The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

Prevalence of metabolic syndrome in patients with psoriasis: a cross-sectional study in Singapore

INTRODUCTIONPsoriasis is a chronic inflammatory condition that affects the skin and joints, and is associated with cardiovascular risk factors, including metabolic syndrome (MetS). We aimed to assess the prevalence of MetS in patients with psoriasis and determine whether there was a correlation between psoriasis severity and MetS in a Singapore population.METHODSThis was a cross-sectional study of patients with psoriasis, aged 18–69 years, who attended a tertiary dermatology referral centre in Singapore from October 2007 to February 2009. Fasting glucose, lipids, blood pressure, Psoriasis Area and Severity Index, and body mass index were measured. MetS was diagnosed in the presence of three or more criteria of the modified National Cholesterol Education Program Adult Treatment Panel III.RESULTSAmong 338 patients with psoriasis, there were 238 (70.4%) men and 100 (29.6%) women, who were Chinese (n = 228; 67.5%), Malay (n = 52; 15.4%) and Indian (n = 58; 17.2%). The prevalence of MetS was 45.1%. MetS was 44% more prevalent in patients older than 50 years (p = 0.02). Malay patients with psoriasis were significantly more likely to have hypertriglyceridaemia, elevated fasting plasma glucose and abdominal obesity. There was no significant correlation between psoriasis severity and risk of MetS.CONCLUSIONThe prevalence of MetS in patients with psoriasis in Singapore was 45.1%, or nearly threefold higher than the Singapore general population. Patients with psoriasis should be screened yearly for MetS and any modifiable cardiovascular risk factors should be actively controlled.     

Quality of Regional Nodal Irradiation Plans in Breast Cancer Patients Across a Large Network—Can We Translate Results From Randomized Trials Into the Clinic?

PurposeRegional nodal irradiation (RNI) improved disease-free survival by 3% to 5% in 2 large randomized trials, but this small absolute advantage relies on accurate contouring and dose delivery. We audited our network to determine compliance on regional nodal coverage, contouring, and dosimetric parameters with respect to accepted guidelines.Methods and MaterialsIn our network, we have established a clinical pathway for patients with node-positive breast cancer that guides indications for RNI and dosimetric goals. We reviewed records of 183 patients with nodal macrometastases after upfront surgery or involved nodes of any size after neoadjuvant chemotherapy. Radiation treatment plans were examined to determine lymph node volumes treated, whether nodes were contoured, quality of nodal contours, and whether target coverage and normal organ dosimetric constraints were met when RNI was delivered.ResultsDespite the presence of macrometastases on sentinel lymph node biopsy, no lymph nodes were treated in 2.2% (4 of 183). Of 179 patients who received nodal irradiation, 18 received radiation to axillary levels 1 and 2 only, and 161 patients received RNI. Overall, regional nodes were not treated despite strong indications in 7.6% (14 of 183). Treated nodes were not contoured for 2.2% (4 of 179), and lymph node contours were unacceptable in 15.4% (27 of 175). Of patients receiving RNI, 14.9% (24 of 161) did not have adequate nodal target volume coverage, mean heart dose was >4 Gy for 3.1% (5 of 161), and lung V20 Gy was >35% for 8.7% (14 of 161).ConclusionsAdherence to indications for regional nodal treatment was high, but nodes were either not contoured or had unacceptable contour quality in 18% of plans, and coverage was inadequate in 15%. Because the small disease-free survival advantage seen in trials may be decreased with these deviations, routine clinical practice requires detailed peer review to fully translate results of clinical trials.     

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors