Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients, and can be classified into mild, moderate, and severe by the Glasgow coma scale (GCS). Prehospital, initial emergency department, and subsequent intensive care unit (ICU) management of severe TBI should focus on avoiding secondary brain injury from hypotension and hypoxia, with appropriate reversal of anticoagulation and surgical evacuation of mass lesions as indicated. Utilizing principles based on the Monro–Kellie doctrine and cerebral perfusion pressure (CPP), a surrogate for cerebral blood flow (CBF) should be maintained by optimizing mean arterial pressure (MAP), through fluids and vasopressors, and/or decreasing intracranial pressure (ICP), through bedside maneuvers, sedation, hyperosmolar therapy, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or decompressive craniectomy (DC). While controversial, direct ICP monitoring, in conjunction with clinical examination and imaging as indicated, should help guide severe TBI therapy, although new modalities, such as brain tissue oxygen (PbtO2) monitoring, show great promise in providing strategies to optimize CBF. Optimization of the acute care of severe TBI should include recognition and treatment of paroxysmal sympathetic hyperactivity (PSH), early seizure prophylaxis, venous thromboembolism (VTE) prophylaxis, and nutrition optimization. Despite this, severe TBI remains a devastating injury and palliative care principles should be applied early. To better affect the challenging long-term outcomes of severe TBI, more and continued high quality research is required.

Objective: We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI).Summary Background Data: After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors. Methods:We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3-and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms

Objective: The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). Summary Background Data: Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. Methods: This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from −1 (worse than death) to 1 (full health), with 0 as reference (death). Results: Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. Conclusions: In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.

BACKGROUND Civilian penetrating traumatic brain injury (pTBI) is a serious public health problem in the United States, but predictors of outcome remain largely understudied. We previously developed the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) score, a logistic, regression-based risk stratification scale for estimating in-hospital and 6-mo survival after civilian pTBI with excellent discrimination (area under the receiver operating curve [AUC-ROC = 0.96]) and calibration, but it has not been validated. OBJECTIVE To validate the SPIN score in a multicenter cohort. METHODS We identified pTBI patients from 3 United States level-1 trauma centers. The SPIN score variables (motor Glasgow Coma Scale [mGCS], sex, admission pupillary reactivity, self-inflicted pTBI, transfer status, injury severity score, and admission international normalized ratio [INR]) were retrospectively collected from local trauma registries and chart review. Using the original SPIN score multivariable logistic regression model, AUC-ROC analysis and Hosmer–Lemeshow goodness of fit testing were performed to determine discrimination and calibration. RESULTS Of 362 pTBI patients available for analysis, 105 patients were lacking INR, leaving 257 patients for the full SPIN model validation. Discrimination (AUC-ROC = 0.88) and calibration (Hosmer–Lemeshow goodness of fit, P value = .58) were excellent. In a post hoc sensitivity analysis, we removed INR from the SPIN model to include all 362 patients (SPINNo-INR), still resulting in very good discrimination (AUC-ROC = 0.82), but reduced calibration (Hosmer–Lemeshow goodness of fit, P value = .04). CONCLUSION This multicenter pTBI study confirmed that the full SPIN score predicts survival after civilian pTBI with excellent discrimination and calibration. Admission INR significantly adds to the prediction model discrimination and should be routinely measured in pTBI patients.

INTRODUCTION Intensive care unit (ICU) survivorship is associated with long-term cognitive impairment (LTCI). Our work has found post-ICU depression in up to 30% and posttraumatic stress disorder (PTSD) in up to 10% of ICU survivors. We hypothesized that post-ICU depression and PTSD are independently associated with LTCI in ICU survivors. METHODS This is a five-center nested prospective cohort of critically ill patients admitted to medical and surgical ICUs who underwent neuropsychological assessments at 3 and 12 months posthospital discharge. Our primary outcome was global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making Test, Part B, a test of executive functioning, at 3- and 12-month follow-up. Our independent variables were Beck Depression Inventory II and the PTSD Checklist—Specific Version measured at 3 and 12 months. We performed multivariable linear regression models controlling for covariates such as age, years of education, preexisting cognitive impairment, comorbidities, ventilator days, hypoxemia episodes, and days of delirium or coma. RESULTS Of 1,047 patients in the combined cohort, 679 were alive and available for follow-up at 3 months. A total of 590 (87%) ICU survivors completed at least one 3-month assessment, and of the 554 who survived to 12 months, 519 (94%) completed both a 3- and 12-month assessment with a median age of 61 years (52–70 years) and mean daily Sequential Organ Failure Assessment score of 6 (4–8), 520 (88%) were mechanically ventilated, and 420 (71%) were with delirium. Of these, 113 (19%) had PTSD and 187 (32%) had depression at 3 months with similar rates at 12 months. Depression at 3 months was associated with lower 3-month RBANS (coefficient, −2.25; −3.10 to −1.39) and lower Trails B scores at both 3 months (odds ratio, 0.69; 0.56–0.85) and 12 months (odds ratio, 0.66; 0.52–0.84). Posttraumatic stress disorder at 3 months had no association with RBANS or Trails B scores at 3 or 12 months. CONCLUSION Early post-ICU depression, but not PTSD, is independently associated with coexisting LTCI, even when controlling for past ICU delirium. Treatment for early depression represents a novel intervention area for LTCI prevention in ICU survivors. LEVEL OF EVIDENCE Prognostic/epidemiological, level III.

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Critical illness is often painful, both from the underlying source of illness, as well as necessary procedures performed for the monitoring and care of these patients. Pain is often under-recognized in the critically ill, especially among those who cannot self-report, so accurate assessment and management continue to be major consideration in their care. Pain management in the intensive care unit (ICU) is an evolving practice, with a focus on accurate and frequent pain assessment, and targeted pharmacologic and non-pharmacologic treatment methods to maximize analgesia and minimize sedation. In this review, we will evaluate several validated methods of pain assessment in the ICU and present management options. We will review the evidence-based recommendations put forth by the largest critical care societies and several high-quality studies related to both the in-hospital approach to pain, as well as the short- and long-term consequences of untreated pain in ICU patients. We conclude with future directions.