Summary
The anti‐tumor immune response is considered to be due to the T‐cell receptor (TCR) binding to tumor antigens, which can be either wild‐type, early stem cell proteins, presumably foreign to a developed immune system; or mutant peptides, foreign to the immune system because of a mutant amino acid (aa) or otherwise somatically altered aa sequence. Recently, very large numbers of TCR complementarity‐determining region‐3 (CDR3) aa sequences obtained from tumor specimens have become available. We developed a novel algorithm for assessing the complementarity of tumor mutant peptides and TCR CDR3s, based on the retrieval of TCR CDR3 aa sequences from both tumor specimen and patient blood exomes and by using an automated process of assessing CDR3 and mutant aa electrical charges. Results indicated many instances where high electrostatic complementarity was associated with a higher survival rate. In particular, our approach led to the identification of specific genes contributing significantly to the complementary, TCR CDR3‐mutant aa. These results suggest a novel approach to tumor immunoscoring and may lead to the identification of high‐priority neo‐antigen, peptide vaccines; or to the identification of ex vivo stimulants of tumor‐infiltrating lymphocytes.
Objective: To assess 4 measures of the accumulating deficits model of frailty for postoperative mortality and readmissions including their stability over time. Background: Frailty has been assessed by multiple methods. It is unclear whether variation in how frailty is measured is important and would be stable over time. Methods: Rockwood's 57-item frailty index was mapped onto 14,568 ICD9 diagnosis codes from Healthcare Cost and Utilization Project State Inpatient Database for the state of Florida (HCUP-SID-FL) for calendar years 2011 to 2015, inclusive, with 962 ICD9 codes matching onto 42 items. This became the modified frailty index (mFI) used. Three measures of the mFI were differentiated: the number of admission diagnoses, number of chronic conditions upon admission, and number of increased deficits accumulated during the admission. The Charlson Co-Morbidity Index was a fourth measure of frailty. The mFI of patients who survived or died and were readmitted or not were compared.Results: Across all years, 4,796,006 patient observations were compared to the number of diagnoses matched on the 42 items of the mFI. The median mFI scores for each method was statistically significantly higher for patients who died compared those that survived and for patients readmitted compared to patients not readmitted for all years. There was little-to-no variation in the year to year median mFI scores. Conclusions: The 4 methods of calculating frailty performed similarly and were stable. The actual method of determining the accumulated deficits may not be as important as enumerating their number.
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