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Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors., Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS)., Design, Setting, and Participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023., Interventions: Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab., Main Outcomes and Measures: The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months., Results: Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively., Conclusions and Relevance: In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS., Trial Registration: ClinicalTrials.gov Identifier: NCT03181100.

Hypothesis: Normal resuscitation (oxygen delivery index [DO2I] >/=500 mL/min per square meter), compared with supranormal trauma resuscitation (DO2I >/=600 mL/min per square meter), requires less crystalloid volume, thus decreasing the incidence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS)., Design: Retrospective analysis of a prospective database., Setting: Twenty-bed intensive care unit (ICU) in a regional level I trauma center., Patients: Patients with major trauma (injury severity score >15, initial base deficit >/=6 mEq/L, or need for >/=6 units of packed red blood cells in the first 12 hours) or age 65 years or older with any 2 of the previous criteria., Interventions: Shock/trauma resuscitation protocol: pulmonary artery catheter, gastric tonometry, urinary bladder pressure measurements, lactated Ringer infusion, packed red blood cell transfusion, and moderate inotrope support, as needed, in that sequence, to attain and maintain a DO2I greater than or equal to 600 mL/min per m2 (16 months, ending January 1, 2001, n = 85) or a DO2I greater than or equal to 500 mL/min per square meter (16 months, starting January 1, 2001, n = 71) for the first 24 hours in the ICU., Main Outcome Measures: Lactated Ringer infusion volume (liters) at ICU admission, gastric partial carbon dioxide minus end-tidal carbon dioxide(GAPCO2), IAH (urinary bladder pressure measurements >20 mm Hg), ACS (urinary bladder pressure measurements >25 mm Hg with organ dysfunction), multiple organ failure, and mortality., Results: Demographics, injury severity, and shock severity parameters were similar in both groups. The supranormal resuscitation group required more lactated Ringer infusion volume in the first 24 hours in the ICU (mean +/- SD, 13 +/- 2 vs 7 +/- 1 L; P<.05) and had higher GAPCO2 (16 +/- 2 vs 7 +/- 1 mm Hg; P<.05). In the supranormal group, IAH (42% vs 20%; P<.05) and ACS (16% vs 8%; P<.05) were more frequent. The conventional trauma outcomes, such as multiple organ failure (22% vs 9%; P<.05) and mortality (27% vs 11%; P<.05) were less favorable in the supranormal resuscitation group., Conclusion: Supranormal resuscitation, compared with normal resuscitation, was associated with more lactated Ringer infusion, decreased intestinal perfusion (higher GAPCO2), and an increased incidence of IAH, ACS, multiple organ failure, and death.

Hypothesis: Women respond better to standardized shock resuscitation compared with similarly severely injured men., Design: Severely injured patients who met specific criteria were resuscitated using a standardized protocol with no adjustment for gender. The resuscitation protocol was used to attain and to maintain an oxygen delivery index of 600 mL/min. m(2) or greater (DO(2)I > or = 600) for the first 24 hours in the intensive care unit (ICU). Interventions, responses, and outcomes for the 2 cohorts were compared. Data were analyzed using analysis of variance, chi(2), and t tests; P<.05 was considered significant., Setting: A 20-bed regional level I trauma center ICU., Patients: Patients at high risk of postinjury multiple organ failure (major organ or vascular injury and/or skeletal fractures, initial arterial base deficit of 6 mEq/L or greater, requirement for 6 units or more of packed red blood cells in the first 12 hours after hospital admission, or age > or = 65 years with any 2 previous criteria)., Interventions: Pulmonary artery catheter, packed red blood cell transfusion, crystalloid fluid infusion, inotrope, and vasopressor support, as needed, in that sequence, to maintain DO(2)I > or = 600., Main Outcome Measures: Hemodynamic response to resuscitation, fluid, and packed red blood cell volume., Results: During 2000, 58 patients (38 men, 20 women) met criteria and were resuscitated using our standardized protocol. Demographics and outcomes were similar for both cohorts. Requirements for and responses to standardized resuscitation were also similar, except for volume loading. The female cohort required less lactated Ringer solution volume (12 +/- 1 vs 8 +/- 2 L, P<.05), required less Starling curve intervention (42% vs 15%, P<.05), and maintained the DO(2)I goal with average pulmonary capillary wedge pressure that was less than that of the male cohort., Conclusion: Review of prospective data from standardized shock resuscitation for female and male cohorts demonstrates that women respond better to standardized resuscitation compared with similarly severely injured men.

Hypothesis: Old and young trauma patients are capable of hyperdynamic response during standardized shock resuscitation., Design: The responses of old and young trauma patients resuscitated using a standardized protocol are compared in an inception cohort study. A standardized resuscitation protocol was used to attain and maintain an oxygen delivery index of 600 mL/min x m2 or greater (DO2I > or = 600) for the first 24 hours in the intensive care unit. Interventions, responses, and outcomes for old (> or = 65 years) and young (<65 years) patients are described. Data were analyzed using analysis of variance, the chi2 test, and the t test; P<.05 was considered significant., Setting: A 20-bed shock trauma intensive care unit in a regional level I trauma center., Patients: Patients at high risk of postinjury multiple organ failure, ie, major organ or vascular injury and/or skeletal fractures, initial base deficit of 6 mEq/L or greater, need for 6 units or more of packed red blood cells in the first 12 hours, or age of 65 years or older with any 2 previous criteria., Interventions: Pulmonary artery catheter, crystalloid fluid infusion, packed red blood cell transfusion, and moderate inotrope support, as needed in that sequence, to attain DO2I > or = 600., Main Outcome Measures: Intensive care unit length of stay and survival., Results: During 19 months ending June 1999, 12 old patients (58% male; age, 76 +/- 2 years [mean +/- SEM] [P<.0011; Injury Severity Score, 20 +/- 2 [P=.02]) and 54 young patients (61% male; age, 37 +/- 2 years; Injury Severity Score, 32 +/- 2) were resuscitated. Initially, for old patients (cardiac index, 2.0 +/- 0.2 L/min x m2) and for young patients (cardiac index, 3.0 +/- 0.2 L/min x m2; P=.01), 24-hour volumes were as follows: 16 +/- 3 L of crystalloid and 12 +/- 3 units of packed red blood cells for the old patients and 21 +/- 2 L of crystalloid and 19 +/- 2 units of packed red blood cells for the young patients. For old patients, 9 (75%) attained DO2I > or = 600, and 11 (92%) survived 7 or more days and 5 (42%) 30 or more days. For young patients, 45 (83%) attained the DO2I goal, and 48 (89%) survived 30 or more days. Intensive care unit length of stay was 25 +/- 9 days for the old patients and 23 +/- 2 days for the young patients., Conclusions: Elderly patients have initially depressed cardiac index but generate hyperdynamic response. Although ultimate outcome is poorer than in the younger cohort, resuscitation is not futile.