The Mangled Extremity Severity Score Fails to be a Good Predictor for Secondary Limb Amputation After Trauma with Vascular Injury in Central Europe.

BACKGROUND: The Mangled Extremity Severity Score (MESS) was constructed as an objective quantification criterion for limb trauma. A MESS of or greater than 7 was proposed as a cut-off point for primary limb amputation. Opinions concerning the predictive value of the MESS vary broadly in the literature. The aim of this study was to evaluate the applicability of the MESS in a contemporary civilian Central European cohort. METHODS: All patients treated for extremity injuries with arterial reconstruction at two centres between January 2005 and December 2014 were assessed. The MESS and the amputation rate were determined. RESULTS: Seventy-one patients met the inclusion criteria and could be evaluated for trauma mechanism and injury patterns. The mean MESS was 4.97 (CI 4.4-5.6). Seventy-three per cent of all patients (52/71) had a MESS < 7 and 27% (19/71) of ≥7. Eight patients (11%) underwent secondary amputation. Patients with a MESS ≥ 7 showed a higher, but statistically not significant secondary amputation rate (21.1%; 4/19) than those with a MESS < 7 (7.7%; 4/52; p = 0.20). The area under the ROC curve was 0.57 (95% CI 0.41; 0.73). CONCLUSIONS: Based on these results, the MESS appears to be an inappropriate predictor for amputation in civilian settings in Central Europe possibly due to therapeutic advances in the treatment of orthopaedic, vascular, neurologic and soft-tissue traumas.

[Extensive emphysema after intramedullary nailing of a pertrochanteric fracture : Life-threatening infection or benign complication]. / Ausgeprägtes Emphysem nach Marknagelung einer pertrochantären Fraktur : Lebensbedrohliche Infektion oder benigne Komplikation.

The development of emphysema after intramedullary nailing can represent an easily manageable complication but in the differential diagnostics it could, however, be a life-threatening infection with Clostridium perfringens. This is a report about the case of an extensive subcutaneous and retroperitoneal emphysema, which developed after intramedullary nailing of a pertrochanteric femoral fracture and where such an infection was suspected.

Clinical Manifestations of Respiratory Bronchiolitis as an Incidental Finding in Surgical Lung Biopsies: A Retrospective Analysis of a Large Austrian Registry.

BACKGROUND: While respiratory bronchiolitis (RB) is a frequent histopathological finding in smoker's lungs, RB-associated interstitial lung disease (RB-ILD) remains a rare disease. OBJECTIVES: We analyzed how the histological finding of RB was associated with clinical information in a series of 684 consecutive surgical lung biopsies. METHODS: Retrospective analysis with delineation of clinical manifestations, smoking habits, pulmonary function test, and blood gas analysis in patients with RB in surgical lung biopsy. In 240 of these biopsies, RB was diagnosed, and in 146 of these cases a full clinical dataset was available. RESULTS: The final diagnosis of these 146 patients was consistent with RB-ILD (n = 18), pulmonary Langerhans cell histiocytosis (n = 7), various ILD (n = 9), spontaneous pneumothorax (n = 43), traumatic pneumothorax (n = 5), lung cancer (n = 41), various benign lung tumors (n = 8), and chronic pulmonary effusion (n = 15). Smoking history was positive in 93% of patients, 72% revealed centrilobular emphysema in their biopsy, and 58% described dyspnea as the main symptom. Amongst these diagnoses there were significant differences in age and smoking habits, but only small distinctions in pulmonary function test and blood gas analysis. Out of the patients with RB-ILD, 17% developed lung cancer in the later course. CONCLUSION: RB is strongly related to smoking, emphysema, and dyspnea and frequently associated with lung cancer. RB-ILD is a rare disease that may represent a considerable risk for lung cancer. Pulmonary function testing and blood gas analysis do not differ between RB-associated diseases. The finding of RB should prompt further diagnostic workup, and in case of RB-ILD, entail regular screening for lung cancer.

Application of Hyperbaric Oxygen Reduce Oxidative Damage of Plasmatic Carbonyl Proteins and 8-OHdG by Activating Glutathion Peroxidase.

BACKGROUND: It is postulated that application of hyperbaric oxygenation may induce the production of radicals after HBO. Higher oxygenation and transport of oxygen increase the mitochondrial energy turnover, whereas inner mitochondrial radical formation decreases. METHODS: Several markers of oxidative stress in healthy volunteers (n = 21), including plasma carbonyl proteins (CP), malondialdehyde (MDA), oxidized LDL (oxLDL), 8-hydroxy-deoxyguanosine (8-OHdG), and erythrocyte glutathione peroxidase (GPx) activity are measured before, during, and after HBO. RESULTS: Median plasma concentrations of CP decreased significantly during HBO compared to CP levels before HBO (from 77.1 to 61.7 pmol/mg; p < 0.001) and increased again after HBO (to 78.1 pmol/mg; p = 0.035). 8-OHdG decreased significantly during HBO (8.1 ng/mL; p < 0.001) and remained constant after HBO (8.1 ng/mL) compared to "before HBO" (9.4 ng/mL). MDA increased significantly from 0.92 µM (before HBO) to 1.26 µM (during HBO, p < 0.01) and decreased again to 1.00 µM (after HBO, p = 0.023). Erythrocyte GPx activity also increased significantly during HBO (26.5 ± 14.7; p = 0.005), but not after HBO (25.6 ± 17.2 IU/mg). A negative correlation was observed between GPx and MDA only during HBO (r = -0.518; p = 0.016). CONCLUSIONS: We assume that higher oxygen consumption decreases, on the one hand, the inner mitochondrial generation of free radicals and, on the other, RONS by activation of detoxifying enzymes like GPx.

Clamshell thoracotomy and open heart massage--A potential life-saving procedure can be taught to emergency physicians: An educational cadaveric pilot study.

AIMS: Selected patients in traumatic cardiac arrest may benefit from pre-hospital thoracotomy. Pre-hospital care physicians rarely have surgical training and the procedure is rarely performed in most European systems. Limited data exists to inform teaching and training for this procedure. We set out to run a pilot study to determine the time required to perform a thoracotomy and the a priori defined complication rate. METHODS: We adapted an existing system operating procedure requiring four instruments (Plaster-of-Paris shears, dressing scissors, non-toothed forceps, scalpel) for this study. We identified a convenience sample of surgically trained and non-surgically trained participants. All received a training package including a lecture, practical demonstration and cadaver experience. Time to perform the procedure, anatomical accuracy and a priori complication rates were assessed. RESULTS: The mean total time for the clamshell thoracotomy from thoracic incision to delivery of the heart was 167 s (02:47 min:sec). There was no statistical difference in the time to complete the procedure or complication rate among surgeons, non-surgeons and students. The complication rate dropped from 36% in the first attempt to 7% in the second attempt but this was not statistically significant. This is a pilot study and small numbers of participants arguably saw it underpowered to define differences between study groups. CONCLUSION: Clamshell thoracotomy can be taught using cadaver models. In this simulated environment, the procedure may be performed rapidly with minimum equipment.

Simultaneous quantitation of alpha-ketoglutaric acid and 5-hydroxymethylfurfural in plasma by HPLC with UV and fluorescence detection.

Alpha-ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) are currently being investigated in clinical trials as an approach in targeted cancer therapy. Hence, a method for the simultaneous determination of KG and HMF in plasma has been developed. Due to the strongly discriminative chemical properties of KG and HMF, SPE purification is performed using an ion-exchange cartridge to separate KG, and a hydrophobic polymeric cartridge to separate HMF. The cartridges are connected together for several steps, thus resulting in a quicker approach for the purification of plasma samples. The derivatization step is based on the reaction of the carbonyl groups of KG and HMF with dansylhydrazine (DNSH) catalyzed by trifluoroacetic acid. The formed derivatives could be separated by reversed-phase LC on a C8-column, and analyzed by UV and fluorescence detection in a single run using a gradient program. The obtained results show good reproducibility, specificity, and detection limits down to the low picomole range.

Biomechanical evaluation of augmented and nonaugmented primary repair of the anterior cruciate ligament: an in vivo animal study.

PURPOSE: The purpose of this study was to evaluate in a sheep model the biomechanical performance of augmented and nonaugmented primary repair of the anterior cruciate ligament (ACL) following transection at the femoral end during a 12-month postoperative observation. METHODS: Forty sheep were randomly assigned to nonaugmented or augmented primary ACL repair using a polyethylene terephthalate (PET) band. At two, six, 16, 26 and 52 weeks postoperatively four sheep in each group were sacrificed and biomechanical testing performed. RESULTS: Compared with nonaugmented primary ACL repair, the PET-augmented repair demonstrated superior biomechanical results from 16 weeks postoperatively onwards in terms of anterioposterior (AP) laxity, tensile strength and ligament stiffness. The augmentation device works as a stress shield during the ligament healing process. The nonaugmented ACL repair also resulted in ligament healing, but the biomechanical properties were at a significantly lower level. CONCLUSION: These results support the previously reported histological findings following augmented primary ACL repair. This animal study on the healing capacity of the ACL may provide some important contributions to how primary healing in certain types of ruptures can be achieved. CLINICAL RELEVANCE: I.

Management of esophageal perforation in 120 consecutive patients: clinical impact of a structured treatment algorithm.

INTRODUCTION: The therapy of esophageal perforation is still challenging. The aim of this study was to assess the etiology, specific treatment, and outcome of esophageal disruption in order to generate an optimal therapeutic approach to improve patient's outcome. METHODS: We reviewed the cases of 120 consecutive patients with esophageal perforation treated within 10 years. RESULTS: Iatrogenic perforation was the most frequent cause of esophageal perforation (58.3 %); Boerhaave's syndrome was detected in 15 cases (6.8 %). Surgery was performed in 66 patients (55 %), 17 (14 %) patients received conservative treatment and 37 (31 %) patients underwent endoscopic stenting after tumorous perforation. Statistically significant impact on mean survival had Boerhaave's syndrome (p = 0.005), initial sepsis (p = 0.002), pleural effusion/empyema (p = 0.001), mediastinitis (p = 0.003), peritonitis (p = 0.001), and redo-surgery (p = 0.000). Overall mortality rate was 11.7 %, in the esophagectomy group 17 % and in the patients with Boerhaave's syndrome 33.3 %. CONCLUSIONS: An approach considering etiology and extent of perforation, diagnostic delay, and septic status is required to improve patient's outcome. Primary repair is feasible in patients without intrinsic esophageal disease and evidence of sepsis. The greater the diagnostic delay, the more the destruction of the esophageal wall especially in the case of septic esophageal disease, thus the stronger the argument for esophagectomy if anatomically and/or oncologically possible.

Determination of metabolites of 5-hydroxymethylfurfural in human urine after oral application.

5-Hydroxymethylfurfural (5-HMF) is a natural occurring substance taken up by everyday food. In former studies it was shown that 5-HMF is completely decomposed in the body after oral or intravenous application resulting in three main metabolites named 5-hydroxymethylfuroic acid, 2,5-furandicarboxylic acid, and N-(hydroxymethyl)furoyl glycine, and possibly a forth metabolic substance, termed 5-sulphoxymethylfurfural, is formed. Determination is possible via HPLC using a hydrophilic interaction chromatography (HILIC) column with an appropriate gradient system (ACN/ammonium formate 100 mM, pH 2.35). Urine samples were purified by use of an SPE method beforehand working with ScreenA cartridges. This cleaning procedure was validated based on ICH guidelines in terms of linearity, quantification, and detection limit, as well as precision, repeatability, and accuracy. Analysis of real-life samples coming from two healthy probands and one cancer patient, who all received 240 mg 5-hydroxymethylfurfural orally once a day, showed dicarboxylic acid and the glycine conjugate in their urine samples. Recovery of the initial compound in form of transformed metabolites was up to 90% within 48 h. Potentially toxic 5-sulphoxymethylfurfural could not be found.

Vitamin D and cancer mortality: systematic review of prospective epidemiological studies.

Accumulating evidence from experimental and epidemiological studies suggests that vitamin D deficiency might be a causal risk factor for cancer and therewith associated mortality. We performed a systematic review in Medline up to February 2012 to identify prospective studies on 25-hydroxyvitamin D (25[OH]D) and cancer mortality as well as on 25(OH)D and survival in cancer patients. Our search retrieved 13 studies on cancer-specific mortality and 20 studies on overall mortality in cancer patients. Data on 25(OH)D and cancer mortality were mainly derived from general populations. The results were inconsistent and yielded either no, inverse or positive associations. By contrast, the majority of studies in cancer patients showed that patients with higher 25(OH)D levels had a decreased risk of mortality. This relationship was particularly evident in cohorts of colorectal cancer patients. In contrast, there was no indication for increased mortality risk with higher vitamin D levels in any cancer cohort. In conclusion, the relationship of vitamin D status and cancerspecific mortality is still unclear and warrants further studies. Our results provide a strong rationale to perform prospective randomized controlled studies to document a potential effect of vitamin D supplementation on survival in cancer patients.

Multimodal therapy of malignant pleural mesothelioma: is the replacement of radical surgery imminent?

OBJECTIVES: Malignant pleural mesothelioma (MPM) remains an aggressive thoracic malignancy associated with poor prognosis. There is no standard treatment regimen, and particularly, the impact of radical surgery remains controversial. The main goal of our retrospective single-centre study was to evaluate the surgical and non-surgical treatment modalities applied at our division regarding their effect on the patient's survival. METHODS: During the last decade, 82 patients with histologically confirmed MPM were treated at our division. The complete clinical records of 61 patients were eligible for statistical evaluation. RESULTS: There were 14 women (23%) and 47 men (77%) with a mean age of 63.7 years. Epitheloid subtype was found in 48 patients (78.7%), sarcomatoid in 3 (4.9%) and biphasic in 10 (16%). Surgery as the first treatment modality was performed in 44 patients (72.1%). Pleurectomy/decortication was done in 28 cases (45.9%), extended pleurectomy/decortication was performed in 13 (21.3%) and extrapleural pneumonectomy in 3 (4.9%). Additional intraoperative photodynamic therapy was administered in 20 patients, 34 underwent chemotherapy (55.7%) and 12 had radiotherapy (19.7%). Mean survival time for the collective was 18.3 months. Five-year survival was 17% in the epitheloid histology group, where patients treated with chemotherapy alone yielded a significant increase in survival (P = 0.049), and those with other subtypes survived for a maximum of 20.6 months. CONCLUSIONS: Chemotherapy and pleurectomy/decortication can extend the survival time of patients with MPM remarkably. The adequate treatment options have to be tailored to the specific particular needs of each patient considering histological subtype, tumour stage and patient's individual functional assessment as well as comorbidity.

Individualized, multimodal palliative treatment of inoperable esophageal cancer: clinical impact of photodynamic therapy resulting in prolonged survival.

BACKGROUND AND OBJECTIVE: In esophageal carcinoma palliative treatment is often required due to advanced tumor stage or patient-related factors. The main goal of our retrospective single center study was to evaluate the effect of an individualized multimodal palliative treatment, focusing on the efficacy of different treatment options. MATERIALS AND METHODS: Between 1999 and 2009, 640 patients suffering from esophageal carcinoma were referred to our division. Two hundred fifty out of those (39.1%) were treated with palliative intention by using a individualized, multimodal concept including endoscopic dilatation, photodynamic therapy (PDT), endoluminal brachytherapy, external radiation, chemotherapy, stenting, feeding tube, and palliative resection. RESULTS: There were 37 women (14.9%) and 211 men (85.1%). The treatment included PDT in 171 cases (in 118 as first measure), stenting in 124 (38), dilatation in 83 (24), endoluminal brachytherapy in 92 (20), feeding enterostomy in 40 (14), external radiation in 67 (23), chemotherapy in 57 (29), and palliative resection in 3 patients. The mean number of palliative treatments per patient was 2.6. Mean survival time for the collective was 34 months. Distant metastases and nodal positivity were connected with a significantly reduced survival. If PDT was used in the first place, median survival was 50.9 months compared to 17.3 months if other options were used as initial modality (P = 0.012). CONCLUSION: By using an individualized multimodal approach, an acceptable mean survival time can be achieved in advanced esophageal cancer treated with palliative intention. PDT, if used as initial endoluminal treatment in patients without gross tumor infiltration into the mediastinum, the great vessels or the tracheo-bronchial tree, enables a considerable beneficial effect in the palliative setting.

Method development and validation for the analysis of a new anti-cancer infusion solution via HPLC.

A fast and simple HPLC method has been developed and validated for the quantification of a completely new anti-cancer drug during the manufacturing process. The combination of four compounds including α-ketoglutaric acid, hydroxymethylfurfural, N-acetyl-L-methionine and N-acetyl-L-selenomethionine, administered intravenously, is still in test phase but has already shown promising results in cancer therapy. HPLC separation was achieved on an RP-18 column with a gradient system. However, the highly different concentrations of the compounds required a variation in the detection wavelength within one run. In order to produce a chromatogram where peaks were comparable on a similar range scale, detection at absorption maxima for the two most concentrated components was avoided. After optimization of the gradient program it was possible to detect all four substances within 14 min in spite of their strongly different chemical structure. The method developed was validated for accuracy, repeatability, reproducibility and robustness in relation to temperature and pH of buffer. Linearity as well as the limit of detection and quantification were determined. This HPLC method was found to be precise, accurate and reproducible and can be easily used for in-line process control during the manufacture of the anti-tumour infusion solution.

High extracellular levels of cefpirome in unaffected and infected lung tissue of patients.

OBJECTIVES: the objective of the present investigation was to measure the extracellular concentrations of cefpirome in unaffected and infected lung tissue of septic patients. METHODS: a single intravenous dose of 30 mg/kg total body weight of cefpirome was administered to eight patients every 12 h prior to insertion of microdialysis probes into lung tissue. RESULTS: the median (minimum, maximum) peak concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve from 0 to 4 h (AUC(0-4)) and AUC(0-∞) of unbound cefpirome for unaffected lung were 48 (32, 107) mg/L, 0.83 (0.17, 3.17) h, 117 (60, 177) mg ·â€Šh/L and 182 (80, 382) mg ·â€Šh/L, respectively. The corresponding values for infected lung tissue were 45 (6, 122) mg/L, 1.17 (0.83, 2.83) h, 92 (17, 253) mg ·â€Šh/L and 206 (49, 379) mg ·â€Šh/L, respectively. The median apparent terminal elimination half-lives (t(½z)) of cefpirome were 2.61, 3.05 and 3.39 h for plasma, unaffected lung and infected lung, respectively. The median ratios of the AUC(0)(-∞) for lung to the AUC(0)(-∞) for plasma were 0.63 (0.19, 1.55) and 0.46 (0.32, 0.98) for unaffected and infected lung, respectively. CONCLUSIONS: we provide strong evidence that cefpirome penetrates effectively into the extracellular space fluid of lung tissue. Under steady-state conditions, the median concentrations of cefpirome in plasma, unaffected lung and infected lung exceeded the MICs of the majority of relevant bacteria over the entire dosing interval of up to 12 h after intravenous administration of a dose of 30 mg/kg total body weight.

Creation of a prevascularized site for cell transplantation in rats.

INTRODUCTION: Transplanted cells, especially islet cells, are likely to become apoptotic due to local hypoxia leading to graft dysfunction. Isolated pancreatic islet cells depend on the diffusion of oxygen from the surrounding tissue; therefore, access to sufficient oxygen supply is beneficial, particularly when microcapsules are used for immunoisolation in xenotransplantation. The aim of this study was to create a prevascularized site for cell transplantation in rats and test its effectiveness with microencapsulated HEK293 cells. METHODS: The combination of implantation of a foam dressing, vacuum-assisted wound closure (foam+VAC) and hyperbaric oxygenation (HBO) was used in 40 Sprague-Dawley rats. Blood flow and vascular endothelial growth factor (VEGF) levels were determined. Sodium cellulose sulphate (SCS)-microencapsulated HEK293 cells were xenotransplanted into the foam dressing in rats pre-treated with HBO, and angiogenesis and apoptosis were assessed. RESULTS: Vessel ingrowth and VEGF levels increased depending on the duration of HBO treatment. The area containing the foam was perfused significantly better in the experimental groups when compared to controls. Only a small amount of apoptosis occurs in SCS-microencapsulated HEK293 cells after xenotransplantation. CONCLUSION: As ischemia-damaged cells are likely to undergo cell death or loose functionality due to hypoxia, therefore leading to graft dysfunction, the combination foam+VAC and HBO might be a promising method to create a prevascularized site to achieve better results in xenogeneic cell transplantation.

Traumatic pericardial rupture with cardiac herniation.

If undiagnosed, traumatic pericardial rupture with herniation of the heart may have fatal consequences. We report two cases of multiple trauma with pericardial rupture, which was missed in the preoperative diagnoses of both patients, in spite of suggestive signs on computed tomographic scans. One patient had unexplained, persistent hemodynamic instability; the second patient had cardiac arrest during laparotomy for minor hepatic laceration. In both, the left-sided rupture of the pericardium with cardiac herniation into the pleural space was found and corrected in an emergency intervention. Both patients recovered completely.

Extracellular concentrations of fosfomycin in lung tissue of septic patients.

OBJECTIVES: The present investigation explored the ability of fosfomycin to penetrate lung tissue of septic patients by utilizing the microdialysis technique. METHODS: After microdialysis probe insertion into healthy and infected lung tissue, a single intravenous dose of 4 g of fosfomycin was administered. RESULTS: The mean C(max), T(max), AUC(0-4) and AUC(0-infinity) for healthy lung were 131.6 +/- 110.6 mg/L, 1.1 +/- 0.4 h, 242.4 +/- 101.6 mgxh/L and 367.6 +/- 111.9 mgxh/L, respectively. The corresponding values for infected lung were 107.5 +/- 60.2 mg/L, 1.4 +/- 0.5 h, 203.5 +/- 118.4 mgxh/L and 315.1 +/- 151.2 mgxh/L. The half-life of fosfomycin ranged from 2.2 to 2.7 h between compartments. The magnitude of lung tissue penetration, as determined by the ratios of the AUC(0-infinity) for lung to the AUC(0-infinity) for plasma, was 0.63 +/- 0.31 and 0.53 +/- 0.31 for healthy and infected lung, respectively. CONCLUSIONS: We conclude that fosfomycin achieves antimicrobially effective concentrations in infected lung tissue.

Severe hydrogen sulphide poisoning treated with 4-dimethylaminophenol and hyperbaric oxygen.

UNLABELLED: INTRODUCTION Hydrogen sulphide (H2S) is a highly toxic gas which originates mainly during breakdown of organic matter under anaerobic conditions. After inhalation, H2S binds to mitochondrial respiratory enzymes preventing oxidative phosphorylation, thereby causing reversible inhibition of aerobic metabolism and cellular anoxia. The use of hyperbaric oxygen therapy (HBOT) for H2S poisoning remains controversial, but has a similar underlying rationale to that in carbon monoxide poisoning. METHODS: A retrospective review of patients with severe H2S intoxication who presented during 2006 and 2007 was carried out. Ten victims of severe occupational H2S poisoning were identified, of whom four died at the site of the accident. Two further patients required cardiopulmonary resuscitation at the site of the accident and the remaining four all received 100% oxygen followed by endotracheal intubation and artificial ventilation prior to hospital admission. In these six cases, 4-dimethylaminophenol was administered on admission as an antidote, followed immediately by HBOT using the schedule otherwise used in carbon monoxide intoxication. CLINICAL OUTCOME: The two patients who required cardiopulmonary resuscitation at the site of exposure died of cerebral ischaemia or pulmonary oedema on the first and seventh days after the accident respectively. The remaining four patients recovered without any neurological sequelae and were discharged for outpatient care after a median of nine days (range 8-12 days). No antidote-related adverse effects could be detected. Acid-base status and oxygenation improved and methaemoglobin fell with the first HBOT in all six cases. CONCLUSION: In severe H2S intoxication, supportive HBOT may play a useful role in improving oxygenation and acid-base status quickly and counteracting the decrement in oxygen carriage caused by methaemoglobinaemia due to antidote administration.

Transdiaphragmatic repositioning of the heart in the setting of emergency laparotomy after blunt trauma.

Cardiac luxation after blunt trauma is a rare condition that carries a high mortality rate. We report a case of a left pericardial rupture with partial dislocation of the heart into the left pleural cavity and cardiac strangulation in a polytraumatized patient after a severe motor vehicle accident. This case is of special interest because the patient not only had cardiovascular compromise but was also actually in cardiac arrest and being resuscitated when an emergency repositioning of the heart through the diaphragm in the setting of damage control laparotomy restored circulation. This report stresses the need for a high index of suspicion for accurate early diagnosis of pericardial rupture.