Publications by authors named "Michael Feldman"

344 Publications

An Examination of Standardized Letters of Recommendation Rating Scales Among Neurosurgical Residency Candidates During the 2020-2021 Application Cycle.

Neurosurgery 2021 Oct 8. Epub 2021 Oct 8.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Letters of recommendation (LORs) are historically an important, though subjective, component of the neurosurgery residency application process. Standardized LORs (SLORs) were introduced during the 2020 to 2021 application cycle. The intent of SLORs is to allow objective comparison of applicants and to reduce bias.

Objective: To examine the utility of SLORs during this application cycle. We hypothesized that "grade inflation" and poor inter-rater reliability, as described by other specialties using SLORs, would limit the utility of SLORs in their current form.

Methods: This cross-sectional study analyzed all SLORs submitted to a single neurosurgery residency program over the 2020 to 2021 cycle. Data from 7 competency domains and the overall rating were recorded and stratified by academic category of letter writer. Inter-rater reliability was evaluated using Krippendorff's alpha.

Results: One or more SLORs was submitted as part of 298 of 393 applications (76%). Approximately 58.3% of letters written by neurosurgery chairpersons rated a given applicant as being within the top 5% across all competencies. Approximately 44.4% of program director letters similarly rated applicants as amongst the top 5%, while 73.2% and 81.4% of letters by other neurosurgeons and general surgery evaluators, respectively, rated applicants in the top 5%. Inter-rater reliability was poor (<0.33) in all rating categories, including overall (α = 0.18).

Conclusion: The utility of the first iteration of SLORs in neurosurgery applications is undermined by significant "grade inflation" and poor inter-rater reliability. Improvements are necessary for SLORs if they are to provide meaningful information in future application cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyab346DOI Listing
October 2021

Evaluation of Scopio Labs X100 Full Field PBS: The first high-resolution full field viewing of peripheral blood specimens combined with artificial intelligence-based morphological analysis.

Int J Lab Hematol 2021 Sep 21. Epub 2021 Sep 21.

Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Background: Current digital cell imaging systems perform peripheral blood smear (PBS) analysis in limited regions of the PBS and require the support of manual microscopy without achieving full digital microscopy. We report a multicenter study that validated the Scopio Labs X100 Full Field PBS, a novel digital imaging system that utilizes a full field view approach for cell recognition and classification, in a decision support system mode.

Methods: We analyzed 335 normal and 310 abnormal PBS from patients with various clinical conditions and compared the performance of Scopio's Full Field PBS as the test method, with manual PBS analysis as the reference method. Deming regression analysis was utilized for comparisons of WBC and platelet estimates. Measurements of WBC and platelet estimation accuracy along with the agreement on RBC morphology evaluation were performed. Reproducibility and repeatability (R&R) of the system were also evaluated.

Results: Scopio's Full Field PBS WBC accuracy was evaluated with an efficiency of 96.29%, sensitivity of 87.86%, and specificity of 97.62%. The agreement between the test and reference method for RBC morphology reached 99.77%, and the accuracy for platelet estimation resulted in an efficiency of 94.89%, sensitivity of 90.00%, and specificity of 96.28%, with successful R&R tests. The system enabled a comprehensive review of full field PBS as shown in representative samples.

Conclusions: Scopio's Full Field PBS showed a high degree of correlation of all tested parameters with manual microscopy. The novel full field view of specimens facilitates the long-expected disengagement between the digital application and the manual microscope.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijlh.13681DOI Listing
September 2021

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

JAMA Oncol 2021 Sep 16. Epub 2021 Sep 16.

Medical Oncology, Swedish Cancer Institute, Seattle, Washington.

Importance: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.

Objective: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival.

Design, Setting, And Participants: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate.

Interventions: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery.

Main Outcomes And Measures: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS).

Results: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis.

Conclusions And Relevance: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy.

Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2021.3690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446908PMC
September 2021

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma.

Int Forum Allergy Rhinol 2021 Sep 12. Epub 2021 Sep 12.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.

Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma.

Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors.

Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation).

Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22882DOI Listing
September 2021

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19): Possible Role for the NLRP3 Inflammasome.

Res Sq 2021 Sep 1. Epub 2021 Sep 1.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue. Lung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects [of which 8 were acute respiratory disease syndrome (ARDS) affected and 3 were from subjects with non-respiratory diseases] were stained for H & E to ascertain histopathological features including presence of thrombi/microthrombi. Inflammation along the vessel wall was also monitored by quantification of the expression of moieties of the NLRP3 inflammasome pathway (NLRP3 and caspase-1). In lungs from "fatal COVID-19", vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from "non-COVID-19 non respiratory disease" affected subjects. The NLRP3 pathway components were significantly higher in lungs from COVID-19 subjects as compared to non-COVID-19 fatal cases without respiratory disease. No significant differences were observed between COVID-19 lungs and non-COVID-19 ARDS lungs. We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation that accompanies COVID-19. Thus, the NLRP3 inflammasome pathway seems to be probable candidate that drives amplification of inflammation post SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21203/rs.3.rs-842167/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423225PMC
September 2021

Prognostic correlations with the microbiome of breast cancer subtypes.

Cell Death Dis 2021 09 4;12(9):831. Epub 2021 Sep 4.

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Alterations to the natural microbiome are linked to different diseases, and the presence or absence of specific microbes is directly related to disease outcomes. We performed a comprehensive analysis with unique cohorts of the four subtypes of breast cancer (BC) characterized by their microbial signatures, using a pan-pathogen microarray strategy. The signature (includes viruses, bacteria, fungi, and parasites) of each tumor subtype was correlated with clinical data to identify microbes with prognostic potential. The subtypes of BC had specific viromes and microbiomes, with ER+ and TN tumors showing the most and least diverse microbiome, respectively. The specific microbial signatures allowed discrimination between different BC subtypes. Furthermore, we demonstrated correlations between the presence and absence of specific microbes in BC subtypes with the clinical outcomes. This study provides a comprehensive map of the oncobiome of BC subtypes, with insights into disease prognosis that can be critical for precision therapeutic intervention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-04092-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418604PMC
September 2021

Improving Discharge Instructions Following a Concussion Diagnosis in the Pediatric Emergency Department: A Pre-post Intervention Study.

Pediatr Qual Saf 2021 Sep-Oct;6(5):e456. Epub 2021 Aug 26.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tenn.

Introduction: Many children are discharged from the pediatric emergency department (PED) with incomplete or inappropriate instructions following a concussion. Our objective was to evaluate the effectiveness of a simple intervention in improving discharge instruction disbursement and completeness following PED diagnosis of concussion.

Methods: A pre/post intervention study of 935 patients (375 preintervention and 560 postintervention) ages 5-19, diagnosed with a concussion and discharged from the PED between July 2016 and November 2019, was performed at a single United States pediatric tertiary-care center. Dedicated provider education sessions were held, and a consensus guideline-based set of discharge instructions were implemented in the electronic health record. Primary outcomes included the presence of return-to-play (RTP) instructions, return-to-learn (RTL) instructions, follow-up recommendations, and "complete" discharge (ie, all 3 components present). Statistical process control charts were generated and tested for special cause variation.

Results: More patients received instructions for RTP (87% versus 59%) and RTL (60% versus 3%), and a complete discharge was more frequent (45% versus 2%), following the conclusion of the intervention. Only the improvement in RTP instructions was completely sustained into the following academic year, whereas RTL and complete discharge rates declined to 27% and 20%, respectively.

Conclusions: A simple, low-cost intervention such as peer-to-peer education and consensus guideline-based discharge instruction templates can significantly improve discharge readiness after pediatric concussion. Further work is needed to maintain progress and continue improvements, at our large academic trauma center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/pq9.0000000000000456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389964PMC
August 2021

Formation of a de novo intracranial arteriovenous fistula in a child with PTEN hamartoma tumor syndrome.

Childs Nerv Syst 2021 Aug 18. Epub 2021 Aug 18.

Cerebrovascular Program, Vanderbilt University Medical Center and Vanderbilt Children's Hospital, Nashville, TN, USA.

Purpose: Dural arteriovenous fistulae (dAVF) are an uncommon feature of PTEN hamartoma tumor syndrome (PHTS). We report a case of an adolescent male diagnosed with PHTS following the treatment of multiple intracranial dAVF to emphasize the association of vascular anomalies with this disorder and discuss potential implications.

Case Report: An adolescent male presented with bilateral proptosis secondary to intracranial venous hypertension. Workup revealed the presence of a complex intracranial dAVF which was treated with several embolization procedures. Following treatment, a de novo dAVF was identified on surveillance imaging. A genetic workup revealed a pathogenic mutation in PTEN consistent with a diagnosis of PHTS.

Conclusions: Recognition that PHTS may be associated with dAVF, and potentially delayed spontaneous formation of dAVF, is critically important due to the potential for devastating yet preventable neurologic sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00381-021-05321-6DOI Listing
August 2021

Multiplexed detection of SARS-CoV-2 genomic and subgenomic RNA using hybridization.

bioRxiv 2021 Aug 11. Epub 2021 Aug 11.

The widespread Coronavirus Disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have a limited toolset available for visualizing SARS-CoV-2 in cells and tissues, particularly in tissues from patients who died from COVID-19. Generally, single-molecule RNA FISH techniques have shown mixed results in formalin fixed paraffin embedded tissues such as those preserved from human autopsies. Here, we present a platform for preparing autopsy tissue for visualizing SARS-CoV-2 RNA using RNA FISH with amplification by hybridization chain reaction (HCR). We developed probe sets that target different regions of SARS-CoV-2 (including ORF1a and N) as well as probe sets that specifically target SARS-CoV-2 subgenomic mRNAs. We validated these probe sets in cell culture and tissues (lung, lymph node, and placenta) from infected patients. Using this technology, we observe distinct subcellular localization patterns of the ORF1a and N regions, with the ORF1a concentrated around the nucleus and the N showing a diffuse distribution across the cytoplasm. In human lung tissue, we performed multiplexed RNA FISH HCR for SARS-CoV-2 and cell-type specific marker genes. We found viral RNA in cells containing the alveolar type 2 (AT2) cell marker gene ( ) and the alveolar macrophage marker gene ( ), but did not identify viral RNA in cells containing the alveolar type 1 (AT1) cell marker gene ( ). Moreover, we observed distinct subcellular localization patterns of viral RNA in AT2 cells and alveolar macrophages, consistent with phagocytosis of infected cells. In sum, we demonstrate the use of RNA FISH HCR for visualizing different RNA species from SARS-CoV-2 in cell lines and FFPE autopsy specimens. Furthermore, we multiplex this assay with probes for cellular genes to determine what cell-types are infected within the lung. We anticipate that this platform could be broadly useful for studying SARS-CoV-2 pathology in tissues as well as extended for other applications including investigating the viral life cycle, viral diagnostics, and drug screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.08.11.455959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366794PMC
August 2021

Collagen fiber orientation disorder from H&E images is prognostic for early stage breast cancer: clinical trial validation.

NPJ Breast Cancer 2021 Aug 6;7(1):104. Epub 2021 Aug 6.

Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA.

Collagen fiber organization has been found to be implicated in breast cancer prognosis. In this study, we evaluated whether computerized features of Collagen Fiber Orientation Disorder in Tumor-associated Stroma (CFOD-TS) on Hematoxylin & Eosin (H&E) slide images were prognostic of Disease Free Survival (DFS) in early stage Estrogen Receptor Positive (ER+) Invasive Breast Cancers (IBC). A Cox regression model named M, was constructed using cohort S (N = 78) to predict DFS based on CFOD-TS features. The prognostic performance of M was validated on cohort S (N = 219), a prospective clinical trial dataset (ECOG 2197). M was prognostic of DFS in both S and S, independent of clinicopathological variables. Additionally, the molecular pathways regarding cell cycle regulation were identified as being significantly associated with M derived risk scores. Our results also found that collagen fiber organization was more ordered in patients with short DFS. Our study provided a H&E image-based pipeline to derive a potential prognostic biomarker for early stage ER+ IBC without the need of special collagen staining or advanced microscopy techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00310-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346522PMC
August 2021

Accurate and Robust Alignment of Differently Stained Histologic Images Based on Greedy Diffeomorphic Registration.

Appl Sci (Basel) 2021 Feb 21;11(4). Epub 2021 Feb 21.

Center for Biomedical Image Computing & Analytics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Histopathologic assessment routinely provides rich microscopic information about tissue structure and disease process. However, the sections used are very thin, and essentially capture only 2D representations of a certain tissue sample. Accurate and robust alignment of sequentially cut 2D slices should contribute to more comprehensive assessment accounting for surrounding 3D information. Towards this end, we here propose a two-step diffeomorphic registration approach that aligns differently stained histology slides to each other, starting with an initial affine step followed by estimating a deformation field. It was quantitatively evaluated on ample ( = 481) and diverse data from the automatic non-rigid histological image registration challenge, where it was awarded the second rank. The obtained results demonstrate the ability of the proposed approach to robustly (average robustness = 0.9898) and accurately (average relative target registration error = 0.2%) align differently stained histology slices of various anatomical sites while maintaining reasonable computational efficiency (<1 min per registration). The method was developed by adapting a general-purpose registration algorithm designed for 3D radiographic scans and achieved consistently accurate results for aligning high-resolution 2D histologic images. Accurate alignment of histologic images can contribute to a better understanding of the spatial arrangement and growth patterns of cells, vessels, matrix, nerves, and immune cell interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/app11041892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291745PMC
February 2021

A Natural Language Processing-Assisted Extraction System for Gleason Scores: Development and Usability Study.

JMIR Cancer 2021 Jul 2;7(3):e27970. Epub 2021 Jul 2.

Perelman School of Medicine, Philadelphia, PA, United States.

Background: Natural language processing (NLP) offers significantly faster variable extraction compared to traditional human extraction but cannot interpret complicated notes as well as humans can. Thus, we hypothesized that an "NLP-assisted" extraction system, which uses humans for complicated notes and NLP for uncomplicated notes, could produce faster extraction without compromising accuracy.

Objective: The aim of this study was to develop and pilot an NLP-assisted extraction system to leverage the strengths of both human and NLP extraction of prostate cancer Gleason scores.

Methods: We collected all available clinical and pathology notes for prostate cancer patients in an unselected academic biobank cohort. We developed an NLP system to extract prostate cancer Gleason scores from both clinical and pathology notes. Next, we designed and implemented the NLP-assisted extraction system algorithm to categorize notes into "uncomplicated" and "complicated" notes. Uncomplicated notes were assigned to NLP extraction and complicated notes were assigned to human extraction. We randomly reviewed 200 patients to assess the accuracy and speed of our NLP-assisted extraction system and compared it to NLP extraction alone and human extraction alone.

Results: Of the 2051 patients in our cohort, the NLP system extracted a prostate surgery Gleason score from 1147 (55.92%) patients and a prostate biopsy Gleason score from 1624 (79.18%) patients. Our NLP-assisted extraction system had an overall accuracy rate of 98.7%, which was similar to the accuracy of human extraction alone (97.5%; P=.17) and significantly higher than the accuracy of NLP extraction alone (95.3%; P<.001). Moreover, our NLP-assisted extraction system reduced the workload of human extractors by approximately 95%, resulting in an average extraction time of 12.7 seconds per patient (vs 256.1 seconds per patient for human extraction alone).

Conclusions: We demonstrated that an NLP-assisted extraction system was able to achieve much faster Gleason score extraction compared to traditional human extraction without sacrificing accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/27970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285739PMC
July 2021

Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 Isolates.

Open Forum Infect Dis 2021 Jul 4;8(7):ofab300. Epub 2021 Jun 4.

Division of Pediatric Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

We report the genome of a B.1.1.7+E484K severe acute respiratory syndrome coronavirus 2 from Southeastern Pennsylvania and compare it with all high-coverage B.1.1.7+E484K genomes (n = 235) available. Analyses showed the existence of at least 4 distinct clades of this variant circulating in the United States and the possibility of at least 59 independent acquisitions of the E484K mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofab300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244812PMC
July 2021

Arthroscopic Repair of a PASTA of the Shoulder Using a Bursal Split.

Arthrosc Tech 2021 May 22;10(5):e1403-e1408. Epub 2021 Apr 22.

Department of Orthopaedic Surgery, University of Arizona, Tucson, Arizona, U.S.A.

PASTA (partial articular supraspinatus tendon avulsion) lesions are a subset of partial rotator cuff tears that are commonly treated by surgeons. Multiple surgical techniques exist for managing these lesions, including debridement, transtendinous repair, and completion of the tear and repair. Each of these techniques provides its own set of advantages and disadvantages, and currently there is no consensus on which method provides the best clinical outcomes or ease of procedure. Here, we present our repair technique for PASTA lesions, which involves a bursal split that takes the advantages of previous techniques by allowing improved visualization of the footprint and suture passing while avoiding the takedown any of Sharpey's fibers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eats.2021.01.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185807PMC
May 2021

Encephalopathy at admission predicts adverse outcomes in patients with SARS-CoV-2 infection.

CNS Neurosci Ther 2021 10 16;27(10):1127-1135. Epub 2021 Jun 16.

Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.

Aims: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered.

Results: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001).

Conclusions: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cns.13687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444722PMC
October 2021

Chronic liver disease not a significant comorbid condition for COVID-19.

Sci Rep 2021 06 3;11(1):11734. Epub 2021 Jun 3.

Department of Diagnostic Imaging, Rhode Island Hospital, Philadelphia, PA, 19104, USA.

To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91238-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175434PMC
June 2021

Risk factors for the presence of residual disease in women after partial mastectomy for invasive breast cancer: A single institution experience.

Surg Oncol 2021 Jun 25;37:101608. Epub 2021 May 25.

Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: We hypothesize that in addition to specimen margin widths other clinical variables may help predict the presence of residual disease in the lumpectomy bed.

Methods: Patients with Stage I-III invasive breast cancer (BC) who underwent partial mastectomy (PM) and re-excision from July 2010-June 2015 were retrospectively reviewed. Bivariate analyses were conducted using two-sample t-tests for continuous variables and Fisher's Exact tests for categorical variables. A multivariate logistic regression was then performed on significant bivariate analyses variables.

Results: ne-hundred and eighty-four patients were included in our analysis; 47% had residual disease on re-excision, while 53% had no residual disease. Tumor and nodal stage, operation type, type of disease present at margin, and number of positive margins were significantly associated with residual disease. On multivariate logistic regression, DCIS alone at the margin (p = 0.02), operation type (PM with cavity margins) (p = 0.003), and number of positive margins (3 or more) (p < 0.001) remained predictive of residual disease at re-excision.

Conclusion: Based on a more comprehensive review of the initial pathology, there are additional factors that can help predict the likelihood of finding residual disease and help guide the surgeon in the decision for re-excision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2021.101608DOI Listing
June 2021

A 15-Year Review of Iatrogenic Burn Injuries in an Academic Public Hospital.

J Burn Care Res 2021 May 31. Epub 2021 May 31.

Virginia Commonwealth University School of Medicine, School of Medicine, Box 980565, Richmond, VA, US.

Hospital-acquired burn injuries can result in increased length of hospitalization, costs of stay, and potential for additional procedures. The aim of this study is to describe iatrogenic burn injuries over a 15-year period at an academic public hospital system. Data was collected from January 2004 to June 2019. Data included time of injury, hospital location, mechanism, level of harm caused, and anatomic location of the injury. Demographic information included patient age, gender, body mass index, payer status, primary admission diagnosis and length of stay. 122 patients were identified through an internal hospital database that tracked reported injuries. Incidence was highest between 2005-2012 (12.3 ± 4.1 per year) as compared to 2013-2019 (2.9 ± 2.1 per year). A majority (77%) resulted in harm caused to the patient. Most (41%) of the injuries occurred on the general medical floors, followed by the operating room (33.6%). The most common etiology was scald (23%), followed by electrocautery (14.8%). Five of the injuries resulted in burn consults, although none of these patients required surgery. Iatrogenic burns appear to be decreasing. While a majority were reported to have caused patient harm, none were serious enough to warrant surgery. Most injuries occurred on the medical floors with a scald mechanism. This review presents an opportunity to emphasize in-hospital burn prevention, as well as an opportunity for the burn team to affect change in concert with hospital administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jbcr/irab096DOI Listing
May 2021

Alpha-defensins: risk factor for thrombosis in COVID-19 infection.

Br J Haematol 2021 07 30;194(1):44-52. Epub 2021 May 30.

Department of Clinical Biochemistry, Hadassah-Hebrew University, Jerusalem, IL-91120, Israel.

The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers. Immunohistochemistry revealed intense deposition of α-defensins in lung vasculature and thrombi. IL-6 stimulated the release of α-defensins from neutrophils, thereby accelerating coagulation and inhibiting fibrinolysis in human blood, imitating the coagulation pattern in COVID-19 patients. The procoagulant effect of IL-6 was inhibited by colchicine, which blocks neutrophil degranulation. These studies describe a link between inflammation and the risk of thromboembolism, and they identify a potential new approach to mitigate this risk in patients with COVID-19 and potentially in other inflammatory prothrombotic conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239944PMC
July 2021

An automated computational image analysis pipeline for histological grading of cardiac allograft rejection.

Eur Heart J 2021 06;42(24):2356-2369

Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Nord Hall Suite 500, Cleveland, OH 44106, USA.

Aim: Allograft rejection is a serious concern in heart transplant medicine. Though endomyocardial biopsy with histological grading is the diagnostic standard for rejection, poor inter-pathologist agreement creates significant clinical uncertainty. The aim of this investigation is to demonstrate that cellular rejection grades generated via computational histological analysis are on-par with those provided by expert pathologists.

Methods And Results: The study cohort consisted of 2472 endomyocardial biopsy slides originating from three major US transplant centres. The 'Computer-Assisted Cardiac Histologic Evaluation (CACHE)-Grader' pipeline was trained using an interpretable, biologically inspired, 'hand-crafted' feature extraction approach. From a menu of 154 quantitative histological features relating the density and orientation of lymphocytes, myocytes, and stroma, a model was developed to reproduce the 4-grade clinical standard for cellular rejection diagnosis. CACHE-grader interpretations were compared with independent pathologists and the 'grade of record', testing for non-inferiority (δ = 6%). Study pathologists achieved a 60.7% agreement [95% confidence interval (CI): 55.2-66.0%] with the grade of record, and pair-wise agreement among all human graders was 61.5% (95% CI: 57.0-65.8%). The CACHE-Grader met the threshold for non-inferiority, achieving a 65.9% agreement (95% CI: 63.4-68.3%) with the grade of record and a 62.6% agreement (95% CI: 60.3-64.8%) with all human graders. The CACHE-Grader demonstrated nearly identical performance in internal and external validation sets (66.1% vs. 65.8%), resilience to inter-centre variations in tissue processing/digitization, and superior sensitivity for high-grade rejection (74.4% vs. 39.5%, P < 0.001).

Conclusion: These results show that the CACHE-grader pipeline, derived using intuitive morphological features, can provide expert-quality rejection grading, performing within the range of inter-grader variability seen among human pathologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216729PMC
June 2021

Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study.

NPJ Precis Oncol 2021 May 3;5(1):35. Epub 2021 May 3.

Department of Urology, Case Western Reserve University, Cleveland, OH, USA.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03-3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40-3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-021-00174-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093226PMC
May 2021

Computationally Derived Cribriform Area Index from Prostate Cancer Hematoxylin and Eosin Images Is Associated with Biochemical Recurrence Following Radical Prostatectomy and Is Most Prognostic in Gleason Grade Group 2.

Eur Urol Focus 2021 Jul 30;7(4):722-732. Epub 2021 Apr 30.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA. Electronic address:

Background: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement.

Objective: To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups.

Design, Setting, And Participants: A machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured.

Outcome Measurements And Statistical Analysis: The association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR).

Results And Limitations: CAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03-1.38; p = 0.018).

Conclusions: Automated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role.

Patient Summary: Machine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euf.2021.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419103PMC
July 2021

Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 isolates from Pennsylvania.

bioRxiv 2021 Apr 21. Epub 2021 Apr 21.

Division of Pediatric Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Rapid whole genome sequencing of SARS-CoV-2 has presented the ability to detect new emerging variants of concern in near real time. Here we report the genome of a virus isolated in Pennsylvania in March 2021 that was identified as lineage B.1.1.7 (VOC-202012/01) that also harbors the E484K spike mutation, which has been shown to promote "escape" from neutralizing antibodies . We compare this sequence to the only 5 other B.1.1.7+E484K genomes from Pennsylvania, all of which were isolated in mid March. Beginning in February 2021, only a small number (n=60) of isolates with this profile have been detected in the US, and only a total of 253 have been reported globally (first in the UK in December 2020). Comparative genomics of all currently available high coverage B.1.1.7+E484K genomes (n=235) available on GISAID suggested the existence of 7 distinct groups or clonal complexes (CC; as defined by GNUVID) bearing the E484K mutation raising the possibility of 7 independent acquisitions of the E484K spike mutation in each background. Phylogenetic analysis suggested the presence of at least 3 distinct clades of B.1.1.7+E484K circulating in the US, with the Pennsylvanian isolates belonging to two distinct clades. Increased genomic surveillance will be crucial for detection of emerging variants of concern that can escape natural and vaccine induced immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.04.21.440801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077577PMC
April 2021

The microbiome of HPV-positive tonsil squamous cell carcinoma and neck metastasis.

Oral Oncol 2021 06 24;117:105305. Epub 2021 Apr 24.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, United States.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) has now surpassed cervical cancer as the most common site of HPV-related cancer in the United States. HPV-positive OPSCCs behave differently from HPV-negative tumors and often present with early lymph node involvement. The bacterial microbiome of HPV-associated OPSCC may contribute to carcinogenesis, and certain bacteria may influence the spread of cancer from the primary site to regional lymphatics.

Objective: To determine the bacterial microbiome in patients with HPV-associated, early tonsil SCC and compare them to benign tonsil specimens.

Method: The microbiome of primary tumor specimens and lymph nodes was compared to benign tonsillectomy specimens with pan-pathogen microarray (PathoChip).

Results: A total of 114 patients were enrolled in the study. Patients with OPSCC had a microbiome that shifted towards more gram-negative. Numerous signatures of bacterial family and species were associated with the primary tumors and lymph nodes of cancer patients, including the urogenital pathogens Proteus mirabilis and Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, and Orientia tsutsugamushi.

Conclusion: Our results suggest that detection of urogenital pathogens is associated with lymph node metastasis for patients with HPV-positive OPSCCs. Additional studies are necessary to determine the effects of the OPSCC microbiome on disease progression and clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2021.105305DOI Listing
June 2021

Editorial Commentary: Suture Button-Anchor Fixation Is Preferable to Hook Plate Fixation for Acute Acromioclavicular Joint Dislocations: Form and Function Need to Be United.

Arthroscopy 2021 05;37(5):1424-1426

Both hook plate fixation and suture button-anchor fixation have been reported to yield good results in the treatment of acute acromioclavicular joint reconstruction. In addition to a mandatory secondary procedure, hook plate fixation clearly has an increased prevalence of post-traumatic acromioclavicular arthritis in the short term that is likely to progress in the long term. Conversely, suture button-anchor fixation-a minimally invasive technique that creates less soft-tissue disruption, does not require hardware removal, and does not violate the acromioclavicular joint-is more likely to promote primary healing of the coracoclavicular ligaments, reduce the risk of late displacement, and minimize the development of post-traumatic acromioclavicular arthritis. As stated by the noted architect Frank Lloyd Wright, it is not only about form (i.e., alignment), it is about function as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2021.01.051DOI Listing
May 2021

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19) Infection: Possible role for the NLRP3 inflammasome.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue. Here we document histopathological features and monitor the NLRP3 inflammasome in fatal cases of disease caused by SARS Cov2 (COVID-19). We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation that accompanies COVID-19 and that it is a probable candidate that drives amplification of inflammation post infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.03.19.21253815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010767PMC
March 2021

Prognostication of patients with COVID-19 using artificial intelligence based on chest x-rays and clinical data: a retrospective study.

Lancet Digit Health 2021 05 24;3(5):e286-e294. Epub 2021 Mar 24.

Department of Diagnostic Imaging, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA. Electronic address:

Background: Chest x-ray is a relatively accessible, inexpensive, fast imaging modality that might be valuable in the prognostication of patients with COVID-19. We aimed to develop and evaluate an artificial intelligence system using chest x-rays and clinical data to predict disease severity and progression in patients with COVID-19.

Methods: We did a retrospective study in multiple hospitals in the University of Pennsylvania Health System in Philadelphia, PA, USA, and Brown University affiliated hospitals in Providence, RI, USA. Patients who presented to a hospital in the University of Pennsylvania Health System via the emergency department, with a diagnosis of COVID-19 confirmed by RT-PCR and with an available chest x-ray from their initial presentation or admission, were retrospectively identified and randomly divided into training, validation, and test sets (7:1:2). Using the chest x-rays as input to an EfficientNet deep neural network and clinical data, models were trained to predict the binary outcome of disease severity (ie, critical or non-critical). The deep-learning features extracted from the model and clinical data were used to build time-to-event models to predict the risk of disease progression. The models were externally tested on patients who presented to an independent multicentre institution, Brown University affiliated hospitals, and compared with severity scores provided by radiologists.

Findings: 1834 patients who presented via the University of Pennsylvania Health System between March 9 and July 20, 2020, were identified and assigned to the model training (n=1285), validation (n=183), or testing (n=366) sets. 475 patients who presented via the Brown University affiliated hospitals between March 1 and July 18, 2020, were identified for external testing of the models. When chest x-rays were added to clinical data for severity prediction, area under the receiver operating characteristic curve (ROC-AUC) increased from 0·821 (95% CI 0·796-0·828) to 0·846 (0·815-0·852; p<0·0001) on internal testing and 0·731 (0·712-0·738) to 0·792 (0·780-0 ·803; p<0·0001) on external testing. When deep-learning features were added to clinical data for progression prediction, the concordance index (C-index) increased from 0·769 (0·755-0·786) to 0·805 (0·800-0·820; p<0·0001) on internal testing and 0·707 (0·695-0·729) to 0·752 (0·739-0·764; p<0·0001) on external testing. The image and clinical data combined model had significantly better prognostic performance than combined severity scores and clinical data on internal testing (C-index 0·805 vs 0·781; p=0·0002) and external testing (C-index 0·752 vs 0·715; p<0·0001).

Interpretation: In patients with COVID-19, artificial intelligence based on chest x-rays had better prognostic performance than clinical data or radiologist-derived severity scores. Using artificial intelligence, chest x-rays can augment clinical data in predicting the risk of progression to critical illness in patients with COVID-19.

Funding: Brown University, Amazon Web Services Diagnostic Development Initiative, Radiological Society of North America, National Cancer Institute and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(21)00039-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990487PMC
May 2021

Machine Learning-Based Prediction of COVID-19 Severity and Progression to Critical Illness Using CT Imaging and Clinical Data.

Korean J Radiol 2021 07 9;22(7):1213-1224. Epub 2021 Mar 9.

Department of Diagnostic Imaging, Rhode Island Hospital, Providence, RI, USA.

Objective: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables.

Materials And Methods: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists.

Results: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone ( < 0.001), 0.847 when based on clinical variables alone ( = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables ( = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively.

Conclusion: CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236359PMC
July 2021

Multi-centre implementation of an Educational program to improve the Cardiac Arrest diagnostic accuracy of ambulance Telecommunicators and survival outcomes for sudden cardiac arrest victims: the EduCATe study design and methodology.

BMC Emerg Med 2021 03 4;21(1):26. Epub 2021 Mar 4.

Clinical Epidemiology Unit, Ottawa Hospital Research Institute, The Ottawa Hospital, Civic Campus, Rm F649, 1053 Carling Ave., Ottawa, Ontario, K1Y 4E9, Canada.

Background: Sudden cardiac death remains a leading cause of mortality in Canada, resulting in more than 35,000 deaths annually. Most cardiac arrest victims collapse in their own home (85% of the time) and 50% are witnessed by a family member or bystander. Survivors have a quality of life similar to the general population, but the overall survival rate for out-of-hospital cardiac arrest (OHCA) rarely exceeds 8%. Victims are almost four times more likely to survive when receiving bystander CPR, but bystander CPR rates have remained low in Canada over the past decade, not exceeding 15-25% until recently. Telecommunication-assisted CPR instructions have been shown to significantly increase bystander CPR rates, but agonal breathing may be misinterpreted as a sign of life by 9-1-1 callers and telecommunicators, and is responsible for as much as 50% of missed OHCA diagnoses. We sought to improve the ability and speed with which ambulance telecommunicators can recognize OHCA over the phone, initiate timely CPR instructions, and improve survival.

Methods: In this multi-center national study, we will implement and evaluate an educational program developed for ambulance telecommunicators using a multiple baseline interrupted time-series design. We will compare outcomes 12 months before and after the implementation of a 20-min theory-based educational video addressing barriers to recognition of OHCA while in the presence of agonal breathing. Participating Canadian sites demonstrated prior ability to collect standardized data on OHCA. Data will be collected from eligible 9-1-1 recordings, paramedic documentation and hospital medical records. Eligible cases will include suspected or confirmed OHCA of presumed cardiac origin in patients of any age with attempted resuscitation.

Discussion: The ability of telecommunication-assisted CPR instructions to improve bystander CPR and survival rates for OHCA victims is undeniable. The ability of telecommunicators to recognize OHCA over the phone is unequivocally impeded by relative lack of training on agonal breathing, and reluctance to initiate CPR instructions when in doubt. Our pilot data suggests the potential impact of this project will be to increase absolute OHCA recognition and bystander CPR rates by at least 10%, and absolute out-of-hospital cardiac arrest survival by 5% or more.

Trial Registration: Prospectively registered on March 28, 2019 at ClinicalTrials.gov identifier: NCT03894059 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12873-021-00416-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931555PMC
March 2021

Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver.

JCI Insight 2021 04 8;6(7). Epub 2021 Apr 8.

Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.146883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119221PMC
April 2021
-->