Mccaffreybraun6968

BACKGROUND Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC. PATIENTS AND METHODS The present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions' longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs). RESULTS The optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS. CONCLUSIONS PD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC. BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. METHODS A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. RESULTS A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. L-Ornithine L-aspartate in vivo Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. CONCLUSIONS Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD. V.BACKGROUND In addition to TNM-based anatomical staging (AS), a novel pathological prognostic staging (PPS) has been proposed by the American Joint Committee on Cancer (AJCC). PPS demonstrated better prognostication, but its superiority in breast cancer subtypes and related to staging discrepancies between AS and PPS are not clear. METHODS A cohort of 1729 patients with breast cancer was staged into AS and PPS according to the latest AJCC staging. Patient characteristic and restaging outcomes were compared. RESULTS Compared with AS, 799 and 135 cases were upstaged and downstaged respectively in PPS, mostly involved stage I cases. For the overall cohort, PPS demonstrated superior prognostic power over AS in both disease-free survival (DFS) and breast cancer-specific survival. However, such superiority was found mainly in estrogen receptor (ER)/progesterone receptor (PR)+ but not ER-PR- cancers. Comparing the restaged cases within the same PPS, PPS 1A cases showed similar survival irrespective of the original AS. Interestingly, in other PPS groups (PPS 1B and higher), there was a difference in outcome among patients with same PPS but different AS. Within PPS 1B patients, downstaged cases from higher AS showed worse DFS (3A>1B vs. 2A>1B χ2 = 4.732, P = .030). CONCLUSIONS PPS may provide a more accurate prognostication, mostly among ER/PR+ cancers and with PPS 1A patients. Patients restaged to higher PPS stages showed significant differential survival even within the same PPS. Also, only limited improvement was observed for ER-PR- cancers. Caution needs to be exercised in using PPS for patient prognostication, as in some cases the outcome can be variable with the same PPS. The gold standard in biomedical research is the multi-center, multi-blinded, randomized control trial (RCT). In pharmacological research the RCT is termed a Phase III clinical trial. This paper presents the core goals and RCT methods developed to investigate automated spirit presence and communication. The goals are (1) to use currently available, reliable, and affordable technology (total hardware cost per system less than $4,000; these systems will be provided free to collaborating laboratories), (2) to automate data collection and real-time analyses employing specially designed software, (3) to only require a quiet space (used at night) in collaborating laboratories, (4) to not necessitate human subjects committee approvals at collaborating institutions (because the participants are hypothesized spirit participants), and (5) to enable international collaboration regardless of the investigator's personal beliefs about the hypothesis. The research design and methods meet a phrase popularized by Carl Sagan "Extraordinary claims require extraordinary evidence." The design minimizes false positives and false negatives. University affiliated investigators in established laboratories who regularly publish in peer reviewed journals, and are interested in collaborating in this RCT, are invited to contact the author. Brains from persons with Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI), exhibit high levels of oxidative damage, including that to phospholipids. One type of oxidative damage is lipid peroxidation, the most important index of which is protein-bound 4-hydroxy-2-trans-nonenal (HNE). This highly reactive alkenal changes the conformations and lowers the activities of brain proteins to which HNE is covalently bound. Evidence exists that suggests that lipid peroxidation is the first type of oxidative damage associated with amyloid β-peptide (Aβ), a 38-42 amino acid peptide that is highly neurotoxic and critical to the pathophysiology of AD. The Butterfield laboratory is one of, if not the, first research group to show that Aβ42 oligomers led to lipid peroxidation and to demonstrate this modification in brains of subjects with AD and MCI. The Mattson laboratory, particularly when Dr. Mattson was a faculty member at the University of Kentucky, also showed evidence for lipid peroxidation associated with Aβ peptides, mostly in in vitro systems.