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21.
PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.  相似文献   
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Iodinated contrast media (ICM) have become one of the major causes of drug hypersensitivity reactions (HSRs) related to increasing numbers of ICM-based radiological imaging procedures. Strategies for diagnosing and preventing ICM-induced HSRs have not been uniformly standardized yet. However, advances have been made based on the results of recent research. A previous history of hypersensitivity to ICM is the most significant risk factor for developing HSR by ICM. Avoidance of culprit agents and premedication is the main strategy to prevent recurrences of HSRs in high-risk patients. In addition, we strongly recommend identifying sensitized ICM using skin tests to determine immunoglobulin E-mediated or delayed-type allergy and to guide the choice of an alternative contrast agent. ICM provocation test procedures have been established and are helpful in selected cases. In this paper, we review how to evaluate patients who have experienced immediate or delayed HSRs caused by ICM to minimize the risk of recurrence and discuss unmet needs that require further research.  相似文献   
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Using administrative data from Norway, we examine the extent to which family doctors influence their clients’ propensity to claim sick-pay. The analysis exploits exogenous switches of family doctors occurring when physicians quit, retire, or for other reasons sell their patient lists. We find that family doctors have significant influence on their clients’ absence behavior, particularly on absence duration. Their influence is stronger in geographical areas with weaker competition between physicians. We conclude that it is possible for family doctors to contain sick-pay expenditures to some extent, and that there is a considerable variation in the way they perform this task.  相似文献   
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Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.  相似文献   
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Kroeger K  Kreuzfelder E 《Herz》2004,29(1):26-31
BACKGROUND: In patients with early manifestation of peripheral arterial occlusive disease (PAOD) and a less classical atherosclerotic risk profile, vasculitis is presumed to be the underlying disease. We performed a prospective study of the importance of determination of autoantibodies used for the diagnosis of vasculitis and collagen diseases in patients with symptomatic PAOD. PATIENTS AND METHOD: 698 consecutive patients (mean age +/- SD: 68 +/- 10 years) were included who were referred from 1998 to 1999 for interventional treatment of PAOD. In 121 PAOD-patients (61 +/- 12 years) with a less pronounced atherosclerotic risk profile, or rarefied distal arteries without sclerosis of the media, or elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) independent from the stage IV of PAOD, the following autoantibodies were investigated: antinuclear antibodies (ANA), antibodies against extractable nuclear antigens (ENA): SCL 70, RNP, SS-A, SS-B, Jo-1, SM), double-stranded DNA antibodies (ds-DNA), antineutrophil cytoplasmatic antibodies (c- and p-ANCA), antiphospholipid antibodies [phosphatidylserine (APSA) and beta(2)-glycoprotein], smooth (SMA) and striated muscle (StrMA). ANA, SMA and StrMA were estimated by indirect immunofluorescence technique, ENA by Western-blot and the others by enzyme linked immunoassay. RESULTS: 38 PAOD-patients (35%) had increased autoantibody concentrations. The rate of different PAOD stages and localization did not differ between the group of patients with increased autoantibody concentrations and the group of patients without. But the group of patients with increased autoantibody concentrations had higher rates of elevated ESR [p-value of 0.0043, odds ratio of 7.1 (95% CI: 1.49-33.81)]. ANA were the most frequent autoantibodies detected in 17 (14%) of the 121 patients followed by APSA and autoantibodies directed against beta(2)-glycoprotein. During follow-up of 24 +/- 6 months no vasculitis or collagen diseases associated with the elevated autoantibody concentrations became clinically manifest in the 38 patients. Two patients died due to coronary heart disease. Four patients had a worsening of their PAOD but no amputation was performed. Out of the 83 patients without elevated concentrations of autoantibodies, eight patients died and three amputations were carried out. CONCLUSION: All in all, increased autoantibody concentrations in patients suffering from peripheral atherosclerosis are not a rare finding. A systematic determination of autoantibodies, especially in patients with a low atherosclerotic risk profile, does not increase the number of manifest or developing vasculitis of collagen disease.  相似文献   
27.
OBJECTIVE: Studies to prove a relationship between fatigue and immunological, inflammatory, or other disease characteristics of systemic lupus erythematosus (SLE) have shown no consistent findings. To further elucidate the basis for fatigue in SLE, we examined the affective states, personality traits, and mental health status in an unselected group of patients with SLE. METHODS: Fifty-seven Caucasian patients with SLE were examined. Fatigue was measured by the Fatigue Severity Scale. Personality traits and psychological function were evaluated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the affective states by Beck Depression Inventory, and mental health status by the General Health Questionnaire version 30 (GHQ-30). RESULTS: Fatigue was closely associated with high scores on subscales Depression (D-2) and Hysteria (Hy-3) on MMPI-2 (R2 = 0.31; p = 0.0002), as well as with high scores on BDI (R2 = 0.22; p = 0.0006) and GHQ (R2 = 0.33; p < 0.0001). CONCLUSION: Fatigue does not seem to be caused by any easily recognizable single or multiple factor(s) of an inflammatory or immunological state. Our results point to fatigue being a multifaceted phenomenon where several psychosocial factors are strongly related, and indicate that fatigue is part of a complex response to chronic disease.  相似文献   
28.
Cannabis is the most commonly used illicit drug in Europe, and is generally regarded as having low acute toxicity. We present the findings of the first 6 months of data collection from the Euro-DEN project on presentations related to cannabis use to further understand the acute toxicity related to the use of cannabis. Data was extracted on clinical features, treatment and outcome from the Euro-DEN minimum dataset for all cases of acute recreational drug toxicity reported 1st October 2013 to 31st March 2014 for all cannabis-related presentations. Of 2198 presentations reported by 14 of the 16 Euro-DEN centres, 356 (16.2 %) involved cannabis either alone or together with other drugs/alcohol. There were 36 that involved lone use of cannabis (1.6 % of all presentations). Of the 35 non-fatal lone cannabis presentations, the most commonly reported features were neuro-behavioural (agitation/aggression 8 (22.9 %), psychosis 7 (20.0 %), anxiety 7 (20.0 %)) and vomiting 6 (17.1 %). Most patients (25, 71.4 %) received no treatment and 30 (85.7 %) were discharged/self-discharged from the ED. There was one fatality amongst these lone-cannabis cases: an 18-year-old male collapsed with an asystolic cardiac arrest whilst smoking cannabis and suffered hypoxic brain injury related to prolonged cardiac arrest. THC was detected in a urine sample taken at ED arrival; no other drugs were detected. Lone acute cannabis toxicity was typically associated with neuro-behavioural symptoms and vomiting. Although uncommon, severe toxicity including cardiovascular toxicity and death may be under-recognised, and it is important that Emergency Physicians are aware of this.  相似文献   
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