Identifying predictors of early non-recovery in a compensation setting: The Whiplash Outcome Study

Context

People with Whiplash Associated Disorder (WAD) often experience pain and disability for extended periods of time. A large proportion of these people will seek treatment through a compensation process. Rarely is data related to people's health collected within the compensation process making it difficult to identify those that are at risk of delayed recovery and appropriately direct interventions.

Study objective

To compare people with WAD who have recovered with those that have not, within 3 months of injury and identify potential predictors of poorer health and non-recovery to inform claim screening processes.

Study design

Cross-sectional analysis of a cohort study.

Participants

People who sustained a WAD and claimed compensation within an Australian Motor Accidents Compensation Scheme between November 2007 and June 2009.

Measure of recovery

Functional Rating Index (FRI) score (≤25).

Health outcome measures

Short Form 36 (SF36), FRI, and the Pain Catastrophising Scale (PCS).

Methods

246 people who had lodged a claim for compensation were enrolled in the Whiplash Outcome Study within 3 months of sustaining a WAD injury. Participants were assigned to a recovered or non-recovered group and analysed for differences between the two groups. Multiple linear regression models were used to identify potential predictors of poorer health and non-recovery.

Results

Overall 23% of the study population had recovered within 3 months of sustaining a WAD, whilst only 9% had finalised their insurance claim. The recovered group had significantly better scores on all health outcome measures; SF36 Physical Component Score, SF36 Mental Component Score and the PCS (p < 0.001). The significant independent predictors of poorer health and non-recovery were helplessness (p < 0.001), older age (p < 0.001) and pre-injury work status being affected (p < 0.001) (r² = .624). Regardless of the health outcome measure used, helplessness was significantly associated with poorer reported health.

Conclusion

Including additional information at claim notification, specifically the PCS and information on the effect the injury has on the working population could significantly improve claim screening processes, identifying those with poorer health and risk of non-recovery.     

Intestinal ischaemia/reperfusion upregulates β-defensin-2 expression and causes acute lung injury in the rat

Objective

Human β-defensin-2 (BD-2) is a positive ion antimicrobial peptide. We investigated the effects of intestinal ischaemia/reperfusion (II/R) on rat BD-2 mRNA and protein expressions in rat lung to address the potential role of BD-2 in acute lung injury (ALI) induced by II/R.

Methods

Rats were randomly divided into two groups (n = 36 each). (i) Sham control and (ii) II/R group (1 h superior mesenteric artery clamping, followed by reperfusion of different durations). In II/R group, 6 animals were sacrificed at 0 min, 15 min, 30 min, 60 min, 3 h and 6 h after reperfusion, and serum, lung tissue and bronchoalveolar lavage fluid were harvested. Samples were taken at the corresponding time points in the sham group. Lung histological changes were observed under microscope and the pulmonary permeability index (PPI) was calculated. The lung tissue levels of TNFα were detected by ELISA. BD-2 mRNA and protein expressions were examined by RT-PCR and western blotting techniques, respectively.

Results

ALI induced by II/R was confirmed by pathological examination and significantly increased PPI (P < 0.05 or 0.01). II/R significantly increased the lung TNFα levels and upregulated the expressions of BD-2 mRNA and protein expressions (P < 0.05 or 0.01). BD-2 mRNA expression was significantly positively correlated to the lung TNFα level (r = 0.823, P < 0.01) and negatively correlated to PPI (r = −0.615, P < 0.05).

Conclusion

II/R can upregulate BD-2 mRNA and protein expressions in rat lung. BD-2 could be an innate protective factor against II/R-induced lung injury.     

Morphological changes of the neural cells after blast injury of spinal cord and neuroprotective effects of sodium β-aescinate in rabbits

Objective

Explosive blast neurotrauma is becoming more and more common not only in the military population but also in civilian life due to the ever-present threat of terrorism and accidents. However, little attention has been offered to the studies associated with blast wave-induced spinal cord injury in the literatures. The purpose of this study is to report a rabbit model of explosive blast injury to the spinal cord, to investigate the histological changes, focusing especially on apoptosis, and to reveal whether β-aescinate (SA) has the neuroprotective effects against the blast injury.

Methods

Adult male New Zealand white rabbits were randomly divided into sham group, experimental group and SA group. All rabbits except the sham group were exposed to the detonation, produced by the blast tube containing 0.7 g cyclotrimethylene trinitramine, with the mean peak overpressure of 50.4 MP focused on the dorsal surface of T9-T10 level. After evaluation of the neurologic function, spinal cord of the rabbits was removed at 8 h, 1, 3, 7,14 or 30 days and the H&E staining, EM examination, DNA gel electrophoresis and TUNEL were progressively performed.

Results

The study demonstrated the occurrence of both necrosis and apoptosis at the lesion site. Moreover, the SA therapy could not only improve the neurologic outcomes (P < 0.05) but also reduce the loss of motoneuron and TUNEL-positive rate (P < 0.05).

Conclusions

In the rabbit model of explosive blast injury to the spinal cord, the coexistent apoptotic and necrotic changes in cells was confirmed and the SA had neuroprotective effects to the blast injury of the spinal cord in rabbits. This is the first report in which the histological characteristics and drug treatment of the blast injury to the spinal cord is demonstrated.     

Risk factors for blunt thoracic aortic injury in children

Background/Purpose

Because blunt thoracic aortic injury is rare in children, a high index of suspicion is needed to identify this injury. The purpose of this study was to use a large national trauma database to define the risk factors for blunt thoracic aortic injury in children.

Methods

Using the National Trauma Database, the authors compared patient demographics, mechanism of injury, and associated injuries between children sustaining blunt trauma with and without a thoracic aortic injury. Factors independently associated with this injury were identified using multivariate methods.

Results

Among 26,940 children with a blunt mechanism of injury, 34 (0.1%) children sustained a thoracic aortic injury, 14 (41%) of whom died. Thoracic aortic injuries were independently associated with age, injury sustained as an occupant in a motor vehicle crash, and severe injuries (Abbreviated Injury Scale value of ≥3) involving the head, thorax (other than aorta), abdomen, and lower extremities.

Conclusions

Older children involved in a motor vehicle crash with severe head, torso, and lower extremity injuries are a group at high risk for injury to the thoracic aorta. These easily identifiable risk factors may facilitate more rapid identification of this rare and potentially fatal injury.     

Femoral nailing during serum bicarbonate-defined hypo-perfusion predicts pulmonary organ dysfunction in multi-system trauma patients

Objective

To assess the value of venous serum bicarbonate as an endpoint of resuscitation and guide to timing of femoral nailing in multi-system trauma patients.

Design

Retrospective cohort study.

Setting

Academic Level 1 Trauma Centre.

Patients

Seventy-two consecutive adult multi-system trauma patients (Injury Severity Score ≥ 15) with femoral shaft fracture (Orthopaedic Trauma Association Class 32-A to 32-C) treated with reamed medullary nail fixation.

Intervention

Femoral nailing in the setting of hypo-perfusion defined by venous serum bicarbonate (SB). Threshold values of SB were determined first by correlating SB and simultaneously drawn arterial base deficit (BD). Then, corresponding values of SB to previously defined thresholds of hypo-perfusion based on BD were identified using regression analysis.

Main outcome measurement

Pulmonary organ dysfunction (POD) component of the Denver Multiple Organ Failure scoring system.

Results

Simultaneous admission SB and BD values were correlated (r = −0.43, p = 0.001). Adjusting for age, ISS and baseline POD, patients with SB < 24.7 mequiv./L within 6 h of treatment had a 12-fold increase in POD (OR 12.2, 95% CI 1.5-98.6, p = 0.019). This association was diminished, but still significant with hypo-perfusion present within 12 h prior to treatment (OR 5.6, 95% CI 1.0-29.1, p = 0.042) and 24 h prior to treatment (OR 5.9, 95% CI 1.1-30.7, p = 0.037).

Conclusions

Medullary fixation of femoral shaft fracture in the setting of serum bicarbonate-defined hypo-perfusion is associated with increased morbidity. Appropriate damage-control measures and aggressive resuscitation prior to definitive fracture care are advised and physiologic markers such as serum bicarbonate should guide clinical decision making rather than temporal distinctions.     

The health status of people claiming compensation for musculoskeletal injuries following road traffic crashes is not altered by an early intervention programme: A comparative study

Objective

To compare health outcomes among claimants compared to those who were ineligible or choose not to lodge a compensation claim. We also evaluated the effect of an early intervention programme on the health outcomes of the participants.

Design

Prospective comparative study using sequential cohorts.

Subjects

People presenting to hospital emergency departments with mild to moderate musculoskeletal injuries following road traffic crashes.

Intervention

referral to an early intervention programme for assessment by musculoskeletal physician, pain management education, promotion of self-management and encouragement of early activity.

Main outcomes

The 36-Item Short-Form Survey (SF-36); Hospital Anxiety and Depression Scale (HADS) and Functional Rating Index (FRI) scores were assessed at post-crash and at 12 months.

Results

At 12 months, mean scores in six and five of the SF-36 domains were significantly lower among participants who claimed compensation versus those who chose not to claim or were ineligible, respectively. Differences in mean SF-36 scores ranged from 3.0 (‘general health perception’) to 8.0 units (‘role limitations due to physical problems’). Participants who claimed compensation had 6.3- and 4.6-units lower SF-36 physical component score compared to those who were ineligible (p = 0.001) or chose not to claim (p = 0.01), respectively. Participants who claimed compensation reported a worse HADS-depression score of 6.46 versus 4.97 and 4.69 observed in those who were ineligible (p = 0.04) or did not claim (p = 0.01). Claimants had worse FRI scores compared to non-claimants (p = 0.01) and those who were ineligible (p = 0.01). The early intervention did not improve health outcomes, 12 months after injury.

Conclusions

Claiming compensation was associated with a worse health status for people with soft tissue injuries caused by road traffic crashes. The health status in people claiming compensation was not altered by an early intervention programme.     

Promotion to professor: a career development resource

Background

Patients with penetrating injuries are known to have worse outcomes than those with blunt trauma. We hypothesize that within each injury mechanism there should be no outcome difference between insured and uninsured patients.

Methods

The National Trauma Data Bank version 7 was analyzed. Patients aged 65 years and older and burn patients were excluded. The insurance status was categorized as insured (private, government/military, or Medicaid) and uninsured. Multivariate analysis adjusted for insurance status, mechanism of injury, age, race, sex, injury severity score, shock, head injury, extremity injury, teaching hospital status, and year.

Results

A total of 1,203,243 patients were analyzed, with a mortality rate of 3.7%. The death rate was significantly higher in penetrating trauma patients versus blunt trauma patients (7.9% vs 3.0%; P < .001), and higher in the uninsured (5.3% vs 3.2%; P < .001). On multivariate analysis, uninsured patients had an increased odds of death than insured patients, in both penetrating and blunt trauma patients. Penetrating trauma patients with insurance still had a greater risk of death than blunt trauma patients without insurance.

Conclusions

Insurance status is a potent predictor of outcome in both penetrating and blunt trauma.     

The changing face of mild head injury: Temporal trends and patterns in adolescents and adults from 1997 to 2008

Objective

To explore the temporal trend of incidence, causes of injury and main characteristics of adolescent and adult subjects with mild head injury (MHI).

Design

This study had a retrospective design.

Setting

The study was conducted in a longitudinal database of an Italian Emergency Department (ED).

Participants

The study comprised 19 124 consecutive subjects who visited and were managed within 24 h from the event, according to a predefined protocol for MHI from 1997 to 2008.

Main outcome measures

Incidence, demography, cause of injury and characteristics of any post-traumatic intracranial lesion within 7 days from MHI.

Results

The number of subjects with MHI decreased from 2019 per year (1997-1999) to 1232 per year (2006-2008; P for linear trend <0.001), without differences in the total number of subjects visited in the ED. The decrease was observed in all age-decades, in particular, in subjects in the age ranges of 20-29 and 30-39 years. Over time, the age of subjects with MHI lost a bimodal distribution, and the mean age increased from 43 (25-69) years (median (interquartile range)) in 1997-1999 to 56 (33-78) years in 2006-2008 (P < 0.001). The prevalence of falls increased from 36.5% to 55.0%, whereas crashes fell from 53.2% to 31.9%. The incidence of subdural haematoma (SDH) and epidural haematoma (EDH) did not change over time, whereas traumatic subarachnoid haemorrhage (t-SAH) and intra-cerebral haematoma/brain contusion (ICH) increased (from 0.7% to 1.9% and from 2.5% to 3.2%; P for trend: <0.001 for both.

Conclusions

The incidence and the clinical characteristics of MHI subjects are rapidly changing in our setting. These data need to be considered in defining the effectiveness of preventive measures and deciding resource allocation.     

Time course of coagulopathy in isolated severe traumatic brain injury

Background

Time aspects of coagulopathy following severe traumatic brain injury (sTBI) are ill defined throughout the literature. Thus, the aim of this study was to evaluate the time course of coagulopathy following isolated sTBI and its relationship to in-hospital outcomes.

Methods

Retrospective analysis of patients sustaining isolated sTBI (head AIS ≥ 3, extracranial injuries AIS < 3). TBI coagulopathy was defined as thrombocytopenia and/or elevated international normalised ratio (INR) and/or prolonged activated partial thromboplastin time (aPTT). Incidence, onset and duration of sTBI-coagulopathy and its impact on morbidity and mortality were analysed.

Results

Overall, 45.7% (n = 127) of the 278 patients included developed coagulopathy. Coagulopathy occurred 23.1 ± 2.2 h [range: 0.1-108.2 h (0-4.5 days)] post-admission with a mean duration of 68.0 ± 7.4 h [range: 2.6-531.4 h (0.1-22.1 days)]. The time interval to onset of coagulopathy decreased significantly with increasing head injury severity (p = 0.015). Early coagulation abnormalities occurring within 12 h of admission along with markers of devastating head injury including head AIS 5, penetrating injury mechanism, subdural hematoma, and a low GCS on admission proved to be independent risk factors for mortality.

Conclusions

The sTBI-associated coagulopathy may ensue as late as 5 days after injury with a prolonged duration (>72 h) in 30% of patients. Early coagulopathy occurring within 12 h after injury is a marker of increased morbidity and poor outcomes. Pertinent prolonged screening of this sequela is warranted.     

Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury

Background

Intracavernous (IC) injection of stem cells has been shown to ameliorate cavernous-nerve (CN) injury-induced erectile dysfunction (ED). However, the mechanisms of action of adipose-derived stem cells (ADSC) remain unclear.

Objectives

To investigate the mechanism of action and fate of IC injected ADSC in a rat model of CN crush injury.

Design, setting, and participants

Sprague-Dawley rats (n = 110) were randomly divided into five groups. Thirty-five rats underwent sham surgery and IC injection of ADSC (n = 25) or vehicle (n = 10). Another 75 rats underwent bilateral CN crush injury and were treated with vehicle or ADSC injected either IC or in the dorsal penile perineural space. At 1, 3, 7 (n = 5), and 28 d (n = 10) postsurgery, penile tissues and major pelvic ganglia (MPG) were harvested for histology. ADSC were labeled with 5-ethynyl-2-deoxyuridine (EdU) before treatment. Rats in the 28-d groups were examined for erectile function prior to tissue harvest.

Measurements

IC pressure recording on CN electrostimulation, immunohistochemistry of the penis and the MPG, and number of EdU-positive (EdU+) cells in the injection site and the MPG.

Results and limitations

IC, but not perineural, injection of ADSC resulted in significantly improved erectile function. Significantly more EdU+ ADSC appeared in the MPG of animals with CN injury and IC injection of ADSC compared with those injected perineurally and those in the sham group. One day after crush injury, stromal cell-derived factor-1 (SDF-1) was upregulated in the MPG, providing an incentive for ADSC recruitment toward the MPG. Neuroregeneration was observed in the group that underwent IC injection of ADSC, and IC ADSC treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum.

Conclusions

CN injury upregulates SDF-1 expression in the MPG and thereby attracts intracavernously injected ADSC. At the MPG, ADSC exert neuroregenerative effects on the cell bodies of injured nerves, resulting in enhanced erectile response.     

A comparison of two mechanisms of severe paediatric injury in Northern Israel

Background

An increased incidence of severe injury due to falls from buildings (FFB) is reported in the rural area of northern Israel. This makes FFB, and motor vehicle collision (MVC) the two leading causes of severe paediatric trauma.

Methods

A single-centre, age-sex matched comparison analysis of the two mechanisms of injury was conducted. Children involved in MVC (study subjects) or FFB (controls), who were brought by the Emergency Medical System Mobile-Intensive-Care-Unit from the field to the trauma bay of the Emergency Department (ED) were enrolled on the basis of a convenience sample. Immediately following ED admission, heart rate (HR), systolic blood pressure (SBP), and base deficit (BD) were recorded. Types of injuries, Glasgow Coma Score (GCS) on scene, and Injury Severity Score (ISS) were also obtained.

Results

Eleven study subjects and 22 controls were enrolled during a 1-year period. The mean ISS for the study subjects group and for the controls was 23.4 and 19.5, respectively. No difference was found in comparing the ISS, BD, SBP and HR of the two groups (p = 0.261, p = 0.421, p = 0.314, and p = 0.824, respectively). Controls had a lower GCS (p < 0.031) and were more likely to have a skull fracture (p < 0.0082). Study subjects were more likely to have limb injuries (p < 0.0001) and thoracoabdominal injuries (p < 0.0059).

Conclusions

This study suggests that the Injury Severity Score of the two mechanisms of paediatric injury is high. The haemodynamic characteristics on ED admission were comparable between the two groups of patients but the likelihood of specific type of injury was different.     

Factors that predict poor outcomes in patients with traumatic vertebral body fractures

Study design

Prospective cohort study.

Objective

To identify factors that predict poor patient-reported outcomes in patients with traumatic vertebral body fracture(s) of the thoracic and/or lumbar spine without neurological deficit.

Summary of background data

There is a paucity of information on factors that predict poor patient-reported outcomes in patients with traumatic vertebral body fracture(s) of the thoracic and/or lumbar spine without neurological deficit.

Methods

Patients were identified from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). VOTOR includes all patients with orthopaedic trauma admitted to the two adult Level 1 trauma centres in Victoria, Australia. Patient-reported outcomes and data on possible predictive factors, including demographic details, injury-related and treatment-based factors, were obtained from the VOTOR database. Patient-reported outcomes were measured at 12 months post-injury using the 12-Item Short-Form Health Survey (SF-12), a Numerical Rating Scale (NRS) for pain, global outcome questions and data was collected on return to work or study. For the identification of predictive factors, univariate analyses of outcome vs. each predictor were carried out first, followed by logistic multiple regression.

Results

344 patients were eligible for the study and data were obtained for 264 (76.7%) patients at 12 months follow-up. Patients reported ongoing pain at 12 months post-injury (moderate-severe: 33.5%), disability (70.1%) and inability to return to work or study (23.3%). A number of demographic, injury-related and treatment-based factors were identified as being predictive of poor patient-reported outcomes. Patients who had associated radius fracture(s) were more likely to have moderate to severe disability (odds ratio (OR) = 3.85, 95% confidence interval = 1.30-11.39), a poorer physical health status (OR = 3.73, 1.37-10.12) and moderate to severe pain (OR = 3.23, 1.22-8.56) at 12 months post-injury than patients without radius fracture. Patients who did not receive compensation for work-related or road traffic-related injuries were less likely to report moderate to severe pain (OR = 0.45, 0.23-0.90) or have a poorer mental health status (OR = 0.17, 0.04-0.70) at 12 months post-injury than those who received compensation.

Conclusions

The prognostic factors identified in this study may assist clinicians in the identification of patients requiring more intensive follow-up or additional rehabilitation to ultimately improve patient care.     

Non-operative management of right side thoracoabdominal penetrating injuries—The value of testing chest tube effluent for bile

Introduction

While mandatory surgery for all thoracoabdominal penetrating injuries is advocated by some, the high rate of unnecessary operations challenges this approach. However, the consequences of intrathoracic bile remains poorly investigated. We sought to evaluate the outcome of patients who underwent non-operative management of right side thoracoabdominal (RST) penetrating trauma, and the levels of bilirubin obtained from those patients’ chest tube effluent.

Patients and methods

We managed non-operatively all stable patients with a single RST penetrating injury. Chest tube effluent samples were obtained six times within (4-8 h; 12-16 h; 20-24 h; 28-32 h; 36-40 h; 48 h and 72 h) of admission for bilirubin measurement and blood for complete blood count, bilirubin, alanine (ALT) and aspartate aminotransferases (AST) assays. For comparison we studied patients with single left thoracic penetrating injury.

Results

Forty-two patients with RST injuries were included. All had liver and lung injuries confirmed by CT scans. Only one patient failed non-operative management. Chest tube bilirubin peaked at 48 h post-trauma (mean 3.3 ± 4.1 mg/dL) and was always higher than both serum bilirubin (p < 0.05) and chest tube effluent from control group (27 patients with left side thoracic trauma). Serum ALT and AST were higher in RST injury patients (p < 0.05). One RST injury patient died of line sepsis.

Conclusion

Non-operative management of RST penetrating trauma appears to be safe. Bile originating from the liver injury reaches the right thoracic cavity but does not reflect the severity of that injury. The highest concentration was found in the patient failing non-operative management. The presence of intrathoracic bile in selected patients who sustain RST penetrating trauma, with liver injury, does not preclude non-operative management. Our study suggests that monitoring chest tube effluent bilirubin may provide helpful information when managing a patient non-operatively.     

Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors

Background

Severe brain trauma leads to an activation of the immune system. To this date, neither the exact perturbation of the specific immune reaction induced by the traumatic brain injury (TBI), nor the interactions leading to the infiltration of peripheral immune cells into the brain are fully understood.

Patients and methods

Serum was collected from 17 patients with TBI and a long bone fracture, 24 patients with an isolated long bone fracture and from healthy individuals. The effect of the serum on normal human monocytes and T-lymphocytes was tested in vitro by assessing proliferation and expression of surface markers, chemokine receptors and cytokines.

Results

Serum collected from patients with a TBI and a long bone fracture increased the expression of the chemokine receptor CCR4 in monocytes when compared to patients with an isolated long bone fracture. Extending this comparison to T-lymphocytes, the serum from TBI patients induced lower proliferation rates and decreased expression of the pro-inflammatory cytokine TNF-α, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-β) (p < 0.05).

Conclusion

Patients with a TBI release currently unknown soluble factors into the circulating blood that up regulate expression of chemokine receptor CCR4 in peripheral blood monocytes whilst concurrently inducing expression of immunosuppressive cytokines by activated T-lymphocytes.     

Predictors of in-hospital mortality and 6-month functional outcomes in older adults after moderate to severe traumatic brain injury

Introduction

Traumatic brain injury (TBI) is the single largest cause of death and disability following injury worldwide. While TBI in older adults is less common, it still contributes to significant morbidity and mortality in this group. Understanding the patient characteristics that result in good and poor outcome after TBI is important in the clinical management and prognosis of older adult TBI patients. This population-based study investigated predictors of mortality and longer term functional outcomes following serious TBI in older adults.

Methods

All older adults (aged > 64 years), isolated moderate to severe TBI cases from the population-based Victorian State Trauma Registry for the period July 2005 to June 2007 (inclusive) were extracted for analysis. Demographic, injury event, injury diagnosis, management and comorbid status information were obtained and the outcomes of interest were in-hospital mortality, and the Glasgow Outcome Scale-Extended (GOS-E) score at 6 months post-injury. Multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality and independent living (GOS-E > 4) status at 6 months.

Results

Of the 428 isolated, older adult TBI cases, the majority were the result of a fall (88%), male (55%), and aged > 74 years (76%). The in-hospital death rate was 28% and increasing age (p = 0.009), decreasing GCS (p < 0.001) and injury type (p = 0.002) were significant independent predictors of in-hospital mortality. Of the 310 patients who survived to discharge, 65% were successfully followed-up 6 months following injury. There was no difference between patients lost to follow-up and those successfully followed-up with respect to the key population indicators of age, gender, or head injury severity. Younger (<75 years) patients, and those with an SBP on arrival at hospital of 131-150 mmHg, were at increased odds of living independently at follow-up. No patients with a GCS < 9 had a good 6-month outcome, and most of them died. The survival rate for brainstem injury was also low (21%).

Conclusion

In this population-based study, we found that age, GCS, brainstem injury, and systolic blood pressure were the most important factors in predicting outcome in older adults with an isolated moderate to severe TBI.     

Ischaemic post-conditioning protects lung from ischaemia-reperfusion injury by up-regulation of haeme oxygenase-1

Objective

The emergence of ischaemic post-conditioning (IPO) provides a potential method for experimentally and clinically attenuating various types of organ injuries. There has been little work, however, examining its effects in the setting of lung ischaemia reperfusion (IR). The stress protein, haeme oxygenase-1 (HO-1), has been found to exert a potent, protective role in a variety of lung injury models. In this study, we hypothesised that the induction of HO-1 by IPO plays a protective role against the deleterious effects of IR in the lung.

Methods

Anaesthetised and mechanically ventilated adult Sprague-Dawley rats were randomly assigned to one of the following groups (n = 8 each): the sham-operated control group, the IR group (40 min of left-lung ischaemia and 105 min of reperfusion), the IPO group (three successive cycles of 30-s reperfusion per 30-s occlusion before restoring full perfusion) and the ZnPPIX + IPO group (ZnPPIX, an inhibitor of HO-1, was injected intra-peritoneally at 20 mg kg⁻¹ 24 h prior to the experiment and the rest of the procedures were similar to that of the IPO group). Lung injury was assessed by arterial blood gas analysis, wet-to-dry lung weight ratio and tissue histological changes. The extent of lipid peroxidation was determined by measuring plasma levels of malondialdehyde (MDA) production. Expression of HO-1 was determined by immunohistochemistry.

Results

Lung IR resulted in a significant reduction of PaO₂ (data in IR, P < 0.05 vs. data in sham) and increase of lung wet-to-dry weight ratio, accompanied with increased MDA production and severe lung pathological morphological changes as well as a compensatory increase in HO-1 protein expression, as compared with sham (All P < 0.05). IPO markedly attenuated all the above pathological changes seen in the IR group and further increased HO-1 expression. Treatment with ZnPPIX abolished all the protective effects of post-conditioning.

Conclusion

It may be concluded that IPO protects IR-induced lung injury via induction of HO-1.     

Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer

Background

Cigarette smoking is the most well-established risk factor for developing bladder cancer.

Objective

To investigate the role of smoking status on the clinical outcome of patients with non-muscle-invasive bladder cancer.

Design, setting, and participants

Data obtained during a prospective phase 3 study with three schedules of epirubicin were used for statistical analysis. Smoking status (obtained when entering the study), other prognostic variables, and clinical outcome measures of 718 patients were analyzed. Mean follow-up was 2.5 yr.

Measurements

The primary outcome measure was recurrence-free survival (RFS).

Results and limitations

Demographics were similar for nonsmokers versus ex-smokers and current smokers, except for gender (p < 0.001) and grade (p = 0.022). In univariate analyses, RFS was significantly shorter in male patients (p = 0.020), in patients with a history of recurrences (p < 0.003), in patients with multiple tumors (p < 0.004), in patients with a history of intravesical therapy (p = 0.037), and in ex-smokers and current smokers (p = 0.005). In multivariate analyses, a history of recurrences, multiplicity, and smoking status remained significant factors for predicting RFS. Gender and initial therapy were no longer a significant influence on RFS.Because progression was uncommon (n = 25) and follow-up was short and focused only on recurrences, no conclusion can be drawn on progression-free survival. A limitation of the study were the questionnaires. They were only used when entering the study, and there were no questions about passive smoking and other causal factors.

Conclusions

In this prospective study, the significance of known factors (history of recurrences and number of tumors) in predicting RFS was confirmed. Another significant factor that appears to predict RFS is smoking status: ex-smokers and current smokers had a significantly shorter RFS compared with nonsmokers.