Utility of fine-needle aspiration in the diagnosis of primary osteosarcoma

Fine-needle aspiration (FNA) is a reliable, safe, and cost-effective procedure with a well-established role in the diagnosis of various solid tissue neoplasms. The role of FNA in the diagnosis of primary bone tumors, including osteosarcoma (OGS), is controversial and has yet to be established. We reviewed our experience with the use of FNA as a diagnostic technique over the past 8 yr at our institution. Diagnosis was conclusive in 26 (65%) of 40 patients, 18 of whom went to neoadjuvant therapy and/or resection based solely on the FNA interpretation of either "high grade sarcoma" or "osteosarcoma." Of the remaining 14 (25%) patients, 12 had inconclusive diagnosis and two (5%) were false-negatives. An inconclusive diagnosis was most likely to be an inadequate or paucicellular aspirate, seen in six (15%) patients. An additional six patients had variants of osteosarcoma (four chondroid, one "giant cell rich," one parosteal) that made definitive diagnosis impossible. The two that were incorrectly classified were diagnosed as fracture callus and plasmacytoma. FNA is an accurate and cost-effective tool for the initial diagnosis of primary osteosarcoma with a sensitivity of 65% and accuracy of 95%. Inconclusive diagnoses are likely to be due to insufficient sample cellularity or the presence of OGS variant. In our experience, FNA is sufficient to provide the diagnosis of OGS prior to definitive treatment when interpreted in conjunction with imaging studies and clinical findings. In those cases where FNA fails to yield a diagnostic sample, a traditional biopsy can be performed.     

Stroke-prone rats exhibit prolonged behavioral deficits without increased brain injury: an indication of disrupted post-stroke brain recovery of function

Stroke-prone rat strains exhibit an increased stroke risk and sensitivity, and reduced endogenous mechanisms of ischemic brain tolerance. This experiment provides a comparative, serial evaluation of neurological deficits and brain injury following middle cerebral artery occlusion/permanent focal stroke in this high-risk strain. Stroke-prone spontaneously hypertensive (SHR-SP), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated over 28 days using magnetic resonance imaging (MRI), histopathology, and neurobehavioral testing. T2- and diffusion weighted-MRI was performed after 1, 10 and 28 days to measure the degree of stroke-induced brain injury. Normotensive WKY rats receiving the same stroke and other SHR-SP rats receiving sham surgery were used for control comparisons. Functional deficits were scored after 1, 4, 11, 18 and 28 days. The degree of brain infarction/injury was practically identical in hypertensive and stroke-prone rats. WKY rats exhibited significantly smaller infarcts (P<0.05), with neurological function recovering quickly to normal by day 11 in this strain. Functional deficits persisted longer in hypertensive rats, with function recovering to normal by day 18 (P<0.05). Functional deficits in SHR-SP rats persisted the longest, and were observed even after 28 days (P<0.05). This increased and prolonged neurologic dysfunction exhibited by SHR-SP compared to SHR rats, while exhibiting practically identical degrees of brain injury/infarction, reflects the increased stroke risk and sensitivity of this strain and suggests a reduced SHR-SP brain plasticity following injury. Therefore, the stroke-prone rat provides an enhanced and prolonged functional deficit model that can be used to elucidate those mechanisms/novel targets critical to longitudinal neurobehavioral recovery post-stroke.     

Determinants of cockroach and mouse exposure and associations with asthma in families and elderly individuals living in New York City public housing.

BACKGROUND: Asthma prevalence is high in the inner city, and morbidity has been associated with cockroach and mouse allergens. OBJECTIVE: To characterize the relationships among pests, allergens, pesticides, and asthma in New York City public housing. METHODS: In 324 apartments, dust samples collected from beds and kitchens were analyzed for cockroach (Bla g 2) and mouse (mouse urinary protein [MUP]) allergens, pest populations were monitored, and residents were interviewed about home characteristics and asthma symptoms. RESULTS: Cockroaches were found in 77% of the apartments, and evidence of mice was found in 13%. Allergens and pesticide use were associated with pest infestation, and 15% of residents reported using illegal pesticides. The percentage of apartments with high allergen levels varied significantly by building (Bla g 2: P = .002; MUP: P = .03), as did the percentage of apartments with cockroaches (P = .002) and daily mouse sightings (P = .02). Thirty-seven percent of the apartments had at least 1 resident with physician-diagnosed asthma. In family buildings, apartments with high Bla g 2 levels had 1.7 times greater odds of having an asthmatic resident (95% confidence interval, 1.2-2.3). In senior citizen buildings, apartments with high MUP levels had 6.6 times greater odds of having an asthmatic resident (95% confidence interval, 1.4-31.7), controlling for smoking and other potential confounders. CONCLUSIONS: Previous studies have identified home characteristics associated with the presence of cockroaches and mice, but the present findings suggest that building-level characteristics can affect high pest exposure. Furthermore, the high asthma prevalence in residents and the use of illegal pesticides highlight the need for safe and effective building-wide pest control strategies.     

The neural basis of the psychomotor vigilance task

STUDY OBJECTIVE: To identify brain regions underlying the fastest and slowest reaction times on the Psychomotor Vigilance task (PVT) under well-rested conditions, as well as brain regions related to particularly poor performance after sleep deprivation. DESIGN: Subjects took the PVT twice while undergoing functional magnetic resonance imaging: once 12 hours after waking from a normal night of sleep and once after 36 hours of total sleep deprivation (TSD). Session order was counterbalanced. SETTING: UCSD J. Christian Gillin Laboratory for Sleep and Chronobiology (the sleep core of the General Clinical Research Center) and UCSD Magnetic Resonance Institute. PATIENTS OR PARTICIPANTS: Twenty right-handed healthy adults (8 women; age = 27.4 +/- 6.7 years; education = 15.6 +/- 1.5 years). MEASUREMENTS AND RESULTS: After a normal night of sleep, optimal performance was related to greater cerebral responses within a cortical sustained attention network and the cortical and subcortical motor systems. Slow reaction times, particularly after TSD, were associated with greater activity in the "default mode network" consisting of frontal and posterior midline regions. CONCLUSIONS: Optimal performance on the PVT appears to rely on activation both within the sustained attention system and within the motor system. Poor performance following TSD may result from a disengagement from the task and related inattention, and brain regions responsible for this localize within midline structures shown to be involved in the brain's "default mode." Finally, particularly poor performance after TSD may elicit a subsequent attentional recovery that manifests as greater activation within the same regions normally responsible for fast reaction times.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Internet teleconferencing method for telepathology consultations from lung and heart transplant patients

Current Internet-based teleconferencing techniques allow a referring pathologist to transmit real-time images from a microscope to a consultant, while maintaining a verbal conversation using Internet telephony. In our study, 50 randomly selected transbronchial biopsies from lung allograft recipients and 58 randomly selected endomyocardial biopsies from heart transplant patients were diagnosed by consultant pathologists using Internet-based teleconferencing methods. The referring pathologists acquired the real-time video images from the biopsies using a light microscope equipped with a phototube adapter and a video camera. The consultant pathologists viewed the processed images on a video monitor at 800 x 600 resolution, using a standard microcomputer equipped with Netmeeting software, and directed the referring pathologist to move the slide under the microscopy and/or change image magnification. The validity of telepathology diagnoses was assessed with kappa coefficients. Consultations were completed in 5 to 15 minutes per case. Sound transmission was unreliable, and in approximately 25% of consultations the referring pathologist needed to "call back" to reestablish verbal communication. In all but 2 transbronchial biopsies there was agreement between the original diagnosis and the diagnosis by telepathology (kappa = 0.92). In 48 of 58 endomyocardial biopsies there was concordance between the 2 diagnoses (kappa = 0.692). Only 3 out of 10 of these discrepancies were clinically significant (kappa = 0.897). Internet-based teleconferencing techniques provide effective and relatively inexpensive tools for real time telepathology consultations. The technology is probably best suited for the study of small specimens from patients that require rapid diagnosis by a consultant.     

AMPK调节骨骼肌细胞GLUT4基因表达的机制研究

腺苷酸活化蛋白激酶(AMPK)能调节运动/肌肉收缩所引起的骨骼肌细胞葡萄糖转运蛋白4(GLUT4)基因的表达,但至今它的调节机制不清.研究显示在非运动刺激引起的细胞信号事件中由组蛋白去乙酰化酶(HDACs)以及组蛋白乙酰化酶(HATs)控制的组蛋白乙酰化状态是调节基因表达的重要机制,所以我们假设AMPK信号途径是通过征用HDACs中的HDAC5(在骨骼肌细胞内高表达)来实现对运动/肌肉收缩引起的GLUT4基因表达控制.细胞分为正常浓度葡萄糖对照组(NGLU组)、正常浓度AICAR组(NGLU AICAR组)、高浓度对照组(HGLU组)、高浓度AICAR组(HGLU AICAR组).用5 mmol/L和20 mmol/L葡萄糖浓度培养骨骼肌细胞后,NGLU AICAR组和HGLU AICAR组与肌肉收缩模拟信号刺激5-氨基-4-甲酰胺咪唑核糖核苷酸(AICAR)孵育.AICAR能激活NGLU组骨骼肌细胞AMPKα2、减少骨骼肌细胞核HDAC5蛋白、促使HDAC5与骨骼肌细胞加强因子(MEF2)蛋白分离和上调GLUT4基因的表达;相反,高浓度葡萄糖延迟由AICAR引起的AMPKα2磷酸化、AMPKα2向细胞核转入、HDAC5向细胞核转出和GLUT4基因的表达.实验结果说明在不同葡萄糖浓度下的骨骼肌细胞GLUT4基因表达变化都对应着上游AMPK蛋白和下游HDAC5蛋白的变化,AMPK可能是征用转录抑制子HDAC5来调节MEF2的活性而达到控制肌肉收缩所引起的GLUT4基因表达.     

The impact of decentralisation on the performance of health care systems: a non-linear relationship

The European Journal of Health Economics - This paper examines the role of institutions—notably the degree of administrative decentralisation across levels of government—in health care...     

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer

ContextMolecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.ObjectiveTo perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).Evidence acquisitionThe review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446–52) and American Urology Association (AUA) criteria.Evidence synthesisIn total, 42 studies and 30 407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n = 12 141), prospective registries (n = 17 053), and prospective and post hoc randomized trial analyses (n = 1213). In 32 studies (n = 12 600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n = 8543). GC use changed the management in active surveillance (number needed to test [NNT] = 9) and postprostatectomy (NNT = 1.5–4) settings in five studies (n = 4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.ConclusionsConsistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.Patient summaryIn this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.