Assessment Of Specific T-Cell Receptor Engagement Without Necessity For Identification Of The Relevant Antigen

Individual cancers, even of the same cell type, express unique arrays of distinctive tumor antigens, requiring accurate laboratory measurement of induced immunity against them problematic. Fluorescently tagged reagents (dextramers) that selectively engage clonal T-cell receptors (TCR) can cytofluorographically quantify both frequency and avidity antigen-specific T-cells, but cannot be synthesized without prior identification of the relevant antigen. Since clinically evident tumors may contain as many as 300 unique point mutations capable of generating a large number of uniquely antigenic proteins, and since procurement of such information for each cancer is currently unrealistic, it is presently only possible to assess responses to anti-cancer immunotherapy by clinical determination of estimation of the tumor burden capacity. Therefore, there is a need to develop methodology that can quantify the collective anti-tumor T-cell response, without prior identification of the full array of expressed tumor antigens. We have developed a practical high-resolution method to measure antigen-specific CD8 T-cell responses, via T-cell proton extrusion, an immediate result of selective TCR engagement by antigen presenting cells. The fluorescent emission characteristics of hydroxypyrene trisulfonate (HPTS) correlate with solution-phase proton concentrations, manifesting as increased emission signals. We exploit this TCR characteristic within the context of T-cell activation and show that stimulation with anti-CD3 immunoglobulin stimulates measureable TCR to release protons to a significantly higher degree than unengaged TCR (

Cranial neural crest cell contribution to craniofacial formation, pathology, and future directions in tissue engineering

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108634/1/bdrc21075.pd

The effect of comorbidities on overall mortality in Stevens- Johnson Syndrome: an analysis of the Nationwide Inpatient Sample

Background: Stevens Johnson Syndrome (SJS) is a lifethreateningskin condition with an overall mortalityrate of 5%. Although the causes and pathologyof the disease have been well studied, the factorsthat significantly contribute to mortality remainunclear. Objective: To determine relevant risk factorsthat increase the likelihood of inpatient mortalityafter diagnosis of SJS. Methods: A retrospectivecohort study of the 2010-2011 Healthcare Costsand Utilization Project (HCUP) Nationwide InpatientSample (NIS) database was conducted. This studyincluded 1,811 patients who encountered inpatienthospital stays with a discharge diagnosis of SJS.Results: The primary outcome of our study was inhospitalmortality. We analyzed the prevalence andassociated inpatient mortality of underlying criticalillness in patients with SJS. Three age ranges ofpatients in this study showed significantly increasedrates of inpatient mortality by odds-ratio with a 95%CI: 70-79 years (10.91% mortality, OR=4.57, p=0.001),80-89 years (10.67% mortality, OR=4.48, p=0.001), and90+ years (9.30% mortality, OR=4.22, p=0.028). Twocomorbid conditions showed significant associationwith increased inpatient mortality in SJS by odds-ratiowith a 95% CI: cirrhosis (14.58% mortality, OR=2.79,p=0.028) and metastatic disease (10.62% mortality,OR=1.87, p=0.031). Interpretation: Age (70+ years),cirrhosis, and metastatic disease were identified assignificantly associated with inpatient mortality afterdiagnosis with SJS. These findings enhance currentunderstanding of the pathology of this disease, aswell as help improve clinical management of high-riskpatients to reduce inpatient mortality

The effect of comorbidities on overall mortality in Stevens- Johnson Syndrome: an analysis of the Nationwide Inpatient Sample

Background: Stevens Johnson Syndrome (SJS) is a lifethreateningskin condition with an overall mortalityrate of 5%. Although the causes and pathologyof the disease have been well studied, the factorsthat significantly contribute to mortality remainunclear. Objective: To determine relevant risk factorsthat increase the likelihood of inpatient mortalityafter diagnosis of SJS. Methods: A retrospectivecohort study of the 2010-2011 Healthcare Costsand Utilization Project (HCUP) Nationwide InpatientSample (NIS) database was conducted. This studyincluded 1,811 patients who encountered inpatienthospital stays with a discharge diagnosis of SJS.Results: The primary outcome of our study was inhospitalmortality. We analyzed the prevalence andassociated inpatient mortality of underlying criticalillness in patients with SJS. Three age ranges ofpatients in this study showed significantly increasedrates of inpatient mortality by odds-ratio with a 95%CI: 70-79 years (10.91% mortality, OR=4.57, p=0.001),80-89 years (10.67% mortality, OR=4.48, p=0.001), and90+ years (9.30% mortality, OR=4.22, p=0.028). Twocomorbid conditions showed significant associationwith increased inpatient mortality in SJS by odds-ratiowith a 95% CI: cirrhosis (14.58% mortality, OR=2.79,p=0.028) and metastatic disease (10.62% mortality,OR=1.87, p=0.031). Interpretation: Age (70+ years),cirrhosis, and metastatic disease were identified assignificantly associated with inpatient mortality afterdiagnosis with SJS. These findings enhance currentunderstanding of the pathology of this disease, aswell as help improve clinical management of high-riskpatients to reduce inpatient mortality

Prescribing trends for biologic drugs among Ohio dermatologists

The role of biologic therapies in the field of dermatology continues to evolve as newer drugs and biosimilars are introduced to the U.S. market. Prescribing patterns and expenditures regarding biologic drugs are not well described. To address this knowledge gap, a retrospective review was conducted using the Medicare Provider Utilization and Payment Data: Part D Prescriber dataset between January 1st, 2013 and December 31st, 2015. The primary outcome was claims per provider per calendar year. Secondary outcomes included drug cost, shared cost per dermatologist, and practice location. Median claims per provider remained stable between 2013 and 2014 (24 versus 23, respectively; P=0.64). The majority of 2015 claims were for adalimumab (50.1%) and etanercept (41.4%). Total spending from Medicare payment data for biologic drugs prescribed by Ohio dermatologists increased by $3 million during the study period. The Gini coefficient for provider contributions to overall costs was 0.47, indicating moderate inequality among Ohio dermatologists. Spending associated with biologic drugs used for dermatologic indications is increasing in Ohio. As the market changes, providers should be aware of these patterns to better care for patients in need of biologic therapies

Prescribing trends for biologic drugs among Ohio dermatologists

The role of biologic therapies in the field of dermatology continues to evolve as newer drugs and biosimilars are introduced to the U.S. market. Prescribing patterns and expenditures regarding biologic drugs are not well described. To address this knowledge gap, a retrospective review was conducted using the Medicare Provider Utilization and Payment Data: Part D Prescriber dataset between January 1st, 2013 and December 31st, 2015. The primary outcome was claims per provider per calendar year. Secondary outcomes included drug cost, shared cost per dermatologist, and practice location. Median claims per provider remained stable between 2013 and 2014 (24 versus 23, respectively; P=0.64). The majority of 2015 claims were for adalimumab (50.1%) and etanercept (41.4%). Total spending from Medicare payment data for biologic drugs prescribed by Ohio dermatologists increased by $3 million during the study period. The Gini coefficient for provider contributions to overall costs was 0.47, indicating moderate inequality among Ohio dermatologists. Spending associated with biologic drugs used for dermatologic indications is increasing in Ohio. As the market changes, providers should be aware of these patterns to better care for patients in need of biologic therapies