International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy.

INTRODUCTION: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria. METHODS: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion. RESULTS: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma. CONCLUSIONS: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.

An analysis of research biopsy core variability from over 5000 prospectively collected core samples.

Factors correlated with biopsy tissue adequacy and the prevalence of within-biopsy variability were evaluated. Totally, 1149 research biopsies were performed on 686 patients from which 5090 cores were assessed. Biopsy cores were reviewed for malignant percentage (estimated percentage of cells in the core that were malignant) and malignant area (estimated area occupied by malignant cells). Linear mixed models and generalized linear mixed models were used for the analysis. A total of 641 (55.8%) biopsies contained a core with <10% malignant percentage (inadequate core). The chance of an inadequate core was not influenced by core order, though the malignant area decreased with each consecutive core (p < 0.001). Younger age, bone biopsy location, appendiceal tumor pathology, and responding/stable disease prior to biopsy increased the odds of a biopsy containing zero adequate cores. Within-biopsy variability in core adequacy is prevalent and suggests the need for histological tumor quality assessment of each core in order to optimize translational analyses.

Distributed Learning Fractal Algorithm for Optimizing a Centralized Control Topology of Wireless Sensor Network Based on the Hilbert Curve L-System.

Wireless sensor networks (WSNs) consist of a large number of small devices or nodes, called micro controller units (MCUs) and located in homes and/or offices, to be operated through the internet from anywhere, making these devices smarter and more efficient. Quality of service routing is one of the critical challenges in WSNs, especially in surveillance systems. To improve the efficiency of the network, in this article we proposes a distributed learning fractal algorithm (DFLA) to design the control topology of a wireless sensor network (WSN), whose nodes are the MCUs distributed in a physical space and which are connected to share parameters of the sensors such as concentrations of C O 2 , humidity, temperature within the space or adjustment of the intensity of light inside and outside the home or office. For this, we start defining the production rules of the L-systems to generate the Hilbert fractal, since these rules facilitate the generation of this fractal, which is a fill-space curve. Then, we model the optimization of a centralized control topology of WSNs and proposed a DFLA to find the best two nodes where a device can find the highly reliable link between these nodes. Thus, we propose a software defined network (SDN) with strong mobility since it can be reconfigured depending on the amount of nodes, also we employ a target coverage because distributed learning fractal algorithm (DLFA) only consider reliable links among devices. Finally, through laboratory tests and computer simulations, we demonstrate the effectiveness of our approach by means of a fractal routing in WSNs, by using a large amount of WSNs devices (from 16 to 64 sensors) for real time monitoring of different parameters, in order to make efficient WSNs and its application in a forthcoming Smart City.

Severe Undifferentiated Vasoplegic Shock Refractory to Vasoactive Agents Treated with Methylene Blue.

Methylene blue is a phenothiazine-related heterocyclic aromatic molecule presently used in the treatment of methemoglobinemia. Recently, it has been implicated in the treatment of severe refractory vasoplegic shock caused by anaphylaxis, sepsis, or postcardiopulmonary bypass. We present a case of a 27-year-old male with profound vasoplegic shock of unknown etiology which was refractory to vasopressors who responded within hours to a single dose of methylene blue. Additionally, we review the evidence of methylene blue's role in the treatment of shock. This case illustrates a diagnostic approach and treatment options in the setting of undifferentiated vasodilatory shock and outlines a new and emerging role for methylene blue in this clinical setting.

Global quantitative assessment of the colorectal polyp burden in familial adenomatous polyposis by using a web-based tool.

BACKGROUND: Accurate measures of the total polyp burden in familial adenomatous polyposis (FAP) are lacking. Current assessment tools include polyp quantitation in limited-field photographs and qualitative total colorectal polyp burden by video. OBJECTIVE: To develop global quantitative tools of the FAP colorectal adenoma burden. DESIGN: A single-arm, phase II trial. PATIENTS: Twenty-seven patients with FAP. INTERVENTION: Treatment with celecoxib for 6 months, with before-treatment and after-treatment videos posted to an intranet with an interactive site for scoring. MAIN OUTCOME MEASUREMENTS: Global adenoma counts and sizes (grouped into categories: <2 mm, 2-4 mm, and >4 mm) were scored from videos by using a novel Web-based tool. Baseline and end-of-study adenoma burden results were summarized by using 5 models. Correlations between pairs of reviewers were analyzed for each model. RESULTS: Interobserver agreement was high for all 5 measures of polyp burden. Measures that used both polyp count and polyp size had better interobserver agreement than measures based only on polyp count. The measure in which polyp counts were weighted according to diameter, calculated as (1) × (no. of polyps <2 mm) + (3) × (no. of polyps 2-4 mm) + (5) × (no. of polyps >4 mm) had the highest interobserver agreement (Pearson r = 0.978 for two gastroenterologists, 0.786 and 0.846 for the surgeon vs each gastroenterologist). Treatment reduced the polyp burden by these measurements in 70% to 89% of patients (P < .001). LIMITATIONS: Phase II study. CONCLUSION: This novel, Web-based polyp scoring method provides a convenient and reproducible way to quantify the global colorectal adenoma burden in FAP patients and a framework for developing a clinical staging system for FAP.

[Four years of raw mortality in an intensive care unit]. / Cuatro años de mortalidad cruda en una Unidad de Cuidados Intensivos.

OBJECTIVE: To characterize magnitude and variability of raw mortality in a Mexican Intensive Care Unit (ICU). MATERIAL AND METHODS: Demographic and clinical data were analyzed in 1,746 patients discharged from the ICU of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. The data was obtained from an administrative database and covered four years (2003-2006). RESULTS: Overall ICU-mortality was 23% (410/1746) and was associated with two binary variables (higher mortality in weekend admissions and non-surgical cases) and three multicategorical variables (gradient of increasing mortality with increasing age, increasing diagnostic risk and increasing number of high-rish diagnoses). First biennium mortality was significantly higher than in the second biennium (29% us 19%). This higher mortality was not associated with the high risk categories of the five variables described above nor with other ICU-variables such as number of nurses and admission and discharge criteria. The only biennium difference was a higher number of physicians (specialists + residents) in the second biennium (16-20 versus 14-15 in the first). CONCLUSIONS: The four-year long-term ICU-mortality showed a significant decrease in the second biennium. Number of physicians was the only variable associated with the decreased mortality.