We recruited 985 patients with COPD but without hypoxemia or other serious disease, treated them in a standard fashion, and followed them closely for nearly 3 yr. At the time of recruitment the patients were carefully characterized as to symptom severity, lung function, exercise tolerance, and quality of life, and studies of lung function were repeated during follow-up. Overall mortality was 23% in 3 yr of follow-up. Patient age and the initial value of the FEV1 were the most accurate predictors of death; when FEV1 before bronchodilator was used, the response to bronchodilators was directly related to survival, but this relationship became nonsignificant when postbronchodilator FEV1 was used as a primary predictor. After adjustment for age and FEV1, mortality was related positively to TLC, resting heart rate, and perceived physical disability, and related negatively to exercise tolerance. These relationships, though significant, were relatively weak. When standardized for age and FEV1, mortality in the present series was less than that of a previous series (4), and the same as that of hypoxemic patients with COPD who received continuous home O2 therapy. Changes in FEV1 with time averaged -44 ml/yr, but the standard deviation was large. Patients with low initial values of FEV1 showed relatively little further decline, probably indicating a survivor effect. In patients with well-preserved initial FEV1, rate of decline correlated negatively with bronchodilator response, symptomatic wheezing, and psychological disturbances.

The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub-study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty-two physicians with varying levels of experience read 13 cine angiograms -- blind -- on two different occasions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement -- namely, the right main coronary artery and presence of ventricular aneurysm -- there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.

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Recent discoveries have provided valuable insight into the genomic landscape of pediatric low-grade gliomas (LGGs) at diagnosis, facilitating molecularly targeted treatment. However, little is known about their temporal and therapy-related genomic heterogeneity. An adequate understanding of the evolution of pediatric LGGs’ genomic profiles over time is critically important in guiding decisions about targeted therapeutics and diagnostic biopsy at recurrence. Fluorescence in situ hybridization, mutation-specific immunohistochemistry, and/or targeted sequencing were performed on paired tumor samples from primary diagnostic and subsequent surgeries. Ninety-four tumor samples from 45 patients (41 with two specimens, four with three specimens) from three institutions underwent testing. Conservation of BRAF fusion, BRAFV600E mutation, and FGFR1 rearrangement status was observed in 100%, 98%, and 96% of paired specimens, respectively. No loss or gain of IDH1 mutations or NTRK2, MYB, or MYBL1 rearrangements were detected over time. Histologic diagnosis remained the same in all tumors, with no acquired H3K27M mutations or malignant transformation. Changes in CDKN2A deletion status at recurrence occurred in 11 patients (42%), with acquisition of hemizygous CDKN2A deletion in seven and loss in four. Shorter time to progression and shorter time to subsequent surgery were observed among patients with acquired CDKN2A deletions compared to patients without acquisition of this alteration [median time to progression: 5.5 versus 16.0 months (p = 0.048); median time to next surgery: 17.0 months versus 29.0 months (p = 0.031)]. Most targetable genetic aberrations in pediatric LGGs, including BRAF alterations, are conserved at recurrence and following chemotherapy or irradiation. However, changes in CDKN2A deletion status over time were demonstrated. Acquisition of CDKN2A deletion may define a higher risk subgroup of pediatric LGGs with a poorer prognosis. Given the potential for targeted therapies for tumors harboring CDKN2A deletions, biopsy at recurrence may be indicated in certain patients, especially those with rapid progression.