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Immune checkpoint inhibitors (ICI) are now routinely used in multiple cancers but may induce autoimmune-like side effects known as immune-related adverse events (irAE). Although classical autoimmune diseases have well-known risk factors, including age, gender, and seasonality, the clinical factors that lead to irAEs are not well-defined. To explore these questions, we assessed 455 patients with advanced melanoma treated with ICI at our center and a large pharmacovigilance database (VigiBase). We found that younger age was associated with a similar rate of any irAEs but more frequent severe irAEs and more hospitalizations (OR, 0.97 per year). Paradoxically, however, older patients had more deaths and increased length of stay (LOS) when hospitalized. This was partially due to a distinct toxicity profile: Colitis and hepatitis were more common in younger patients, whereas myocarditis and pneumonitis had an older age distribution both in our center and in VigiBase. This pattern was particularly apparent with combination checkpoint blockade with ipilimumab and nivolumab. We did not find a link between gender or seasonality on development of irAEs in univariate or multivariate analyses, although winter hospitalizations were associated with marginally increased LOS. This study identifies age-specific associations of irAEs.
©2020 American Association for Cancer Research.

BACKGROUND - Musculoskeletal pediatric firearm injuries are a clinically significant and expensive public health problem in the United States. In this retrospective cohort analysis, we sought to characterize musculoskeletal firearm injuries in children and to describe the financial burden associated with these injuries.
METHODS - This study is a single center, retrospective review. Patients were identified from January 2002 - December 2015 from an institutional database using ICD-9 codes pertaining to firearm injury. Inclusion criteria were: 1) age < 18 years at injury; 2) firearm injury to an extremity, spine, or pelvis; and 3) patient received orthopedic evaluation and/or treatment. 140 patients with 142 distinct orthopedic injuries meeting inclusion criteria were analyzed (N = 142). Primary measures were demographic and situational data including intent, length of stay, follow-up, and complications; and financial outcomes including charges, costs, and net revenues.
RESULTS - Median age was 15.3 years [IQR: 13.3, 16.4], 84% were male, and 52% were African American. 59% of the firearm injuries were of violent intent. 32% of patients were privately insured, 61% were publicly insured, and 6% were uninsured. Median length of stay was 2 days [0, 4], with 73% of patients being admitted. 43% of patients required additional hospitalizations, emergency room visits, and/or outpatient surgeries, and 93% of patients had outpatient follow-up. 42% of patients experience an injury-related or long-term orthopedic complication. Total charges for the cohort were $11.4 million, with $3.7 million in costs and $45,042 in net revenues. In the multivariable analysis, more surgeries predicted higher charges, and more secondary encounters predicted higher costs and net revenues. Only privately-insured patients had a positive median net revenue.
CONCLUSIONS - Children who sustain musculoskeletal injuries from firearms experience high rates of orthopedic complications. Institutional costs to manage these preventable injuries are excessive. Policy makers should continue to pursue measures to reduce gun violence and improve gun safety in the pediatric population.
LEVEL OF EVIDENCE - Level III, economic/decision.
Copyright © 2019 Elsevier Inc. All rights reserved.

BACKGROUND - Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for.
METHODS - Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation.
RESULTS - Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2-6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28-3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10-4.10, P = 0.024).
CONCLUSIONS - First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.

Background - Trauma-related hospitalizations drive a high percentage of health care expenditure and inpatient resource consumption, which is directly related to length of stay (LOS). Robust and reliable interactions among health care employees can reduce LOS. However, there is little known about whether certain patterns of interactions exist and how they relate to LOS and its variability. The objective of this study is to learn interaction patterns and quantify the relationship to LOS within a mature trauma system and long-standing electronic medical record (EMR).
Methods - We adapted a spectral co-clustering methodology to infer the interaction patterns of health care employees based on the EMR of 5588 hospitalized adult trauma survivors. The relationship between interaction patterns and LOS was assessed via a negative binomial regression model. We further assessed the influence of potential confounders by age, number of health care encounters to date, number of access action types care providers committed to patient EMRs, month of admission, phenome-wide association study codes, procedure codes, and insurance status.
Results - Three types of interaction patterns were discovered. The first pattern exhibited the most collaboration between employees and was associated with the shortest LOS. Compared to this pattern, LOS for the second and third patterns was 0.61 days (P = 0.014) and 0.43 days (P = 0.037) longer, respectively. Although the 3 interaction patterns dealt with different numbers of patients in each admission month, our results suggest that care was provided for similar patients.
Discussion - The results of this study indicate there is an association between LOS and the extent to which health care employees interact in the care of an injured patient. The findings further suggest that there is merit in ascertaining the content of these interactions and the factors that induce these differences in interaction patterns within a trauma system.

BACKGROUND - The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.
METHODS - Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status.
RESULTS - Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829).
CONCLUSIONS - Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000-2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P = 0.001), lower operative blood loss (192 vs 392 mL; P = 0.001), and shorter hospital stay(5 vs 7 days; P = 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n = 46) had similar advantages as laparoscopic/robotic (n = 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P = 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P = 0.001) and shorter hospital stay (5 vs 7 days; P = 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN.

INTRODUCTION - Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.
METHODS - An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.
RESULTS - Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality.
CONCLUSION - Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.

Obstetric care refers to the care provided to patients during ante-, intra-, and postpartum periods. Predicting length of stay (LOS) for these patients during their hospitalizations can assist healthcare organizations in allocating hospital resources more effectively and efficiently, ultimately improving maternal care quality and reducing costs to patients. In this paper, we investigate the extent to which LOS can be forecast from a patient's medical history. We introduce a machine learning framework to incorporate a patient's prior conditions (e.g., diagnostic codes) as features in a predictive model for LOS. We evaluate the framework with three years of historical billing data from the electronic medical records of 9188 obstetric patients in a large academic medical center. The results indicate that our framework achieved an average accuracy of 49.3%, which is higher than the baseline accuracy 37.7% (that relies solely on a patient's age). The most predictive features were found to have statistically significant discriminative ability. These features included billing codes for normal delivery (indicative of shorter stay) and antepartum hypertension (indicative of longer stay).

BACKGROUND - The prognostic importance of subsyndromal delirium is unknown.
OBJECTIVE - To test whether duration of subsyndromal delirium is independently associated with institutionalization.
METHODS - The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was used twice daily to assess for subsyndromal delirium in patients with respiratory failure or shock. Delirium was considered present if the assessment was positive. Subsyndromal delirium was considered present if the assessment was negative but the patient exhibited any CAM-ICU features. Multivariable regression was used to determine the association between duration of subsyndromal delirium and institutionalization, adjusting for age, education, baseline cognition and disability, comorbidities, severity of illness, delirium, coma, sepsis, and doses of sedatives and opiates.
RESULTS - Subsyndromal delirium, lasting a median of 3 days, developed in 702 of 821 patients (86%). After adjusting for covariates, duration of subsyndromal delirium was an independent predictor of increased odds of institutionalization ( = .007). This association was greatest in patients with less delirium ( for interaction = .01). Specifically, of patients who were never delirious, those with 5 days of subsyndromal delirium (upper interquartile range [IQR]) were 4.2 times more likely to be institutionalized than those with 1.5 days of subsyndromal delirium (lower IQR).
CONCLUSIONS - Subsyndromal delirium occurred in most critically ill patients, and its duration was an independent predictor of institutionalization. Routine monitoring of all delirium symptoms may enable detection of full and subsyndromal forms of delirium.
©2017 American Association of Critical-Care Nurses.