Early Antibiotic Administration Is Associated with a Reduced Infection Risk When Combined with Primary Wound Closure in Patients with Open Tibia Fractures

BackgroundEarly administration of antibiotics and wound coverage have been shown to decrease the deep infection risk in all patients with Type 3 open tibia fractures. However, it is unknown whether early antibiotic administration decreases infection risk in patients with Types 1, 2, and 3A open tibia fractures treated with primary wound closure.Questions/purposes(1) Does decreased time to administration of the first dose of antibiotics decrease the deep infection risk in all open tibia fractures with primary wound closure? (2) What patient demographic factors are associated with an increased deep infection risk in Types 1, 2, and 3A open tibia fractures with primary wound closure?MethodsWe identified 361 open tibia fractures over a 5-year period at a Level I regional trauma center that receives direct admissions and transfers from other hospitals which produces large variation in the timing of antibiotic administration. Patients were excluded if they were younger than 18 years, had associated plafond or plateau fractures, associated with compartment syndrome, had a delay of more than 24 hours from injury to the operating room, underwent repeat débridement procedures, had incomplete data, and were treated with negative-pressure dressings or other adjunct wound management strategies that would preclude primary closure. Primary closure was at the descretion of the treating surgeon. We included patients with a minimum follow-up of 6 weeks with assessment at 6 months and 12 months. One hundred forty-three patients with were included in the analysis. Our primary endpoint was deep infection as defined by the CDC criteria. We obtained chronological data, including the time to the first dose of antibiotics and time to surgical débridement from ambulance run sheets, transferring hospital records, and the electronic medical record to answer our first question. We considered demographics, American Society of Anesthesiologists classification, mechanism of injury, smoking status, presence of diabetes, and Injury Severity Score in our analysis of other factors. These were compared using one-way ANOVA, chi-square, or Fisher’s exact tests. Binary regression was used to to ascertain whether any factors were associated with postoperative infection. Receiver operator characteristic curves were used to identify threshold values.ResultsIncreased time to first administration of antibiotics was associated with an increased infection risk in patients who were treated with primary wound closure; the greatest inflection point on that analysis occurred at 150 minutes, when the increased infection risk was greatest (20% [8 of 41] versus 4% [3 of 86]; odds ratio 5.6 [95% CI 1.4 to 22.2]; p = 0.01). After controlling for potential confounding variables like age, diabetes and smoking status, none of the variables we evaluated were associated with an increased risk of deep infection in Type 1, 2, and 3A open tibia fractures in patients treated with primary wound closure.ConclusionOur findings suggest that in open tibia fractures, which receive timely antibiotic administration, primary wound closure is associated with a decreased infection risk. We recognize that more definitive studies need to be performed to confirm these findings and confirm feasibility of early antibiotic administration, especially in the pre-hospital context.Level of EvidenceLevel III, therapeutic study.     

Biomechanical parameters of the BP-enriched bone cement

Bisphosphonates (BPs) are well-known substances with very efficient antiresorptive properties. Their beneficial actions are useful not only in achieving better bone mineral density but also in improving bone microarchitecture, strength and, consequently, its quality. Surgical cement, being a polymer composite, is required to be highly biocompatible and biotolerant. The goal of the presented study was to assess whether the enrichment of cement with pamidronate has changed its biomechanical properties. We compared the biomechanical parameters of clean bone cement and BP-enriched bone cement, which were both used formerly in our rat models. Biomechanical properties of BP-enriched bone cement are defined by two basic terms: stress and strain, which are caused by the influence of external force. In the investigatory process of the bone’s biomechanical parameters, the compressive test and the three-point flexural tests were used. During the three-point flexural investigation, the sample was supported at both ends and loaded in the middle, resulting in a flexure. After a specific range of flexure, the sample was fractured. In obtained results, there were no significant differences in the values of the stress determined at the point of maximal load and the energy stored in the samples for proportional stress–strain limit (elastic region). There were also no significant differences in the density of the samples. The study shows that the enrichment of bisphosphonates causes yielding of the bone cement material. In the presented data, we conclude that use of pamidronate implanted in bone cement did not have a detrimental effect on its biomechanical properties. Therefore, the obtained results encouraged us to perform further in vivo experiments which assess the biomechanical properties of bones implanted with BP-enriched bone cement.     

Contrast-enhanced 3D-MRA of the upper abdomen with a bolus-injectable SPIO (SH U 555 A).

The purpose of this study was to study temporal changes in signal intensity of liver, spleen, abdominal vessels, and focal liver lesions following iv bolus injection of a superparamagnetic iron oxide (SPIO) using a breath-held three-dimensional magnetic resonance angiography (3D-MRA) sequence. Dynamic SH U 555 A-enhanced 3D-MRA studies were performed in 20 patients with focal liver lesions. Sequential coronal 3D-MRA-FISP scans were acquired (TR 5.0 msec, TE 2.0 msec, flip angle 25 degrees, 140 x 256 matrix, and 80 mm slab) within 15 seconds. Scanning was started immediately after bolus injection of 10 micromol Fe/kg bodyweight and was repeated at multiple time points (baseline and 30, 60, 90, 120, 180, 240, 300, 360, and 420 seconds). Signal intensity values of liver, focal liver lesions, spleen, the portal venous system, the abdominal aorta, and the inferior vena cava were obtained to calculate relative enhancement (ENH = [SI post - SI pre]/SI pre x 100). Visibility of vessels was assessed by consensus of two readers. Signal enhancement within abdominal vessels peaked during the first pass; however, significant signal enhancement was still present 420 seconds following injection. The liver and the spleen also demonstrated a biphasic enhancement pattern with prolonged parenchymal enhancement. Dynamic MRA with bolus injectable SH U 555 A is clinically feasible, and significant vessel enhancement can be achieved even at the dose of 10 micromol Fe/kg bodyweight. However, further refinements are required to improve contrast effects.     

Energy and nutritional value of diets used in patients alimentation and their assessment by patients of selected clinical department in the Military Medical Institute in Warsaw

The aim of the work was laboratory assessment of energy and nutritional value of general and light diets used in patients of selected clinical department in the Military Medical Institute in Warsaw alimentation. Using questionnaire method the assessment of diets was done by patients too. Meals given to patients in hospital not always fulfilled nutritional requirements. Additional consumption of supplementary products did not always meet the requirements of proper nutrition. Half of examined patients appraised nutrition variety as good but at the same time claimed the there was not enough fruits and vegetables.     

Comparison of solid-phase microextraction and liquid-liquid extraction in 96-well format for the determination of a drug compound in human plasma by liquid chromatography with tandem mass spectrometric detection

Two sensitive and selective methods based on solid phase microextraction (SPME) and liquid-liquid extraction (LLE) in 96-well format, in combination with high performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection have been developed to determine a model drug compound in human plasma. Both assays were performed on an Applied Biosystems-Sciex API 4000 tandem mass spectrometer interfaced with a turbo ion-spray probe and operated in the negative ionization mode. A lower limit of quantitation (LLOQ) of 1 ng/mL achieved when 0.25 mL of human plasma was processed. In both methods, a stable isotope labeled internal standard was utilized. The methods were validated in the concentration range of 1-500 ng/mL. The intraday precision (%C.V.) of the method using LLE was 0.8% at LLOQ, and was equal to or lower than 3.3% at all other concentrations, while the intraday precision (%C.V.) of the method using SPME was 6.9% at LLOQ, and was equal to or lower than 5.7% at all other concentrations. Based on the direct comparison of the two methods and their successful applications in clinical sample analysis, it may be concluded that SPME may be considered and used as an alternative approach for quantitative determination of drugs in pharmacokinetic studies.     

Patterns of autobiographical memory impairment according to disease severity in semantic dementia

Studies of autobiographical memory in semantic dementia (SD) have yielded either a reversed temporal gradient or spared performances across the entire lifetime. This discrepancy might be owing to the fact that these studies did not take into account disease severity. Our aim was to study patterns of autobiographical memory impairment according to disease severity and to unravel their mechanisms in 14 SD patients, using an autobiographical memory task assessing overall and strictly episodic memories across the entire lifetime. We divided our patients in 2 subgroups of 7 patients each, one mild and one moderate according to their level of disease severity. The results indicated for the mild subgroup selective preserved performances for the most recent time period (last 12 months period) for both autobiographical memory scores. In the moderate subgroup, performances were impaired for both scores whatever the time period. Within-group comparisons across time periods showed a recency effect and a reminiscence bump in the mild subgroup and only a less important recency effect in the moderate subgroup, suggesting that with disease severity, old memories (reminiscence bump) tend to vanish and even recent memories are less well retrieved. A correlation analysis was carried out on the entire group, between the overall autobiographical memory score and performances provided by a general cognitive evaluation (semantic memory, executive functions, working and episodic memory). The results of this analysis reflect that mechanisms of disruption of autobiographical memory in SD predominantly involve a deficit of storage of semantic information in addition to faulty executive retrieval strategies. Finally, our result and those of the literature suggest the existence of 3 distinct autobiographical memory impairment patterns in SD according to disease severity: firstly preserved performances whatever the time period, secondly a reversed temporal gradient with a reminiscence bump and thirdly the appearance of a “step-function”.     

In search of autobiographical memories: A PET study in the frontal variant of frontotemporal dementia

Patients suffering from frontal variant of frontotemporal dementia (fv-FTD) undergo autobiographical amnesia encompassing all time periods. We previously demonstrated in a group of 20 fv-FTD patients that this impairment involved deficits in executive function and semantic memory for all periods as well as new episodic learning and behavioural changes for the most recent period covering the last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalevée, C., Pélerin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical memories: Insights from the frontal variant of frontotemporal dementia, Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the neural bases of this impairment by mapping in a subgroup of patients correlations between resting-state brain glucose utilization measured by FDG-PET and measures of autobiographical memory (AM) using the TEMPau task which is designed to gauge personal event recollection across five life time periods. Like in our previous report, the group of patients was impaired regardless of time periods compared to healthy subjects providing generic memories instead of event specific sensory-perceptual-affective details, i.e., episodic memories. New data showed that the patients were also impaired in sense of reliving and self-perspective during retrieval. The cognitivo-metabolic correlations between the AM score and resting normalized FDG-Uptake were computed using statistical parametric mapping (SPM2) and controlling for age and dementia severity. They revealed that AM deficits were mainly subserved by the dysfunction of left-sided orbitofrontal and also temporal neocortical areas whatever the period. Additional analysis showed that specific memories were associated with left orbitofrontal areas whereas generic memories were mainly associated with the left temporal pole. This study supports the view that fv-FTD patients undergo a breakdown of generative processes which relies regardless of the remoteness on the left orbitofrontal cortex and temporal neocortex to gain access to AM.     

Prediction of antiangiogenic treatment efficacy by iron oxide enhanced parametric magnetic resonance imaging

RATIONALE AND OBJECTIVES: Tools for monitoring modern target-specific antiangiogenic and antivascular therapies are highly desirable because treatment strategies are time consuming, expensive, and yet sometimes ineffective. Therefore, the aim of this experimental study was to evaluate the predictive value of steady-state ultrasmall particles of iron oxide (USPIO; SH U 555 C)-enhanced magnetic resonance imaging (MRI) for early assessment of antivascular tumor-treatment effectiveness. METHODS: Mice were inoculated with an HT-1080 fibrosarcoma xenograft and subjected to target-specific antivascular therapy using a selective thrombogenic vascular-targeting agent (truncated tissue factor fused to RGD peptide) or saline as control. Four to 8 hours after treatment, the USPIO-induced change in the transverse relaxation rate DeltaR2* was measured by MRI, and the vascular volume fraction (VVF) was calculated by calibrating DeltaR2* of the tumor by DeltaR2* of muscle tissue. Treatment response was defined by histologic grading of vascular thrombosis and tumor necrosis. RESULTS: After thrombogenic treatment, half of the HT-1080 xenograft-bearing animals showed only minor (=nonresponder) whereas the other half showed extensive tumor thrombosis (=responders). For responders, a significant decrease of DeltaR2* and VVF was observed compared with the control group (DeltaR2*: controls: 16 +/- 1 s-1 vs. responder: 4 +/- 2 s-1; P < 0.001) whereas DeltaR2* and VVF remained nearly unchanged for nonresponders (DeltaR2*: nonresponder 14 +/- 2 s-1). VVF and DeltaR2* values correlated inversely with the histologic grading of vascular thrombosis and tumor necrosis (VVF: r = -0.8; DeltaR2*: r = -0.71; P < 0.01). CONCLUSION: USPIO-enhanced MRI allows a noninvasive, early assessment of treatment efficacy of thrombogenic vascular-targeting agents.