Reliable and reproducible methods for identifying PD-L1 expression on tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested the reproducibility of the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) tissue samples by pathologists. NSCLC samples were stained with PD-L1 22C3 pharmDx kit using the Dako Autostainer Link 48 Platform. Two sample sets of 60 samples each were designed to assess inter- and intraobserver reproducibility considering two cut points for positivity: 1% or 50% of PD-L1 stained tumor cells. A randomization process was used to obtain equal distribution of PD-L1 positive and negative samples within each sample set. Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all samples on two consecutive days. Subgroup 2 performed the same assessments, except they received a 1-hour training session prior to the second assessment. For intraobserver reproducibility, the overall percent agreement (OPA) was 89.7% [95% confidence interval (CI), 85.7-92.6] for the 1% cut point and 91.3% (95% CI, 87.6-94.0) for the 50% cut point. For interobserver reproducibility, OPA was 84.2% (95% CI, 82.8-85.5) for the 1% cut point and 81.9% (95% CI, 80.4-83.3) for the 50% cut point, and Cohen's κ coefficients were 0.68 (95% CI, 0.65-0.71) and 0.58 (95% CI, 0.55-0.62), respectively. The training was found to have no or very little impact on intra- or interobserver reproducibility. Pathologists reported good reproducibility at both 1% and 50% cut points. More adapted training could potentially increase reliability, in particular for samples with PD-L1 proportion, scores around 50%. .
A 21 year old man presented with a right sided pleural effusion. Destruction of the 11th and 12th right ribs and adjacent vertebral bodies was noted on computed tomographic scanning. An open rib biopsy revealed the histopathological changes of Gorham's syndrome. In view of the progressive vertebral destruction and inevitable spinal cord compromise, he was treated with high dose radiotherapy. The process was arrested and he remains well with no signs of recurrence after four years. Pleural effusion and vertebral destruction complicating Gorham's syndrome carry a poor prognosis but, in this case, high dose radiotherapy has been effective in controlling both the effusion and the progressive bony destruction.
A survey of the Diels-Alder reactions of eight l-(acylamino)-1,3-dienes with thirteen varied dienophiles is reported. These reactions provide convenient access to diversely substituted, amino-functionalized cyclohexanes and octalones. Of particular note are (a) the successful Diels-Alder reactions of diene carbamates 14 and 18 with the notoriously poor dienophiles 2-cyclohexanone, styrene, and 3,4-methylenedioxystyrene, (b) the nearly total regioselectivity observed in reactions of all
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