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971.
J. Alfred Witjes Marek Babjuk Paolo Gontero Didier Jacqmin Alexander Karl Stephan Kruck Paramananthan Mariappan Juan Palou Redorta Arnulf Stenzl Roland van Velthoven Dirk Zaak 《European urology》2014
Context
Non–muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates.Objective
To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input.Evidence acquisition
PubMed and conference searches, supplemented by personal experience.Evidence synthesis
Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time.Conclusions
HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system.Patient summary
Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours. 相似文献972.
Raffaella Greco MD Attilio Bondanza MD PhD Luca Vago MD PhD Lucia Moiola MD Paolo Rossi MD Roberto Furlan MD PhD Gianvito Martino MD Marta Radaelli MD Vittorio Martinelli MD Maria Rosaria Carbone MSc Maria Teresa Lupo Stanghellini MD Andrea Assanelli MD Massimo Bernardi MD Consuelo Corti MD Jacopo Peccatori MD Chiara Bonini MD Paolo Vezzulli MD Andrea Falini MD PhD Fabio Ciceri MD Giancarlo Comi MD 《Annals of neurology》2014,75(3):447-453
Neuromyelitis optica is a rare neurological autoimmune disorder characterized by a poor prognosis. Immunosuppression can halt disease progression, but some patients are refractory to multiple treatments, experiencing frequent relapses with accumulating disability. Here we report on durable clinical remissions after allogeneic hematopoietic stem cell transplantation in 2 patients suffering from severe forms of the disease. Immunological data evidenced disappearance of the pathogenic antibodies and regeneration of a naive immune system of donor origin. These findings correlated with evident clinical and radiological improvement in both patients, warranting extended clinical trials to investigate this promising therapeutic option. ANN NEUROL 2014;75:447–453 相似文献
973.
Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations 下载免费PDF全文
Ingrid E. Scheffer MB BS PhD Sarah E. Heron BSc PhD Brigid M. Regan BSc Simone Mandelstam MB ChB Douglas E. Crompton MBBS PhD Bree L. Hodgson Dip Biomed Sci Laura Licchetta MD Federica Provini MD PhD Francesca Bisulli MD PhD Lata Vadlamudi MB BS PhD Jozef Gecz PhD Alan Connelly PhD Paolo Tinuper MD Michael G. Ricos BSc PhD Samuel F. Berkovic MD FRS Leanne M. Dibbens BSc PhD 《Annals of neurology》2014,75(5):782-787
We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787 相似文献
974.
Giangennaro Coppola Alessandra D’Amico Erica Pironti Federica Martino Elena Santoro Nilde Di Paolo Claudia Isone Gennaro Catone 《Brain & development》2014
We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes. 相似文献
975.
976.
The presence of depressive symptoms in comorbidity with Alzheimer's disease does not influence changes in serum brain‐derived neurotrophic factor levels in older patients 下载免费PDF全文
977.
Piero Ruggenenti Barbara Ruggiero Paolo Cravedi Marina Vivarelli Laura Massella Maddalena Marasà Antonietta Chianca Nadia Rubis Bogdan Ene-Iordache Michael Rudnicki Rosa Maria Pollastro Giovambattista Capasso Antonio Pisani Marco Pennesi Francesco Emma Giuseppe Remuzzi 《Journal of the American Society of Nephrology : JASN》2014,25(4):850-863
The outcome of steroid-dependent or frequently relapsing nephrotic syndrome of minimal change disease (MCD), mesangial proliferative GN (MesGN), or FSGS may be poor and with major treatment toxicity. This academic, multicenter, off-on trial (ClinicalTrials.gov #) primarily evaluated the effects of rituximab therapy followed by immunosuppression withdrawal on disease recurrence in 10 children and 20 adults with MCD/MesGN (n=22) or FSGS who had suffered ≥2 recurrences over the previous year and were in steroid-induced remission for ≥1 month. Participants received one dose (n=28) or two doses of rituximab (375 mg/m2 intravenously). At 1 year, all patients were in remission: 18 were treatment-free and 15 never relapsed. Compared with the year before rituximab treatment, total relapses decreased from 88 to 22 and the per-patient median number of relapses decreased from 2.5 (interquartile range [IQR], 2–4) to 0.5 (IQR, 0–1; P<0.001) during 1 year of follow-up. Reduction was significant across subgroups (children, adults, MCD/MesGN, and FSGS; P<0.01). After rituximab, the per-patient steroid maintenance median dose decreased from 0.27 mg/kg (IQR, 0.19–0.60) to 0 mg/kg (IQR, 0–0.23) (P<0.001), and the median cumulative dose to achieve relapse remission decreased from 19.5 mg/kg (IQR, 13.0–29.2) to 0.5 mg/kg (IQR, 0–9.4) (P<0.001). Furthermore, the mean estimated GFR increased from 111.3±25.7 to 121.8±29.2 ml/min per 1.73 m2 (P=0.01), with the largest increases in children and in FSGS subgroups. The mean height z score slope stabilized in children (P<0.01). Treatment was well tolerated. Rituximab effectively and safely prevented recurrences and reduced the need for immunosuppression in steroid-dependent or frequently relapsing nephrotic syndrome, and halted disease-associated growth deficit in children.Idiopathic nephrotic syndrome (NS) in children and young adults is almost invariably the clinical counterpart of a continuum of glomerular diseases ranging from the relatively frequent minimal change disease (MCD) and the less frequent mesangial proliferative GN (MesGN), which are predominantly observed in children, to the relatively uncommon FSGS that is observed more frequently in adult patients. NCT009818381 In a small minority of patients that are generally resistant to immunosuppressive therapies, the disease is due to molecular defects of one of the podocyte genes.2 In all of the other cases, it appears to be immune-mediated, but the pathophysiologic process underlying glomerular injury remains poorly understood.3Independent of the underlying renal pathology, prednisone continues to be the cornerstone treatment at disease onset, achieving remission within 4 weeks in approximately 90% of children with MCD and in 20%–60% of those with FSGS.4,5 However, 60%–70% of patients relapse after steroid tapering or withdrawal, and most require repeat courses of prednisone to achieve remission of recurrent episodes and/or the addition of other immunosuppressive medications, such as calcineurin inhibitors, mycophenolate mofetil, or alkylating agents, to reduce the number of relapses and prevent major side effects of steroid treatment.6 According to their relapse rate, these patients are classically labeled as “steroid-dependent” or “frequently relapsing”. In these patients, serious adverse effects of treatment associate with complications of relapsing episodes of heavy proteinuria. These are the patients in most urgent need of more effective and safer treatment.The possibility of a specific and, hopefully, safer approach to patients with steroid-dependent or frequently relapsing NS emerged in 2004 when the B cell–depleting mAb rituximab was reported to induce remission of proteinuria in a child with frequently relapsing NS secondary to MCD who had received this medication to cure a supervened idiopathic thrombocytopenic purpura.7 Subsequent uncontrolled observations found some effect of rituximab in patients with steroid-dependent or frequently relapsing MCD,8–11 suggesting that B-cell immunity could play a key role in the pathophysiology of the disease. Controlled studies in support of this hypothesis, however, have been both scanty and almost confined to children12,13 or to patients with MCD who were evaluated in the context of a retrospective, observational design.14 Indeed, less attention was given to adults and patients with FSGS given difficulties in designing adequately powered trials.Here, we designed a longitudinal, off-on study (ClinicalTrials.gov #) to evaluate the efficacy of rituximab in reducing the incidence of relapses and need for steroid and other immunosuppressive medications in children and adults with steroid-dependent or frequently relapsing NS due to MCD, MesGN, or FSGS. To minimize the side effects and costs of rituximab, we abandoned the standard four-dose protocol originally implemented for the treatment of B-cell lymphomas, NCT0098183815 and adopted a new B cell–driven regimen we found to achieve remission of NS in patients with idiopathic membranous nephropathy (IMN) as effectively as the standard protocol, but with fewer side effects and less costs.16 相似文献
978.
Alberto Di Leo Corrado Pedrazzani Maria Bencivenga Arianna Coniglio Fausto Rosa Paolo Morgani Daniele Marrelli Alberto Marchet Luca Cozzaglio Simone Giacopuzzi Guido Alberto Massimo Tiberio Giovanni Battista Doglietto Giovanni Vittimberga Franco Roviello Francesco Ricci 《Annals of surgical oncology》2014,21(8):2594-2600
Purpose
The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease.Methods
We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6–207) months.Results
One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2–T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002).Conclusions
Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC. 相似文献979.
980.