Globally, intracranial pressure (ICP) monitoring use in severe traumatic brain injury (sTBI) is inconsistent and susceptible to resource limitations and clinical philosophies. For situations without monitoring, there is no published comprehensive management algorithm specific to identifying and treating suspected intracranial hypertension (SICH) outside of the one ad hoc Imaging and Clinical Examination (ICE) protocol in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST:TRIP) trial. As part of an ongoing National Institutes of Health (NIH)-supported project, a consensus conference involving 43 experienced Latin American Intensivists and Neurosurgeons who routinely care for sTBI patients without ICP monitoring, refined, revised, and augmented the original BEST:TRIP algorithm. Based on BEST:TRIP trial data and pre-meeting polling, 11 issues were targeted for development. We used Delphi-based methodology to codify individual statements and the final algorithm, using a group agreement threshold of 80%. The resulting CREVICE (Consensus REVised ICE) algorithm defines SICH and addresses both general management and specific treatment. SICH treatment modalities are organized into tiers to guide treatment escalation and tapering. Treatment schedules were developed to facilitate targeted management of disease severity. A decision-support model, based on the group's combined practices, is provided to guide this process. This algorithm provides the first comprehensive management algorithm for treating sTBI patients when ICP monitoring is not available. It is intended to provide a framework to guide clinical care and direct future research toward sTBI management. Because of the dearth of relevant literature, it is explicitly consensus based, and is provided solely as a resource (a ''consensus-based curbside consult'') to assist in treating sTBI in general intensive care units in resource-limited environments.
5012 Background: Cisplatin-based neoadjuvant chemotherapy (CT) followed by radical cystectomy (RC) is a standard treatment for MIBC. PD-1/L1 inhibitors as single agent induce pathological complete responses (pCR) in this setting. Predictors of response are still ill defined. DUTRENEO trial aimed to prospectively explore the activity of anti-PDL1 + anti-CTLA4 vs CT in pts selected according to a tumor pro-inflammatory IFN-gamma signature (tumor immune score, TIS). Methods: Cisplatin-eligible pts with urothelial MIBC (cT2-T4a, N≤1, M0) candidates to RC were classified as “hot” or “cold” according to a tumor TIS determined by Nanostring technology. Patients with "hot" tumors were randomized to DU 1500 mg + TRE 75 mg every 4 weeks x 3 cycles or standard cisplatin-based CT (GEMCIS or MVACdd). Pts in the “cold” arm received standard CT. Primary endpoint was to achieve ≥8 pCR in the DU+TRE arm. PDL1 expression was assessed using immunohistochemistry. Results: 61 pts were recruited in 10 sites between oct-2018 and dec-2019. Pts randomized in the “hot” arms received standard CT (n = 22) or DU+TRE (n = 23) and had a pCR rate of 8/22 pts (36.4%) vs 8/23 pts (34.8%), respectively [OR = 0.923 (0.26 – 3.24)]. In the “cold” arm, 16 pts received CT obtaining a pCR rate of 68.8% (11/16 pts). There were more PDL1 low tumors in the "cold" TIS arm (10/12, 83.3%). pCR rate by PDL1 status is shown in the table. One pt in the DU+TRE arm refused RC. Full treatment was delivered to 81.3% of CT "cold" vs 59.1% of CT "hot" vs 73.9% in the DU+TRE arm pts. Grade 3-4 toxicities were more frequent in the CT arms. Conclusions: The combination of DU+TRE is safe and active in MIBC patients in the neoadjuvant setting. Nevertheless prospective stratification by a pro-inflammatory IFN-gamma signature failed to select patients more likely to benefit from IO vs CT in this context. Further studies are required to guide treatment selection. Clinical trial information: NCT03472274 . [Table: see text]
Abstract. The L2 Global Harmonization Team on large molecule specific assay operation for protein bioanalysis in support of pharmacokinetics focused on the following topics: setting up a balanced validation design, specificity testing, selectivity testing, dilutional linearity, hook effect, parallelism, and testing of robustness and ruggedness. The team additionally considered the impact of lipemia, hemolysis, and the presence of endogenous analyte on selectivity assessments as well as the occurrence of hook effect in study samples when no hook effect had been observed during pre-study validation.
This work describes the solvent-induced hallucinatory experiences of 10 male and seven female teenagers in Mexico City from 1998 to 2000. The youth were recruited from public schools through a combined snowball and convenience sampling procedure. Inclusion criteria were: 13-18 years of age, school attendance, living with family, and weekly toluene-based solvent misuse. Interested students were interviewed and transcripts were analyzed. Hallucinations and illusions were common, including changes in color perception, visual, somatic, auditory, and tactile hallucinations. Some users described their hallucinatory experience as being able to be shared by a group and modulated by their environment. The pharmacological linkages with hallucinations are discussed. The study's limitations are noted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.