Tumor Infiltrating Lymphocytes(Fujian Cancer Hospital)

Intracranial pressure (ICP) data from traumatic brain injury (TBI) patients in the intensive care unit (ICU) cannot be interpreted appropriately without accounting for the effect of administered therapy intensity level (TIL) on ICP. A 15-point scale was originally proposed in 1987 to quantify the hourly intensity of ICP-targeted treatment. This scale was subsequently modified-through expert consensus-during the development of TBI Common Data Elements to address statistical limitations and improve usability. The latest 38-point scale (hereafter referred to as TIL) permits integrated scoring for a 24-h period and has a five-category, condensed version (TIL^(Basic)) based on qualitative assessment. Here, we perform a total- and component-score analysis of TIL and TIL^(Basic) to: 1) validate the scales across the wide variation in contemporary ICP management; 2) compare their performance against that of predecessors; and 3) derive guidelines for proper scale use. From the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, we extract clinical data from a prospective cohort of ICP-monitored TBI patients (n = 873) from 52 ICUs across 19 countries. We calculate daily TIL and TIL^(Basic) scores (TIL₂₄ and TIL^(Basic)₂₄, respectively) from each patient's first week of ICU stay. We also calculate summary TIL and TIL^(Basic) scores by taking the first-week maximum (TIL_max and TIL^(Basic)_max) and first-week median (TIL_median and TIL^(Basic)_median) of TIL₂₄ and TIL^(Basic)₂₄ scores for each patient. We find that, across all measures of construct and criterion validity, the latest TIL scale performs significantly greater than or similarly to all alternative scales (including TIL^(Basic)) and integrates the widest range of modern ICP treatments. TIL_median outperforms both TIL_max and summarized ICP values in detecting refractory intracranial hypertension (RICH) during ICU stay. The RICH detection thresholds which maximize the sum of sensitivity and specificity are TIL_median ≥ 7.5 and TIL_max ≥ 14. The TIL₂₄ threshold which maximizes the sum of sensitivity and specificity in the detection of surgical ICP control is TIL₂₄ ≥ 9. The median scores of each TIL component therapy over increasing TIL₂₄ reflect a credible staircase approach to treatment intensity escalation, from head positioning to surgical ICP control, as well as considerable variability in the use of cerebrospinal fluid drainage and decompressive craniectomy. Since TIL^(Basic)_max suffers from a strong statistical ceiling effect and only covers 17% (95% confidence interval [CI]: 16-18%) of the information in TIL_max, TIL^(Basic) should not be used instead of TIL for rating maximum treatment intensity. TIL^(Basic)₂₄ and TIL^(Basic)_median can be suitable replacements for TIL₂₄ and TIL_median, respectively (with up to 33% [95% CI: 31-35%] information coverage) when full TIL assessment is infeasible. Accordingly, we derive numerical ranges for categorising TIL₂₄ scores into TIL^(Basic)₂₄ scores. In conclusion, our results validate TIL across a spectrum of ICP management and monitoring approaches. TIL is a more sensitive surrogate for pathophysiology than ICP and thus can be considered an intermediate outcome after TBI.