The treatment of wegener's granulomatosis with glucocorticoids and methotrexate

Objective. To identify alternatives to daily low-dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG). Methods. An open-label pilot study of weekly low-dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty-nine patients who did not have immediately life-threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy. Results. Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2–6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months. Conclusion. Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often-fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low-dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life-threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently.     

The effect of food on the absorption of methotrexate sodium tablets in healthy volunteers

Objective. To examine the effect of food on the absorption and bioavailability of low-dose orally administered methotrexate sodium tablets. Methods. In this randomized, 2-way crossover study, a 7.5-mg dose of methotrexate (three 2.5-mg tablets) was administered to 12 healthy male volunteers after an overnight fast or within 10 minutes of consuming a high fat-content breakfast. Serum methotrexate concentrations over the next 24 hours were used to determine the area under the concentration–time curve (AUC), the maximum concentration, the time to maximum concentration (t_max), and the serum half-life for each phase. Results. Food delayed the t_max by approximately 30 minutes, but the extent of absorption, as measured by the AUC, for both phases was similar. Conclusion. These results demonstrate that the bioavailability of low-dose orally administered methotrexate sodium tablets is not influenced by food.     

A highly predictive autoantibody-based biomarker panel for prognosis in early-stage NSCLC with potential therapeutic implications

Background Lung cancer is the leading cause of cancer-related death worldwide. Surgical resection remains the definitive curative treatment for early-stage disease offering an overall 5-year survival rate of 62%. Despite careful case selection, a significant proportion of early-stage cancers relapse aggressively within the first year post-operatively. Identification of these patients is key to accurate prognostication and understanding the biology that drives early relapse might open up potential novel adjuvant therapies.Methods We performed an unsupervised interrogation of >1600 serum-based autoantibody biomarkers using an iterative machine-learning algorithm.Results We identified a 13 biomarker signature that was highly predictive for survivorship in post-operative early-stage lung cancer; this outperforms currently used autoantibody biomarkers in solid cancers. Our results demonstrate significantly poor survivorship in high expressers of this biomarker signature with an overall 5-year survival rate of 7.6%.Conclusions We anticipate that the data will lead to the development of an off-the-shelf prognostic panel and further that the oncogenic relevance of the proteins recognised in the panel may be a starting point for a new adjuvant therapy.Subject terms: Non-small-cell lung cancer, Tumour biomarkers     

Development and cross-validation of a system for classifying homeless persons

The present study used cluster analysis to empirically derive and cross-validate a system for classifying homeless persons on the basis of their service needs. Variables used in the subgroup identification phase of the study included psychopathology, alcoholism, social support, socioeconomic status, and health status. Four subgroups were identified: (1) an economically disadvantaged group, (2) an alcoholic group, (3) a mentally ill group, and (4) a relatively advantaged group. Subsequent analysis revealed few differences between the four groups in background characteristics. Moreover, subgroups were similar in service willingness and utilization, with the exception of utilization and willingness to receive treatment for alcohol and mental health problems. The results suggest the need for policies and services that address the core socioeconomic needs that cut across all subgroups, as well as for additional, specialized services for those with psychiatric or alcohol problems.     

Standalone epicardial left atrial appendage exclusion for thromboembolism prevention in atrial fibrillation

Open in a separate window OBJECTIVESMost strokes associated with atrial fibrillation (AF) result from left atrial appendage thrombi. Oral anticoagulation can reduce stroke risk but is limited by complication risk and non-compliance. Left atrial appendage exclusion (LAAE) is a new surgical option to reduce stroke risk in AF. The study objective was to evaluate the safety and feasibility of standalone thoracoscopic LAAE in high stroke risk AF patients.METHODSThis was a retrospective, multicentre study of high stroke risk AF patients who had oral anticoagulation contraindications and were not candidates for ablation nor other cardiac surgery. Standalone thoracoscopic LAAE was performed using 3 unilateral ports access and epicardial clip. Periprocedural adverse events, long-term observational clinical outcomes and stroke rate were evaluated.RESULTSProcedural success was 99.4% (174/175 patients). Pleural effusion occurred in 4 (2.3%) patients; other periprocedural complications were <1% each. One perioperative haemorrhagic stroke occurred (0.6%). No phrenic nerve palsy or cardiac tamponade occurred. Predicted annual ischaemic stroke rate of 4.8/100 patient-years (based on median CHA₂DS₂-VASc score of 4.0) was significantly higher than stroke risk observed in follow-up after LAAE. No ischaemic strokes occurred (median follow-up: 12.5 months), resulting in observed rate of 0 (95% CI 0–2.0)/100 patient-years (P < 0.001 versus predicted). Six all-cause (non-device-related) deaths occurred during follow-up.CONCLUSIONSStudy proved that a new surgical option, standalone thoracoscopic LAAE, is feasible and safe. With this method, long-term stroke rate may be reduced compared to predicted for high-risk AF population.     

美国国立神经疾病和卒中研究所-加拿大卒中网血管性认知障碍统一标准

背景和目的：1／3的个体会罹患卒中和（或）痴呆,而且,除卒中或痴呆外,2倍于此数的人会出现认知障碍。常用的卒中量表并不能评价认知功能,而痴呆的诊断标准则集中在认知障碍的晚期阶段,且在很大程度上偏向Alzheimer病（AD）的诊断。尚缺乏普遍公认的标准用于识别和描述存在认知障碍的个体,尤其是在早期阶段,而且特别是与血管因素有关的认知障碍或血管性认知障碍。方法：美国国立神经疾病和卒中研究所（MINDS）与加拿大卒中网（CSN）召集临床诊断、流行病学、神经心理学、脑影像学、神经病理学、试验模型、生物标记物、遗传学和临床试验方面的研究人员,为血管性认知障碍的描述和研究推荐一些最低限度的常用的临床和研究标准。结果：将这些讨论的结果发表于此。结论：一个统一标准的制定代表着使用、确认和改进过程中的第一步。使用相同的标准将有助于在认知障碍的早期阶段识别患者,使不同的研究具有可比性,并且通过整合知识来加速研究进展的步伐。     

Problem-solving task performance in brain-damaged subjects

Investigated the relationship between the Halstead Category Test and the Wisconsin Card Sorting Test. A correlational analysis revealed a statistically significant but modest relationship between the two variables in separate samples of brain-damaged and non-brain-damaged individuals (N = 156). Thus, in spite of the apparent similarity of the two measures, their relationship is not sufficiently close to suggest that in fact they are measuring the same abilities. However, the combination of hit rates of the two measures and the high base rate of brain dysfunction in the present sample yielded good diagnostic accuracy for decisions with regard to the presence of brain damage.     

Factor structure,construct validity and reliability of the seeking of noetic goals (SONG) and purpose in life (PIL) tests

Examined the factor structure, construct validity, and reliability of the SONG and the PIL in a sample of 248 introductory psychology students. Ten interpretable independent dimensions of satisfaction with life were extracted, with 6 factors that loaded on the PIL and 4 that loaded on the SONG. These data support Crumbaugh's (1977) assertion that the SONG is a complementary scale to the PIL contributing factors that deal with the strength of motivation to find meaning and purpose in life. In addition, the SONG and the PIL were shown to be highly reliable and valid instruments. Further research that uses SONG-PIL factor scores and profile analysis is recommended.