Validation of Syndromic Surveillance for Respiratory Pathogen Activity

The studied respiratory syndromes are suitable for syndromic surveillance because they reflect respiratory pathogen activity pattern

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up

SummaryObjectivesAge-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA.DesignThe 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed.ResultsBoth pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R2 = 0.60–0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R2 = 0.07–0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis.ConclusionPentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline

FDG-PET/CT Limited to the Thorax and Upper Abdomen for Staging and Management of Lung Cancer.

This study evaluates the diagnostic accuracy of [F-18]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) of the chest/upper abdomen compared to the generally performed scan from head to upper thighs, for staging and management of (suspected) lung cancer in patients with no history of malignancy or complaints outside the thorax.FDG-PET/CT scans of 1059 patients with suspected or recently proven lung cancer, with no history of malignancy or complaints outside the thorax, were analysed in a retrospective multi-centre trial. Suspect FDG-avid lesions in the chest and upper abdomen, the head and neck area above the shoulder line and in the abdomen and pelvis below the caudal tip of the liver were noted. The impact of lesions detected in the head and neck area and abdomen and pelvis on additional diagnostic procedures, staging and treatment decisions was evaluated.The head and neck area revealed additional suspect lesions in 7.2%, and the abdomen and pelvis in 15.8% of patients. Imaging of the head and neck area and the abdomen and pelvic area showed additional lesions in 19.5%, inducing additional diagnostic procedures in 7.8%. This resulted in discovery of additional lesions considered malignant in 10.7%, changing patient management for lung cancer in 1.2%. In (suspected) lung cancer, PET/CT limited to the chest and upper abdomen resulted in correct staging in 98.7% of patients, which led to the identical management as full field of view PET in 98.8% of patients.High value of FDG-PET/CT for staging and correct patient management is already achieved with chest and upper abdomen. Findings in head and neck area and abdomen and pelvis generally induce investigations with limited or no impact on staging and treatment of NSCLC, and can be interpreted accordingly

Additional investigations.

<p>Additional investigations.</p

Example head/neck area.

<p>Significant false-positive finding on PET/CT in the head/neck area. Intense FDG uptake in a lymph node (red arrow), revealing inflammation in a patient who eventually did not have lung cancer. Bowel-hotspots were ignored (blue arrows). Left: maximum intensity projection of PET. Right: Corresponding transverse slices of PET (top), PET/CT (middle), and CT (bottom).</p

FDG PET-findings summarised by scan area.

<p>FDG PET-findings summarised by scan area.</p

Example abdominal/pelvic area.

<p>True-positive but no-impact findings on PET/CT in the lower abdominal and pelvic area. Multiple skeletal metastases were detected (blue arrows), but these had no impact on staging as the thoracic field of view already showed multiple distant metastases (skeletal, adrenal glands, liver). An intense bowel hotspot (red arrow) is probably a colon carcinoma or large dysplastic polyp, but this was ignored as the prognosis of this patient was determined by the lung cancer. Imaging of the lower abdomen and pelvic area did not change the stage or therapy for this patient. Left: Coronal maximum intensity projection of PET. Right: Corresponding transverse slices of PET (top), PET/CT (middle), and CT (bottom).</p

Scan regions.

<p>The regions evaluated in this study. The head and neck area (HN): all above the shoulder line. The lower abdominal and pelvic area (LAP): all below the caudal tip of the right liver lobe. The region between HN and LAP (chest and upper abdomen, thoracic range) is the region of interest for imaging of (suspected) lung cancer.</p