Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke.

BACKGROUND AND PURPOSE: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. METHODS: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05. RESULTS: Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. CONCLUSIONS: Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients.

A Comparative Study of Two Topical Treatments for Photoaging of the Hands.

BACKGROUND: Multiple effective treatments exist for correction of skin photoaging. Topical L-ascorbic acid (Vitamin C) is a well-known anti-oxidant and topical human platelet extract (HPE), a novel off-the-shelf cosmetic ingredient has shown positive results in recent clinical studies. HPE is a leukocyte-depleted allogeneic product derived from U.S.-sourced, pooled, apheresed platelets produced with consistent batch quality, purity, and effect. AIMS: The authors sought to characterize the effect of topical HPE (plated ) Intense Serum (Rion Aesthetics, Rochester, MN) compared to vitamin C (C E Ferulic® with 15% L-Ascorbic Acid, SkinCeuticals, L'Oréal, Paris) in skin rejuvenation of dorsal hands after 12 to 26-weeks twice daily use. METHODS: This prospective, longitudinal study sought to compare the effectiveness of two known treatments for skin rejuvenation. Evaluations at baseline, 6, 12, and 26 weeks included photo documentation to assess common skin concerns related to aging. RESULTS: For age-related skin appearance on the dorsal hands, topical HPE was non-inferior to topical vitamin C for improvement in brown spot fractional area, wrinkle fractional area, and improvement in luminosity at 12 weeks after twice-daily topical use. CONCLUSIONS: HPE performed as well as vitamin C to rejuvenate the skin on the dorsal hands after 12 to 26 weeks of twice daily topical use. Both topical serums may yield similar or superior results than invasive procedures, such as intense pulsed light (IPL), in reducing brown spots on the dorsal hands. These topical products work equally well in both sexes. Skin improvements lasted through 6 months.

RAPID aneurysm accurately measures aneurysm size on CT angiography compared to three-dimensional digital subtraction angiography.

BACKGROUND: Cerebral aneurysms are often identified and characterized on non-invasive CT Angiography (CTA) images, but digital subtraction angiography (DSA) is the gold standard for aneurysm evaluation. OBJECTIVE: We compared cerebral aneurysm size measurements as measured from CTA processed by a semi-automated artificial intelligence software program (RAPID Aneurysm) and three-dimensional rotational DSA (3D-DSA). METHODS: We performed a retrospective cohort study of consecutive patients with a cerebral aneurysm who underwent CTA and DSA with 3D reformations. CTA images were processed by RAPID Aneurysm to determine aneurysm height, width, and neck width. The reference standard was aneurysm measurements on 3D-DSA as measured by two neurointerventionalists. Both readers were blinded to RAPID Aneurysm measurements. Correlation and bias between these measurements were determined. RESULTS: Results from 50 patients with 50 aneurysms were compared. 32 patients (64%) were female. Median age was 65 (IQR: 56.25-71.75). 37 patients (74%) presented with ruptured aneurysms. The aneurysms represented a range of aneurysm sizes (1.9-33.3 mm; IQR 3.6-7.2 mm). RAPID Aneurysm size measurements showed excellent correlation and low bias (correlation, mean difference) when compared to the reference standard for aneurysm height (0.98, -0.9 mm), width (0.98, 0.1 mm), and neck width (0.94, 1.1 mm). The inter-reader comparison between the two neurointerventionalists was similarly excellent for aneurysm height (0.97, -0.4 mm), width (0.98, -0.2 mm), and neck width (0.89, 0.8 mm). CONCLUSION: RAPID Aneurysm measurement of cerebral aneurysm height, width, and neck width on CTA is strongly correlated to expert neurointerventionalist measurements on 3D-DSA.

Effect of Topical Platelet Extract Daily Serum as a Cosmetic Product to Reduce Facial Redness.

Objective: The primary objective of this pilot study was to demonstrate the benefits of topical human platelet extract (plated)™ serum for the improvement of persistent facial redness. Methods: This single-center, open-label pilot study evaluated six subjects using (plated)™ serum containing human platelet extract (HPE) with Renewosome™ technology twice daily for six weeks. The primary efficacy endpoint was a reduction in the Clinical Erythema Assessment (CEA) grade, and a reduction in Patient Subjective Assessment grade at six weeks. Secondary endpoints included an improvement in quality of life related to facial redness, and a reduction in redness by Mexameter™ spectrometry measurement. Safety data included monitoring for adverse events. Results: Topical HPE serum demonstrated a statistically significant improvement in facial redness at Week 9 when averaging the Mexameter™ spectrometry results across nine regions of the face (p=0.0052). The primary and secondary endpoints were achieved. CEA grade at Week 6 demonstrated that all subjects improved by at least one grade, while one subject improved by two grades. One patient reported dryness. No other adverse effects were observed. Limitations: Study limitations included a small sample size and lack of darker skin types (Fitzpatrick IV-VI). Conclusion: This study demonstrates that topical HPE with Renewosome™ technology provides statistically significant reduction in facial redness and is safe and well-tolerated.

Safety and efficacy of human platelet extract in skin recovery after fractional CO2 laser resurfacing of the face: A randomized, controlled, evaluator-blinded pilot study.

BACKGROUND: Fractional carbon dioxide (CO2 ) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising. AIMS: The primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO2 ablative laser resurfacing treatment to the entire face versus standard of care. METHODS: In a single-center, randomized, evaluator-blinded pilot study, a total of 18 subjects were randomized into two groups, CO2 facial resurfacing followed by post-procedural standard of care (Stratacel silicone gel) or CO2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum. RESULTS: CALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively). CONCLUSIONS: This study demonstrates that Renewosome™ technology provides statistically significant post-laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated.

Excellent Recanalization and Small Core Volumes Are Associated With Favorable AM-PAC Score in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion.

Objective: To assess pretreatment and interventional parameters as predictors of favorable Activity Measure for Post-Acute Care (AM-PAC) scores for optimal discharge planning. Design: In this prospectively collected, retrospectively reviewed multicenter study from 9/1/2017 to 9/22/2022, patients were dichotomized into favorable and unfavorable AM-PAC. Multivariate logistic regression and receiver operator characteristics analyses were performed for the identified significant variables. A P value of ≤.05 was significant. Setting: Hospitalized care. Participants: In total, 229 patients (mean ±SD 70.65 ±15.2 [55.9% women]) met our inclusion criteria. Inclusion criteria were (a) computed tomography (CT) angiography confirmed LVO from 9/1/2017 to 9/22/2022; (b) diagnostic CT perfusion; and (c) available AM-PAC scores. Interventions: None. Main Outcome Measures: Favorable AM-PAC, defined as a daily activity score ≥19 and basic mobility score of ≥17. Results: Patients with favorable AM-PAC were younger (61.3 vs 70.7, P<.001), had lower admission glucose (mean, 124 vs 136, P=.042), lower blood urea nitrogen (mean, 15.59 vs 19.11, P<.001), and lower admission National Institutes of Health Stroke Scale (NIHSS) (mean, 10.58 vs 16.15, P<.001). No differences in sex were noted. Multivariate regression analyses revealed age, admission NIHSS, relative cerebral blood flow (rCBF) <30% volume, and modified thrombolysis in cerebral infarction (mTICI) score to be independent predictors of favorable AM-PAC (P<.047 for all predictors). The combined model revealed an area under the curve (AUC) of 0.83 (IQR 0.75-0.86). Conclusion: Excellent recanalization, smaller core volumes, younger age, and lower stroke severity independently predict favorable outcomes as measured by AM-PAC.

RAPID Aneurysm: Artificial intelligence for unruptured cerebral aneurysm detection on CT angiography.

OBJECTIVES: Cerebral aneurysms may result in significant morbidity and mortality. Identification of these aneurysms on CT Angiography (CTA) studies is critical to guide patient treatment. Artificial intelligence platforms to assist with automated aneurysm detection are of high interest. We determined the performance of a semi-automated artificial intelligence software program (RAPID Aneurysm) for the detection of cerebral aneurysms. MATERIALS AND METHODS: RAPID Aneurysm was used to detect retrospectively the presence of cerebral aneurysms in CTA studies performed between January 2019 and December 2020. The gold standard was aneurysm presence and location as determined by the consensus of three expert neuroradiologists. Aneurysm detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID Aneurysm were determined. RESULTS: 51 patients (mean age, 56±15; 24 women [47.1%]) with a single CTA were included. A total of 60 aneurysms were identified. RAPID Aneurysm had a sensitivity of 0.950 (95% CI: 0.863-0.983), specificity of 1.000 (95% CI: 0.996-1.000), a positive predictive value (PPV) of 1.000 (95% CI: 0.937-1.000), a negative predictive value (NPV) of 0.997 (95% CI: 0.991-0.999), and an accuracy of 0.997 (95% CI: 0.991-0.999) for cerebral aneurysm detection. CONCLUSIONS: RAPID Aneurysm is highly accurate for the detection of cerebral aneurysms on CTA.

Hereditary cancer risk assessment and genetic testing in the community urology practice setting.

OBJECTIVES: To evaluate the feasibility of integrating a hereditary cancer risk assessment (HCRA) process in the community urology practice setting for patients with prostate cancer (PCa). METHODS: In this prospective intervention, an HCRA process was implemented across six different community urology clinics between May 2019 and April 2020. The intervention included a process integration during which the workflow at each site was refined, a post-integration period during which HCRA was conducted in all patients with PCa, and a follow-up period during which healthcare providers and patients reported their satisfaction with the HCRA and genetic testing process. RESULTS: Among patients who completed a family history assessment during the post-integration period, 23.6% met guideline criteria for genetic testing. Of all patients seen at the clinic during the post-integration period, 8.7% completed genetic testing; this was a twofold increase over the period immediately preceding process integration (4.2%), and a sevenfold increase over the same period 1 year prior (1.2%). The majority of providers reported that the HCRA was as important as other regularly performed assessments (61.0%) and planned to continue using the process in their practice (68.3%). Most patients believed that the genetic test results were important for their future cancer care (84.7%) and had already shared their test results with at least one family member (63.2%). CONCLUSIONS: This study demonstrated that implementing an HCRA process in the community urology practice setting was feasible, generally favored by providers and patients, and resulted in an increase in the number of patients with PCa who completed genetic testing.

Assistance from Automated ASPECTS Software Improves Reader Performance.

PURPOSE: To compare physicians' ability to read Alberta Stroke Program Early CT Score (ASPECTS) in patients with a large vessel occlusion within 6 hours of symptom onset when assisted by a machine learning-based automatic software tool, compared with their unassisted score. MATERIALS AND METHODS: 50 baseline CT scans selected from two prior studies (CRISP and GAMES-RP) were read by 3 experienced neuroradiologists who were provided access to a follow-up MRI. The average ASPECT score of these reads was used as the reference standard. Two additional neuroradiologists and 6 non-neuroradiologist readers then read the scans both with and without assistance from the software reader-augmentation program and reader improvement was determined. The primary hypothesis was that the agreement between typical readers and the consensus of 3 expert neuroradiologists would be improved with software augmented vs. unassisted reads. Agreement was based on the percentage of the individual ASPECT regions (50 cases, 10 regions each; N=500) where agreement was achieved. RESULTS: Typical non-neuroradiologist readers agreed with the expert consensus read in 72% of the 500 ASPECTS regions, evaluated without software assistance. The automated software alone agreed in 77%. When the typical readers read the scan in conjunction with the software, agreement improved to 78% (P<0.0001, test of proportions). The software program alone achieved correlations for total ASPECT scores that were similar to the expert readers who had access to the follow-up MRI scan to help enhance the quality of their reads. CONCLUSION: Typical readers had statistically significant improvement in their scoring of scans when the scan was read in conjunction with the automated software, achieving agreement rates that were comparable to neuroradiologists.

High-Performance Automated Anterior Circulation CT Angiographic Clot Detection in Acute Stroke: A Multireader Comparison.

Background Identification of large vessel occlusion (LVO) is critical to the management of acute ischemic stroke and prerequisite to endovascular therapy in recent trials. Increasing volumes and data complexity compel the development of fast, reliable, and automated tools for LVO detection to facilitate acute imaging triage. Purpose To investigate the performance of an anterior circulation LVO detection platform in a large mixed sample of individuals with and without LVO at cerebrovascular CT angiography (CTA). Materials and Methods In this retrospective analysis, CTA data from recent cerebrovascular trials (CRISP [ClinicalTrials.gov NCT01622517] and DASH) were enriched with local repositories from 11 worldwide sites to balance demographic and technical variables in LVO-positive and LVO-negative examinations. CTA findings were reviewed independently by two neuroradiologists from different institutions for intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) M1 LVO; these observers were blinded to all clinical variables and outcomes. An automated analysis platform was developed and tested for prediction of LVO presence and location relative to reader consensus. Discordance between readers with respect to LVO presence or location was adjudicated by a blinded tertiary reader at a third institution. Sensitivity, specificity, and receiver operating characteristics were assessed by an independent statistician, and subgroup analyses were conducted. Prespecified performance thresholds were set at a lower bound of the 95% CI of sensitivity and specificity of 0.8 or greater at mean times to notification of less than 3.5 minutes. Results A total of 217 study participants (mean age, 64 years ± 16 [standard deviation]; 116 men; 109 with positive findings of LVO) were evaluated. Prespecified performance thresholds were exceeded (sensitivity, 105 of 109 [96%; 95% CI: 91, 99]; specificity, 106 of 108 [98%; 95% CI: 94, 100]). Sensitivity and specificity estimates across age, sex, location, and vendor subgroups exceeded 90%. The area under the receiver operating characteristic curve was 99% (95% CI: 97, 100). Mean processing and notification time was 3 minutes 18 seconds. Conclusion The results confirm the feasibility of fast automated high-performance detection of intracranial internal carotid artery and middle cerebral artery M1 occlusions. © RSNA, 2021 See also the editorial by Kloska in this issue.

Diagnostic accuracy of combined WBC, ANC and CRP in adult emergency department patients suspected of acute appendicitis.

OBJECTIVES: To assess the sensitivity, specificity, and negative predictive value (NPV) of normal total white blood cell count (WBC) and normal absolute neutrophil count (ANC) combined with a normal proprietary C-reactive protein (pCRP) level in adult emergency department (ED) patients with abdominal pain suspected of possible acute appendicitis. METHODS: We prospectively enrolled patients ≥18 years of age at seven U.S. emergency departments with ≤72 h of abdominal pain and other signs and symptoms suggesting possible acute appendicitis. Sensitivity, specificity, and NPV for normal WBC and ANC combined with normal pCRP were correlated with the final diagnosis of acute appendicitis. RESULTS: We enrolled 422 patients with a prevalence of acute appendicitis of 19.1%. The combination of normal WBC and pCRP exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), an NPV of 98.8% (95% CI, 95.9-99.7%) and a specificity of 50.0% (95% CI, 44.7-55.3%) for acute appendicitis. Normal ANC and pCRP resulted in a sensitivity of 100% (95% CI, 95.4-100%), a negative predictive value of 100% (95% CI, 97.5-100%) and a specificity of 44.4% (95% CI, 39.2-49.7%) for acute appendicitis. Normal WBC and pCRP correctly identified 171 of 342 (50.0%) patients who did not have appendicitis with 2 (2.5%) false negatives, while normal ANC and pCRP identified 150 of 338 (44.3%) of patients without appendicitis with no false negatives. CONCLUSION: The combination of normal WBC and ANC with normal pCRP levels exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult patient cohort. Confirmation and validation of these findings with further study using commercially available CRP assays is needed.

Impact of Preanalytical Factors During Histology Processing on Section Suitability for Digital Image Analysis.

Digital image analysis (DIA) is impacted by the quality of tissue staining. This study examined the influence of preanalytical variables-staining protocol design, reagent quality, section attributes, and instrumentation-on the performance of automated DIA software. Our hypotheses were that (1) staining intensity is impacted by subtle differences in protocol design, reagent quality, and section composition and that (2) identically programmed and loaded stainers will produce equivalent immunohistochemical (IHC) staining. We tested these propositions by using 1 hematoxylin and eosin stainer to process 13 formalin-fixed, paraffin-embedded (FFPE) mouse tissues and by using 3 identically programmed and loaded immunostainers to process 5 FFPE mouse tissues for 4 cell biomarkers. Digital images of stained sections acquired with a commercial whole slide scanner were analyzed by customizable algorithms incorporated into commercially available DIA software. Staining intensity as viewed qualitatively by an observer and/or quantitatively by DIA was affected by staining conditions and tissue attributes. Intrarun and inter-run IHC staining intensities were equivalent for each tissue when processed on a given stainer but varied measurably across stainers. Our data indicate that staining quality must be monitored for each method and stainer to ensure that preanalytical factors do not impact digital pathology data quality.

Clinical Immunoassay for Human Hepcidin Predicts Iron Deficiency in First-Time Blood Donors.

BACKGROUND: Serum markers currently used as indicators of iron status have clinical limitations. Hepcidin, a key regulator of iron homeostasis, is reduced in iron deficiency (ID) and increased in iron overload. We describe the first CLIA-validated immunoassay with excellent accuracy and precision to quantify human serum hepcidin. Its diagnostic utility for detecting ID in first-time blood donors was demonstrated. METHODS: A monoclonal competitive ELISA (C-ELISA) was developed for the quantitation of human hepcidin and validated according to CLIA guidelines. Sera from nonanemic first-time blood donors (n = 292) were analyzed for hepcidin, ferritin, transferrin, and serum iron. Logistic regression served to determine the utility of hepcidin as a predictor of ID. RESULTS: The C-ELISA was specific for human hepcidin and had a low limit of quantitation (4.0 ng/mL). The hepcidin concentration measured with the monoclonal C-ELISA was strongly correlated with a previously established, extensively tested polyclonal C-ELISA (Blood 2008;112:4292-7) (r = 0.95, P < 0.001). The area under the receiver operating characteristic curve for hepcidin as a predictor of ID, defined by 3 ferritin concentration thresholds, was >0.9. For predicting ID defined by ferritin <15 ng/mL, hepcidin <10 ng/mL yielded sensitivity of 93.1% and specificity of 85.5%, whereas the same hepcidin cutoff for ferritin <30 ng/mL yielded sensitivity of 67.6% and specificity of 91.7%. CONCLUSION: The clinical measurement of serum hepcidin concentrations was shown to be a potentially useful tool for diagnosing ID.

Optical density-based image analysis method for the evaluation of hematoxylin and eosin staining precision.

Staining quality and reproducibility are essential factors to monitor laboratory quality assurance. In the last decade, there has been an increase in the use of digital pathology and image analysis. While the adoption of these tools provides a potential means to track staining precision by optical density (OD), it also presents challenges. Results from image analysis are more sensitive to variations in staining than microscopic evaluation by a pathologist. There are two goals with this study. The first was to track the precision of hematoxylin and eosin (H&E) staining, in both nuclear and cytoplasmic components by OD. The second was to determine the impact of different pre-analytical and analytical variables on the OD results. Specifically, the endpoints investigated were quality parameters including impacts of section thickness, protocol manipulation, expired hematoxylin on staining precision and reproducibility of staining over time. Our results show that image analysis of H&E-stained tissue sections is a viable tool for assessing and verifying staining quality. We also show that OD analysis results for H&E-stained sections are affected by changing pre-analytical and/or reagent variables. These authors chose a graphical rather than fully statistical analysis of the results to highlight the utility of visual aids in demonstrating H&E staining reproducibility.

An Image Analysis Solution For Quantification and Determination of Immunohistochemistry Staining Reproducibility.

With immunohistochemical (IHC) staining increasingly being used to guide clinical decisions, variability in staining quality and reproducibility are becoming essential factors in generating diagnoses using IHC tissue preparations. The current study tested a method to track and quantify the interrun, intrarun, and intersite variability of IHC staining intensity. Our hypothesis was that staining precision between laboratory sites, staining runs, and individual slides may be verified quantitatively, efficiently and effectively utilizing algorithm-based, automated image analysis. To investigate this premise, we tested the consistency of IHC staining in 40 routinely processed (formalin-fixed, paraffin-embedded) human tissues using 10 common antibiomarker antibodies on 2 Dako Omnis instruments at 2 locations (Carpinteria, CA: 30 m above sea level and Longmont, CO: 1500 m above sea level) programmed with identical, default settings and sample pretreatments. Digital images of IHC-labeled sections produced by a whole slide scanner were analyzed by a simple commercially available algorithm and compared with a board-certified veterinary pathologist's semiquantitative scoring of staining intensity. The image analysis output correlated well with pathology scores but had increased sensitivity for discriminating subtle variations and providing reproducible digital quantification across sites as well as within and among staining runs at the same site. Taken together, our data indicate that digital image analysis offers an objective and quantifiable means of verifying IHC staining parameters as a part of laboratory quality assurance systems.

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells.

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1, encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro-derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition.

A Retrospective Chart Review of Chronic Wound Patients Treated with Topical Oxygen Therapy.

Objective: Topical oxygen devices are Food and Drug Administration (FDA) cleared for the following indications for use of various etiologies: skin ulcerations due to diabetes, venous stasis, postsurgical infections and gangrenous lesions, decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite. The goal of this study was to understand the impact of topical oxygen therapy (TOT) on patient outcomes, including amputation and healing rates. Approach: This retrospective chart review included records collected between January 1, 2007, and July 18, 2016, from male and female patients ranging in age from 4 years to 105 years. All wounds were at least 1 cm2 and were treated with at least one separate modality before treatment with TOT and then treated with TOT for a minimum of 2 weeks in compliance with the FDA-approved indications. All records were from wounds that were no longer being treated with TOT. Results: In this study, TOT was associated with an overall rate of 59.4% for a reduction in chronic wound size, while 41.6% of wounds had no healing. The overall amputation rate was 2.4% for wounds in this study. Innovation: To our knowledge, this retrospective chart review represents one of the largest data sets (4,127 total wounds) collected over one of the longest time periods (9.5 years) to evaluate patient outcomes following TOT. Conclusion: This study revealed healing and amputation rates similar to those reported in controlled clinical studies using TOT to treat chronic wounds.

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain.

OBJECTIVES: Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. METHODS: This study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. RESULTS: 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6-41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. CONCLUSION: This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis.

Addition of a biomarker panel to a clinical score to identify patients at low risk for appendicitis.

BACKGROUND: The diagnosis of pediatric acute appendicitis can be difficult. Although scoring systems such as the Pediatric Appendicitis Score (PAS) are helpful, they lack adequate sensitivity and specificity as standalone diagnostics. When used for risk stratification, they often result in large percentages of moderate-risk patients requiring further diagnostic evaluation. METHODS: We applied a biomarker panel (the APPY1 Test) that has high sensitivity and negative predictive value (NPV) to patients with PAS in the moderate-risk range (3-7) and reclassified those patients with a negative result to the low-risk group. We compared the specificity, sensitivity, and NPV of the original and reclassified low-risk groups at several different PAS low-risk cutoffs. RESULTS: The application of a negative biomarker panel to a group of patients with a moderate risk for appendicitis (PAS, 3-7) resulted in 4 times more patients (586 vs 145) being safely classified as low risk. Reclassification increased the overall specificity or the proportion of patients without appendicitis who were correctly identified as low risk, from 10.3% to 42.0%. The high NPV (97.2%) in the original group was preserved (97.6%) in the reclassified low-risk group, as was the sensitivity (original 99.1% vs reclassified 96.9%). CONCLUSION: The addition of negative biomarker test results to patients with a moderate risk of appendicitis based on the PAS can safely reclassify many to a low-risk group. This may allow clinicians to provide more conservative management in children with suspected appendicitis and decrease unnecessary resource utilization.

Prospective validation of a biomarker panel to identify pediatric ED patients with abdominal pain who are at low risk for acute appendicitis.

OBJECTIVES: The objective of the study is to prospectively validate the diagnostic accuracy of a biomarker panel consisting of white blood cell, C-reactive protein, and myeloid-related protein 8/14 levels in identifying pediatric patients with abdominal pain who are at low risk for appendicitis. METHODS: This prospective observational study enrolled subjects aged 2 to 20 years presenting to 29 US emergency departments with abdominal pain suggesting possible acute appendicitis. Blood samples were analyzed for white blood cell, C-reactive protein, and myeloid-related protein 8/14 levels from which the composite biomarker panel results were calculated, then correlated with the final diagnosis either positive or negative for acute appendicitis. RESULTS: A total of 2201 patients were enrolled, with 1887 completing all aspects of the study. Prevalence of appendicitis in this cohort was 25.3%. The biomarker panel exhibited a sensitivity of 97.1% (95% confidence interval [CI], 95.1%-98.2%), negative predictive value of 97.4% (95% CI, 95.8%-98.5%), negative likelihood ratio of 0.08 (95% CI, 0.05-0.13), with a specificity of 37.9% (95% CI, 35.4%-40.4%) for appendicitis. The panel correctly identified 534 (37.8%) of 1410 patients who did not have appendicitis with 14 false negatives (2.9%). Overall, 23.7% (132/557) of computed tomographic (CT) scans were done for patients with negative biomarker panel results, including 31.2% (131/420) of patients who had CT but did not have appendicitis. CONCLUSION: This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this large prospective cohort. This panel may be useful in identifying pediatric patients who are at low risk for appendicitis and might be followed clinically, potentially reducing the dependence on CT in the evaluation for acute appendicitis.