Citations

Abstract Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age‐related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age‐related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.

AbstractObjectivesPatient throughput is an increasingly important cause of emergency department (ED) crowding. The authors previously reported shorter patient length of stay (LOS) when adding a triage liaison provider, which required additional personnel. Here, the objective was to evaluate the effect of moving a fast‐track provider to the triage liaison role.MethodsThis was a prospective observational before‐and‐after study design with predefined outcomes measures. A “standard staffing” situation (where an advanced practice provider staffed treatment rooms in the fast track) was compared with an advanced practice provider performing the triage liaison staffing role, with no additional staff. Eleven intervention (“triage liaison staffing”) days were compared with 11 matched control (“standard staffing”) days immediately preceding the intervention. Total LOS was measured for all adult Emergency Severity Index (ESI) 3, 4, and 5 patients (excluding behavioral health patients), and results were compared using Wilcoxon rank‐sum and chi‐square tests.ResultsA total of 681 patients registered on control days and 599 on intervention days. There was no significant difference in total patient LOS: median = 273 minutes, interquartile range (IQR) 176 to 384 minutes on intervention days versus median = 253 minutes, IQR = 175 to 365 minutes on control days (p = 0.20). There was no difference in left‐without‐being‐seen (LWBS) rates (n = 48, 7% on control days vs. n = 35, 6% on intervention days; p=0.38). Secondary analysis of only ESI 3 patients showed no difference in total LOS between periods (median = 284 minutes, IQR = 194 to 396 minutes on intervention days vs. median = 290 minutes, IQR = 217 to 397 minutes on control days; p = 0.22). There was, however, significantly greater total LOS for ESI 4 and 5 patients during the intervention period (median = 238 minutes, IQR = 124 to 350 minutes on intervention days vs. median = 192 minutes, IQR = 124 to 256 minutes on control days; p = 0.011).ConclusionsThe previously reported benefits on patient LOS and LWBS rates after adding a triage liaison (resource additive) were lost when that provider was moved from fast track to the triage role (resource neutral). While the triage liaison provider role may be a way to improve ED throughput when additional resources are available, as evidenced by our prior study, the triage liaison model itself does not appear to replace the staffing of treatment rooms, as evidenced by this study.

AbstractThe development of adenocarcinoma of the lung is believed to proceed from in situ disease (adenocarcinoma in situ, AIS) to minimally invasive disease with prominent lepidic growth (minimally invasive adenocarcinoma, MIA), then to fully invasive adenocarcinoma (AD), but direct evidence for this model has been lacking. Because some lung adenocarcinomas show prominent lepidic growth (AD-L), we designed a study to address the lineage relationship between the lepidic (noninvasive) component (L) and the adjacent nonlepidic growth component representing invasive disease within individual tumors. Lineage relationships were evaluated by next-generation DNA sequencing to define large genomic rearrangements in microdissected tissue specimens collected by laser capture. We found a strong lineage relationship between the majority of adjacent lepidic and invasive components, supporting a putative AIS–AD transition. Notably, many rearrangements were detected in the less aggressive lepidic component, although the invasive component exhibited an overall higher rate of genomic rearrangement. Furthermore, a significant number of genomic rearrangements were present in histologically normal lung adjacent to tumor, but not in host germline DNA, suggesting field defects restricted to zonal regions near a tumor. Our results offer a perspective on the genetic pathogenesis underlying adenocarcinoma development and its clinical management. Cancer Res; 74(11); 3157–67. ©2014 AACR.

Transthoracic fine needle aspiration (TFNA)/core needle biopsy (CNB) under computed tomography (CT) guidance has proved useful in the assessment of pulmonary nodules. We sought to determine the TFNA false‐negative (FN) rate at our institution and identify potential causes of FN diagnoses. Medical records were reviewed from 1,043 consecutive patients who underwent CT‐guided TFNA with or without CNB of lung nodules over a 5‐year time period (2003–2007). Thirty‐seven FN cases of “negative” TFNA/CNB with malignant outcome were identified with 36 cases available for review, of which 35 had a corresponding CNB. Cases were reviewed independently (blinded to original diagnosis) by three pathologists with 15 age‐ and sex‐matched positive and negative controls. Diagnosis (i.e., nondiagnostic, negative or positive for malignancy, atypical or suspicious) and qualitative assessments were recorded. Consensus diagnosis was suspicious or positive in 10 (28%) of 36 TFNA cases and suspicious in 1 (3%) of 35 CNB cases, indicating potential interpretive errors. Of the 11 interpretive errors (including both suspicious and positive cases), 8 were adenocarcinomas, 1 squamous cell carcinoma, 1 metastatic renal cell carcinoma, and 1 lymphoma. The remaining 25 FN cases (69.4%) were considered sampling errors and consisted of 7 adenocarcinomas, 3 nonsmall cell carcinomas, 3 lymphomas, 2 squamous cell carcinomas, and 2 renal cell carcinomas. Interpretive and sampling error cases were more likely to abut the pleura, while histopathologically, they tended to be necrotic and air‐dried. The overall FN rate in this patient cohort is 3.5% (1.1% interpretive and 2.4% sampling errors). Diagn. Cytopathol. 2014;42:1063–1068;. © 2014 Wiley Periodicals, Inc.

Abstract Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic alterations in KRAS with a fostering microenvironment shaped by immune cell influx and fibrotic changes; identification of the earliest tumorigenic molecular mediators evokes the proverbial chicken and egg problem. Matrix metalloproteinases (MMP) are key drivers of tumor progression that originate primarily from stromal cells activated by the developing tumor. Here, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are expressed in PDA cells, that the expression levels of the two markers are highly correlated, and that the subcellular distribution of Rac1b in PDA is significantly associated with patient outcome. Using transgenic mouse models, coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates metaplasia and immune cell infiltration, priming the stromal microenvironment for early tumor development. Finally, exposure of cultured pancreatic cancer cells to recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness, and activation of tumorigenic transcriptional profiles. Implications: MMP3 acts as a coconspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and progression, both through Rac1b-mediated phenotypic control of pancreatic cancer cells themselves, and by giving rise to the tumorigenic microenvironment; these findings also point to inhibition of this pathway as a potential therapeutic strategy for pancreatic cancer. Mol Cancer Res; 12(10); 1430–9. ©2014 AACR.