Estimating the changing burden of disease attributable to alcohol use in South Africa for 2000, 2006 and 2012.

BACKGROUND: Alcohol use was one of the leading contributors to South Africa (SA)'s disease burden in 2000, accounting for 7% of deaths and disability-adjusted life years (DALYs) in the first South African Comparative Risk Assessment Study (SACRA1). Since then, patterns of alcohol use have changed, as has the epidemiological evidence pertaining to the role of alcohol as a risk factor for infectious diseases, most notably HIV/AIDS and tuberculosis (TB). OBJECTIVES: To estimate the burden of disease attributable to alcohol use by sex and age group in SA in 2000, 2006 and 2012. METHODS: The analysis follows the World Health Organization (WHO)'s comparative risk assessment methodology. Population attributable fractions (PAFs) were calculated from modelled exposure estimated from a systematic assessment and synthesis of 17 nationally representative surveys and relative risks based on the global review by the International Model of Alcohol Harms and Policies. PAFs were applied to the burden of disease estimates from the revised second South African National Burden of Disease Study (SANBD2) to calculate the alcohol-attributable burden for deaths and DALYs for 2000, 2006 and 2012. We quantified the uncertainty by observing the posterior distribution of the estimated prevalence of drinkers and mean use among adult drinkers (≥15 years old) in a Bayesian model. We assumed no uncertainty in the outcome measures. RESULTS: The alcohol-attributable disease burden decreased from 2000 to 2012 after peaking in 2006, owing to shifts in the disease burden, particularly infectious disease and injuries, and changes in drinking patterns. In 2012, alcohol-attributable harm accounted for an estimated 7.1% (95% uncertainty interval (UI) 6.6 - 7.6) of all deaths and 5.6% (95% UI 5.3 - 6.0) of all DALYs. Attributable deaths were split three ways fairly evenly across major disease categories: infectious diseases (36.4%), non-communicable diseases (32.4%) and injuries (31.2%). Top rankings for alcohol-attributable DALYs for specific causes were TB (22.6%), HIV/AIDS (16.0%), road traffic injuries (15.9%), interpersonal violence (12.8%), cardiovascular disease (11.1%), cancer and cirrhosis (both 4%). Alcohol remains an important contributor to the overall disease burden, ranking fifth in terms of deaths and DALYs. CONCLUSION: Although reducing overall alcohol use will decrease the burden of disease at a societal level, alcohol harm reduction strategies in SA should prioritise evidence-based interventions to change drinking patterns. Frequent heavy episodic (i.e. binge) drinking accounts for the unusually large share of injuries and infectious diseases in the alcohol-attributable burden of disease profile. Interventions should focus on the distal causes of heavy drinking by focusing on strategies recommended by the WHO's SAFER initiative.

PDGFRß promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T cell lymphoma commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK and transcriptionally regulate PDGFRß. Blocking PDGFRß kinase activity with imatinib effectively reduces tumor burden and prolongs survival, although the downstream molecular mechanisms remain elusive. METHODS AND RESULTS: In a transgenic mouse model that mimics PDGFRß-driven human ALCL in vivo, we identify PDGFRß as a driver of aggressive tumor growth. Mechanistically, PDGFRß induces the pro-survival factor Bcl-xL and the growth-enhancing cytokine IL-10 via STAT5 activation. CRISPR/Cas9 deletion of both STAT5 gene products, STAT5A and STAT5B, results in the significant impairment of cell viability compared to deletion of STAT5A, STAT5B or STAT3 alone. Moreover, combined blockade of STAT3/5 activity with a selective SH2 domain inhibitor, AC-4-130, effectively obstructs tumor development in vivo. CONCLUSIONS: We therefore propose PDGFRß as a novel biomarker and introduce PDGFRß-STAT3/5 signaling as an important axis in aggressive ALCL. Furthermore, we suggest that inhibition of PDGFRß or STAT3/5 improve existing therapies for both previously untreated and relapsed/refractory ALK+ ALCL patients.

A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo.

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.

A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.

BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, ß3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.

Optimized automated data analysis for the cytokinesis-block micronucleus assay using imaging flow cytometry for high throughput radiation biodosimetry.

The cytokinesis-block micronucleus (CBMN) assay is a well-established technique that can be employed in triage radiation biodosimetry to estimate whole body doses of radiation to potentially exposed individuals through quantitation of the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using traditional microscope-based methods and most recently has been modified for application on the ImageStream(X) (IS(X) ) imaging flow cytometer. This modification has allowed for a similar number of BNCs to be automatically scored as compared to traditional microscopy in a much shorter time period. However, the MN frequency measured was much lower than both manual and automated slide-based methods of performing the assay. This work describes the optimized analysis template which implements newly developed functions in the IDEAS(®) data analysis software for the IS(X) that enhances specificity for BNCs and increases the frequency of scored MN. A new dose response calibration curve is presented in which the average rate of MN per BNC is of similar magnitude to those presented in the literature using automated CBMN slide scoring methods. In addition, dose estimates were generated for nine irradiated, blinded samples and were found to be within ±0.5 Gy of the delivered dose. Results demonstrate that the improved identification accuracy for MN and BNCs in the IS(X) -based version of the CBMN assay will translate to increased accuracy when estimating unknown radiation doses received by exposed individuals following large-scale radiological or nuclear emergencies. © 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.

[Current standard of care for initial management of open fractures in emergency departments : A nationwide survey in German trauma centers]. / Realität initialer Versorgung offener Frakturen in deutschen Notaufnahmen : Eine Umfrage aus der Sektion NIS der DGU.

BACKGROUND: Limiting the morbidity of open fractures requires highly specific initial treatment. In addition to a stringent surgical strategy, correct antibiotic prophylaxis seems to be associated with an improved outcome. In the current literature, the duration and type of antibiotic prophylaxis are under discussion. The aim of the study was to survey the current initial treatment regimes for open fractures in German emergency departments. MATERIAL AND METHODS: With an online-based anonymous 16-item questionnaire all 3006 members of the German Trauma Society were surveyed. A total of 585 questionnaires (19.5 %) were returned completed. This article presents a descriptive analysis of the current state of treatment. RESULTS: Mainly specialists (35 %), senior physicians (30 %) and chief physicians (17 %) answered as well as interns (8 %) and out-patient practitioners (10 %). Of the participants 65 % did not accept the classification of emergency services; however, 93 % carried out urgent or emergency surgery, 84 % started an antibiotic prophylaxis in the emergency department and 63 % used a standard operating procedure (SOP). A total of 60 % used 1 antibiotic drug, 25 % used 2 and 15 % used 3 or more substances. An antibiotic treatment for more than 3 days was performed by 60 % of participants. CONCLUSION: The early initiation of antibiotic prophylaxis seems to be the standard practice in German emergency departments as well as early surgery. Strategies to improve the communication between prehospital and in-hospital teams, as well as graded antibiotic prophylaxis depending on the severity of soft tissue damage are needed.

Human factors engineering approaches to patient identification armband design.

The task of patient identification is performed many times each day by nurses and other members of the care team. Armbands are used for both direct verification and barcode scanning during patient identification. Armbands and information layout are critical to reducing patient identification errors and dangerous workarounds. We report the effort at two large, integrated healthcare systems that employed human factors engineering approaches to the information layout design of new patient identification armbands. The different methods used illustrate potential pathways to obtain standardized armbands across healthcare systems that incorporate human factors principles. By extension, how the designs have been adopted provides examples of how to incorporate human factors engineering into key clinical processes.

Patterns of early resuscitation associated with mortality after penetrating injuries.

BACKGROUND: Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. METHODS: Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU® were analysed. Patients with a primary admission and an Injury Severity Score (ISS) of at least 9 were included. The Revised Injury Severity Classification (RISC) II score was used for mortality prediction, and a standardized mortality ratio (SMR) calculated per hospital. Hospitals with favourable outcome (SMR below 1) were compared with those with poor outcome (SMR 1 or more). RESULTS: A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15.7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24.4 per cent). Predicted mortality rates according to RISC-II were 20.4 and 20.5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) (P = 0.121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. CONCLUSION: Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality.

[Current practice in coagulation and transfusion therapy in multiple trauma patients: A German nation-wide online survey]. / Stand der Gerinnungs- und Transfusionstherapie beim Schwerverletzten : Eine deutschlandweite Online-Umfrage.

BACKGROUND: In recent years, the treatment of trauma-associated coagulopathy and bleeding has advanced enormously. The aim of this study was to assess the current practice of coagulation and transfusion management in Germany. PATIENTS AND METHODS: From October 2011 until January 2012 we conducted a survey via online-questionnaire that was sent per E-Mail to all members of the German Society for Trauma Surgery. It comprised 12 questions with respect to current treatment of coagulopathy and haemorrhage in trauma patients. RESULTS: The response rate was 145/3006 (5 %). The respondents had following specialties: 77.2 % trauma surgery 15.9 % anesthesiology, 6.9 % others. 64 % of respondents were employed by a Level 1 trauma centre, wheras 17 % worked in a local level 3 centre. The majority (94 %) claimed to treat hypothermia regularly. Only about half of the participants reported to follow a massive transfusion protocol in their institution. The potential components of these protocols were reported in varying rates, being it well-established components (e.g. FFP 78 %; Fibrinogen 75 %) or therapies with poor evidence in multiple trauma (Desmopressin 39 %, rFVIIa 47 %). Calcium was provided by only 48 % of respondents although generally recommended in all guidelines. CONCLUSION: The current study suggests that in Germany strategies and principles regarding management of trauma-associated coagulopathy are standardized only poorly. Level 1 centres appear to apply a more advanced approach, however to much variability exists with respect to the components of the transfusion protocols. The low response rate indicates that most German trauma surgeons consider coagulation and hemorrhage as "expert-topics" beyond their field of duty.

Diversity of aflatoxin-producing fungi and their impact on food safety in sub-Saharan Africa.

Crops frequently contaminated by aflatoxins are important sources of revenue and daily nourishment in many portions of sub-Saharan Africa. In recent years, reports have associated aflatoxins with diminished human health and export opportunities in many African Nations. Aflatoxins are highly carcinogenic metabolites mainly produced by members of Aspergillus sect. Flavi. The current study examined aflatoxin-producing fungi associated with maize grain intended for human consumption in 18 sub-Saharan African countries. 4469 Aspergillus sect. Flavi isolates were obtained from 339 samples. The majority (75%) of isolates belonged to the L strain morphotype of A. flavus. Minor percentages were A. tamarii (6%), A. parasiticus (1%), and isolates with S strain morphology (3%). No A. bombycis or A. nomius isolates were detected. Phylogenetic analyses of partial sequences of the nitrate reductase gene (niaD, 1.3kb) and the aflatoxin pathway transcription factor gene (aflR, 1.7kb) were used to verify isolate assignments into species and lineages. Phylogenetics resolved S strain isolates producing only B aflatoxins into two lineages fully supported by sizes of deletions in the gene region spanning the aflatoxin biosynthesis genes cypA (aflU) and norB (aflF). One lineage was the A. flavus S strain with either 0.9 or 1.5kb deletions. The second lineage, recently described from Kenya, has a 2.2kb deletion. Taxa with S strain morphology differed in distribution with strain SBG limited to West Africa and both A. minisclerotigenes and the new lineage from Kenya in Central and East Africa. African A. flavus L strain isolates formed a single clade with L strain isolates from other continents. The sampled maize frequently tested positive for aflatoxins (65%), fumonisins (81%), and deoxynivalenol (40%) indicating the presence of fungi capable of producing the respective toxins. Percentage of samples exceeding US limits for total aflatoxins (regulatory limit), fumonisins (advisory limit), and deoxynivalenol (advisory limit) were 47%, 49%, 4%, respectively.

Natural history of pyuria and microhematuria after prostate surgery.

OBJECTIVE: Urinalysis alterations are common after prostatic surgery. However, time to normalization has not been established. Presence of pyuria and microhematuria can lead to unnecessary diagnostic procedures. The objective of this study is to determine the time to normalization for both parameters. MATERIAL AND METHODS: We reviewed medical records of patients who underwent prostatic surgery without infectious complications during follow-up. We included patients who underwent transurethral resection of the prostate (TURP) with either monopolar or bipolar energy, or open prostatectomy (OP). Kaplan-Meier curves were used to determine the time of persistence of both parameters. ANOVA was used to compare the 3 groups according to the type of surgery. We analyzed the impact of preoperative use of 5-α-reductase inhibitors, and searched for a correlation between the weight of resected tissue and persistence of both parameters. RESULTS: 85 patients were analyzed: 44 underwent monopolar TURP, 27 bipolar TURP, and 14 OP. Persistence of pyuria was significantly longer than microhematuria with a median of 274 days vs. 176 days. Neither the use of monopolar or bipolar energy, nor the use of preoperative 5α-reductase inhibitors affected the persistence time. We found a positive correlation between the resected tissue weight and the persistence of leukocyturia after endoscopic surgery: 23 g was the best cut-off point. CONCLUSIONS: Pyuria persists longer than microhematuria regardless of the type of surgery. There is a correlation between the resected tissue weight and the persistence of pyuria. The presence of pyuria and microhematuria after prostatic surgery is not always a pathological finding.

Proteomic analysis reveals differentially expressed proteins in macrophages infected with Leishmania amazonensis or Leishmania major.

CBA macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. Employing a transcriptomic approach, we previously showed the up-regulation of the genes involved in the classical pathway of macrophage activation in resistant mice. However, microarray analyses do not evaluate changes in gene expression that occur after translation. To circumvent this analytical limitation, we employed a proteomics approach to increase our understanding of the modulations that occur during infection and identify novel targets for the control of Leishmania infection. To identify proteins whose expression changes in CBA macrophages infected with L. major or L. amazonensis, protein extracts were obtained and digested and the peptides were characterized using multi-dimensional liquid chromatography coupled with tandem mass spectrometry analyses. A total of 162 proteins were selected as potentially modulated. Using biological network analyses, these proteins were classified as primarily involved in cellular metabolism and grouped into cellular development biological networks. This study is the first to use a proteomics approach to describe the protein modulations involved in cellular metabolism during the initial events of Leishmania-macrophage interaction. Based on these findings, we hypothesize that these differentially expressed proteins likely play a pivotal role in determining the course of infection.

GABA-B-receptor antibodies in paraneoplastic brainstem encephalitis.

BACKGROUND: Gamma-aminobutyric-acid B (GABA-B)-receptor encephalitis represents a novel entity among autoimmune CNS disorders. Most cases are characterised by limbic encephalitis. CASE REPORT: A 63-year-old patient presented with acute vertigo, nausea and vomiting, facial palsy and dysarthria. He developed dysphagia, gait ataxia and, finally, respiratory failure. Antibodies to GABA-B receptors were positive and declined under treatment with intravenous methylprednisolone and plasma exchange, followed by clinical improvement and stabilisation. Broad tumour screening revealed oesophageal carcinoma. CONCLUSION: The spectrum of neurological manifestations and tumours associated with the paraneoplastic variant of anti-GABA-B-receptor encephalitis may be broader than previously reported.

Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric manifestations are present in 30-40% of patients with systemic lupus erythematosus (SLE). Recently, antibodies to aquaporin-4 (termed AQP4-Ab, or NMO-IgG), a water channel protein, were reported to be present in a subset of patients with SLE and neurological involvement. To evaluate the syndrome specificity and prevalence of serum NMO-IgG/anti-AQP4 antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Sera of 76 patients with SLE and neurological symptoms, 50 of whom met the ACR case definitions of NPSLE, were tested for AQP4-Ab in an indirect immunofluorescence assay employing HEK293 cells transfected with recombinant human AQP4. Only one of the examined sera was positive for NMO-IgG/AQP4-Ab. This patient suffered from TM, ranging over two vertebral segments on spinal MRI. None of the 75 NPSLE without TM was found to be seropositive for NMO-IgG/AQP4-Ab. NMO-IgG/AQP4-Ab in NPSLE were present only in a patient with TM and were not detectable in NPSLE patients with other neurological manifestations. Testing for NMO-IgG/AQP4-Ab positivity should be considered in patients presenting with SLE and TM. Non-longitudinally extensive lesions do no not exclude NMO-IgG/AQP4-Ab in patients presenting with SLE and TM.

[Cardiopulmonary bypass in cardiac surgery]. / Kardiopulmonaler bypass in der herzchirurgie.

Cardiopulmonary bypass (CPB) is a standard procedure in cardiac surgery; however, apart from its therapeutic options a CPB might also initiate systemic and organ-specific complications, such as heart failure, renal and pulmonary dysfunction, impaired coagulation as well as neurological and cognitive dysfunction. The immunological response to the extracorporeal circulation generates systemic inflammation which often meets the definition of systemic inflammatory response syndrome (SIRS). The main inducers of SIRS are contact of blood with the artificial surfaces of the CPB, mechanical stress which affects the blood components and the extensive surgical trauma. Hence, a number of technical and surgical developments aim at reduction of the inflammatory response caused by the CPB. By reason of surgical demands, the majority of cardiothoracic procedures still depend on the use of CPB; however, there is an on-going development of new techniques trying to reduce the surgical trauma and the negative consequences of CPB. Here, minimized systems with biocompatible surfaces have been shown to be effective in attenuating the inflammatory response to CPB. Alternative procedures such as off-pump surgery may help to avoid CPB-associated complications but due to specific limitations will not replace conventional bypass surgery.

Minimally displaced tibial tuberosity avulsion fracture in nine skeletally immature large breed dogs.

OBJECTIVE: The objective of this study was to describe the clinical and radiographic features, as well as the treatment and outcome of minimally displaced tibial-tuberosity-avulsion-fractures (MDTTAF). MATERIALS AND METHODS: Signalment, history, diagnostics, therapy, and outcome were recorded. Follow-up was documented as re-examination, radiographic assessment or telephone conversation. RESULTS: Nine large breed dogs that were presented with lameness originating from the proximal tibia were included. All showed signs of pain when pressure was applied to the tibial tuberosity. There was no stifle instability or intra-articular disease. The main feature on mediolateral radiographs was a widened tibial-tuberosity-physis with reactive new bone and loss of edge definition of the epiphyseal and metaphyseal margins. Non-surgical treatment was chosen in eight dogs, and surgery in one dog. Radiographic follow-up showed progressive closure of the tibial-tuberosity-physis and healing. Clinical signs resolved at a median of 28 days (range: 14-120). DISCUSSION: Minimally displaced tibial-tuberosity-avulsion-fractures should be a differential diagnosis in skeletally immature large breed dogs older than nine months of age with signs of subtle pelvic-limb lameness, and signs of proximal tibial pain, but no evidence of stifle joint disease. Thorough clinical examination and critical review of bilateral radiographs are important to diagnose MDTTAF. The outcome in these cases suggests that the prognosis for MDTTAF is excellent. Age and size of the affected dogs in this study differ from an earlier publication that illustrated more severely displaced tibial tuberosity avulsion fractures, occurring mainly in terriers around five months of age.

Productive capacity of alveolar macrophages and pulmonary organ damage after femoral fracture and hemorrhage in IL-6 knockout mice.

Alveolar macrophages (AM) play an important role in the pathogenesis of posttraumatic pulmonary failure, and have been identified as major source of pulmonary cytokines. The effects of locally generated IL-6 as well as femoral fracture on the pulmonary inflammatory response and organ damage have not been fully elucidated. In the present study we evaluated the influence of femoral fracture, isolated or in combination with hemorrhage, on the immune function of AM and remote lung injury, and investigated the role of pulmonary IL-6 within this setting. 18 wild type (WT) and 18 IL-6 knockout mice (IL-6(-/-)) underwent standardized femoral fracture, isolated or in combination with volume-controlled hemorrhage, followed by fluid resuscitation and splint fixation of the fracture. Animals were sacrificed 4h after induction of fracture and hemorrhage. Animals were randomly assigned to three study groups (each consisting of six animals). Besides sham groups, experimental groups included animals with isolated femoral fracture or in combination with hemorrhagic shock. Cytokine release of AM was determined by flow cytometry. Pulmonary damage in terms of interstitial thickening and lung neutrophil infiltration was assessed by histology and immunohistology. The productive capacity of AM for pro-inflammatory cytokines was increased after isolated femoral fracture in WT and IL-6(-/-) mice. An additional hemorrhagic insult resulted in a further enhancement of pro-inflammatory cytokine release and an increased MCP-1 secretion in WT and IL-6(-/-) animals. MCP-1 and pro-inflammatory cytokine production of AM was attenuated in IL-6(-/-) mice compared to the respective WT groups. Interstitial thickening and lung neutrophil infiltration was only observed after femoral fracture combined with hemorrhagic shock with an attenuation of the pulmonary organ damage in IL-6(-/-) compared to WT animals. These results support the role of IL-6 as a therapeutic target for posttraumatic immune modulation. With an increased pro-inflammatory mediator release, already an isolated femoral fracture seems to influence the immune response of AM.

[First results with a multidirectional fixed angle implant for internal fixation of distal radius fractures]. / Erste Ergebnisse der multidirektional-winkelstabilen palmaren Osteosynthese der distalen Radiusfraktur.

BACKGROUND: The management of fractures of the distal radius continues to evolve. New operative strategies have recently been developed including the use of fixed-angle plates. This study reviews the results of 20 patients with fractures of the distal radius treated with a new multidirectional fixed angle plate. METHOD AND MATERIALS: A total of 20 patients with closed Colles type fractures of the distal radius were treated with Medartis (Aptus 2.5) palmar fixed-angle plates. Surgery was performed under plexus anesthesia using the standard or extended flexor carpi radialis (FCR) approach. Patients were evaluated prospectively with a mean follow-up of 26 weeks (range 23-28 weeks). Pain, range of motion, grip strength, DASH score, modified Mayo wrist score and radiographs were obtained. The level of significance was set at 95% and the χ(2) and ANOVA tests in combination with a post hoc Tukey test were used for statistical analysis. RESULTS: The average range of motion (ROM) in extension-flexion was 87° (76% of the contralateral side) and in ulnar-radial deviation 42° (88% of the contralateral side). Pain values (visual analogue scale 0-100) at follow-up were 3 (without stress) and 24 (with stress). Grip strength improved to 84% of the contralateral side, the mean DASH score was 13 points and the modified Mayo wrist score confirmed the excellent results with a mean value of 83±27 points. Radiological examination showed a satisfactory result with an ulna variance of 0.9±0.4 mm, radio-ulnar inclination of 21±5° and palmar inclination of 4±6°. CONCLUSIONS: Our data show that treating unstable distal radius fractures with multidirectional palmar fixed-angle plates is reliable and effective and produces good early functional and radiological results. However, long-term results with a larger number of patients and randomized prospective studies comparing this technique with other established procedures are required.

Anti-SOX1 antibodies in patients with paraneoplastic and non-paraneoplastic neuropathy.

Anti-SOX1 antibodies have been described to be positive in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and, in a lower amount, in patients with anti-Hu positive paraneoplastic neurological syndromes, and with SCLC alone, respectively. We found 5/32 patients with paraneoplastic neuropathy and, surprisingly, 4/22 patients with neuropathy of unknown origin positive for anti-SOX1 antibodies, whereas no patient with inflammatory neuropathy and no healthy controls showed any reactivity (p=0.007). All patients with neuropathy of unknown origin where followed up for four years without diagnosis of a tumour so far. Anti-SOX1 antibodies are associated with paraneoplastic neuropathies and may define another group of non-paraneoplastic, immune-mediated neuropathies.

[Diagnostics and treatment of primary bone tumors]. / Diagnostik und Therapie primärer Knochentumoren.

Primary bone tumors can be either benign or malignant. Metastization is a characteristic feature of malignant bone tumors. Malignant tumors are characterized by a local aggressive and destructive behavior. The behavior of a tumor is dependent on its entity, the differentiation grade and localization and these factors are of decisive importance for the correct therapy. Even benign tumors can behave very aggressively. Different stages are defined. Patient history and conventional radiographs are the most powerful primary diagnostic tools. Many tumors show typical characteristics and if a malignant lesion is suspected a biopsy should be carried out. Several quality standards have to be respected when making the biopsy. The approach to malignant tumors is always interdisciplinary. Several biological as well as alloplastic reconstruction techniques exist. The treatment of primary malignant bone tumors requires a lot of experience and should only be done in specialized centers.