The presence of S-sulfonated transthyretin in commercial human serum albumin solutions: Potential contribution to neuropathy.

BACKGROUND: Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. METHODS: Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. RESULTS: The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. CONCLUSIONS: Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.

Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways.

Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation.

Subway-Related Trauma: An Urban Public Health Issue with a High Case-Fatality Rate.

BACKGROUND: Between 1990 and 2003, there were 668 subway-related fatalities in New York City. However, subway-related trauma remains an understudied area of injury-related morbidity and mortality. OBJECTIVE: The objective of this study was to characterize the injuries and events leading up to the injuries of all patients admitted after subway-related trauma. METHODS: We conducted a retrospective case series of subway-related trauma at a Level I trauma center from 2001 to 2016. Descriptive epidemiology of patient demographics, incident details, injuries, and outcomes were analyzed. RESULTS: Over 15 years, 254 patients were admitted for subway-related trauma. The mean (standard error of the mean) age was 41 (1.0) years, 80% were male (95% confidence interval [CI] 74-84%) and median Injury Severity Score was 14 (interquartile range [IQR] 5-24). The overall case-fatality rate was 10% (95% CI 7-15%). The most common injuries were long-bone fractures, intracranial hemorrhage, and traumatic amputations. Median length of stay was 6 days (IQR 1-18 days). Thirty-seven percent of patients required surgical intervention. At the time of injury, 55% of patients (95% CI 49-61%) had a positive urine drug or alcohol screen, 16% (95% CI 12-21%) were attempting suicide, and 39% (95% CI 33-45%) had a history of psychiatric illness. CONCLUSIONS: Subway-related trauma is associated with a high case-fatality rate. Alcohol or drug intoxication and psychiatric illness can increase the risk of this type of injury.

Communication skills training in surgical residency: a needs assessment and metacognition analysis of a difficult conversation objective structured clinical examination.

BACKGROUND: The objective structured clinical examination (OSCE) can be used to evaluate the Accreditation Council for Graduate Medical Education Core Competencies of Professionalism and Interpersonal and Communication Skills. The aim of this study was to describe general surgery resident performance on a "difficult conversation" OSCE. METHODS: In this prospective study, junior and senior residents participated in a 2-station OSCE. Junior stations involved discussing operative risks and benefits and breaking bad news. Senior stations involved discussing goals of care and discussing transition to comfort measures only status. Residents completed post-OSCE checklist and Likert-based self-evaluations of experience, comfort, and confidence. Trained standardized patients (SPs) evaluated residents using communication skill-based checklists and Likert-based assessments. Pearson correlation coefficients were determined between self-assessment and SP assessment. Mann-Whitney U tests were conducted between junior and senior resident variables, using α = 0.05. RESULTS: There were 27 junior residents (age 28.1 ± 1.9 years [29.6% female]) and 27 senior residents (age 32.1 ± 2.5 years [26.9% female]). The correlation of self-assessment and SP assessment of overall communication skills by junior residents was -0.32 on the risks and benefits case and 0.07 on the breaking bad news case. The correlation of self-assessment and SP assessment of overall communication skills by senior residents was 0.30 on the goals of care case and 0.26 on the comfort measures only case. SP assessments showed that junior residents had higher overall communication skills than senior residents (p = 0.03). Senior residents perceived that having difficult conversations was more level appropriate (p < 0.001), and they were less nervous having difficult conversations (p < 0.01) than junior residents. CONCLUSIONS: We found that residents perform difficult conversations well, that subjective and objective skills are correlated, and that skills-based training is needed across all residency levels. This well-received method may be used to observe, document, and provide resident feedback for these important skills.

Evaluation and management of geriatric trauma: an Eastern Association for the Surgery of Trauma practice management guideline.

BACKGROUND: Aging patients constitute an increasing proportion of patients treated at trauma centers. Previous and existing guidelines addressing care of the injured elder have not adequately addressed emerging data regarding optimal means for undertaking triage decisions, correcting coagulopathy, and the limitations of supraphysiologic resuscitation. METHODS: More than 400 MEDLINE citations published between the years 2000 and 2008 were identified and screened. A total of 90 references were selected for the evidentiary table followed by consensus-based discussions regarding the level of evidence and the strength of recommendations that could be derived from the related findings of the individual studies. RESULTS: In general, a lower threshold for trauma activation should be used for injured patients aged 65 years or older who are evaluated at trauma centers. Furthermore, elderly patients with at least one body system with an AIS score of 3 or higher or a base deficit of -6 or less should be treated at trauma centers, preferably in intensive care units staffed by surgeon-intensivists. In addition, all elderly patients who receive daily therapeutic anticoagulation should have appropriate assessment of their coagulation profile and cross-sectional imaging of the brain as soon as possible after admission where appropriate. In patients aged 65 years or older with a Glasgow Coma Scale (GCS) score less than 8, if substantial improvement in GCS is not realized within 72 hours of injury, consideration should be given to limiting further aggressive therapeutic interventions. CONCLUSION: Effective evidence-based care of aging patients necessitates aggressive triage, correction of coagulopathy, and limitation of care when clinical evidence points toward an overwhelming likelihood of poor long-term prognosis.

Defining geriatric trauma: when does age make a difference?

BACKGROUND: Injured elderly patients experience high rates of undertriage to trauma centers (TCs) whereas debate continues regarding the age defining a geriatric trauma patient. We sought to identify when mortality risk increases in injured patients as the result of age alone to determine whether TC care was associated with improved outcomes for these patients and to estimate the added admissions burden to TCs using an age threshold for triage. METHODS: We performed a retrospective cohort study of injured patients treated at TCs and non-TCs in Pennsylvania from April 1, 2001, to March 31, 2005. Patients were included if they were between 19 and 100 years of age and had sustained minimal injury (Injury Severity Score < 9). The primary outcome was in-hospital mortality. We analyzed age as a predictor of mortality by using the fractional polynomial method. RESULTS: A total of 104,015 patients were included. Mortality risk significantly increased at 57 years (odds ratio 5.58; 95% confidence interval 1.07-29.0; P = .04) relative to 19-year-old patients. TC care was associated with a decreased mortality risk compared with non-TC care (odds ratio 0.83; 95% confidence interval 0.69-0.99; P = .04). Using an age of 70 as a threshold for mandatory triage, we estimated TCs could expect an annual increase of approximately one additional admission per day. CONCLUSION: Age is a significant risk factor for mortality in trauma patients, and TC care improves outcomes even in older, minimally injured patients. An age threshold should be considered as a criterion for TC triage. Use of the clinically relevant age of 70 as this threshold would not impose a substantial increase on annual TC admissions.

Radiographic assessment of splenic injury without contrast: is contrast truly needed?

INTRODUCTION: Computed tomography (CT) has become an essential tool in the assessment of the stable trauma patient. Intravenous (i.v.) contrast is commonly relied upon to provide superior image quality, particularly for solid-organ injury. However, a substantial proportion of injured patients have contraindications to i.v. contrast. Little information exists concerning the repercussions of CT imaging without i.v. contrast, specifically for splenic injury. METHODS: We performed a retrospective analysis using data from our trauma registry and chart review as part of a quality improvement project at our institution. All patients with splenic injury, during a 3-year period (2008-2010), where a CT of the abdomen without i.v. contrast (DRY) early during their admission were selected. All splenic injuries had to have been verified with abdominal CT imaging with i.v. contrast (CONTRAST) or via intraoperative findings. DRY images were independently read by a single, blinded, radiologist and assessed for parenchymal injury or "suspicious" splenic injury findings and compared with CONTRAST imaging results or intraoperative findings. RESULTS: During the time period of the study, 319 patients had documented splenic injury with 44 (14%) patients undergoing DRY imaging, which was also verified by CONTRAST imaging or operative findings. Splenic parenchymal injury was only visualized in 38% of patients DRY patients. "Suspicious" splenic injury radiographic findings were common. When these less-specific findings for splenic injury were incorporated in the radiographic assessment, DRY imaging had more than 93% sensitivity for detecting splenic injury. CONCLUSION: DRY imaging is increasingly being performed after injury and has a low sensitivity in detecting splenic parenchymal injury. However, less-specific radiographic findings suspicious for splenic injury in combination provide high sensitivity for the detection of splenic injury. These results suggest CONTRAST imaging is preferred to detect splenic injury; however, in those patients who have contraindications to i.v. contrast, DRY imagining may be able to select those who require close monitoring or intervention.

Massive transfusion: an evidence-based review of recent developments.

The design and implementation of massive transfusion protocols with ratio-based transfusion of blood and blood products are important and active areas of investigation. A significant yet controversial body of literature exists to support the use of hemostatic resuscitation in massive transfusion and new data to support the use of adjuncts, such as recombinant factor VIIa and tranexamic acid. We review the developments in massive transfusion research during the past 5 years, including protocol implementation, hemostatic resuscitation, the use of tranexamic acid, and goal-directed therapy for coagulopathy. Furthermore, we provide a level of evidence analysis of the data surrounding the use of component therapy and recombinant factor VIIa in massive transfusion, summary recommendations for the various agents of resuscitation, and new methods of goal-directed therapy.

Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury.

BACKGROUND: Platelet transfusion is utilized increasingly for traumatic brain injury (TBI) for the reversal of aspirin (ASA) therapy. Assessment of platelet inhibition and reversal by platelet transfusion after TBI has not been adequately characterized. METHODS: A retrospective cohort analysis of TBI patients at a level I trauma center (January 2008-December 2009) was performed. The Aspirin Response Test (ART; VerifyNow) was used to assess platelet inhibition in TBI patients and guide platelet transfusion in patients with ASA-induced suppression. A follow-up ART was obtained after platelet administration. Primary endpoints were progression of intracranial hemorrhage on computed tomography, need for craniotomy, and mortality. RESULTS: We analyzed 84 patients (median age, 78 [interquartile range, 64-86)]; 54% male). ASA use was documented in 36 (42%) patients. Initial ART indicated platelet dysfunction in 54 (64%) patients, including 42% of patients without a documented history of ASA use. Of the patients with a documented history of ASA, 2.4% had a normal ART. Of those with an initial ART of <550 ASA response units, 45 received platelets. Repeat ART demonstrated reversal of inhibition in 29 patients (64.4%). Initial responders to transfusion received a greater volume of platelets, suggesting a dose-response relationship. Logistic regression revealed a trend toward higher mortality in nonresponders to transfusion (P = .09). Receiver operating characteristic curve analysis revealed that ART results increased prediction of poor outcome compared with ASA history alone (area under the curve = 0.760 and 0.775, respectively). CONCLUSION: The ART should be used to better target and guide platelet transfusions in TBI patients with known or suspected ASA use history. Patients with occult platelet dysfunction can be identified, unnecessary platelet transfusions avoided, and the adequate volume of platelets administered to correct drug-induced dysfunction. A dose-response relationship between quantity of platelets transfused and reversal of ASA inhibition was observed.

Early lower extremity fracture fixation and the risk of early pulmonary embolus: filter before fixation?

BACKGROUND: Venous thromboembolism is a major cause of morbidity and mortality after injury. Prophylactic anticoagulation is often delayed as a result of injuries or required procedures. Those patients at highest risk in this early vulnerable window postinjury are not well characterized. We sought to determine those patients at highest risk for an early pulmonary embolism (PE) after injury. METHODS: A retrospective analysis using data derived from a large state wide trauma registry (1997-2007) was performed. Patients with a documented PE and time of occurrence were selected (n = 712). Patients with fat emboli and lower extremity vascular injuries were excluded. Patients with a PE within the first 72 hours of admission (EARLY, n = 122) were compared with those with DELAYED presentation. Kaplan-Meier survival analysis was used to characterize the timing of death between the two groups. Backward stepwise logistic regression was used to determine independent risk factors for EARLY PE relative to those with DELAYED PE. RESULTS: EARLY and DELAYED groups were similar in age, gender, Glasgow Coma Scale, emergency department systolic blood pressure, and injury mechanism. The EARLY PE group had a lower Injury Severity Score but injuries more commonly included femur fracture. Kaplan-Meier analysis revealed that EARLY PE patients have a significantly higher risk of early mortality relative to DELAYED PE patients (p = 0.012). Regression analysis revealed that the only independent risk factor for EARLY PE was lower extremity/pelvic orthopedic fixation (<48 hours from injury). The risk of EARLY PE was more than threefold higher (odds ratios, 3.85; 95% CI, 1.9-7.6; p < 0.001) for those who underwent early lower extremity orthopedic fixation versus those who did not. CONCLUSION: Early lower extremity/pelvis orthopedic fixation is the single independent predictor of EARLY PE in this patient cohort. Venous thromboembolism/PE prevention strategies should be made a priority in this group of patients, including early preoperative institution of anticoagulation prophylaxis. These results suggest that those with contraindications to early anticoagulation may benefit from insertion of retrievable inferior vena cava filters preoperatively.

Over reliance on computed tomography imaging in patients with severe abdominal injury: is the delay worth the risk?

BACKGROUND: Computed tomography (CT) has a high sensitivity and specificity for detecting abdominal injuries. Expeditious abdominal imaging in "quasi-stable" patients may prevent negative laparotomy. However, the significance of potential delay to laparotomy secondary to abdominal imaging remains unknown. We sought to analyze whether the use of abdominal CT (ABD CT) in patients with abdominal injury requiring laparotomy results in a significant delay and a higher risk of poor outcome. METHODS: A retrospective analysis of data from the National Trauma Data Bank (version 7.1) was performed. Inclusion criteria were adult patients (age>14 years), a scene admission (nontransfer), hypotension on arrival (emergency department systolic blood pressure<90 mm Hg), an abdominal Abbreviated Injury Scale (AIS) score>3, and undergoing a laparotomy within 90 minutes of arrival. Patients with severe brain injury (head AIS score>3) were excluded. The independent mortality risk associated with a preoperative ABD CT was determined using logistic regression after controlling important confounders. RESULTS: This cohort of patients (n=3,218) was significantly injured with a median Injury Severity Score of 25 ([interquartile range, 16-34]). Patients who underwent ABD CT had similar Glasgow Coma Scale scores, a lower head AIS, longer time delays to the operating room, and a higher crude mortality (45% vs. 30%; p=0.001). Logistic regression revealed that ABD CT was independently associated with more than a 70% higher risk of mortality (odds ratios, 1.71; 95% CI, 1.2-2.2; p<0.001). When stratified by injury mechanism, intubation status and whether or not a head CT was performed, the mortality risk remained significantly increased for each subgroup. When the laparotomy was able to occur within 30 minutes of arrival, an ABD CT was independently associated with more than a sevenfold higher risk of mortality (odds ratios, 7.6; p=0.038). CONCLUSION: Delay secondary to abdominal imaging in patients who require operative intervention results in an independent higher risk of mortality. ABD CT imaging is an important and useful tool after injury; however, these results suggest that delay caused by overreliance on ABD CT may result in poor outcome in specific patients. Clinicians who take care of critically injured patients should be aware of and understand these potential risks.

Incidental radiographic findings after injury: dedicated attention results in improved capture, documentation, and management.

BACKGROUND: With liberal use of computed tomography in the diagnostic management of trauma patients, incidental findings are common and represent a major patient-care and medical-legal concern. Consequently, we began an initiative to capture, notify, and documentadequately incidental finding events with a dedicated incidental finding coordinator. We hypothesized a dedicated incidental finding coordinator would increase incidental finding capture and promote notification, follow-up, and documentation of incidental finding events. METHODS: A quality-improvement project to record and follow-up incidental findings postinjury was initiated at our level I trauma center (April 2007-March 2008, prededicated incidental finding). Because of concerns for inadequate documentation of identified incidental finding events, we implemented a dedicated incidental finding coordinator (April 2008-March 2009, postdedicated incidental finding). The dedicated incidental finding coordinator documented incidental findings daily from trauma admission radiology final reads. Incidental findings were divided into 3 groups; category 1: attention prior to discharge; category 2: follow-up with primary doctor within 2 weeks; category 3: no specific follow-up. For category 1 incidental findings, in-hospital consultation of the appropriate service was verified. On discharge, patient notification, follow-up, and documentation of events were confirmed. Certified mail or telephone contact was used to notify either the patient or the primary doctor in those who lacked appropriate notification or documentation. RESULTS: Admission rates and incidental finding categories were similar across the 2 time periods. Implementation of a dedicated incidental finding coordinator resulted in more than a 165% increase in incidental finding capture (n = 802 vs n = 302; P < .001). Patient notification was attempted, and appropriate documentation of events was confirmed in 99.8% of patients. Patient notification was verified, and follow-up was initiated in 95.8% of cases. CONCLUSION: The implementation of a dedicated incidental finding coordinator resulted in more than a 2.5-fold higher capture of incidental findings. Dedicated attention to incidental findings resulted in a near complete initiation of patient notification, follow-up, and hospital record documentation of incidental finding events. Inadequate patient notification and follow-up would delay appropriate care and potentially would result in morbidity or even mortality. A dedicated incidental finding coordinator represents a potential solution to this patient-care and medical-legal dilemma.

Pentobarbital coma for refractory intra-cranial hypertension after severe traumatic brain injury: mortality predictions and one-year outcomes in 55 patients.

OBJECTIVE: To identify predictors of mortality and long-term outcomes in survivors after pentobarbital coma (PBC) in patients failing current treatment standards for severe traumatic brain injuries (TBI). This is a retrospective cohort study of severe TBI patients receiving PBC at Level I Trauma Center and tertiary university hospital. METHODS: Four thousand nine hundred thirty-four patients were admitted to the trauma intensive care unit with severe TBI (head Abbreviated Injury Scale >or= 3) between April 1998 and December 2004. Six hundred eleven received intracranial pressure (ICP) monitoring and 58 received PBC. Three patients underwent craniotomy for intracranial mass lesion and were excluded. The study group received standardized medical management for severe TBI including opiates, benzodiazepines, elevation of the head of bed, avoidance of hypotension and hypercapnia and hyperosmolar therapy (HOsmRx). In addition, 31 of 55 patients (56%) underwent placement of intraventricular catheters for cerebrospinal fluid drainage. If routine medical management and cerebrospinal fluid diversion failed to control ICP, then the patient was determined to have refractory intracranial hypertension (RICH) and PBC treatment was initiated. PBC was performed with pentobarbital infusion with continuous electroencephalogram monitoring to ensure adequate burst suppression. The measurements include serum sodium (Na) and osmolality (Osm) were assessed as indicators for initiation of PBC and to estimate the 50% mortality cut-points when controlling for ICP. Follow-up functional outcomes were assessed using the Glasgow Outcome Scale and stratified according to admission Glasgow Coma Scale score and Marshall computed tomography classification. Of the 55 PBC patients, 22 (40%) survived at discharge. 19 of 22 had long-term follow-up (1 year or more) available. Of these, 13 (68%) were normal or functionally independent (Glasgow Outcome Scale score 4 or 5). Serum Na and Osm were associated with death (p < 0.05) when controlling for ICP. The 50% mortality cut-points were Na of 160 mEq/L and Osm of 330 mOsm/kg H2O. Median minimum cerebral perfusion pressure after PBC was 42 mm Hg in survivors and 34 mm Hg in nonsurvivors (p = 0.013). CONCLUSIONS: In patients with severe TBI and RICH, survival at discharge of 40% with good functional outcomes in 68% of survivors at 1 year or more can be achieved with PBC after failure of HOsmRx. Based on 50% mortality cut-points, analysis suggests the limits of HOsmRx to be Na of 160 mEq/L and Osm of 330 mOsm/Kg H2O. Maintenance of higher cerebral perfusion pressure after PBC is associated with survival. PBC treatment of RIH may be even more important when other treatments of RIH, such as decompressive craniectomy, are not available.