Citations

Background Detection of small renal calculi has benefitted from recent advances in computed tomography (CT) scanner design. Information regarding observer performance when using state-of-the-art CT scanners for this application is needed. Purpose To assess observer performance and the impact of radiation dose for detection and size measurement of <4 mm renal stones using CT with integrated circuit detectors and iterative reconstruction. Material and Methods Twenty-nine <4 mm calcium oxalate stones were randomly placed in 20 porcine kidneys in an anthropomorphic phantom. Four radiologists used a workstation to record each calculus detection and size. JAFROC Figure of Merit (FOM), sensitivity, false positive detections, and calculus size were calculated. Results Mean calculus size was 2.2 ± 0.7 mm. The CTDI vol values corresponding to the automatic exposure control settings of 160, 80, 40, 25, and 10 Quality Reference mAs (QRM) were 15.2, 7.9, 4.2, 2.7, and 1.3 mGy, respectively. JAFROC FOM was ≥ 0.97 at ≥ 80 QRM, ≥ 0.89 at ≥ 25 QRM, and was inferior to routine dose (160 QRM) at 10 QRM (0.72, P < 0.05). Per-calculus sensitivity remained ≥ 85% for every reader at ≥ 25 QRM. Mean total false positive detections per reader were ≤ 3 at ≥ 80 QRM, but increased substantially for two readers ( ≥ 12) at ≤ 40 QRM. Measured calculus size significantly decreased at ≤ 25 QRM ( P ≤ 0.01). Conclusion Using low dose renal CT with iterative reconstruction and ≥ 25 QRM results in high sensitivity, but false positive detections increase for some readers at very low dose levels (≤ 40 QRM). At very low doses with iterative reconstruction, measured calculus size will artifactually decrease.

ABSTRACTSaturated fatty acids (SFA) and their toxic metabolites contribute to hepatocyte lipotoxicity in nonalcoholic steatohepatitis (NASH). We previously reported that hepatocytes, under lipotoxic stress, express the potent macrophage chemotactic ligand C‐X‐C motif chemokine 10 (CXCL10), and release CXCL10‐enriched extracellular vesicles (EV) by a mixed lineage kinase (MLK) 3‐dependent mechanism. In the current study, we sought to examine the signaling pathway responsible for CXCL10 induction during hepatocyte lipotoxicity. Here, we demonstrate a role for signal transducer and activator of transcription (STAT) 1 in regulating CXCL10 expression. Huh7 and HepG2 cells were treated with lysophosphatidylcholine (LPC), the toxic metabolite of the SFA palmitate. In LPC‐treated hepatocytes, CXCL10 induction is mediated by a mitogen activated protein kinase (MAPK) signaling cascade consisting of a relay kinase module of MLK3, MKK3/6, and p38. P38 in turn induces STAT1 Ser727 phosphorylation and CXCL10 upregulation in hepatocytes, which is reduced by genetic or pharmacological inhibition of this MAPK signaling cascade. The binding and activity of STAT1 at the CXCL10 gene promoter were identified by chromatin immunoprecipitation and luciferase gene expression assays. Promoter activation was attenuated by MLK3/STAT1 inhibition or by deletion of the consensus STAT1 binding sites within the CXCL10 promoter. In lipotoxic hepatocytes, MLK3 activates a MAPK signaling cascade, resulting in the activating phosphorylation of STAT1, and CXCL10 transcriptional upregulation. Hence, this kinase relay module and/or STAT1 inhibition may serve as a therapeutic target to reduce CXCL10 release, thereby attenuating NASH pathogenesis. J. Cell. Biochem. 118: 3249–3259, 2017. © 2017 Wiley Periodicals, Inc.

Abstract Despite significant advances in our understanding and management of patients with acute respiratory distress syndrome (ARDS), the morbidity and mortality from ARDS remains high. Given the limited number of effective treatments for established ARDS, the strategic focus of ARDS research has shifted toward identifying patients with or at high risk of ARDS early in the course of the underlying illness, when strategies to reduce the development and progression of ARDS and associated organ failures can be systematically evaluated. In this review, we summarize the rationale, current evidence, and future directions in ARDS prevention.

Abstract Rationale Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. Objectives To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. Methods Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. Measurements and Main Results The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34–83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. Conclusions Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Abstract Rationale The release of eosinophil granule proteins in the lungs of patients with asthma has been dogmatically linked with lung remodeling and airway hyperresponsiveness. However, the demonstrated inability of established mouse models to display the eosinophil degranulation occurring in human subjects has prevented a definitive in vivo test of this hypothesis. Objectives To demonstrate in vivo causative links between induced pulmonary histopathologies/lung dysfunction and eosinophil degranulation. Methods A transgenic mouse model of chronic T-helper cell type 2–driven inflammation overexpressing IL-5 from T cells and human eotaxin 2 in the lung (I5/hE2) was used to test the hypothesis that chronic histopathologies and the development of airway hyperresponsiveness occur as a consequence of extensive eosinophil degranulation in the lung parenchyma. Measurement and Main Results Studies targeting specific inflammatory pathways in I5/hE2 mice surprisingly showed that eosinophil-dependent immunoregulative events and not the release of individual secondary granule proteins are the central contributors to T-helper cell type 2–induced pulmonary remodeling and lung dysfunction. Specifically, our studies highlighted a significant role for eosinophil-dependent IL-13 expression. In contrast, extensive degranulation leading to the release of major basic protein-1 or eosinophil peroxidase was not causatively linked to many of the induced pulmonary histopathologies. However, these studies did define a previously unappreciated link between the release of eosinophil peroxidase (but not major basic protein-1) and observed levels of induced airway mucin. Conclusions These data suggest that improvements observed in patients with asthma responding to therapeutic strategies ablating eosinophils may occur as a consequence of targeting immunoregulatory mechanisms and not by simply eliminating the destructive activities of these purportedly end-stage effector cells.

Abstract Rationale Studies have shown the importance of simulation-based training on the outcomes of central venous catheter (CVC) insertion by trainees. Objectives To compare the performance of internal medicine trainees who underwent standardized simulation training of CVC insertion with that of internal medicine trainees who had traditional CVC training and were already deemed competent to perform the procedure during a proficiency evaluation using a training mannequin. Methods Trainees who perform CVC insertion were enrolled in the institutional Central Line Workshop, which includes both an online and an experiential simulation component. The training is followed by a certification station proficiency assessment. Residents and fellows previously certified competent to perform CVC placement without supervision completed the online module, but they could opt out of the experiential component and proceed directly to the evaluation. Results Forty-eight trainees participated in the study. Twenty-one (44%), 15 (31%), 6 (13%), 1 (2%), 2 (4%), and 3 (6%) were in postgraduate year 1 (PGY1), PGY2, PGY3, PGY4, PGY5, and PGY6, respectively. Twenty-nine completed the hands-on instruction, 28 (97%) of whom successfully passed the simulation-based assessment on their first attempt. Nineteen trainees previously credentialed to perform CVC placement without supervision opted out of the simulation-based experiential training. Of these, five (26%) failed in their first attempt (P = 0.02 vs. trainees who completed the simulation training). Conclusions Standardized simulation-based training can improve CVC insertion proficiency, even among trainees with previous experience sufficient to have been deemed competent in the procedure. Improved performance at simulation-based testing may translate to improved outcomes of CVC placement by trainees.

Abstract Rationale The implementation of team-based care models in residency programs is one method to improve patient and provider outpatient satisfaction. However, to our knowledge, this has not yet been studied in fellowship programs. Objectives We instituted a pilot project to test a team-based model of care in our pulmonary and critical care medicine (PCCM) fellows’ clinic by creating a new outpatient role called the “Fellow of the Day,” with the goal of reducing clinical disruption for the fellows, providing more educational value for medical students, and improving patient care. Methods Data were collected over a 4-month time period from electronic surveys from medical students, fellows, and supervising faculty. We also used timestamp data to determine fellows’ response times to patient messages. Results After implementation of the Fellow of the Day designation, (1) fellows were more engaged in teaching the medical student (P = 0.007); (2) fellows spent less of their personal time (P = 0.04) or time away from critically ill patients to focus on patient care–related messages (P = 0.04) and paperwork (P = 0.02); and (3) medical students had improved experience with more enjoyment (P = 0.03) and active engagement in clinic (P = 0.03). The Fellow of the Day role did not affect faculty workflow. Patients received responses to their postvisit messages in a more timely manner (P = 0.003). Conclusions The Fellow of the Day role was successfully implemented at our institution with multiple benefits, not only to fellows but also to patients, medical students, and supervising faculty. Our education committee has recommended continuation of the role in our fellowship program.