Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation.

BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 â€‹h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â€‹+ â€‹renal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â€‹% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

The patient's voice matters: The impact of advance directives on elderly trauma patients.

BACKGROUND: Geriatric trauma rates are increasing, yet trauma centers often struggle to provide autonomy regarding decision making to these patients. Advance care planning can assist with this process. Currently, there are limited data on the impact of advance directives (ADs) in elderly trauma patients. The purpose of this study was to evaluate the prevalence of preinjury AD in geriatric trauma patients and its impact on outcomes, with the hypothesis that ADs would not be associated with an increase in mortality. METHODS: A multicenter retrospective review was conducted on patients older than 65 years with traumatic injury between 2017 and 2019. Three Level I trauma centers and one Level II trauma center were included. Exclusion criteria were readmission, burn injury, transfer to another facility, discharge from emergency department, and mortality prior to being admitted. RESULTS: There were 6,135 patients identified; 751 (12.2%) had a preinjury AD. Patients in the AD+ group were older (86 vs. 77 years, p < 0.0001), more likely to be women (67.0% vs. 54.8%, p < 0.0001), and had more comorbidities. Hospital length of stay and ventilator days were similar. In-hospital mortality occurred in 236 patients, and 75.4% of them underwent withdrawal of care (WOC). The mortality rate was higher in AD+ group (10.5% vs. 2.9%, p < 0.0001). No difference was seen in the rate of AD between the WOC+ and WOC- group (31.5% vs. 39.6%, p = 0.251). A preinjury AD was identified as an independent predictor of mortality, but not a predictor of WOC. CONCLUSION: Despite a high WOC rate in patients older than 65 years, most patients did not have an AD prior to injury. As the elderly trauma population grows, advance care planning should be better integrated into geriatric care to encourage a patient-centered approach to end-of-life care. LEVEL OF EVIDENCE: Prognostic and epidemiological, level IV.

Early ventilator liberation and decreased sedation needs after tracheostomy in patients with COVID-19 infection.

BACKGROUND: Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, published tracheostomy guidelines have generally recommended deferral of the procedure beyond the initial weeks of intubation given high mortality as well as concerns about transmission of the infection to providers. It is unclear whether tracheostomy in patients with COVID-19 infection facilitates ventilator weaning, and long-term outcomes are not yet reported in the literature. METHODS: This is a retrospective study of tracheostomy outcomes in patients with COVID-19 infection at a single-center academic tertiary referral intensive care unit. Patients underwent percutaneous tracheostomy at the bedside; the procedure was performed with limited staffing to reduce risk of disease transmission. RESULTS: Between March 1 and June 30, 2020, a total of 206 patients with COVID-19 infection required mechanical ventilation and 26 underwent tracheostomy at a mean of 25±5 days after initial intubation. Overall, 81% of tracheostomy patients were liberated from the ventilator at a mean of 9±6 days postprocedure, and 54% were decannulated prior to hospital discharge at a mean of 21±10 days postprocedure. Sedation and pain medication requirements decreased significantly in the week after the procedure. In-hospital mortality was 15%. Among tracheostomy survivors, 68% were discharged to a facility. DISCUSSION: The management of patients with COVID-19 related respiratory failure can be challenging due to prolonged ventilator dependency. In our initial experience, outcomes post-tracheostomy in this population are encouraging, with short time to liberation from the ventilator, a high rate of decannulation prior to hospital discharge, and similar mortality to tracheostomy performed for other indications. Barriers to weaning ventilation in this cohort may be high sedation needs and ventilator dyssynchrony. LEVEL OF EVIDENCE: Level V-Therapeutic/care management.

A quasiexperimental study of targeted normoxia in critically ill trauma patients.

BACKGROUND: Avoidance of hypoxia and hyperoxia may reduce morbidity and mortality in critically ill civilian and military trauma patients. The objective of this study was to determine if a multimodal quality improvement intervention increases adherence to a consensus-based, targeted normoxia strategy. We hypothesized that this intervention would safely improve compliance with targeted normoxia. METHODS: This is a pre/postquasiexperimental pilot study to improve adherence to normoxia, defined as a pulse oximetry (SpO2) of 90% to 96% or an arterial partial pressure oxygen (PaO2) of 60 to 100 mm Hg. We used a multimodal informatics and educational intervention guiding clinicians to safely titrate supplemental oxygen to normoxia based on SpO2 monitoring in critically ill trauma patients admitted to the surgical-trauma or neurosurgical intensive care unit within 24 hours of emergency department arrival. The primary outcome was effectiveness in delivering targeted normoxia (i.e., an increase in the probability of being in the targeted normoxia range and/or a reduction in the probability of being on a higher fraction-inspired oxygen concentration [FiO2]). RESULTS: Analysis included 371 preintervention subjects and 201 postintervention subjects. Preintervention and postintervention subjects were of similar age, race/ethnicity, and sex and had similar comorbidities and Acute Physiologic and Chronic Health Evaluation II scores. Overall, the adjusted probability of being hyperoxic while on supplemental oxygen was reduced during the postintervention period (adjusted odds ratio, 0.74; 95% confidence interval, 0.57-0.97). There was a higher probability of being on room air (FiO2, 0.21) in the postintervention period (adjusted odds ratio, 1.38; 95% confidence interval, 0.83-2.30). In addition, there was a decreased amount of patient time spent on higher levels of FiO2 (FiO2, >40%) without a concomitant increase in hypoxia. CONCLUSION: A multimodal intervention targeting normoxia in critically ill trauma patients increased normoxia and lowered the use of supplemental oxygen. A large clinical trial is needed to validate the impact of this protocol on patient-centered clinical outcomes. LEVEL OF EVIDENCE: Therapeutic/care management, level II.

The Extremity/Mechanism/Shock Index/GCS (EMS-G) score: A novel pre-hospital scoring system for early and appropriate MTP activation.

BACKGROUND: Numerous in-hospital scoring systems to activate massive transfusion protocols (MTP) have been proposed; however, to date, pre-hospital scoring systems have not been robustly validated. Many trauma centers do not have blood or pre-thawed plasma available in the trauma bay, leading to delays in balanced transfusion. This study aims to assess pre-hospital injury and physiologic parameters to develop a pre-hospital scoring system predictive of need for massive transfusion (MT) prior to patient arrival. METHODS: A retrospective review of all adult full and partial trauma team activations from July 2014-July 2018 from an urban level 2 trauma center was performed utilizing our trauma registry. Stepwise logistic regression analysis was performed to develop a new scoring system, with point totals assigned proportional to the odds ratios of requiring MT for each variable. Internal validation of the EMS-G score was performed using a subset of the data which was not utilized for development of the scoring system, and sensitivity and specificity were compared to previously validated in-hospital scoring systems applied in the pre-hospital setting. RESULTS: 763 patients were included with 94 patients (12.3%) receiving early MT, defined as 4 units pRBC in 4 h or ED death. In-hospital models for predicting MT such as Assessment of Blood Consumption (ABC) or Shock Index (SI) have sensitivities and specificities of 46/85% and 94/79% respectively for early MTP utilization based on pre-hospital data. Pre-hospital variables found to be predictive of MT were used to develop the EMS-G (Extremity, Mechanism, Shock Index, GCS) score. This system assigns obvious extremity injury-1-point, penetrating mechanism -2 points, shock index ≥0.9-2 points, GCS ≤8-3 points. A score of 3 or greater was chosen to maximize sensitivity and specificity for pre-hospital MT activation. EMS-G score based on pre-hospital report is 89% sensitive, 84% specific, with a PPV of 44% and NPV of 98% for early MT. Using this system, 25% of full and partial trauma team activations met criteria for pre-hospital MTP activation. CONCLUSION: The EMS-G Score has increased sensitivity and specificity compared to the ABC Score in the pre-hospital setting and appears more appropriate than shock index alone at predicting massive transfusion. This scoring system allows trauma centers to activate MTP prior to patient arrival to ensure early and appropriate blood product administration without blood product wastage.

Protocol driven management of suspected common duct stones: A Southwestern Surgical Congress multi-centered trial.

BACKGROUND: Several options exist for the diagnosis and management of suspected common duct stones. We hypothesized that a protocol-directed approach would shorten length of stay in this patient population. METHODS: Patients from four participating institutions with a peak bilirubin <4 mg/dL underwent surgery as the initial procedure, whereas patients with a bilirubin ≥4 mg/dL underwent endoscopy. The primary endpoint was length of stay. Analysis involved chi square and Wilcoxon-Mann-Whitney test with significance at p < 0.05. RESULTS: 214 patients were managed under the protocol during six-month study period. 111 patients (52%) required endoscopy and surgery. Length of stay and the number of MRCPs performed pre-operatively significantly decreased following protocol implementation (p < 0.05). CONCLUSIONS: "Surgery first" approach in patients with bilirubin <4 ml/dL resulted in low morbidity and mortality, reduced MRCP, and length of stay.

Preventable death and interpersonal violence in the United States: Who can be saved?

BACKGROUND: Public health initiatives to reduce mortality from penetrating trauma have largely developed from patterns of injury observed in military casualties, with a focus on hemorrhage control and use of tourniquets. Recent efforts show that injury patterns differ between civilian mass casualty events and combat settings, and no studies characterize wounding patterns in all types of civilian homicide. We hypothesize that many homicide deaths are due to nonsurvivable injuries, and that an effective strategy to reduce mortality must focus on both primary prevention as well as improvement in trauma prehospital care. METHODS: We analyzed homicides from the National Violent Death Reporting System from 2012 to 2015. We excluded deaths due to poisoning, intentional neglect, or unknown weapon. Deaths were classified as "dead on scene" (DOS), "dead on arrival" (DOA), or "dead at or after hospital" (DAH) if the patient was admitted to a hospital. Injury patterns for penetrating weapons (firearms and sharp instruments) were further categorized. RESULTS: We included 18,051 homicides, the vast majority of which were due to firearms (n = 12,901 or 71.5%) or sharp instruments (n = 2,265 or 12.5%). The most common injury patterns included wounds to the chest or head, with isolated extremity injuries representing a minority of both firearms deaths (n = 397 of 12,901, 3.1%) and deaths from sharp instruments (n = 50 of 2,265, 2.2%). Furthermore, over half of all deaths occurred prehospital, with only 13.3% of victims admitted prior to death. CONCLUSION: The vast majority of deaths from interpersonal violence are due to firearm injuries. Few deaths appear to be related to extremity hemorrhage alone, and over half of all fatally injured died at the scene. Strategies to decrease mortality from interpersonal violence must go beyond treating injuries that have already occurred, and must address violence prevention directly. LEVEL OF EVIDENCE: Epidemiological study, level IV.

Cervical spine clearance when unable to be cleared clinically: a pooled analysis of combined computed tomography and magnetic resonance imaging.

BACKGROUND: The role of cervical spine magnetic resonance imaging (MRI) in the evaluation of clinically unevaluable blunt trauma patients has been called into question by several recent studies. METHODS: A PubMed search was performed for all studies comparing computed tomography and MRI in the assessment of the cervical spine in patients who cannot be evaluated clinically. The radiologic findings and clinical outcomes from each study were collated for analysis. RESULTS: Data for 1,714 patients were available. All patients had a negative computed tomography scan and then underwent an MRI. There were 271 (15.8%) patients who had a previously undocumented finding on MRI with the majority (98.2%) being a ligamentous injury. Only 5 injuries (1.8%) resulted in surgical intervention. CONCLUSIONS: MRI identifies additional injuries; however, the vast majority are of minor clinical significance. Routine MRI after a negative computed tomography of the cervical spine is not supported by the current literature.

Re-evaluating the need for hospital admission and observation of pediatric traumatic brain injury after a normal head CT.

There is no consensus on the optimal management of pediatric patients with suspected trauma brain injury and a normal head CT. This study characterizes the clinical outcomes of patients with a normal initial CT scan of the head. A retrospective chart review of pediatric blunt trauma patients who underwent head CT for closed head injury at two trauma centers was performed. Charts were reviewed for demographics, neurologic function, CT findings, and complications. 631 blunt pediatric trauma patients underwent a head CT. 63% had a negative CT, 7% had a non-displaced skull fracture, and 31% had an intracranial hemorrhage and/or displaced skull fracture. For patients without intracranial injury, the mean age was 8 years, mean ISS was 5, and 92% had a GCS of 13-15 on arrival. All patients with an initial GCS of 13-15 and no intracranial injury were eventually discharged to home with a normal neurologic exam and no patient required craniotomy. Not admitting those children with an initial GCS of 13-15, normal CT scan, and no other injuries would have saved 1.8 ± 1.5 hospital days per patient. Pediatric patients who have sustained head trauma, have a negative CT scan, and present with a GCS 13-15 can safely be discharged home without admission.

Hyperosmolarity invokes distinct anti-inflammatory mechanisms in pulmonary epithelial cells: evidence from signaling and transcription layers.

Hypertonic saline (HTS) has been used intravenously to reduce organ dysfunction following injury and as an inhaled therapy for cystic fibrosis lung disease. The role and mechanism of HTS inhibition was explored in the TNFα and IL-1ß stimulation of pulmonary epithelial cells. Hyperosmolar (HOsm) media (400 mOsm) inhibited the production of select cytokines stimulated by TNFα and IL-1ß at the level of mRNA translation, synthesis and release. In TNFα stimulated A549 cells, HOsm media inhibited I-κBα phosphorylation, NF-κB translocation into the nucleus and NF-κB nuclear binding. In IL-1ß stimulated cells HOsm inhibited I-κBα phosphorylation without affecting NF-κB translocation or nuclear binding. Incubation in HOsm conditions inhibited both TNFα and IL-1ß stimulated nuclear localization of interferon response factor 1 (IRF-1). Additional transcription factors such as AP-1, Erk-1/2, JNK and STAT-1 were unaffected by HOsm. HTS and sorbitol supplemented media produced comparable outcomes in all experiments, indicating that the effects of HTS were mediated by osmolarity, not by sodium. While not affecting MAPK modules discernibly in A549 cells, both HOsm conditions inhibit IRF-1 against TNFα or IL-1ß, but inhibit p65 NF-kB translocation only against TNFα but not IL-1ß. Thus, anti-inflammatory mechanisms of HTS/HOsm appear to disrupt cytokine signals at distinct intracellular steps.

Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells.

Resuscitation with hypertonic saline (HTS) attenuates acute lung injury (ALI) and modulates postinjury hyperinflammation. TNF-alpha-stimulated pulmonary epithelium is a major contributor to hemorrhage-induced ALI. We hypothesized that HTS would inhibit TNF-alpha-induced nuclear factor (NF)-kappaB proinflammatory signaling in pulmonary epithelial cells. Therefore, we pretreated human pulmonary epithelial cells (A549) with hypertonic medium (180 mM NaCl) for 30 min, followed by TNF-alpha stimulation (10 ng/mL). Key regulatory steps and protein concentrations in this pathway were assessed for significant alterations. Hypertonic saline significantly reduced TNF-alpha-induced intercellular adhesion molecule 1 levels and NF-kappaB nuclear localization. The mechanism is attenuated phosphorylation and delayed degradation of IkappaB alpha. Hypertonic saline did not alter TNF-alpha-induced p38 mitogen-activated protein kinase phosphorylation or constitutive vascular endothelial growth factor expression, suggesting that the observed inhibition is not a generalized suppression of protein phosphorylation or cellular function. These results show that HTS inhibits TNF-alpha-induced NF-kappaB activation in the pulmonary epithelium and, further, our understanding of its beneficial effects in hemorrhage-induced ALI.

Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal.

Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long-term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow-up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1- and 5-year recurrence-free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one-half of the patients were able to remain CS-free.

Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience.

Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long-term outcome. This study sought to identify clinical and pathologic variables predictive of long-term disease-free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus-based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence-free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P<0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.