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Recent documents in eScholarship@UMMS
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Review of paratesticular pathology: findings on ultrasound and MRI

Mon, 05/15/2017 - 2:06pm

The paratesticular scrotal contents consist of the spermatic cord, epididymis, and fascia, which originate from the embryologic descent of the testis through the abdominal wall. Historically, the primary diagnostic modality has been high-resolution ultrasound. Magnetic resonance imaging (MRI) is an alternative imaging option. Both contrast MRI and diffusion weighted imaging can assist in differentiating between benign and malignant lesions. Unlike the testis which most disease processes are malignant, a wide spectrum of benign disease processes affects the paratesticular region either in isolation or as part of a contiguous disease process from adjacent organs. The familiarity with the epidemiology, pathogenesis, and imaging features can aid the radiologic diagnoses and guide appropriate clinical management. In this article, we review the ultrasound and MR characteristics of various paratesticular pathologies.

Correction of hysteretic respiratory motion in SPECT myocardial perfusion imaging: Simulation and patient studies

Mon, 05/15/2017 - 2:06pm

PURPOSE: Amplitude-based respiratory gating is known to capture the extent of respiratory motion (RM) accurately but results in residual motion in the presence of respiratory hysteresis. In our previous study, we proposed and developed a novel approach to account for respiratory hysteresis by applying the Bouc-Wen (BW) model of hysteresis to external surrogate signals of anterior/posterior motion of the abdomen and chest with respiration. In this work, using simulated and clinical SPECT myocardial perfusion imaging (MPI) studies, we investigate the effects of respiratory hysteresis and evaluate the benefit of correcting it using the proposed BW model in comparison with the abdomen signal typically employed clinically.

METHODS: The MRI navigator data acquired in free-breathing human volunteers were used in the specially modified 4D NCAT phantoms to allow simulating three types of respiratory patterns: monotonic, mild hysteresis, and strong hysteresis with normal myocardial uptake, and perfusion defects in the anterior, lateral, inferior, and septal locations of the mid-ventricular wall. Clinical scans were performed using a Tc-99m sestamibi MPI protocol while recording respiratory signals from thoracic and abdomen regions using a visual tracking system (VTS). The performance of the correction using the respiratory signals was assessed through polar map analysis in phantom and 10 clinical studies selected on the basis of having substantial RM.

RESULTS: In phantom studies, simulations illustrating normal myocardial uptake showed significant differences (P < 0.001) in the uniformity of the polar maps between the RM uncorrected and corrected. No significant differences were seen in the polar map uniformity across the RM corrections. Studies simulating perfusion defects showed significantly decreased errors (P < 0.001) in defect severity and extent for the RM corrected compared to the uncorrected. Only for the strong hysteretic pattern, there was a significant difference (P < 0.001) among the RM corrections. The errors in defect severity and extent for the RM correction using abdomen signal were significantly higher compared to that of the BW (severity = -4.0%, P < 0.001; extent = -65.4%, P < 0.01) and chest (severity = -4.1%, P < 0.001; extent = -52.5%, P < 0.01) signals. In clinical studies, the quantitative analysis of the polar maps demonstrated qualitative and quantitative but not statistically significant differences (P = 0.73) between the correction methods that used the BW signal and the abdominal signal.

CONCLUSIONS: This study shows that hysteresis in respiration affects the extent of residual motion left in the RM-binned data, which can impact wall uniformity and the visualization of defects. Thus, there appears to be the potential for improved accuracy in reconstruction in the presence of hysteretic RM with the BW model method providing a possible step in the direction of improvement.

Towards standardization of x-ray beam filters in digital mammography and digital breast tomosynthesis: Monte Carlo simulations and analytical modelling

Mon, 05/15/2017 - 2:05pm

In digital breast tomosynthesis and digital mammography, the x-ray beam filter material and thickness vary between systems. Replacing K-edge filters with Al was investigated with the intent to reduce exposure duration and to simplify system design. Tungsten target x-ray spectra were simulated with K-edge filters (50 microm Rh; 50 microm Ag) and Al filters of varying thickness. Monte Carlo simulations were conducted to quantify the x-ray scatter from various filters alone, scatter-to-primary ratio (SPR) with compressed breasts, and to determine the radiation dose to the breast. These data were used to analytically compute the signal-difference-to-noise ratio (SDNR) at unit (1 mGy) mean glandular dose (MGD) for W/Rh and W/Ag spectra. At SDNR matched between K-edge and Al filtered spectra, the reductions in exposure duration and MGD were quantified for three strategies: (i) fixed Al thickness and matched tube potential in kilovolts (kV); (ii) fixed Al thickness and varying the kV to match the half-value layer (HVL) between Al and K-edge filtered spectra; and, (iii) matched kV and varying the Al thickness to match the HVL between Al and K-edge filtered spectra. Monte Carlo simulations indicate that the SPR with and without the breast were not different between Al and K-edge filters. Modelling for fixed Al thickness (700 microm) and kV matched to K-edge filtered spectra, identical SDNR was achieved with 37-57% reduction in exposure duration and with 2-20% reduction in MGD, depending on breast thickness. Modelling for fixed Al thickness (700 microm) and HVL matched by increasing the kV over (0,4) range, identical SDNR was achieved with 62-65% decrease in exposure duration and with 2-24% reduction in MGD, depending on breast thickness. For kV and HVL matched to K-edge filtered spectra by varying Al filter thickness over (700, 880) microm range, identical SDNR was achieved with 23-56% reduction in exposure duration and 2-20% reduction in MGD, depending on breast thickness. These simulations indicate that increased fluence with Al filter of fixed or variable thickness substantially decreases exposure duration while providing for similar image quality with moderate reduction in MGD.

Reduced Patient Radiation Exposure during Neurodiagnostic and Interventional X-Ray Angiography with a New Imaging Platform

Mon, 05/15/2017 - 2:05pm

BACKGROUND AND PURPOSE: Advancements in medical device and imaging technology as well as accruing clinical evidence have accelerated the growth of the endovascular treatment of cerebrovascular diseases. However, the augmented role of these procedures raises concerns about the radiation dose to patients and operators. We evaluated patient doses from an x-ray imaging platform with radiation dose-reduction technology, which combined image noise reduction, motion correction, and contrast-dependent temporal averaging with optimized x-ray exposure settings.

MATERIALS AND METHODS: In this single-center, retrospective study, cumulative dose-area product inclusive of fluoroscopy, angiography, and 3D acquisitions for all neurovascular procedures performed during a 2-year period on the dose-reduction platform were compared with a reference platform. Key study features were the following: The neurointerventional radiologist could select the targeted dose reduction for each patient with the dose-reduction platform, and the statistical analyses included patient characteristics and the neurointerventional radiologist as covariates. The analyzed outcome measures were cumulative dose (kerma)-area product, fluoroscopy duration, and administered contrast volume.

RESULTS: A total of 1238 neurointerventional cases were included, of which 914 and 324 were performed on the reference and dose-reduction platforms, respectively. Over all diagnostic and neurointerventional procedures, the cumulative dose-area product was significantly reduced by 53.2% (mean reduction, 160.3 Gy x cm2; P < .0001), fluoroscopy duration was marginally significantly increased (mean increase, 5.2 minutes; P = .0491), and contrast volume was nonsignificantly increased (mean increase, 15.3 mL; P = .1616) with the dose-reduction platform.

CONCLUSIONS: A significant reduction in patient radiation dose is achievable during neurovascular procedures by using dose-reduction technology with a minimal impact on workflow.

Prioritizing the Protocol: Improving the Process of Scheduling Imaging Examinations in a Radiology Department With Partially Integrated IT Systems

Mon, 05/15/2017 - 2:05pm

The final product of a diagnostic imaging study is the completed image set on the radiologists’ PACS and radiology information system worklist. Before the case is completed, multiple prior steps are required. The clinical provider must order the imaging study, the radiologist must complete the protocol, the administration must obtain insurance preauthorization, and the schedulers must book the imaging examination. Improving the process of scheduling these examinations has become a priority at our institution.

The Relevance of Ultrasound Imaging of Suspicious Axillary Lymph Nodes and Fine-needle Aspiration Biopsy in the Post-ACOSOG Z11 Era in Early Breast Cancer

Mon, 05/15/2017 - 2:05pm

RATIONALE AND OBJECTIVES: Evaluation of nodal involvement in early-stage breast cancers (T1 or T2) changed following the Z11 trial; however, not all patients meet the Z11 inclusion criteria. Hence, the relevance of ultrasound imaging of the axilla and fine-needle aspiration biopsy (FNA) in early-stage breast cancers was investigated.

MATERIALS AND METHODS: In this single-center, retrospective study, 758 subjects had pathology-verified breast cancer diagnosis over a 3-year period, of which 128 subjects with T1 or T2 breast tumors had abnormal axillary lymph nodes on ultrasound, had FNA, and proceeded to axillary surgery. Ultrasound images were reviewed and analyzed using multivariable logistic regression to identify the features predictive of positive FNA. Accuracy of FNA was quantified as the area under the receiver operating characteristic curve with axillary surgery as reference standard.

RESULTS: Of 128 subjects, 61 were positive on FNA and 65 were positive on axillary surgery. Sensitivity, specificity, positive predictive value, and negative predictive value of FNA were 52 of 65 (80%), 54 of 63 (85.7%), 52 of 61(85.2%), and 54 of 67 (80.5%), respectively. After adjusting for neoadjuvant chemotherapy between FNA and surgery, a positive FNA was associated with higher likelihood for positive axillary surgery (odds ratio: 22.7; 95% confidence interval [CI]: 7.2-71.3, P < .0001), and the accuracy of FNA was 0.801 (95% CI: 0.727-0.876). Among ultrasound imaging features, cortical thickness and abnormal hilum were predictive (P < .017) of positive FNA with accuracy of 0.817 (95% CI: 0.741-0.893).

CONCLUSIONS: Ultrasound imaging and FNA can play an important role in the management of early breast cancers even in the post-Z11 era. Higher weightage can be accorded to cortical thickness and hilum during ultrasound evaluation.

Evaluation of Long-Term Cryostorage of Brain Tissue Sections for Quantitative Histochemistry

Mon, 05/15/2017 - 2:05pm

Storage of tissue sections for long periods allows multiple samples, acquired over months or years, to be processed together, in the same reagents, for quantitative histochemical studies. Protocols for freezer storage of free-floating frozen sections using sucrose with different additives have been reported and assert that storage has no effect on histochemistry, but no quantitative support has been provided. The present study analyzed the efficacy of long-term storage of brain tissue sections at -80C in buffered 15% glycerol. To determine whether histochemical reactivity is affected, we analyzed 11 datasets from 80 monkey brains that had sections stored for up to 10 years. For processing, sections from multiple cases were removed from storage, thawed, and batch-processed at the same time for different histochemical measures, including IHC for neuronal nuclear antigen, parvalbumin, orexin-A, doublecortin, bromodeoxyuridine, the pro-form of brain-derived neurotrophic factor, and damaged myelin basic protein as well as a histochemical assay for hyaluronic acid. Results were quantified using stereology, optical densitometry, fluorescence intensity, or percent area stained. Multiple regression analyses controlling for age and sex demonstrated the general stability of these antigens for up to a decade when stored in 15% glycerol at -80C.

Emergency Radiology Practice Patterns: Shifts, Schedules, and Job Satisfaction

Mon, 05/15/2017 - 2:05pm

PURPOSE: To assess the practice environment of emergency radiologists with a focus on schedule, job satisfaction, and self-perception of health, wellness, and diagnostic accuracy. METHODS: A survey drawing from prior radiology and health care shift-work literature was distributed via e-mail to national societies, teleradiology groups, and private practices. The survey remained open for 4 weeks in 2016, with one reminder. Data were analyzed using hypothesis testing and logistic regression modeling. RESULTS: Response rate was 29.6% (327/1106); 69.1% of respondents (n = 226) were greater than 40 years old, 73% (n = 240) were male, and 87% (n = 284) practiced full time. With regard to annual overnight shifts (NS): 36% (n = 118) did none, 24.9% (n = 81) did 182 or more, and 15.6% (n = 51) did 119. There was a significant association between average NS worked per year and both perceived negative health effects (P < .01) and negative impact on memory (P < .01). There was an inverse association between overall job enjoyment and number of annual NS (P < .05). The odds of agreeing to the statement "I enjoy my job" for radiologists who work no NS is 2.21 times greater than for radiologists who work at least 119 NS, when shift length is held constant. Radiologists with 11+ years of experience who work no NS or 1 to 100 NS annually have lower odds of feeling overwhelmed when compared with those working the same number of NS with <10 years' experience. CONCLUSION: There is significant variation in emergency radiology practice patterns. Annual NS burden is associated with lower job satisfaction and negative health self-perception.

Surpass Flow Diverter for Treatment of Posterior Circulation Aneurysms

Mon, 05/15/2017 - 2:05pm

BACKGROUND AND PURPOSE: Flow diverters for the treatment of posterior circulation aneurysms remain controversial. We aimed to identify factors contributing to outcome measures in patients treated with the Surpass flow diverter for aneurysms in this location.

MATERIALS AND METHODS: We conducted an observational study of 53 patients who underwent flow-diverter treatment for posterior circulation aneurysms at 15 centers. Key outcome measures were mortality, complete aneurysm occlusion, and modified Rankin Scale score at follow-up.

RESULTS: At follow-up (median, 11.3 months; interquartile range, 5.9-12.7 months), 9 patients had died, resulting in an all-cause mortality rate of 17.3% (95% CI, 7%-27.6%); 7 deaths (14%) were directly related to the procedure and none occurred in patients with a baseline mRS score of zero. After adjusting for covariates, a baseline mRS of 3-5 was more significantly (P = .003) associated with a higher hazard ratio for death than a baseline mRS of 0-2 (hazard ratio, 17.11; 95% CI, 2.69-109.02). After adjusting for follow-up duration, a 1-point increase in the baseline mRS was significantly (P < .001) associated with higher values of mRS at follow-up (odds ratio, 2.93; 95% CI, 1.79-4.79). Follow-up angiography in 44 patients (median, 11.3 months; interquartile range, 5.9-12.7 months) showed complete aneurysm occlusion in 29 (66%; 95% CI, 50.1%-79.5%).

CONCLUSIONS: Clinical results of flow-diverter treatment of posterior circulation aneurysms depend very much on patient selection. In this study, poorer outcomes were related to the treatment of aneurysms in patients with higher baseline mRS scores. Angiographic results showed a high occlusion rate for this subset of complex aneurysms.

Revisiting the indirect signs of a temporal bone fracture: air, air, everywhere

Mon, 05/15/2017 - 2:05pm

BACKGROUND AND PURPOSE: The standard head CT protocol makes detection of a temporal bone fracture difficult. The purposes of our study are to revisit the finding of air in various locations around the temporal bone as an indirect sign of fracture and determine if findings could predict fracture pattern.

MATERIALS AND METHODS: We searched the radiology reports for the keyword "temporal bone fracture." We recorded the presence of air in multiple locations around the temporal bone and pneumocephalus, opacification of the mastoid air cells or the middle ear cavity, and dominant fracture pattern. Statistical analyses were performed using statistical software.

RESULTS: A total of 135 patients (mean age 40 +/- 20.1 years, 101 male, 34 female, range 1-91) had 152 fractures. At least one indirect finding was present in 143 (94.1%) fractures. Air was present adjacent to the styloid process in 94 (61.8%), in the temporomandibular joint in 80 (52.6%), adjacent to the mastoid process in 57 (37.5%), and along the adjacent dural venous sinus in 33 (21.7%) fractures. Mastoid opacification was present in 139 (91.4%) fractures. Opacification of the middle ear cavity was present in 121 (79.6%) fractures. A complex fracture significantly and positively correlated with pneumocephalus.

CONCLUSION: In the setting of trauma, air around the temporal bone and opacification of the mastoid air cells or middle ear cavity should prompt consideration of a temporal bone fracture even if the fracture line is not visible. The presence of pneumocephalus predicts a higher chance of complex fracture pattern.

Education Mitigates the Relationship of Stress and Mental Disorders Among Rural Indian Women

Mon, 05/15/2017 - 10:43am

BACKGROUND: Common mental disorders (CMD) are a constellation of mental health conditions that include depression, anxiety, and other related nonpsychotic affective disorders. Qualitative explanatory models of mental health among reproductive-aged women in India reveal that distress is strongly associated with CMD. The relationship of perceived stress and CMD might be attenuated or exacerbated based on an individual's sociodemographic characteristics.

OBJECTIVES: To screen for Common Mental Disorders (CMD) among reproductive-aged women from rural western India and explore how the relationship between perceived stress and CMD screening status varies by sociodemographic characteristics.

METHODS: Cross-sectional survey of 700 women from rural Gujarat, India. CMD screening status was assessed using Self-Reported Questionnaire 20 (SRQ-20). Factors associated with CMD screening status were evaluated using multivariable logistic regression. Effect modification for the relationship of perceived stress and CMD screening status was assessed using interaction terms and interpreted in terms of predicted probabilities.

FINDINGS: The analytic cohort included 663 women, with roughly 1 in 4 screening positive for CMD (157, 23.7%). Poor income, low education, food insecurity, and recurrent thoughts after traumatic events were associated with increased risk of positive CMD screen. Perceived stress was closely associated with CMD screening status. Higher education attenuated the relationship between high levels of stress and CMD screening status (82.3%, 88.8%, 32.9%; P value for trend: 0.03). Increasing income and age attenuated the link between moderate stress and CMD.

CONCLUSIONS: Our findings suggest a high burden of possible CMD among reproductive-aged women from rural western India. Higher education might mitigate the association between elevated stress and CMD. Future efforts to improve mental health in rural India should focus on preventing CMD by enhancing rural women's self-efficacy and problem-solving capabilities to overcome challenging life events and stressors, thereby reducing the risk of CMD.

Are There Two Types of Suicidal Ideation Among Women in Rural India

Mon, 05/15/2017 - 10:43am

We present descriptive findings from a cross-sectional survey conducted in rural Gujarat, India, that expands the discussion on suicide among young women and poses the question: Are there two types of suicidal ideation among women in rural India?

Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic

Mon, 05/15/2017 - 10:43am

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013-2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.

Defining the 5 and 3 landscape of the Drosophila transcriptome with Exo-seq and RNaseH-seq

Mon, 05/15/2017 - 10:43am

Cells regulate biological responses in part through changes in transcription start sites (TSS) or cleavage and polyadenylation sites (PAS). To fully understand gene regulatory networks, it is therefore critical to accurately annotate cell type-specific TSS and PAS. Here we present a simple and straightforward approach for genome-wide annotation of 5- and 3-RNA ends. Our approach reliably discerns bona fide PAS from false PAS that arise due to internal poly(A) tracts, a common problem with current PAS annotation methods. We applied our methodology to study the impact of temperature on the Drosophila melanogaster head transcriptome. We found hundreds of previously unidentified TSS and PAS which revealed two interesting phenomena: first, genes with multiple PASs tend to harbor a motif near the most proximal PAS, which likely represents a new cleavage and polyadenylation signal. Second, motif analysis of promoters of genes affected by temperature suggested that boundary element association factor of 32 kDa (BEAF-32) and DREF mediates a transcriptional program at warm temperatures, a result we validated in a fly line where beaf-32 is downregulated. These results demonstrate the utility of a high-throughput platform for complete experimental and computational analysis of mRNA-ends to improve gene annotation.

Pain and Pharmacologic Pain Management in Long-Stay Nursing Home Residents

Mon, 05/15/2017 - 10:43am

Prior studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set (MDS) 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after these important initiatives of: 1) prevalence and correlates of persistent pain; and 2) prevalence and correlates of untreated or undertreated persistent pain. We identified 1,387,405 long-stay residents in United States NHs between 2011-2012 with 2 MDS assessments 90 days apart. Pain was categorized as persistent (pain on both assessments), intermittent (pain on either assessment), or none. Pharmacologic pain management was classified as untreated pain (no scheduled or as needed medications received) or potentially undertreated (no scheduled received). Modified Poisson models adjusting for resident clustering within NHs provided adjusted prevalence ratios estimates (APR) and 95% confidence intervals (CI).The prevalence of persistent and intermittent pain was 19.5% and 19.2% respectively but varied substantially by age, gender, race/ethnicity, cognitive impairment, and cancer. Of residents in persistent pain, 6.4% and 32.0% were untreated or undertreated. Racial/ethnic minorities (non-Hispanic blacks vs. whites, APR=1.19, 95% CI: 1.13-1.25) and severely cognitively impaired residents (severe vs. no/mild APR=1.51, 95% CI: 1.44-1.57) had an increased prevalence of untreated and undertreated pain. One in five NH residents has persistent pain. Although this estimate is greatly improved, many residents may be undertreated. The disturbing disparities in untreated and undertreated pain need to be addressed.

Statin use and risk of multiple myeloma: An analysis from the Cancer Research Network

Mon, 05/15/2017 - 10:43am

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged >/=40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N=2532). For each case, 5 controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (>/=6 cumulative months) and risk of multiple, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

Show Back: Developing and Testing of a Simulation-Based Assessment Method for Identifying Problems in Self-Management of Medications in Older Adults

Mon, 05/15/2017 - 10:43am

In this study, we developed and tested a comprehensive simulation that assesses older adult medication self-management proficiency.

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Mon, 05/15/2017 - 10:42am

BACKGROUND: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

OBJECTIVE: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

METHODS: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups.

RESULTS: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3.

LIMITATIONS: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response.

CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

Differential Expression of Hedgehog and Snail in Cutaneous Fibrosing Disorders: Implications for Targeted Inhibition

Wed, 05/10/2017 - 9:24am

OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition.

METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 beta (GSK3-beta), beta-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray.

RESULTS: Ihh, but not Shh, was detected in a significantly larger proportion of cells for all case types. Ptch, GSK3-beta, and beta-catenin showed a gradient of expression: highest in NSF and keloid; moderate in normal skin, scar, and Hscar; and lowest in scleroderma. Snail expression was binary: low in normal skin but high in all fibrosing conditions studied.

CONCLUSIONS: Differential overexpression of Hedgehog and Snail in cutaneous fibrosing disorders demonstrates a role for targeted inhibition. Ptch, GSK3-beta, and beta-catenin can help differentiate scleroderma from NSF in histologically subtle cases. Differences in expression between keloid and hypertrophic scar support the concept that they are pathophysiologically distinct disorders. Our findings implicate Snail as a target for the prevention of fibrogenesis or fibrosis progression and may offer a means to assess response to therapy.

Does adding clinical data to administrative data improve agreement among hospital quality measures

Wed, 05/10/2017 - 9:24am

BACKGROUND: Hospital performance measures based on patient mortality and readmission have indicated modest rates of agreement. We examined if combining clinical data on laboratory tests and vital signs with administrative data leads to improved agreement with each other, and with other measures of hospital performance in the nation's largest integrated health care system.

METHODS: We used patient-level administrative and clinical data, and hospital-level data on quality indicators, for 2007-2010 from the Veterans Health Administration (VA). For patients admitted for acute myocardial infarction (AMI), heart failure (HF) and pneumonia we examined changes in hospital performance on 30-d mortality and 30-d readmission rates as a result of adding clinical data to administrative data. We evaluated whether this enhancement yielded improved measures of hospital quality, based on concordance with other hospital quality indicators.

RESULTS: For 30-d mortality, data enhancement improved model performance, and significantly changed hospital performance profiles; for 30-d readmission, the impact was modest. Concordance between enhanced measures of both outcomes, and with other hospital quality measures - including Joint Commission process measures, VA Surgical Quality Improvement Program (VASQIP) mortality and morbidity, and case volume - remained poor.

CONCLUSIONS: Adding laboratory tests and vital signs to measure hospital performance on mortality and readmission did not improve the poor rates of agreement across hospital quality indicators in the VA.

INTERPRETATION: Efforts to improve risk adjustment models should continue; however, evidence of validation should precede their use as reliable measures of quality.