BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1) expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1) therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck). PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months) for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months). No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.
Severe nonthyroidal illness has been claimed to cause secondary hypothyroidism. We reevaluated this concept measuring serum free T4 and free T3 by an ultrafiltration method and serum TSH by an ultrasensitive technique (detection limit, and serum TSH by an ultrasensitive technique (detection limit, 0.05 mU/L). Forty-five critically ill patients suffering from hepatic coma (n = 10), terminal cancer (n = 9), stroke (n = 8), and respiratory insufficiency not treated (n = 7) and treated (n = 11) with dopamine were studied. The mortality rate was 80%. No patients received glucocorticoids, and only patients in the last group received dopamine. Serum total as well as free thyroid hormone index values were grossly reduced in the majority of the patients. The 34 patients not receiving dopamine in general had normal values of serum free T4 (32 of 34) and free T3 (31 of 34), measurable TSH (33 of 34), and detectable TSH responses to iv TRH (33 of 34). In contrast, the dopamine-treated patients had reduced serum free T4 and TSH levels compared to normal subjects (P less than 0.05), as well as reduced TSH responses to TRH (P less than 0.01). Serum free T4 and free T3 were below the normal range in 3 patients and 1 patient, respectively, and serum TSH was below the detection limit in 2 patients. We conclude that critically ill patients with nonthyroidal illness not receiving dopamine have normal pituitary-thyroid function, whereas dopamine induces some degree of secondary hypothyroidism.
Objective: To assess the prevalence of impaired left ventricular systolic function and manifest heart failure in a general population aged 50-89 years. Design: In this cross sectional survey, participants filled in a heart failure questionnaire. ECG, blood tests, and echocardiography were performed. Setting: The study population was recruited from general practitioners situated in the same urban area and examined in a university hospital in Copenhagen, Denmark. Participants: 764 participants (432 women and 332 men, median (SD) age 66 (11) years) participated. The study population was stratified to include a minimum of 150 persons in each age decade. Main outcome measures: Prevalence of impaired systolic function and manifest heart failure. Results: The prevalence of systolic dysfunction (left ventricular ejection fraction ( 40%) was more than twice as high among men (7.6%) as among women (2.6%). In the male population systolic heart failure (left ventricular ejection fraction ( 40% and symptoms) was found in 1.8% of the 50-59 years age group and approximately doubled for each age decade to reach 13.9% in octogenarians. Among women systolic dysfunction increased from 0.8% to 4.3% in the same age groups. Asymptomatic cases accounted for 44.0% of all cases of systolic dysfunction in the male population and only 9.1% in the female population. Conclusions: In this age controlled population study impaired left ventricular systolic function and heart failure increased substantially with age and was more than twice as frequent among men as among women. Asymptomatic left ventricular dysfunction occurred more frequently in men than in women and was less prevalent with increasing age.
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