although previous studies have suggested that the CKD-EPI formula is appropriate to estimate glomerular filtration rate (GFR) in HIV-positive adults with normal kidney function, the optimal way to estimate GFR in those with Stage 3 chronic kidney disease is not known. Moreover, the impact of muscle mass on creatinine level and GFR estimation is unknown. AIM AND METHODS: Our study aimed to evaluate the accuracy of different diagnostic tests available compared to the gold standard measurement of GFR. A group of 44 HIV-1 patients with an estimated GFR between 60 and 30 ml/min/1.73 m2 were included in a single-center cross-sectional study. Serum creatinine and cystatin C were measured. GFR was estimated using Cockcroft-Gault, MDRD, sMDRD, CKD-EPI, CKD-EPIcyst, and CKD-EPIcyst/creat formulae and was measured using isotopic Chrome51 EDTA clearance. Bone density and muscle mass were measured by DXA scan. RESULTS: Mean age was 62±10 years. Mean BMI was 23±4 kg/m2. Prevalence of diabetes was 30% and of hypertension was 47%. Viral load was <40 copies/ml for 90% of the patients, and mean CD4 count was 446±191 cells/mm3. Mean measured GFR was 63.4±16.5 ml/min/1.73 m2. All formulae under-estimated GFR. The best relative precision and accuracy were provided by the CKP-EPI formula. sMDRD, CKD-EPIcyst, and CKD-EPIcyst/creat performed worse than the CKD-EPI formula. Body composition did not significantly influence accuracy or precision of GFR estimation. CONCLUSION: In HIV-infected patients in stable immunovirologic conditions with CKD stage 3 and high prevalence of metabolic associated conditions, the CKD-EPI formula performed best, although all formulae under estimate GFR.
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Composición Corporal , Densidad Ósea , Tasa de Filtración Glomerular , Infecciones por VIH/fisiopatología , Absorciometría de Fotón , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption. METHODS: Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed. RESULTS: Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability. CONCLUSIONS: Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Psicoterapia , Ajuste Social , Núcleo Subtalámico , Adaptación Psicológica , Anciano , Apatía , Cuidadores/psicología , Cognición , Estimulación Encefálica Profunda/efectos adversos , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Educación del Paciente como Asunto , Periodo Perioperatorio , Escalas de Valoración Psiquiátrica , Psicoterapia/métodos , Calidad de Vida , Método Simple Ciego , Núcleo Subtalámico/diagnóstico por imagen , Núcleo Subtalámico/fisiopatología , Resultado del TratamientoRESUMEN
PURPOSE: Macular edema is the leading cause of vision loss in bilateral chronic noninfectious posterior uveitis, and is currently being treated using corticosteroids, immunosuppressive agents, and biotherapies. The aim of this trial was to assess and compare the efficacy and safety of corticosteroids and interferon-α (IFN-α) in adults with such conditions. DESIGN: Randomized controlled trial. METHODS: Subjects: Adult patients with bilateral posterior autoimmune noninfectious and nontumoral uveitis complicated by macular edema in at least 1 eye. INTERVENTION: Patients received either subcutaneous IFN-α2a, systemic corticosteroids, or no treatment for 4 months. The efficacy and safety were assessed for up to 4 months. MAIN OUTCOME MEASURES: The main endpoint was the change of the central foveal thickness (CFT) obtained by optical coherence tomography. RESULTS: Forty-eight patients were included. In intention-to-treat analysis, the median CFT change showed no significant difference. However, the per-protocol analysis showed a significant difference between groups for both eyes (OD and OS), and for the worse and better eyes. Statistically significant difference was found between the control and corticosteroid groups for the OD (P = .0285), and between the control and IFN-α groups for the OD (P = .0424) and worse eye (P = .0354). Serious adverse events occurred in 2 patients in the IFN group, in 1 patient in the corticosteroid group, and in 2 patients in the control group and were completely resolved after switch. CONCLUSIONS: IFN-α and systemic corticosteroids, compared with no treatment, were associated with significant anatomic and visual improvement shown in the per-protocol study.
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Glucocorticoides/administración & dosificación , Interferón-alfa/administración & dosificación , Edema Macular/tratamiento farmacológico , Uveítis Posterior/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Fóvea Central/patología , Humanos , Factores Inmunológicos/administración & dosificación , Inyecciones Subcutáneas , Interferón alfa-2 , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Uveítis Posterior/complicaciones , Uveítis Posterior/diagnóstico , Agudeza Visual , Adulto JovenRESUMEN
OBJECTIVE: Polyglutamine (PolyQ) diseases are dominantly transmitted neurologic disorders, caused by coding and expanded CAG trinucleotide repeats. Cancer was reported retrospectively to be rare in patients with PolyQ diseases and we aimed to investigate its prevalence in France. METHODS: Consecutive patients with Huntington disease (HD) and spinocerebellar ataxia (SCA) were questioned about cancer, cardiovascular diseases, and related risk factors in 4 university hospitals in Paris, Toulouse, Strasbourg, and Montpellier. Standardized incidence ratios (SIR), based on age- and sex-adjusted rate of the French population, were assessed for different types of cancer. RESULTS: We questioned 372 patients with HD and 134 patients with SCA. SIR showed significantly reduced risk of cancer in HD: 23 observed cases vs 111.05 expected ones (SIR 0.21, 95% confidence interval [CI] 0.13-0.31), as well as in SCA: 7 observed cases vs 34.73 expected (SIR 0.23, 95% CI 0.08-0.42). This was surprising since risk behavior for cancer was increased in these patients, with significantly greater tobacco and alcohol consumption in patients with HD vs patients with SCA (p < 0.0056). There was no association between CAG repeat size and cancer or cardiovascular disease. However, in patients with HD, skin cancers were more frequent than expected (5 vs 0.98, SIR 5.11, 95% CI 1.65-11.95). CONCLUSIONS: There was a decreased cancer rate in PolyQ diseases despite high incidence of risk factors. Intriguingly, skin cancer incidence was higher, suggesting a crosstalk between neurodegeneration and skin tumorigenesis.
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Predisposición Genética a la Enfermedad/epidemiología , Enfermedad de Huntington/epidemiología , Neoplasias/epidemiología , Péptidos/genética , Ataxias Espinocerebelosas/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Enfermedad de Huntington/genética , Masculino , Persona de Mediana Edad , Neoplasias/genética , Estudios Retrospectivos , Factores de Riesgo , Ataxias Espinocerebelosas/genéticaRESUMEN
BACKGROUND: Disease activity may change over time in axial spondyloarthritis (axSpA). The objectives were to identify patterns of disease activity evolution in patients with early axSpA. METHODS: Patients from the prospective early axSpA cohort (DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR)) who fulfilled the Assessment in SpondyloArthritis Society (ASAS) criteria for axSpA at baseline and with at least three Ankylosing Spondylitis Disease Activity Score (ASDAS) values available over the 3â years of follow-up were analysed. Statistical analyses: trajectories were estimated by group-based trajectory modelling; predisposing baseline factors for such trajectories were identified by univariate and multivariable multinomial (logit) regression; work disability over time was compared between the trajectories by Cox hazard model. RESULTS: In all, 370 patients were analysed: mean disease duration was 1.6 (±0.9) years. The five distinct trajectories of disease activity over the 3â years were (t1) 'persistent moderate disease activity' (n=134 (36.2%)); (t2) 'persistent inactive disease' (n=66 (17.8%); (t3) 'changing from very high disease activity to inactive disease' ((n=29 (7.8%)); (t4) 'persistent high disease activity' (n=126 (34.1%)) and (t5) 'persistent very high disease activity' (n=15 (4.1%)). After adjustment for other characteristics, t2 was associated with a white-collar job (OR=2.6 (95% CI 1.0 to 6.7)) and t3 with male gender (OR=7.1 (1.6 to 32.2)), higher education level (OR=9.4 (1.4 to 63.4)) and peripheral joint involvement (OR=6.2 (1.23 to 31.32)). Patients from (t4) and (t5) were more often declared work disabled over follow-up (HR=5.2 (1.5 to 18.0) and HR=8.0 (1.3 to 47.9), respectively). CONCLUSIONS: Trajectory modelling of disease activity was feasible in early axSpA: more than 30% patients (141/370) were in a trajectory with a persistent high disease activity. Persistent high disease activity trajectories were significantly associated with consequences on work. TRIAL REGISTRATION NUMBER: NCT01648907.
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Modelos Estadísticos , Espondiloartropatías/tratamiento farmacológico , Adulto , Escolaridad , Humanos , Estudios Longitudinales , Análisis Multivariante , Ocupaciones , Pronóstico , Estudios Prospectivos , Articulación Sacroiliaca , Índice de Severidad de la Enfermedad , Factores Sexuales , Evaluación de Síntomas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Evaluación de Capacidad de Trabajo , Adulto JovenRESUMEN
PURPOSE: To determine the prognostic factors of long-term visual outcome in birdshot retinochoroidopathy (BRC). METHODS: Design: Retrospective case series. Study Population: Successive HLA-A29+ BRC patients whose latest visit was between May and August 2013 at a single tertiary center (Pitié-Salpétrière Hospital, Paris). OBSERVATION PROCEDURE: Endpoint visual status (remission or deterioration) was determined for each patient based on clinical and ancillary data from the latest visit including optical coherence tomography (OCT), automated visual field (AVF), and angiograms. Main Outcome Measure: Epidemiologic, clinical, OCT, AVF, angiographic, and electrophysiological data at baseline were correlated to final visual status. RESULTS: Fifty-five patients were included. Mean observation period was 8 years (range: 0.6-23 years). Mean disease duration was 9.8 years (range: 1.2-32.7 years). Female-to-male sex ratio was 1.6:1. Factors of good visual prognosis (remission vs deterioration) included at baseline: late age of disease onset (49.5 vs 45 years, P = .05), presence of vitreous inflammatory reactions >2+ (35.9% vs 6.2%, P = .04), vascular leakage on fluorescein angiograms (FA) (44.4% vs 12.5%, P = .03), absence of macular pigment epithelium atrophy on FA (88.9% vs 62.5%, P = .05), and presence of macular edema on OCT (33.3% vs 6.2%, P = .04). Preserved electrooculography light peak and Arden ratio (P = .06) and presence of choroidal spots on infracyanine green angiograms (80.0% vs 53.3%, P = .08) seemed associated with the best prognoses. CONCLUSION: This study suggests a series of prognostic factors of long-term visual outcome in BRC. Keeping in mind the insidious evolution of the disease, knowledge of such prognostic factors should help tailor the treatment and monitoring of birdshot patients.
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Coriorretinitis/diagnóstico , Trastornos de la Visión/diagnóstico , Agudeza Visual/fisiología , Campos Visuales/fisiología , Adulto , Anciano , Retinocoroidopatía en Perdigonada , Permeabilidad Capilar , Coriorretinitis/tratamiento farmacológico , Coriorretinitis/inmunología , Coriorretinitis/fisiopatología , Electrooculografía , Oftalmopatías/diagnóstico , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Antígenos HLA-A/inmunología , Humanos , Edema Macular/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Trastornos de la Visión/fisiopatología , Cuerpo Vítreo/patologíaRESUMEN
The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature. In carriers of BRCA2 mutations, the length of the HTT CAG tract was correlated with lower incidence of ovarian cancer. Among carriers of BRCA1 mutations who developed a breast cancer, its onset occurred 2.4 years earlier in individuals with intermediate HTT alleles (≥27) than in those with a CAG tract <27. Finally, in patients with sporadic HER2 breast cancer, metastasis increased by a factor of 11.10 per 10 additional CAG repeats in HTT. We concluded that whereas long CAG length could be associated with lower cancer incidence, it could also be paradoxically associated with cancer severity (age of apparition and metastasis development).
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Proteína Huntingtina/genética , Repeticiones de Trinucleótidos/genética , Adulto , Alelos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Femenino , Heterocigoto , Humanos , Persona de Mediana Edad , Receptor ErbB-2/genéticaRESUMEN
BACKGROUND: Type 1 diabetes patients, although typically lean, experience an increased prevalence of obesity, and bariatric surgery is considered in severe cases. Bariatric surgery in such patients leads to significant weight loss and decreased insulin requirements; however, effects on glycemic control remain discussed. We assessed, in obese patients with type 1 diabetes, the effects of bariatric surgery upon body weight, body composition, and glycemic control, including the occurrence of hypoglycemic events. METHODS: Thirteen obese patients with type 1 diabetes who underwent bariatric surgery (Roux-en-Y gastric bypass n = 6, sleeve gastrectomy n = 7) were matched with obese patients without diabetes and with type 2 diabetes patients during 12 months of follow-up. Outcomes included body weight, DXA-assessed body composition, HbA1c, and incidence of hypoglycemia. RESULTS: At 12 months, median surgery-induced weight loss was 27.9 % (21.1-33.3), 26.1 % (24.8-29.7), and 27.5 % (21.8-32.1) in patients with type 1 diabetes, type 2 diabetes, and without diabetes, respectively, with no significant differences across the groups. Similar findings were observed for body fat changes. At 12 months, median HbA1c decreased from 8.3 to 7.6 % in type 1 diabetes patients versus 8.0 to 5.9 % in type 2 diabetes patients (P = 0.04 between the groups). In type 1 diabetes patients, the number of reported minor hypoglycemia increased transiently only at 6 months. Two patients reported severe hypoglycemia (one episode each). CONCLUSIONS: Type 1 diabetes patients benefit from bariatric surgery in terms of weight loss and glycemic control. Close monitoring of insulin therapy appears warranted to prevent minor hypoglycemia in the first months post-surgery.
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Cirugía Bariátrica , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/cirugía , Obesidad Mórbida/cirugía , Pérdida de Peso , Adulto , Composición Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirugía , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In Huntington disease (HD), polyglutamine expansion in the huntingtin protein causes specific neuronal death. The consequences of the presence of mutant huntingtin in other tissues are less well understood. Here we propose that mutant huntingtin influences breast cancer progression. Indeed, we show that mammary tumours appear earlier in mouse breast cancer models expressing mutant huntingtin as compared to control mice expressing wild-type huntingtin. Tumours bearing mutant huntingtin have a modified gene expression pattern that reflects enhanced aggressiveness with the overexpression of genes favouring invasion and metastasis. In agreement, mutant huntingtin accelerates epithelial to mesenchymal transition and enhances cell motility and invasion. Also, lung metastasis is higher in HD conditions than in control mice. Finally, we report that in HD, the dynamin dependent endocytosis of the ErbB2/HER2 receptor tyrosine kinase is reduced. This leads to its accumulation and to subsequent increases in cell motility and proliferation. Our study may thus have important implications for both cancer and HD.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proteínas del Tejido Nervioso/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal , Animales , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Femenino , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Transgénicos , Mutación , Metástasis de la Neoplasia , Proteínas del Tejido Nervioso/genética , Receptor ErbB-2/genéticaRESUMEN
UNLABELLED: Igf2 gene specific hypomethylation has been demonstrated in hepatocellular carcinoma (HCC) cells and in non-tumoral liver samples from patients with HCV-related cirrhosis who further developed HCC. In patients with colorectal cancers, Igf2 hypomethylation is found in peripheral blood mononuclear cells (PBMC) even prior to the occurrence of cancer. AIM: To compare Igf2 methylation in PBMC from healthy donors and patients with HCV-related cirrhosis without or with history of HCC. PATIENTS AND METHODS: After DNA extraction from frozen PBMC samples of 52 healthy blood donors and 121 patients with HCV-related cirrhosis either without (n=59) or with past or present HCC (n=62), and sodium bisulfite treatment, unbiased PCR amplification and Denaturing High Performance Liquid Chromatography (DHPLC) analysis were used for methylation analysis at the differentially methylated region 2 of Igf2. Methylation profiles were classified in three groups (unmethylated, U; methylated, M; and intermediate, UM) according to the proportions of M and U alleles, blindly to clinical data. In addition, 677C-T mutation of Methylenetetrahydrofolate Reductase (MTHFR) was investigated by fluorescent probes. RESULTS: Prevalences of U, UM and M Igf2 profiles were: 8%, 65% and 27% in blood donors, 0%, 81% and 19% in patients with HCV-related cirrhosis without HCC, 71%, 29% and 0% in patients with HCC (P<0.0001). Igf2 methylation profile was independent from gender, age, body mass index, and presence of 677C-T mutation of MTHFR. CONCLUSION: These observations suggest a decrease of Igf2 methylation from cirrhosis to HCC in patients with HCV infection, which may be an additional risk factor for HCC.
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Carcinoma Hepatocelular/genética , Metilación de ADN , Hepatitis C/genética , Factor II del Crecimiento Similar a la Insulina/genética , Leucocitos Mononucleares , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/complicaciones , Femenino , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: To evaluate disease progression and determine validity of clinical tools for therapeutic trials. DESIGN: Prospective cohort study (36 months). SETTING: Referral center. PATIENTS: One hundred sixty-two patients with autosomal dominant cerebellar ataxia and 64 with hereditary spastic paraplegia. MAIN OUTCOME MEASURES: The quantitative Composite Cerebellar Functional Severity Score with the writing test (CCFSw) and Scale for the Assessment and Rating of Ataxia (SARA) score. RESULTS: Disease worsened in patients with SCA1, SCA2, and SCA3 mutations (mean [SE] increase in CCFSw, +0.014 [0.005] to +0.025 [0.004] per year), improved in patients with SPG4 mutations (mean [SE] increase in CCFSw, -0.012 [0.003] per year; P = .02), and remained stable in patients with SCA6, SCA7, or other SCA mutations (mean [SE] increase in CCFSw, -0.015 [0.011] to +0.009 [0.013] per year) or hereditary spastic paraplegia with other SPG mutations (mean [SE] increase in CCFSw, -0.005 [0.005] per year). Progression was faster in patients with SCA2 mutations and normal alleles with 22 or fewer repeats (P = .02) and in patients with SCA3 mutations with parkinsonism and/or dystonia at baseline (P = .003). Whereas CCFSw distinguished between patients with ataxia and spasticity, SARA scores increased in both groups. A 2-arm trial with SARA score as the outcome measure would require 57 patients with SCA2 mutations, 70 with SCA1 mutations, and 75 with SCA3 mutations per group to detect a 50% reduction in disease progression (power, 80%; α = .05). CONCLUSIONS: Disease progressed faster in SCA s with polyglutamine expansions in SCA1, 2, and 3 than the other groups. Both outcome measures are suitable for therapeutic trials; SARA requires fewer patients to attain the same power, but CCFSw needs less stratification. We demonstrate that the choice of clinical outcome measure is critical for reliable evaluation of progression in neurodegenerative diseases.
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Ataxia Cerebelosa/genética , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Proteínas del Tejido Nervioso/genética , Paraplejía/genética , Péptidos/genética , Adulto , Anciano , Ataxina-1 , Ataxina-3 , Ataxinas , Ataxia Cerebelosa/fisiopatología , Estudios de Cohortes , Femenino , Francia , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , Proteínas Nucleares/genética , Paraplejía/fisiopatología , Proteínas Represoras/genética , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Escritura , Adulto JovenRESUMEN
Medical doctors are required to provide information to their patients regarding their medical procedures according to the law on patient information enacted on March 4, 2002. The objective of this study was to assess patients' awareness and satisfaction with respect to their perception of information obtained prior to or during a medical examination. A self-descriptive patient survey was conducted at the Groupe Hospitalier of Pitié-Salpêtrière in 2005 for this purpose. Data were collected at three distinct moments using a standard questionnaire. 147 patients were interviewed (101 had received and MRI and 46 a bronchoscopy). Twenty percent of the participants reported that they had not been provided with any specific medical or paramedical information before the examination and 4% had received no information at all. Health professionals must ensure that information is given to their patients in a manner that takes into account their expectations and responds to their concerns before a medical procedure is performed in order to improve its delivery and its intrinsic quality.
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Broncoscopía , Comunicación , Diagnóstico , Imagen por Resonancia Magnética , Satisfacción del Paciente , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Bilateral subthalamic high-frequency stimulation significantly improves motor functions in patients with advanced forms of Parkinson disease (PD). This favorable effect contrasts with a growing number of reports that the treatment may result in psychiatric complications. OBJECTIVE: To analyze the presence of behavioral disorders and social maladjustment in PD patients successfully treated with continuous bilateral subthalamic stimulation. DESIGN: Prospective study. SETTING: University hospital. METHODS: Twenty PD patients underwent prospective evaluation for behavioral and personality changes, quality of life, and social functioning, 6 and 24 months after surgery to implant bilateral stimulating electrodes within the subthalamic nucleus. RESULTS: At 6 and 24 months after surgery, parkinsonian motor disability (on-stimulation/off-medication) was improved by 81% and 67%, respectively, and the severity of levodopa-related motor complications was improved by 84% and 70%, respectively. Levodopa-equivalent dosage was decreased by 79% and 66%, respectively; severity of depression was improved by 21% and 33%, respectively; and severity of anxiety was improved by 43% and 64%, respectively. The patients' personality traits were unmodified. Twenty-four months after surgery, the global score for quality of life was improved by 28%, whereas scores for social adjustment remained stable. CONCLUSIONS: Provided that patients with PD are rigorously selected for neurosurgery, subthalamic stimulation (1) improves mood, anxiety, and quality of life; (2) does not result in severe permanent psychiatric disorders or modify patients' personality; and (3) does not ameliorate social adaptation.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/terapia , Ajuste Social , Núcleo Subtalámico , Actividades Cotidianas/psicología , Adulto , Anciano , Conducta/fisiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/psicología , Estudios Prospectivos , Núcleo Subtalámico/fisiologíaRESUMEN
BACKGROUND: Severe forms of dystonia respond poorly to medical treatment. Deep-brain stimulation is a reversible neurosurgical procedure that has been used for the treatment of dystonia, but assessment of its efficacy has been limited to open studies. METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. The severity of dystonia was evaluated before surgery and 3, 6, and 12 months postoperatively during neurostimulation, with the use of the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Scale (range, 0 to 120 and 0 to 30, respectively, with higher scores indicating greater impairment). Movement scores were assessed by a review of videotaped sessions performed by an observer who was unaware of treatment status. At three months, patients underwent a double-blind evaluation in the presence and absence of neurostimulation. We also assessed the patients' quality of life, cognition, and mood at baseline and 12 months. RESULTS: The dystonia movement score improved from a mean (+/-SD) of 46.3+/-21.3 before surgery to 21.0+/-14.1 at 12 months (P<0.001). The disability score improved from 11.6+/-5.5 before surgery to 6.5+/-4.9 at 12 months (P<0.001). General health and physical functioning were significantly improved at month 12; there were no significant changes in measures of mood and cognition. At the three-month evaluation, dystonia movement scores were significantly better with neurostimulation than without neurostimulation (24.6+/-17.7 vs. 34.6+/-12.3, P<0.001). There were five adverse events (in three patients); all resolved without permanent sequelae. CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.