The clinical course of polymyalgia rheumatica in Chinese

Polymyalgia rheumatica (PMR) is diagnosed based on clinical features that may overlap with other rheumatic conditions like rheumatoid arthritis (RA). Furthermore, a proportion of PMR patients may subsequently evolve into RA. The aim of this study was to examine the clinical characteristics of PMR patients in a Chinese cohort compared to a Caucasian series. Patients diagnosed to have PMR during 1997-2008 were reviewed for clinical features and compared to a reported Caucasian series. Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP) antibodies were determined by immunonephelometry and enzyme-linked immunosorbent assay, respectively. Forty-four patients of southern Chinese origin were diagnosed to have PMR according to specialist opinion. Seventy-five percent of patients (n = 33) were >65 years of age at diagnosis (mean ± standard deviation, 75.8 ± 9.6 years). The commonest feature at disease onset was elevated erythrocyte sedimentation rate >40 mm/h (100% vs. 95.7%; p = 0.17) and bilateral shoulder pain or stiffness (95.5% vs. 90.8%; p = 0.31), comparable in frequency to the Caucasian cohort. However, Chinese patients had significantly longer duration of symptoms before diagnosis (p < 0.001) but less bilateral upper arm tenderness (p < 0.001) and generalized stiffness (p = 0.01). Twelve (27.3%) patients evolved into RA after a median duration of 2 months from onset of PMR. RF and anti-CCP antibodies were positive in 66.7% and 60% of these patients compared to 9.4% and 6.2%, respectively, among those who did not evolve into RA during the period observed. Chinese patients with PMR have modestly different clinical profile compared to the Caucasian counterpart. RF and anti-CCP antibodies were more likely to be present in those who subsequently developed into RA. © 2009 Clinical Rheumatology.postprin

Integration of chromosomal microarray into paediatric clinical care in Hong Kong

Poster Presentation 9BACKGROUND AND AIMS: Chromosomal microarray (CMA) has emerged as a major tool to identify unbalanced chromosomal aberrations in children and is recommended as the first tiered investigation for intellectual disability, autism spectrum disorders and multiple congenital anomalies. While the clinical interpretation and genetic counseling remain as ongoing challenge, data about potential downstream benefits and harms of CMA is lacking, especially in paediatric ...postprin

Markers for early detection of cancer: Statistical guidelines for nested case-control studies

BACKGROUND: Recently many long-term prospective studies have involved serial collection and storage of blood or tissue specimens. This has spurred nested case-control studies that involve testing some specimens for various markers that might predict cancer. Until now there has been little guidance in statistical design and analysis of these studies. METHODS: To develop statistical guidelines, we considered the purpose, the types of biases, and the opportunities for extracting additional information. RESULTS: The following guidelines: (1) For the clearest interpretation, statistics should be based on false and true positive rates – not odds ratios or relative risks (2) To avoid overdiagnosis bias, cases should be diagnosed as a result of symptoms rather than on screening. (3) To minimize selection bias, the spectrum of control conditions should be the same in study and target screening populations. (4) To extract additional information, criteria for a positive test should be based on combinations of individual markers and changes in marker levels over time. (5) To avoid overfitting, the criteria for a positive marker combination developed in a training sample should be evaluated in a random test sample from the same study and, if possible, a validation sample from another study. (6) To identify biomarkers with true and false positive rates similar to mammography, the training, test, and validation samples should each include at least 110 randomly selected subjects without cancer and 70 subjects with cancer. CONCLUSION: These guidelines ensure good practice in the design and analysis of nested case-control studies of early detection biomarkers

Clinical Heterogeneity of Duchenne Muscular Dystrophy (DMD): Definition of Sub-Phenotypes and Predictive Criteria by Long-Term Follow-Up

International audienceBACKGROUND: To explore clinical heterogeneity of Duchenne muscular dystrophy (DMD), viewed as a major obstacle to the interpretation of therapeutic trials METHODOLOGY/PRINCIPAL FINDINGS: A retrospective single institution long-term follow-up study was carried out in DMD patients with both complete lack of muscle dystrophin and genotyping. An exploratory series (series 1) was used to assess phenotypic heterogeneity and to identify early criteria predicting future outcome; it included 75 consecutive steroid-free patients, longitudinally evaluated for motor, respiratory, cardiac and cognitive functions (median follow-up: 10.5 yrs). A validation series (series 2) was used to test robustness of the selected predictive criteria; it included 34 more routinely evaluated patients (age>12 yrs). Multivariate analysis of series 1 classified 70/75 patients into 4 clusters with distinctive intellectual and motor outcomes: A (early infantile DMD, 20%): severe intellectual and motor outcomes; B (classical DMD, 28%): intermediate intellectual and poor motor outcome; C (moderate pure motor DMD, 22%): normal intelligence and delayed motor impairment; and D (severe pure motor DMD, 30%): normal intelligence and poor motor outcome. Group A patients had the most severe respiratory and cardiac involvement. Frequency of mutations upstream to exon 30 increased from group A to D, but genotype/phenotype correlations were restricted to cognition (IQ>71: OR 7.7, 95%CI 1.6-20.4, p6 at 8 yrs" with "normal or borderline mental status" reliably assigned patients to group C (sensitivity: 1, specificity: 0.94). These criteria were also predictive of "early infantile DMD" and "moderate pure motor DMD" in series 2. CONCLUSIONS/SIGNIFICANCE: DMD can be divided into 4 sub-phenotypes differing by severity of muscle and brain dysfunction. Simple early criteria can be used to include patients with similar outcomes in future therapeutic trials

An exploration of patient-reported symptoms in systemic lupus erythematosus and the relationship to health-related quality of life

Objective: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics and disease characteristics (duration, activity, organ damage). Methods: In a cross-sectional study, patients with SLE (n=324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analyzed for patient demographics, disease duration, results from the questionnaires: Medical Outcomes Study Short-Form 36, Hospital Anxiety and Depression Scale, Systemic Lupus Activity Measure, SLE disease activity index and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology damage index. Results: 23 symptom categories were identified. Fatigue (51%), Pain (50%) and Musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting Fatigue showed statistically significant impact on both mental and physical components of HRQoL.. Patients with no present symptoms (10%) had higher HRQoL (p<0.001) and lower levels of depression (p<0.001), anxiety (p<0.01) and disease activity (SLAM) (p<0.001). Conclusion: Fatigue, pain or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting Fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue

Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature

<p>Abstract</p> <p>Background</p> <p>Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib.</p> <p>Case presentation</p> <p>Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously.</p> <p>Conclusion</p> <p>We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.</p

Numerical study on load-bearing capabilities of beam-like lattice structures with three different unit cells

The design and analysis of lattice structures manufactured using Additive Manufacturing (AM) technique is a new approach to create lightweight high-strength components. However, it is difficult for engineers to choose the proper unit cell for a certain function structure and loading case. In this paper, three beam-like lattice structures with triangular prism, square prism and hexagonal prism were designed, manufactured by SLM process using AlSi10Mg and tested. The mechanical performances of lattice structures with equal relative density, equal base area and height, and equal length for all unit cells were conducted by Finite Element Analysis (FEA). It was found that effective Young’s modulus is proportional to relative density, but with different affecting levels. When the lattice structures are designed with the same relative density or the same side lengths, the effective Young’s modulus of lattice structure with triangular prism exhibits the maximum value for both cases. When the lattice structures are designed with the same base areas for all unit cells, the effective Young’s modulus of lattice structures with square prism presents the maximum. FEA results also show that the maximum stress of lattice structures with triangular prisms in each comparison is at the lowest level and the stiffness-to-mass ratio remains at the maximum value, showing the overwhelming advantages in terms of mechanical strength. The excellent agreements between numerical results and experimental tests reveal the validity of FEA methods applied. The results in this work provide an explicit guideline to fabricate beam-like lattice structures with the best tensile and bending capabilities

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT