Using the GAP score as a complement to the new injury severity score in identifying severely injured patients- A registry-based cohort study of adult trauma patients in Sweden.

BACKGROUND: New Injury Severity Score (NISS) and Glasgow Coma Scale, Age and Pressure (GAP) scoring systems have cutoffs to define severe injury and identify high-risk patients. This is important in trauma quality monitoring and improvement. The overall aim was to explore if GAP scoring system can be a complement or an alternative to the traditional NISS scoring system. METHODS: Adults exposed to trauma between 2017 and 2021 were included in the study, using data from The Swedish Trauma Registry. The performance of NISS and GAP scores in predicting mortality, and ICU admissions were assessed using the area under the receiver operator characteristics (AUROC) in all patients and in subgroups (blunt, penetrating trauma and older (≥65 years) trauma patients). Patients were classified as severely injured by NISS >15 as Severely Injured NISS (SIN) or with a high-risk for mortality, by GAP 3-18 as High Risk GAP (HRG). Undertriage was calculated based on the cutoffs HRG and SIN. RESULTS: Overall, 37,017 patients were included. The AUROC (95 % CI) for mortality using NISS was 0.84 (0.83-0.85) and for GAP 0.92 (0.91-0.93) (p-value <0.001), the AUROC (95 % CI) for ICU-admissions was 0.82 (0.82-0.83) using NISS and for GAP 0.70 (0.70-0.71) p-value <0.001, in the overall cohort. In older patients the AUROC (95 % CI) for mortality was 0.76 (0.75-0.78) using NISS and 0.79 (0.78-0.81) using GAP, p-value <0.001. Overall, 8,572 (23.2 %) and 2,908 (7.9 %) were classified as SIN and HRG, respectively, with mortality rates of 13.7 % and 34.3 %. In the HRG group low-energy falls dominated and in the SIN group most patients were exposed to MVCs. In the SIN and HRG groups the rate of Emergency Trauma Interventions according to Utstein guidelines (ETIU) and ICU admission was 14.0 vs 9.5 % and 47.0 vs 62.5 % respectively. CONCLUSION: Our findings suggest that the GAP score and its cutoff 3-18 can be used to define severe trauma as complement to NISS >15 and can be a valuable tool in trauma quality monitoring and improvement. However, both scoring systems were less accurate in predicting mortality for the older trauma patients and should be explored further.

A systematic review of hemorrhage and vascular injuries in civilian public mass shootings.

BACKGROUND: Civilian public mass shootings (CPMSs) are a major public health issue and in recent years several events have occurred worldwide. The aim of this systematic review was to characterize injuries and mortality after CPMSs focusing on in-hospital management of hemorrhage and vascular injuries. METHOD: A systematic review of all published literature was undertaken in Medline, Embase and Web of Science January 1st, 1968, to February 22nd, 2021, according to the PRISMA guidelines. Literature was eligible for inclusion if the CPMS included three or more people shot, injured or killed, had vascular injuries or hemorrhage. RESULTS: The search identified 2884 studies; 34 were eligible for inclusion in the analysis. There were 2039 wounded in 45 CPMS events. The dominating anatomic injury location per event was the extremity followed by abdomen and chest. The median number of operations and operated patients per event was 22 (5-101) and 10.5 (4-138), respectively. A total of 899 deaths were reported with a median mortality rate of 36.1% per event (15.9-71.4%) Thirty-eight percent (13/34) of all studies reported on vascular injuries. Vascular injuries ranged from 8 to 29%; extremity vascular injury the most frequent. Specific vascular injuries included thoracic aorta 18% (42/232), carotid arteries 6% (14/232), and abdominal aorta 5% (12/232). Vascular injuries were involved in 8.3%-10% of all deaths. CONCLUSION: This systematic review showed an overall high mortality after CPMS with injuries mainly located to the extremities, thorax and abdomen. About one quarter of deaths was related to hemorrhage involving central large vessel injuries. Further understanding of these injuries, and structured and uniform reporting of injuries and treatment protocols may help improve evaluation and management in the future. Level of Evidence Systematic review and meta-analysis, level III.

Patient and process factors associated with opportunities for improvement in trauma care: a registry-based study.

BACKGROUND: Trauma is one of the leading causes of morbidity and mortality worldwide. Morbidity and mortality review of selected patient cases is used to improve the quality of trauma care by identifying opportunities for improvement (OFI). The aim of this study was to assess how patient and process factors are associated with OFI in trauma care. METHODS: We conducted a registry-based study using all patients between 2017 and 2021 from the Karolinska University Hospital who had been reviewed regarding the presence of OFI as defined by a morbidity and mortality conference. We used bi- and multivariable logistic regression to assess the associations between the following patient and process factors and OFI: age, sex, respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), survival at 30 days, highest hospital care level, arrival on working hours, arrival on weekends, intubation status and time to first computed tomography (CT). RESULTS: OFI was identified in 300 (5.8%) out of 5182 patients. Age, missing Glasgow Coma Scale, time to first CT, highest hospital care level and ISS were statistically significantly associated with OFI. CONCLUSION: Several patient and process factors were found to be associated with OFI, indicating that patients with moderate to severe trauma and those with delays to first CT are at the highest odds of OFI.

Risk-adjusted mortality in severely injured adult trauma patients in Sweden.

BACKGROUND: Risk-adjusted mortality (RAM) analysis and comparisons of clinically relevant subsets of trauma patients allow hospitals to assess performance in different processes of care. The aim of the study was to develop a RAM model and compare RAM ratio (RAMR) in subsets of severely injured adult patients treated in university hospitals (UHs) and emergency hospitals (EHs) in Sweden. METHODS: This was a retrospective study of the Swedish trauma registry data (2013 to 2017) comparing RAMR in patients (aged 15 years or older and New Injury Severity Score (NISS) of more than 15) in the total population (TP) and in multisystem blunt (MB), truncal penetrating (PEN), and severe traumatic brain injury (STBI) subsets treated in UHs and EHs. The RAM model included the variables age, NISS, ASA Physical Status Classification System Score, and physiology on arrival. RESULTS: In total, 6690 patients were included in the study (4485 from UHs and 2205 from EHs). The logistic regression model showed a good fit. RAMR was 4.0, 3.8, 7.4, and 8.5 percentage points lower in UH versus EH for TP (P < 0.001), MB (P < 0.001), PEN (P = 0.096), and STBI (P = 0.005), respectively. The TP and MB subsets were subgrouped in with (+) and without (-) traumatic brain injury (TBI). RAMR was 7.5 and 7.0, respectively, percentage points lower in UHs than in EHs in TP + TBI and MB + TBI (both P < 0.001). In the TP-TBI (P = 0.027) and MB-TBI (P = 0.107) subsets the RAMR was 1.6 and 1.8 percentage points lower, respectively. CONCLUSION: The lower RAMR in UHs versus EH were due to differences in TBI-related mortality. No evidence supported that Swedish EHs provide inferior quality of care for trauma patients without TBI or for patients with penetrating injuries.

Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications.

Patients undergoing major surgery experience postoperative inflammation, which may contribute to postoperative morbidity. Endogenous glucocorticoids (GCs) are an essential part of the stress response, but this response varies between individuals, which may in turn affect clinical outcome and specifically postoperative inflammation. Exon 1 of the NR3C1 gene, encoding the GC receptor (GR), contains an established region of differential regulation. DNA methylation patterns in this region have been found to differ between individuals. The present study investigated the methylation status and genotype in the cytosine­phosphate­guanine (CpG) island in exon 1 of NR3C1 in 24 patients [Median age 65.5 (range 42­81) years, 11 male, 13 female] who underwent major abdominal (12 pancreatic, 12 hepatic) surgery and explored its association with postoperative complications. DNA was extracted from peripheral blood leukocytes and underwent targeted bisulfite sequencing of the CpG island. Complications were graded according to the Clavien­Dindo classification and 14 out of 24 patients had postoperative complications. Multifactorial and partial least square analyses were used to analyse the data. A homogenous demethylated pattern was observed in all patients and no single CpG methylation was associated with postoperative complications. Four SNPs were significantly associated with higher Clavien­Dindo scores. Genetic variability in the chromosome 5:143,402,505­143,405,805 region of exon 1 of the GR gene NR3C1, but not DNA methylation, was associated with more severe postoperative complications in patients having major abdominal surgery. These results indicated that the patients' response to GCs may be of clinical importance for inflammatory conditions.

Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI): study protocol for a multicentre, retrospective, observational cohort study.

INTRODUCTION: Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. METHODS AND ANALYSIS: This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (≥15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission ≥48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT04995068.

A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes.

INTRODUCTION: Trauma accounts for nearly 10% of the global burden of disease. Several trauma life support programmes aim to improve trauma outcomes. There is no evidence from controlled trials to show the effect of these programmes on patient outcomes. We describe the protocol of a pilot study that aims to assess the feasibility of conducting a cluster randomised controlled trial comparing advanced trauma life support (ATLS) and primary trauma care (PTC) with standard care. METHODS AND ANALYSIS: We will pilot a pragmatic three-armed parallel, cluster randomised controlled trial in India, where neither of these programmes are routinely taught. We will recruit tertiary hospitals and include trauma patients and residents managing these patients. Two hospitals will be randomised to ATLS, two to PTC and two to standard care. The primary outcome will be all-cause mortality at 30 days from the time of arrival to the emergency department. Our secondary outcomes will include patient, provider and process measures. All outcomes except time-to-event outcomes will be measured both as final values as well as change from baseline. We will compare outcomes in three combinations of trial arms: ATLS versus PTC, ATLS versus standard care and PTC versus standard care using absolute and relative differences along with associated CIs. We will conduct subgroup analyses across the clinical subgroups men, women, blunt multisystem trauma, penetrating trauma, shock, severe traumatic brain injury and elderly. In parallel to the pilot study, we will conduct community consultations to inform the planning of the full-scale trial. ETHICS AND DISSEMINATION: We will apply for ethics approvals to the local institutional review board in each hospital. The protocol will be published to Clinical Trials Registry-India and ClinicalTrials.gov. The results will be published and the anonymised data and code for analysis will be released publicly.

Long-term follow-up of patients treated for traumatic injury regarding physical and psychological function and health-related quality of life.

PURPOSE: Trauma patients often suffer for long time after their injury with physical and psychological problems. Patient-reported outcome measurements (PROM) help us to understand outcomes beyond mortality. The aim of the study was to describe a sample of Swedish trauma patients, regarding their physical function, psychological morbidity, and quality of life after trauma. METHODS: The study population was sourced from the Swedish Trauma Register: taking 1 month of data from five hospitals, over three consecutive years. 218 patients met the inclusion criteria, 147 data sets were used. Inclusion criteria included: age ≥ 18; New Injury Severity Scale (NISS) ≥ 9; and discharged alive. Data were collected at 3, 6, and 12 months after the trauma. EuroQol-5D (EQ-5D), Posttraumatic Symptom Scale-10 (PTSS-10) questionnaires and Glasgow Outcome Score (GOS) instrument were used with additional questions about pain and return to work. RESULTS: 12 months after the trauma: full functional recovery (GOS 5) was seen in 68% of the patients; 59% reported difficult or moderate pain or discomfort; and 44.5% of the patients had returned to work. In EQ-5D mobility dimension, no recovery was evident between 6 and 12 months. Twenty percent of the patients had significant symptoms for PTSD after 6 months and 16% after 3 months and 12 months. CONCLUSION: Trauma patients had decreased physical function and psychological morbidity up to 1 year after the initial injury. Incorporating PROM in the follow-up after trauma is important to understand the patient's perspective of care and treatment.

Patient experiences of initial trauma care.

BACKGROUND: Correct initial treatment of trauma patients reduces mortality and morbidity. However, the initial examination may be perceived as traumatic because of the stressful situation, the unfamiliar setting and the shock of being seriously injured. To date, little is known about patient's experiences of initial trauma management. The aim of this study was to explore trauma patients' experiences of being exposed to initial full trauma team assessment at a Level 1 trauma centre. METHODS: Interviews with 16 patients who had been exposed to initial trauma care were conducted at a Level 1 trauma centre, at a Swedish University Hospital. The interviews were transcribed verbatim and analysed with qualitative content analysis. RESULTS: Patients' experiences of initial trauma care can be summarized as: feeling safe in a frightening situation. The trauma team members were mostly perceived as professional, well-organised, and efficient. Yet, the patients described an emotional response to the trauma, physical discomfort during the examination, and feeling prioritised or being ignored in the encounter with the trauma team members. CONCLUSION: The initial trauma care may be improved if the trauma team members keep the patient's physical and emotional wellbeing in focus and maintain an informative dialogue with the patient during the whole process.

Predicting prolonged sick leave among trauma survivors.

Many survivors after trauma suffer from long-term morbidity. The aim of this observational cohort study was to develop a prognostic prediction tool for early assessment of full-time sick leave one year after trauma. Potential predictors were assessed combining individuals from a trauma register with national health registers. Two models were developed using logistic regression and stepwise backward elimination. 4458 individuals were included out of which 488 were on sick leave full-time 12 months after the trauma. One comprehensive and one simplified model were developed including nine and seven predictors respectively. Both models showed excellent discrimination (AUC 0.81). The comprehensive model had very good calibration, and the simplified model good calibration. Prediction models can be used to assess post-trauma sick leave using injury-related variables as well as factors not related to the trauma per se. Among included variables, pre-injury sick leave was the single most important predictor for full-time sick leave one year after trauma. These models could facilitate a more efficient use of resources, targeting groups for follow-up interventions to improve outcome. External validation is necessary in order to evaluate generalizability.

A criteria-directed protocol for in-hospital triage of trauma patients.

OBJECTIVE: To better match hospital resources to patients' needs of trauma care, a protocol for facilitating in-hospital triage decisions was implemented at a Swedish level I trauma centre. In the protocol, physiological parameters, anatomical injuries and mechanism of injury were documented, and used to activate full or limited trauma team response. The aim of this study was to evaluate the efficacy of the criteria-directed protocol to determine in-hospital trauma triage in an emergency department. METHODS: Level of triage and triage rates were compared before and after implementation of the protocol. Overtriage and undertriage were assessed with injury severity score higher than 15 as the cutoff for defining major trauma. Medical records for undertriaged patients were retrospectively reviewed. RESULTS: In 2011, 78% of 1408 trauma team activations required full trauma response, with an overtriage rate of 74% and an undertriage rate of 7%. In 2013, after protocol implementation, 58% of 1466 trauma team activations required full trauma response. Overtriage was reduced to 52% and undertriage was increased to 10%. However, there were no preventable deaths in the undertriaged patients. CONCLUSION: A criteria-directed protocol for use in the emergency department was efficient in reducing overtriage rates without risking undertriaged patients' safety.

Post-trauma morbidity, measured as sick leave, is substantial and influenced by factors unrelated to injury: a retrospective matched observational cohort study.

BACKGROUND: Mortality as an endpoint has been the focus of trauma research whereas few studies investigate long-term outcomes in terms of morbidity. An adequate analysis of post-injury morbidity includes several dimensions, for this reason sick leave has been used as a proxy for morbidity in the current study. The aim of this retrospective matched observational cohort study was to investigate sick leave before and after trauma and factors associated with prolonged sick leave. METHODS: Patients from a level one trauma centre 2005-2010 were matched in a 1:5 ratio with uninjured controls. By linkage to national registries, sick leave rates were compared. The association between potential risk factors and full-time sick leave at twelve months post injury, the primary end-point, was examined in trauma patients by logistic regression. RESULTS: Four thousand seven hundred twelve patients and 25,013 controls aged 20-63 were included. Trauma patients had more sick leave both before and after trauma. Age, psychiatric disease, low level of education, serious injury, spinal injury, reduced consciousness at admission, discharge destination other than home, and hospital length of stay >7 days were all associated with the primary end-point. The strongest risk factor was sick leave before trauma; this was also noted in the most seriously injured patients. DISCUSSION: In this retrospective matched observational cohort study we found a significant long-term morbidity, measured as sick leave, among trauma patients. Compared to controls the difference was maximal early after trauma and sustained throughout the follow up period. In the logistic regression, factors associated with the traumatic injury as well as host factors increased the probability of not returning to work. Full sick leavemonth twelve post injury was strongly associated with pre-injury sick leave but also with age, psychiatric comorbidity, level of education, injury severity, spinal injury, low GCS at admission, length of stay at hospital and discharge to other destination than home. CONCLUSIONS: Trauma patients suffer from significant long-term morbidity. The sustained post-trauma morbidity is largely influenced by factors not related to injury per se. These insights enable identification of patients at risk for prolonged sick leave after trauma.

Comparison of risk-adjusted survival in two Scandinavian Level-I trauma centres.

BACKGROUND: Assessment of trauma-system performance is important for improving the care of injured patients. The aim of the study was to compare risk-adjusted survival in two Scandinavian Level-I trauma centres. METHODS: This was an observational, retrospective study of prospectively-collected trauma registry data for patients >14 years from Karolinska University Hospital - Solna (KUH), Sweden, and Oslo University Hospital - Ullevål (OUH), Norway, from 2009-2011. Probability of survival (Ps) was calculated according to the Trauma and Injury Severity Score (TRISS) method. Risk-adjusted survival per patient was calculated by assigning every patient a value corresponding to gained or lost fractional life: Each survivor contributed a reward of 1-Ps and each death a penalty of -Ps. The sum of penalties and rewards, corresponding to the difference between expected and actual mortality, was compared between the centres. We present the data as excess survivors per 100 trauma patients. RESULTS: There were 4485 admissions at KUH and 3591 at OUH. The proportion of severely injured patients was higher at OUH compared with KUH (Injury Severity Score [ISS] >15: 33.9 % vs. 21.1 %, p <0.001). OUH had a larger proportion of patients >65 years (16.0 % vs. 13.4 %, p <0.001) and greater comorbidity (ASA-PS ≥3: 14.6 % vs. 6.9 %, p <0.001) compared with KUH. The frequency of helicopter transport and presence of prehospital physicians was higher at OUH compared with KUH (27.6 % vs. 15.5 % and 30.5 % vs. 3.7 %, both p <0.001). Secondary admissions were 5.2-fold more common at OUH compared with KUH (p <0.001). There were no differences in 30-day mortality for severely injured patients (ISS >15). Risk-adjusted survival rate was higher at OUH than at KUH for primary (0.59 vs. 0.51) but lower for secondary (1.41 vs. 2.85) admissions (both p <0.001). CONCLUSION: Adjustments for age as a continuous variable and comorbidity should be made when comparing risk-adjusted survival between hospitals, but this is not possible with the TRISS model. A survival prediction model that takes this into account may be a better choice for Scandinavian trauma populations. The current study could not rule out the influence of the system differences between the centres on risk-adjusted survival.

An ex vivo RT-qPCR-based assay for human peripheral leukocyte responsiveness to glucocorticoids in surgically induced inflammation.

INTRODUCTION: An assay to determine glucocorticoid (GC) responsiveness in humans could be used to monitor GC non-responsiveness in states of GC insufficiency and could provide a tool to adapt GC treatment to individual patients. We propose an ex vivo assay to test GC responsiveness in peripheral leukocytes. The assay was evaluated in a human experimental model of surgery-induced inflammation. PATIENTS AND METHODS: Changes in expression of the GC-regulated genes GILZ, IL1R2, FKBP5, and HLA-DR and glucocorticoid receptor alpha (GRα) were determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral leukocytes from surgical patients and healthy blood donors (total n=60) in response to low (1 nM) and high (1 µM) dexamethasone (DEX). The final selection of a suitable endogenous control gene was based on the studies of stability during DEX treatment and inflammation. Correlations between pre- and postoperative GC-induced gene expression, the postoperative systemic inflammatory and metabolic response (CRP, IL-6, white blood cell count, cytokines, resistin, free fatty acids, glucose, insulin, and adiponectin), and the clinical outcome were analyzed. The length of stay in the intensive care unit (ICU-LOS), the length of stay in the hospital, and postoperative complications were used to measure clinical outcome. RESULTS: When the blood donors were compared to the patients, there were no significant differences in the regulation of the genes in response to DEX, except for GRα. Preoperative, but not postoperative, gene regulation of GILZ and GRα was negatively correlated to ICU-LOS (P<0.05 and P<0.01, respectively). Preoperative GILZ and FKBP5 gene regulation was negatively correlated to postoperative systemic TNFα and MIP-1α levels. CONCLUSION: We suggest that this assay could be used to determine GC responsiveness. An alteration in preoperative GC responsiveness may be related to a patient's ability to recover from surgically induced inflammatory stress.

Clinical review is essential to evaluate 30-day mortality after trauma.

BACKGROUND: Securing high-quality mortality statistics requires systematic evaluation of all trauma deaths. We examined the proportion of trauma patients dying within 30 days from causes not related to the injury and the impact of exclusion of patients dead on arrival on 30-day trauma mortality. We also defined the demographics, injury characteristics, cause of death and time to death in patients admitted to our trauma center who died within 30 days, between 2007-2011. METHODS: Demographics, injury characteristics, status alive/dead on arrival, cause of death and time to death of all patients were reviewed. Deaths were analyzed based on injury mechanism (penetrating, blunt trauma and low energy blunt trauma) and cause of death (traumatic brain injury (TBI), hemorrhage, organ dysfunction and other/unknown). RESULTS: Of the 7422 admissions, 343 deaths were identified of which 36 (10.5%) involved causes not related to the injury. The overall age was 71 years, Injury Severity Score (ISS) 29 and time to death 24 hours (all medians). Fifty-four patients (17.6%) were dead on arrival. Exclusion of patients dead on arrival reduced the overall mortality rate (P < 0.05) and median ISS (P < 0.05) and increased median age (P < 0.01) and time to death (P < 0.001). Injury mechanism was penetrating trauma in 7.5%, blunt trauma in 56.0%, and low energy blunt trauma in 36.5%. TBI accounted for 58.6%; hemorrhage 16.3%, organ dysfunction 15.0%, and other/unknown for 10.1% of the deaths. Patients who died after low energy blunt trauma were older, had lower ISS and longer time to death compared to those who died after penetrating and blunt trauma (all P < 0.01). CONCLUSIONS: Clinical review of all trauma deaths was essential to interpret mortality. Thirty-day trauma mortality included 10.5% deaths not directly related to the injury and the exclusion of patients dead on arrival significantly affected the unadjusted mortality rate, ISS, median age and time to death.

Isoform-specific alanine aminotransferase measurement can distinguish hepatic from extrahepatic injury in humans.

Serum alanine aminotransferase (ALT) is used as a clinical marker to detect hepatic damage and hepatoxicity. Two isoforms of ALT have been identified, ALT1 and ALT2, which have identical enzymatic capacities and are detected simultaneously in human serum/plasma using classical clinical chemical assays. Differences exist in the expression patterns of the ALT1 and ALT2 proteins in different organs which suggest that changes in the proportion of ALT1 and ALT2 in plasma may arise and reflect damage to different human organs. However, this has not been previously studied due to the lack of a selective methodology that can quantify both ALT1 and ALT2 isoforms in the total ALT activity normally measured in clinical samples. To the best of our knowledge, our current study reveals for the first time, that under 3 different conditions of liver damage (non-alcoholic fatty liver disease, hepatitis C and during liver surgery) the leakage of ALT1 activity into plasma greatly exceeds that of ALT2, and that the measurement of ALT1 during liver damage is equal to the measurement of total ALT activity. By contrast, during skeletal muscle injury, induced in volunteers by physical exertion, the leakage of ALT2 exceeds that of ALT1 and the proportion of circulating ALT isoforms changes accordingly. The ALT isoform changes occurring in plasma reflect previously demonstrated relative contents of ALT1 and ALT2 activities in human liver and skeletal muscle. These data suggest that assessing the percentage contribution of ALT1 and ALT2 activities to total ALT activity in plasma may distinguish hepatic from extrahepatic injury using the same standard analytical platform.

Bile duct obstruction is associated with early postoperative upregulation of liver uncoupling protein-2 and reduced circulating glucose concentration in the rat.

OBJECTIVE: To evaluate whether upregulation of liver and muscle uncoupling protein 2 (UCP-2) is an acute phenomenon in obstructive jaundice and associated with secondary metabolic effects. METHODS: Male Sprague-Dawley rats were divided into four groups: bile duct ligated (BDL) and sham-operated pair-fed (PF), ad libitum fed (AL), and controls. BDL, PF, and AL rats were further divided into subgroups according to the interval postoperatively when they were reanesthetized and sampled for tissue and blood: 2, 4, and 8 d, respectively. Bilirubin, liver enzymes, glucose, free fatty acids, and insulin in blood plasma were analyzed. Liver and muscle tissue were sampled for UCP-2 and adenosine triphosphate analysis. RESULTS: The BDL rats showed an increase of the liver UCP-2 expression compared with PF and AL rats (P<0.05) 4 d postoperatively. Liver adenosine triphosphate in BDL rats showed a decrease compared with sham-operated controls at all intervals (P<0.05). Plasma glucose concentration in BDL rats was decreased compared with the other groups. Free fatty acids showed an initial increase 2 d postoperatively compared with sham-operated controls and PF and AL rats (P<0.05) at the corresponding time point. CONCLUSION: Obstructive jaundice is associated with an early upregulation of liver UCP-2, reduced liver adenosine triphosphate content, and decreased plasma glucose concentration, supporting the hypothesis that obstructive jaundice results in impaired energy homeostasis in the liver, which might cause decreased glucose output and hypoglycemia as a consequence.