Voluntary exercise does not always suppress lung cancer progression.

Physical exercise can lower lung cancer incidence. However, its effect on lung cancer progression is less understood. Studies on exercising mice have shown decreased ectopic lung cancer growth through the secretion of interleukin-6 from muscles and the recruitment of natural killer (NK) cells to tumors. We asked if exercise suppresses lung cancer in an orthotopic model also. Single-housed C57Bl/6 male mice in cages with running wheels were tail vein-injected with LLC1.1 lung cancer cells, and lung tumor nodules were analyzed. Exercise did not affect lung cancer. Therefore, we also tested the effect of exercise on a subcutaneous LLC1 tumor and a tail vein-injected B16F10 melanoma model. Except for one case of excessive exercise, tumor progression was not influenced. Moderately exercising mice did not increase IL-6 or recruit NK cells to the tumor. Our data suggest that the exercise dose may dictate how efficiently the immune system is stimulated and controls tumor progression.

Early radiographic osseointegration of a novel highly porous 3D-printed titanium collar for megaprostheses compared to a previous generation smooth HA-coated collar.

PURPOSE: Extracortical osseointegration at the collar-bone interface of megaprostheses is associated with improved implant stability, lower rates of stem fracture and loosening. The use of hydroxy-apatite (HA-) coated collars showed mixed results in previously published reports. A novel collar system has recently become available utilizing additive manufacturing technology to create a highly porous titanium collar with a calcium-phosphate coated surface. The aim of this study was to evaluate our early experience with this novel collar and compare it to the previously used HA-coated model. METHODS: Twenty patients who underwent megaprostheses implantation utilizing the novel collar system were case matched to 20 patients who had previously undergone a HA-coated collar. A minimum radiological follow-up of three months was available in all included patients. Osseointegration was evaluated using postoperative plain radiographs in two planes based on a previously published semi-quantitative score. RESULTS: Compared to the HA-coated collar the use of the novel highly porous collar was associated with a higher proportion of cases demonstrating osseointegration at the bone-collar interface (80% vs. 65%). Application of the highly porous collar led to a significantly shortened time to reach the final ongrowth score (173 ± 89 days vs. 299 ± 165 days, p < 0.05). At one year follow-up, 90% of the novel collars had reached their final osseoingration grade compared to 50% in the HA-coated collar group (p < 0.001). Radiological osseointegration was seen in 71% for highly porous collars where the indication was revision arthroplasty, compared to 27% in reported in the literature. CONCLUSION: These results indicate more reliable and accelerated osseointegration at the bone-collar interface of a novel highly porous collar system compared to a previously used HA-coated collar. Further studies are warranted to confirm these findings.

Intravenous diclofenac and orphenadrine for the treatment of postoperative pain after remifentanil-based anesthesia : A double-blinded, randomized, placebo-controlled study.

BACKGROUND: Postoperative intravenous diclofenac reduces patient opioid demand and is commonly used in surgical units. Orphenadrine is mainly used in combination with diclofenac for musculoskeletal injuries and postoperative pain control. The objective of this study was to compare the analgesic efficacy of diclofenac-orphenadrine, diclofenac alone and saline. METHODS: We performed a double-blind, randomized, placebo-controlled, parallel-group, single-center clinical study investigating the opioid-sparing effect of a combination of diclofenac and orphenadrine versus diclofenac alone versus isotonic saline solution. Initially 72 patients were included and received total intravenous anesthesia during cruciate ligament surgery. All patients were postoperatively treated with a patient-controlled analgesia (PCA) device containing hydromorphone. Pharmacological safety was assessed by laboratory parameters, vital signs, and delirium detection scores. RESULTS: There was no significant difference between the groups in cumulative dose of PCA analgesics required after 24 h postsurgery, with 5.90 mg (SD ± 2.90 mg) in the placebo group, 5.73 mg (SD ± 4.75 mg) in the diclofenac group, and 4.13 mg (SD ± 2.57 mg) in the diclofenac-orphenadrine group. Furthermore, there was no significant difference between the groups in cumulative dose of PCA analgesics required 2 h postsurgery (n = 65). Mean dose of hydromorphone required after 2 h was 1.54 mg (SD ± 0.57 mg) in the placebo group, 1.56 mg (SD ± 1.19 mg) in the diclofenac-only group, and 1.37 mg (SD ± 0.78 mg) in the diclofenac-orphenadrine group. However, when comparing the diclofenac-orphenadrine group and the diclofenac group combined to placebo there was a significant reduction in PCA usage in the first 24 h postsurgery. In total, there were 25 adverse events reported, none of which were rated as severe. CONCLUSION: Orphenadrine-diclofenac failed to significantly reduce postoperative opioid requirements. However, in an exploratory post hoc analysis the diclofenac-orphenadrine and the diclofenac group combined versus placebo showed a tendency to reduce opioid demand in postoperative pain control. Further research is required to determine the value of orphenadrine as an adjuvant in a multimodal approach for postoperative pain management.

Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis.

AIMS: Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow-mediated dilatation (FMD), and pulse-wave analysis and velocity (PWA/PWV) in patients with CA. METHODS AND RESULTS: Flicker-induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty-three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light-chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross-sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001, after IPW). While PWV was increased (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018, after IPW), no difference in FMD was observed. FIDa was significantly associated with prognostic biomarkers of CA [estimated glomerular filtration rate (r = 0.33; P < 0.001), log-scaled troponin T (r = -0.49; P < 0.001), and N-terminal pro-B-type natriuretic peptide (r = -0.51; P < 0.001)]. CONCLUSIONS: Retinal vascular function is impaired, associated with cardiac and renal biomarkers of CA severity, and may represent a potential therapeutic target in patients with amyloidosis.

Standard radiographic assessments of distal radius fractures miss involvement of the distal radioulnar joint: a diagnostic study.

INTRODUCTION: Distal radius fractures account for one-fifth of all fractures in the emergency department. Their classification based on standard radiographs is common practice although low inter-observer reliabilities and superiority of computer tomography (CT) scanning in evaluation of joint congruency have been reported. MATERIALS AND METHODS: We retrospectively analyzed 96 displaced distal radius fractures scheduled for open reduction and internal fixation using standard radiographic assessment. The radiographs were classified with the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA), Fernandez and Frykman classifications by three observers and inter-rater reliabilities were calculated. Additional CT scanning was performed in all cases and the following parameters were assessed: radiocarpal joint involvement, fracture extent into the radial sigmoid notch, i.e. the distal radio-ulnar joint, comminution of the metaphysis, and concomitant ulnar styloid fracture. The CT scans were used as a reference standard to determine sensitivity and accuracy of standard radiographic assessment in evaluation of distal radius fractures. RESULTS: The inter-rater agreement for the AO classification was 35.4%, 68.8% for the Fernandez and 38.5% for the Frykman classification. Fracture extension into the radiocarpal joint was present in 81 cases (84.4%). Sigmoid notch involvement was found in 81 fractures (84.4%). Involvement of both joints was present in 72 cases (75%). The sensitivity of standard radiographs regarding radiocarpal joint involvement was 93.8%. Considering involvement of the distal radio-ulnar joint the false-negative rate using standard radiographs was 61.7% and the test's accuracy for sigmoid notch involvement was 45.8%. CONCLUSION: This study demonstrates that involvement of the sigmoid notch is frequently missed in standard radiographs. The presented data support the frequent use of CT imaging to allow the holistic illustration of a fracture's complexion and to ensure optimal pre-operative planning.

Intracranial pressure monitoring following traumatic brain injury: evaluation of indications, complications, and significance of follow-up imaging-an exploratory, retrospective study of consecutive patients at a level I trauma center.

BACKGROUND: Measurement of intracranial pressure (ICP) is an essential part of clinical management of severe traumatic brain injury (TBI). However, clinical utility and impact on clinical outcome of ICP monitoring remain controversial. Follow-up imaging using cranial computed tomography (CCT) is commonly performed in these patients. This retrospective cohort study reports on complication rates of ICP measurement in severe TBI patients, as well as on findings and clinical consequences of follow-up CCT. METHODS: We performed a retrospective clinical chart review of severe TBI patients with invasive ICP measurement treated at an urban level I trauma center between January 2007 and September 2017. RESULTS: Clinical records of 213 patients were analyzed. The mean Glasgow Coma Scale (GCS) on admission was 6 with an intra-hospital mortality of 20.7%. Overall, complications in 12 patients (5.6%) related to the invasive ICP-measurement were recorded of which 5 necessitated surgical intervention. Follow-up CCT scans were performed in 192 patients (89.7%). Indications for follow-up CCTs included routine imaging without clinical deterioration (n = 137, 64.3%), and increased ICP values and/or clinical deterioration (n = 55, 25.8%). Follow-up imaging based on clinical deterioration and increased ICP values were associated with significantly increased likelihoods of worsening of CCT findings compared to routinely performed CCT scans with an odds ratio of 5.524 (95% CI 1.625-18.773) and 6.977 (95% CI 3.262-14.926), respectively. Readings of follow-up CCT imaging resulted in subsequent surgical intervention in six patients (3.1%). CONCLUSIONS: Invasive ICP-monitoring in severe TBI patients was safe in our study population with an acceptable complication rate. We found a high number of follow-up CCT. Our results indicate that CCT imaging in patients with invasive ICP monitoring should only be considered in patients with elevated ICP values and/or clinical deterioration.

Implant failure after externally magnetic-controlled nail lengthening.

The number of intramedullary procedures to treat leg length discrepancy (LLD) has risen in the past decade and this has led to increased complications such as nail breakage. The aim of this study was to reveal our experience with implant failure after externally magnetic-controlled telescopic bone lengthening. We observed nail-breakage in 4 out of 24 patients (16.7%) after 6 to 15 months (median 13.5 months) following lower limb lengthening for LLD due to non-union or insufficient bone healing. Three femora and one tibia were treated in one posttraumatic and three congenital cases. Three out of the four patients had an elevated Charleston Comorbidity Index (CCI). Revision surgery involved removal of the broken nail and implantation of a trauma nail. At final follow-up all patients showed subjective satisfaction, achievement of desired lengthening with complete bone healing. Based on our results no unequivocal risk factor including number of previous surgeries, comorbidities and age was identified. In cases of delayed bone formation, early revision surgery with an exchange to a trauma nail has to be considered to prevent breakage of the intramedullary telescopic device.

Does patient positioning influence blood loss and transfusion rate in hip replacement for femoral neck fractures? A single-centre, retrospective chart review.

BACKGROUND: We compared blood loss and transfusion frequency between the lateral decubitus and the supine position in patients undergoing hip replacement surgery due to femoral neck fractures. METHODS: We retrospectively included femoral neck fracture patients treated with either hemi (HA) or total hip arthroplasty (THA). We included a total of 626 patients, of which 313 patients underwent surgery in the lateral decubitus position and 313 patients in the supine position. Preoperative and day 1 postoperative blood measures including hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBC) were evaluated, as well as transfusion records analyzed. RESULTS: The following decrease of laboratory parameters between pre- and 1st day postoperative measures was noted: RBC: -0.77 G/L (± 0.5 G/L, median = -0.80 G/L; range: -0.50 - -1.10 G/L); Hct: -7.08 % (± 4.7 %, range: -4.70 - -9.90 G/L); Hb: -2.36 g/dL (± 1.6 g/dL, range: -1.50. - -3.40 g/dL). We did not observe significant differences in transfusion frequency between the two study cohorts (p = 0.735 for THA, p = 0.273 for HA). No influence of patient positioning on Hb-decrease, Hct-decrease, or RBC-decrease was noted in our two-way ANOVA models with consideration of implant type and fixation technique (F(3,618) = 1.838, p = 0.139; F(3,618) = 2.606, p = 0.051; F(3,618) = 1.407, p = 0.240). CONCLUSIONS: We did not observe  significant differences in perioperative blood values and transfusion rates in association with patient positioning in patients undergoing hip replacement surgery for femoral neck fractures. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Ossification of the pseudarthrosis following the Sauvé-Kapandji procedure: a case report and review of the literature.

We report a case of new onset pain and loss of forearm rotation 3 years after Sauvé-Kapandji (SK) procedure. A revision ulnar osteotomy with application of bone wax restored ROM through 17 months follow-up. A literature review of pseudarthrosis ossification after SK procedure was also performed.

Treatment and outcomes of basicervical femoral neck fractures: A systematic review.

PURPOSE: This study aims to systematically review the literature comparing surgical treatments options and respective failure rates for basicervical hip fractures. METHODS: A comprehensive search of databases, including MEDLINE, Embase, Web of Science, and Cochrane Central for studies published in English on or before June 21, 2019 was performed. Selected search terms included "basicervical," "basi cervical," "AO/OTA type 31-B," "femoral neck fracture" AND "bone nails," "bone screws," "fracture fixation," "internal fixation," "arthroplasty," "cephalomedullary," "sliding hip screw," "ORIF," and "treatment outcome." We included studies that assessed outcomes of basicervical fracture fixation using open reduction internal fixation or arthroplasty. Two authors extracted the following data from each paper: study design, country, cohort year, definition of basicervical, intervention type, sample size, patient demographics, follow-up length, percent of fractures that required revision, and the percent of implants that failed. RESULTS: Sixteen articles encompassing 910 patients were included. The main outcome was the percent of implants that required revision. The total revision rates were 8% (8 studies, 157 patients, range 0%-55%) for cephalomedullary nails, 7% (10 studies, 584 patients, range 0%-18%) for sliding hip screws, 23% (3 studies, 40 patients, range 16%-50%) for cannulated screws, 0% (1 study, 6 patients) for total hip arthroplasty, and 8% (2 studies, 13 patients, range 0%-11%) for hemiarthroplasty. CONCLUSION: Management of basicervical fractures with SHS and CMN produces similar failure and re-operation rates. Limited evidence is available on the use of cannulated screws and arthroplasty, but available studies suggest that cannulated screws have an unacceptable revision rate (23%) while arthroplasty may be acceptable. Future studies examining the comparative efficacy of various fixation methods would benefit from strict definition of fracture type as well as consistent reporting of functional outcomes, re-operation rates, and mortality.

Mid- and Long-Term Outcome After Arthroscopically Assisted Transosseous Triangular Fibrocartilage Complex Refixation-Good to Excellent Results in Spite of Some Loss of Stability of the Distal Radioulnar Joint.

PURPOSE: To evaluate mid- and long-term outcomes after arthroscopically-assisted transosseous reattachment of the triangular fibrocartilage complex (TFCC) and to analyze the association of distal radioulnar joint (DRUJ) stability with the clinical outcome. METHODS: Patients treated with an arthroscopically-assisted transosseous reattachment of the deep layer of the TFCC between 2000 and 2009 and a minimum follow-up of 12 months at mid-term and 4 years at long-term follow-up were retrospectively reviewed. Mayo Modified Wrist Score (MMWS); Disabilities of the Arm, Shoulder and Hand (DASH) score; pain visual analogue scale (VAS); grip strength and stability of the DRUJ were assessed at 2 follow-up clinical examinations. At the last follow-up, the Patient-Rated Wrist Evaluation score was additionally recorded. RESULTS: Thirty patients with a mean age of 29 (±13) years were included. Most of the patients were female (70%, n = 21). The mid-term evaluation took place at a median of 30 months (range, 12-83 months). The assessed scores showed statistically significant clinical improvement (MMWS, P < .001; DASH score P < .001; VAS P < .001). Stability assessment showed a stable DRUJ in 23 (76.7%) patients. At a median of 106 months (range 52-215 months), the long-term clinical assessment was performed. The evaluated scores demonstrated persisting significant improvement (MMWS P < .001; DASH score P < .001; VAS P < .001). Stability assessment showed a stable DRUJ in 19 patients (63.3%). DRUJ instability did not correlate with clinical outcome. No permanent surgery-related complications occurred. CONCLUSION: Arthroscopically-assisted transosseous reattachment of the deep fibers of radioulnar ligaments leads to excellent and good clinical results in mid- and long-term follow-up. In 95.5% of the analyzed patients, the measured improvement in the DASH score exceeded the in literature reported minimal clinically important difference of 13.5. Loss of DRUJ stability during follow-up was not associated with deterioration of clinical parameters and patient satisfaction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Brachial plexus block with ultrasound guidance for upper-limb trauma surgery in children: a retrospective cohort study of 565 cases.

BACKGROUND: Upper-limb trauma is a common indication for surgery in children, and general anaesthesia remains the method of choice for these procedures, even though suitable techniques of brachial plexus block are available and fast provision of regional anaesthesia offers a number of distinct advantages. METHODS: A retrospective analysis was performed of the data of a large cohort of children undergoing ultrasound-guided brachial plexus blocks during a 4-yr period at a major trauma centre with a catchment area of 3.5 million. A total of 565 cases were sourced from two independently operating patient documentation systems. Patient data were stratified into age groups with block success as the primary outcome parameter. The influence of age on the incidence of block failure was assessed with logistic regression. RESULTS: The block failure rate was 5.1%, starting at 1.2% in the youngest (0-3 yr), then continuously increasing up to 12.5% in the oldest (15-18 yr) but also smallest group. Age emerged as an independent predictor of block failure with an odds ratio of 1.115 and a 95% confidence interval of 1.014-1.226 (P=0.025). No complications were observed. CONCLUSIONS: In a cohort of children receiving real-world care, with regional blocks performed by a range of anaesthetists with different skill levels, a success rate of 94.9% for upper-limb blocks in children under various levels of sedation was observed. Upper-limb blocks can be performed with high probability of success and an excellent margin of safety; this particularly applies to small children. CLINICAL TRIAL REGISTRATION: NCT03842423.

IL-33 and its increased serum levels as an alarmin for imminent pulmonary complications in polytraumatized patients.

Background: According to recently published findings, we hypothesized that serum interleukin-33 (IL-33) may qualify for predicting pulmonary complications in polytraumatized patients. Methods: One hundred and thirty patients (age ≥ 18 years, ISS ≥ 16) were included in our prospective analysis after primary admission to our level I trauma center during the first post-traumatic hour. Serum samples immediately after admission and on day 2 after trauma were obtained and analyzed. Results: Median initial IL-33 levels (in picograms per milliliter) were higher in polytrauma victims (1) with concomitant thoracic trauma [5.08 vs. 3.52; p = 0.036], (2) sustaining parenchymal lung injury (PLI) [5.37 vs. 3.71; p = 0.027], and (3) developing acute respiratory distress syndrome (ARDS) [6.19 vs. 4.48; p = 0.003], compared to the respective rest of the study group. The median initial IL-33 levels were higher in patients experiencing both PLI and ARDS compared to those sustaining PLI and not developing ARDS [6.99 vs. 4.69; p = 0.029]. ROC statistics provided an AUC of 0.666 (p = 0.003) and a cut-off value of 4.77 (sensitivity, 71.8%; specificity, 75.7%) for predicting ARDS. Moreover, a higher initial median IL-33 level was revealed in the deceased compared to the survivors [12.25 vs. 4.72; p = 0.021]. ROC statistics identified the initial level of IL-33 as a predictor of death with 11.19 as cut-off value (sensitivity, 80.0%; specificity, 80.0%; AUC = 0.805; p = 0.021). Conclusions: Following tissue damage, IL-33 is abundantly released in the serum of polytraumatized patients immediately after their injuries occurred. As initial IL-33 levels were particularly high in individuals experiencing both PLI and ARDS, IL-33 release after trauma seems to be involved in the promotion of ARDS and might serve already at admission as a solid indicator of impending death in polytraumatized patients.

Iron Homeostasis in the Lungs-A Balance between Health and Disease.

A strong mechanistic link between the regulation of iron homeostasis and oxygen sensing is evident in the lung, where both systems must be properly controlled to maintain lung function. Imbalances in pulmonary iron homeostasis are frequently associated with respiratory diseases, such as chronic obstructive pulmonary disease and with lung cancer. However, the underlying mechanisms causing alterations in iron levels and the involvement of iron in the development of lung disorders are incompletely understood. Here, we review current knowledge about the regulation of pulmonary iron homeostasis, its functional importance, and the link between dysregulated iron levels and lung diseases. Gaining greater knowledge on how iron contributes to the pathogenesis of these diseases holds promise for future iron-related therapeutic strategies.

Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men.

Fibroblast growth factor 23 (FGF23) is a major endocrine regulator of phosphate and 1,25 (OH)2 vitamin D3 metabolism and is mainly produced by osteocytes. Its production is upregulated by a variety of factors including 1,25 (OH)2 vitamin D3, high dietary phosphate intake, and parathyroid hormone (PTH). Recently, iron deficiency and hypoxia have been suggested as additional regulators of FGF23 and a role of erythropoietin (EPO) was shown. However, the regulation of FGF23 by EPO and the impact on phosphate and 1,25(OH)2 vitamin D3 are not completely understood. Here, we demonstrate that acute administration of recombinant human EPO (rhEPO) to healthy humans increases the C-terminal fragment of FGF23 (C-terminal FGF23) but not intact FGF23 (iFGF23). In mice, rhEPO stimulates acutely (24 h) C-terminal FGF23 but iFGF23 only after 4 days without effects on PTH and plasma phosphate. 1,25 (OH)2 D3 levels and αklotho expression in the kidney decrease after 4 days. rhEPO induced FGF23 mRNA in bone marrow but not in bone, with increased staining of FGF23 in CD71+ erythroid precursors in bone marrow. Chronic elevation of EPO in transgenic mice increases iFGF23. Finally, acute injections of recombinant FGF23 reduced renal EPO mRNA expression. Our data demonstrate stimulation of FGF23 levels in mice which impacts mostly on 1,25 (OH)2 vitamin D3 levels and metabolism. In humans, EPO is mostly associated with the C-terminal fragment of FGF23; in mice, EPO has a time-dependent effect on both FGF23 forms. EPO and FGF23 may form a feedback loop controlling and linking erythropoiesis and mineral metabolism.

Femoral shortening does not impair functional outcome after internal fixation of femoral neck fractures in non-geriatric patients.

INTRODUCTION: Aim of this study was to investigate the incidence and extent of femoral shortening in non-geriatric patients after internal fixation of femoral neck fractures in relation to the clinical outcome at mid-term follow-up. MATERIALS AND METHODS: Reviewing our admission data, we identified non-geriatric patients (18-65 years) with femoral neck fractures treated with either dynamic hip screw or cancellous screws between 2007 and 2015. Patients were then contacted and invited to a follow-up clinical investigation including whole-leg standing X-rays. RESULTS: A total of 40 patients with a mean age at surgery of 52 ± 9 years returned for the follow-up examination. Overall, 31 patients (77.5%) had undergone a dynamic hip screw fixation, while 9 patients were treated with cancellous screws (22.5%). The median follow-up time was 65.5 months (5.5 years). We observed shortening of the ipsilateral femur neck in the majority of cases (92.5%). Still, functional outcome in the overall study population was excellent with a median Harris Hip Score of 96. CONCLUSIONS: Femoral neck shortening is common in non-geriatric patients after internal fixation of femoral neck fractures. Nonetheless, observed excellent functional outcome at mid-term follow-up supports joint-preserving strategies in non-geriatric femoral neck fractures.

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.

Increased serum concentrations of soluble ST2 are associated with pulmonary complications and mortality in polytraumatized patients.

BACKGROUND: We sought to evaluate the role of soluble ST2 (suppression of tumorigenicity) serum concentrations in polytraumatized patients and its potential role as biomarker for pulmonary complications. METHODS: We included severely injured patients (injury severity score≥16) admitted to our level I trauma center and analyzed serum samples obtained on the day of admission and on day 2. Furthermore, patients with isolated thoracic injury and healthy probands were included and served as control groups. Serum samples were analyzed for soluble ST2 concentrations with a commercially available ELISA kit. RESULTS: A total of 130 patients were included in the present study. Five patients with isolated thoracic injury and eight healthy probands were further included. Serum analyses revealed significantly elevated concentrations of soluble ST2 in polytraumatized patients compared to patients suffering from isolated thoracic trauma and healthy probands. In polytraumatized patients who developed pulmonary complications (acute respiratory distress syndrome and pneumonia) and in patients who died, significantly higher serum concentrations of soluble ST2 were found on day 2 (p<0.001). Serum concentrations of soluble ST2 on day 2 were of prognostic value to predict pulmonary complications in polytraumatized patients (area under the curve=0.720, 95% confidence interval=0.623-0.816). Concomitant thoracic trauma had no further impact on serum concentrations of soluble ST2. CONCLUSIONS: Serum concentrations of soluble ST2 are upregulated following polytrauma. Increased concentrations were associated with worse outcome.

Reliability and validity of non-invasive determined haemoglobin mass and blood volumes.

INTRODUCTION: The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invasive CO pulse oximeter (Rad-57). METHOD: With simultaneous determination of CO in the circulation by ABL800 (%HbCO) and Rad-57 (SpCO), Hbmass and blood volume (BV) were determined in duplicates in 24 volunteers. Percentage of typical errors (%TE) within methods and linear correlations between the two procedures were computed. RESULTS: Hbmass (Rad-57 = 798 ± 230 g; ABL800 = 781 ± 192 g) and BV (Rad-57 = 5700 ± 1373 ml; ABL800 = 5581 ± 1096 ml) were similar between methods. However, the %TE for Hbmass was higher (P<0·001) for Rad-57 (5·84 ± 5·29%) than for ABL800 (1·35 ± 1·13%). Similarly, the %TE for BV was higher (P<0·001) for Rad-57 (6·06 ± 5·76%) than for ABL800 (1·48 ± 1·25%). Lower (P<0·05) correlation coefficients between the methods were found when Hbmass  > 905 g and BV > 6193 ml. CONCLUSION: Assessment of SpCO by Rad-57 resulted in considerably less precise determinations of Hbmass and BV, especially for high values. Thus, non-invasive assessment of Hbmass and BV cannot be recommended for scientific purposes, but may nonetheless be useful in clinical settings.

Post Mortem Validation of MRI-Identified Veins on the Surface of the Cerebral Cortex as Potential Landmarks for Neurosurgery.

Background and Objective: Image-guided neurosurgery uses information from a wide spectrum of methods to inform the neurosurgeon's judgement about which tissue to resect and which to spare. Imaging data are registered to the patient's skull so that they correspond to the intraoperative macro- and microscopic view. The correspondence between imaging and optical systems breaks down during surgery, however, as a result of cerebro-spinal fluid drain age, tissue resection, and gravity-based brain shift. In this work we investigate whether a map of surface veins, automatically segmented from MRI, could serve as additional reference system. Methods: Gradient-echo based [Formula: see text]-weighted imaging was performed on two human cadavers heads using a 7 Tesla MRI scanner. Automatic vessel segmentation was performed using the Frangi vesselness filter, and surface renderings of vessels compared with photographs of the surface of the brain following craniotomy. Results: A high level of correspondence was established between vessel maps and the post autopsy photographs. Corresponding veins, including the prominent superior anastomotic veins, could be identified in all brain lobes. Conclusion: Automatic surface vessel segmentation is feasible and the high correspondence to post autopsy photographs indicates that they could be used as an additional reference system for image-guided neurosurgery in order to maintain the correspondence between imaging and optical systems.This has the advantage over a skull-based reference system that veins are clearly visible to the surgeon and move and deform with the underlying tissue, potentially making this surface net of landmarks robust to brain shift.