Impact of Anxiety During Hospitalization on the Clinical Outcome of Patients With Osteoporotic Thoracolumbar Vertebral Fracture.

STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVES: Anxiety in combination with osteoporotic vertebral compression fractures (OVCFs) of the spine remains understudied. The purpose of this study was to analyze whether anxiety has an impact on the short-term functional outcome of patients with an OVCF. Furthermore, a direct impact of the fracture on the patient's anxiety during hospitalization should be recognized. METHODS: All inpatients with an OVCF of the thoracolumbar spine from 2017 to 2020 were included. Trauma mechanism, analgetic medication, anti-osteoporotic therapy, timed-up-and-go test (TuG), mobility, Barthel index, Oswestry-Disability Index (ODI) and EQ5D-5L were documented.For statistical analysis, the U test, chi-square independence test, Spearman correlation, General Linear Model for repeated measures, Bonferroni analysis and Wilcoxon test were used. The item anxiety/depression of the EQ5D-5L was analyzed to describe the patients' anxiousness. RESULTS: Data from 518 patients from 17 different hospitals were evaluated. Fracture severity showed a significant correlation (r = .087, P = .0496) with anxiety. During the hospital stay, pain medication (P < .001), anti-osteoporotic medication (P < .001), and initiation of surgical therapy (P < .001) were associated with less anxiety. The anxiety of a patient at discharge was negatively related to the functional outcomes at the individual follow-up: TuG (P < .001), Barthel index (P < .001), ODI (P < .001) and EQ5D-5L (P < .001). CONCLUSIONS: Higher anxiety is associated with lower functional outcome after OVCF. The item anxiety/depression of the EQ5D-5L provides an easily accessible, quick and simple tool that can be used to screen for poor outcomes and may also offer the opportunity for a specific anxiety intervention.

[Nonsurgical and surgical management of osteoporotic vertebral body fractures : Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU)]. / Nichtoperative und operative Behandlung der osteoporotischen Wirbelkörperfraktur : Empfehlungen der Sektion Wirbelsäule der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU).

STUDY DESIGN: Prospective clinical cohort study (data collection); expert opinion (recommendation development). OBJECTIVES: Treatment options for nonsurgical and surgical management of osteoporotic vertebral body fractures differ widely. Based on the current literature, the knowledge of the experts, and their classification for osteoporotic fractures (OF classification), the Spine Section of the German Society for Orthopaedics and Trauma has now introduced general treatment recommendations. METHODS: A total of 707 clinical cases from 16 hospitals were evaluated. An OF classification-based score was developed for guidance in the option of nonsurgical versus surgical management. For every classification type, differentiated treatment recommendations were deduced. Diagnostic prerequisites for reproducible treatment recommendations were defined: conventional X­rays with consecutive follow-up images (standing position whenever possible), magnetic resonance imaging, and computed tomography scans. OF classification allows for upgrading of fracture severity during the course of radiographic follow-up. The actual classification type is decisive for the score. RESULTS: A score of less than 6 points advocates nonsurgical management; in cases with more than 6 points, surgical management is recommended. The primary goal of treatment is fast and painless mobilization. Because of the expected comorbidities in this age group, minimally invasive procedures are preferred. As a general rule, stability is more important than motion preservation. It is mandatory to restore the physiological loading capacity of the spine. If the patient was in a compensated unbalanced state at the time of fracture, reconstruction of the individual prefracture sagittal profile is sufficient. The instrumentation technique has to account for compromised bone quality. We recommend the use of cement augmentation or high purchase screws. The particular situations of injuries with neurological impairment, the necessity to fuse, multiple level fractures, consecutive and adjacent fractures and fractures in ankylosing spondylitis are addressed separately. CONCLUSIONS: The therapeutic recommendations presented here provide a reliable and reproducible basis to decide for the treatment choices available. However, intermediate clinical situations with a score of 6 points remain, allowing for both nonsurgical and surgical options. As a result, individualized treatment decisions may still be necessary. In the subsequent step, the recommendations presented will be further evaluated in a multicentre controlled clinical trial.

[Tibial plateau fractures in winter sports. Current treatment options]. / Tibiakopffrakturen im Wintersport. Aktuelle Behandlungsoptionen.

BACKGROUND: Tibial plateau fractures overall and especially in winter sports are rare. However, the incidence in recent years is increasing. In a retrospective study from 2009-2012, we found 52 injuries affiliated with winter sports. Noticeable was the high rate of severe injury patterns. In 20 of the 52 cases, there were complete articular or bicondylar fractures (38 %). In 25 cases (48 %), fragment dislocation corresponding to the Moore classification was observed. METHODS: The operative algorithm was based on the initial soft tissue damage and the type of fracture. A two or more stage procedure with first line soft tissue management and temporary external fixation stabilization was performed 12 times. The final internal osteosynthesis was based on the morphology of the fracture, i.e., direct exposition and stabilization of relevant fracture patterns. In 24 cases (46 %), there was a need for two (or more) approaches. In the anterior aspect of the tibial head, customary implants were used; posterior pathologies were stabilized with low-dimension implants. RESULTS: Summarizing with regard to the literature, there is a more discriminating view of tibial plateau fractures, regarding all relevant fracture patterns. Thus, different options in operative access and choice of implants can be made.

Tumours and pseudotumours of the soft tissue in adults: perspectives and current role of sonography.

Soft tissue tumours of the musculoskeletal system are reported relatively frequently. The quality of the information gained from different imaging modalities (Doppler sonography, multislice CT, MRI spectroscopy, and diffusion MRI) means that in a growing number of situations, we can envisage determining with great accuracy not only the usual information of tumour size and topography, but often the exact nature of the tissue, almost always identifying whether a lesion is aggressive or not. Of all these techniques, Doppler sonography has become the most widely used due to the striking improvements in its sensors, especially for superficial applications. Some other recent developments are: panoramic imaging, elastography (although its current contribution is still to be determined but it seems to offer promising potential), and, most importantly, specific contrast agents. These techniques have considerably refined the quality of the information obtained, and have particularly enhanced the degree of sensitivity with which lesion progression can be assessed. Ultrasonography is the very first investigation in our protocol. It is also very often used to close investigations, as it accurately guides core needle biopsy from these generally accessible lesions. The purpose of this article is to bring together updated information on the various collections of sonographic features seen in soft tissue tumours and pseudotumours and to emphasise the considerable contributions of these new technological developments, in particular contrast-enhanced sonography. The discussion will follow the World Health Organisation's anatomical pathology classifications of soft tissue tumours. We will close with a synthesis that summarises the main steps in our diagnostic process.

PCR-based detection of canine Leishmania infections in formalin-fixed and paraffin-embedded skin biopsies: elaboration of a protocol for quality assessment of the diagnostic amplification reaction.

Diagnosis of the cutaneous form of canine leishmaniosis is mostly performed by histological or immunohistological examination of skin biopsies. In modern histology, the polymerase chain reaction (PCR) has gained increasing importance as a complementary tool to directly demonstrate the presence of parasite DNA in the tissue sections. For the present study, a previously described Leishmania-PCR has been further developed and optimised in view of its practicability for routine histological application. Since formalin-fixation of histological specimens causes partial DNA-destruction, which may hamper diagnostic PCR analysis, primers specific for the highly conserved alpha-actin gene sequences were used to pre-diagnostically assess the isolated sample-DNA for its functionality in a PCR-reaction. This alpha-actin-specific PCR detects DNA from a large variety of mammalian species and thus exhibits relevance for both human and veterinary medical application. A recombinant internal positive control was introduced to monitor possible sample-related inhibitory effects during the amplification reaction. We performed a retrospective evaluative study with 18 formalin-fixed samples from dogs with suspected or proven leishmaniosis. Six samples were PCR-incompatible. In turn, 9 of the other 12 samples were PCR-positive, and immunohistochemical results matched these findings. Based on these technical achievements, the Leishmania-PCR proved to be a valuable tool to complement conventional histological and immunohistological methods for diagnosis of cutaneous leishmaniosis in formalin-fixed, paraffin-embedded skin biopsies.

Lytic and contracture-lytic prenecrotic damage to cardiomyocytes: photochemical fluorochrome staining and fluorescent microscopy of the myocardium.

Acute prenecrotic damage to cardiomyocytes of lytic (myocytolysis, cytolysis) and contracture-lytic (primary lumpy degradation of myofibrils) types during ischemic and metabolic alteration of the myocardium are detected at the photooptic level by means of photochemical fluorochrome staining and examination under fluorescent light. Comparison of the fluorescent and polarization microscopic pictures showed that changes in cardiomyocytes are determined by local mass redistribution in the sarcomere compartments and transformations of birefraction of myofibrillar system components during necrobiosis. These changes are determined by lysis and coagulation processes in protein structures of sarcomeres.

Prenecrotic contracture damage in cardiomyocytes: photochemical fluorochrome staining and fluorescent microscopy of the myocardium.

Prenecrotic contracture changes in cardiomyocytes during ischemic and metabolic alteration of the myocardium are detected at the photooptic level by photochemical fluorochrome staining and examination in fluorescent light. Comparison of the fluorescent and polarization microscopic pictures of damaged cardiomyocytes showed relationships between optically active and isotropic constituents of the cell myofibrillar system. Contracture changes are determined by local mass redistribution in contractile compartments and transformations of the myofibril components, caused by protein structure coagulation in cardiomyocyte sarcomers.

Wilhelm Ebstein and Ebstein's malformation.

In 1866, Wilhelm Ebstein published a scholarly description of a tricuspid valve anomaly with dilation of the right atrium and patent foramen ovale that bears his name. However, his original report was almost overlooked. Despite a wide range of publications on the history of cardiac pathology and cardiac surgery, the international literature provides only scarce information regarding the personality of Wilhelm Ebstein and his original description of the anomaly that bears his name. In this article, we present biographical data of Wilhelm Ebstein and discuss how his original description of autopsy findings correlates with our current knowledge of this congenital disorder. It is the excellent correlation of Ebstein's pathologic findings with clinical notes of his colleague and Ebstein's hypotheses of the pathophysiology that made his publication a landmark in the description of a new entity. In addition, Ebstein's report provided a strong basis for the development of repair techniques for this rare anomaly 100 years later.

Molecular characterisation of a predominant antigenic region of Giardia lamblia variant surface protein H7.

During infection, the intestinal protozoan parasite Giardia lamblia undergoes continuous antigenic variation which is determined by diversification of the parasite's major surface antigen, named VSP (variant surface protein). One member from this protein family, VSP H7, is expressed by G. lamblia clone GS/M-83-H7. In the present study, we characterised a highly antigenic portion of VSP H7 which is positioned inside a 130 amino acid C-terminal region of the protein. This region overlaps with a cysteine-rich motif that is rather conserved within the VSP family. Detailed molecular dissection of the antigenic portion monitored a 12 amino acid peptidyl structure which constitutes a non-conformational epitope of VSP H7. In the murine host, this epitope is recognised relatively early (before day 10 p.i.) during infection and stimulates a strong intestinal immunoglobulin A response. At late infective stages (after day 10 p.i.) this immune reaction is progressively complemented by reactions against 'late' antigenic epitopes which are also located inside the 130 amino acid antigenic portion but in closer proximity to the C-terminal end of VSP H7 than the 12 amino acid epitope. Both the high antigenicity and the conserved character suggest that the 12 amino acid epitope is a key factor within the immunological interplay between G. lamblia and the experimental murine host.

Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients.

The factors determining the outcome of immunotherapy in metastatic renal cell carcinoma (RCC) patients remain elusive. Macrophages from normal donors that phagocytose apoptotic cells secrete the immunosuppressive cytokine IL-10 in vitro. Conversely, IL-10 genetic deletion enhances the immunogenicity of apoptotic tumor cells in vivo. Elevated pre-treatment levels of IL-10 are associated with an unfavorable outcome of RCC. We examined whether the ability to release IL-10 by macrophages from RCC patients that phagocytosed apoptotic cells correlated with the outcome of immunotherapy. To this aim, we derived macrophages from 30 patients with metastatic RCC and from 21 healthy subjects (11 sex- and age-matched healthy controls and 10 younger donors). Patients either had a clinical response after immunotherapy, with a median survival after treatment of more than 18 months (n = 16), or were beginning immunotherapy after diagnosis of metastatic disease (n = 14). Macrophages from responding patients challenged with apoptotic cells released significantly less IL-10 than controls (p = 0.0075) and recently diagnosed patients (p = 0.0198), as ascertained by a 2-sided Student's t-test. This was not because macrophages from responding patients lost the ability to secrete IL-10, because antibody opsonization of apoptotic cells rescued IL-10 secretion. In contrast, macrophages from all groups of donors released similar amounts of TNF-alpha. The failure in IL-10 secretion by engulfing macrophages of responding subjects may exalt the immunogenicity of dying tumor cells, contributing to the success of immunotherapy.

Mild amyloid pathology in the primary visual system of nonagenarians and centenarians.

In order to study the patterns of Alzheimer disease (AD)-related pathology in the primary visual system of the oldest old, we performed a quantitative analysis of senile plaques (SP), diffuse beta amyloid (A beta) deposit and neurofibrillary tangle (NFT) distribution in primary area 17, and a semi-quantitative analysis in the dorsal lateral geniculate nucleus (LGN), lateral inferior pulvinar (LIP) and superior colliculus (SC) of 21 individuals aged between 93 and 102 years. Among them, 10 cases were considered as non-demented (ND), while 9 presented very mild cognitive impairment (VMCI), and 2 cases had a clinical diagnosis of AD. Silver methenamine and Gallyas staining, A beta and tau immunostaining revealed the distribution of AD lesions. In primary area 17, most cases, either ND or with VMCI displayed a low to medium number of SP. There was no significant difference in SP and A beta deposit densities between ND and VMCI groups. On the whole, 0.4--2.4% of the cross-sectional cortical area was covered with A beta deposits. Only 6 cases, either ND or with VMCI, were totally devoid of SP and diffuse A beta deposits. Among the subcortical structures, the LIP and SC exhibited low densities of SP and A beta deposits in about half of the ND and VMCI cases, while the LGN was totally spared. NFT were almost absent in area 17 and subcortical nuclei of ND and VMCI cases. These data imply that the ageing of the primary visual system in ND and VMCI nonagenarians and centenarians is characterised by the frequent development of mild amyloid pathology in area 17 in the absence of NFT. In agreement with previous studies in very old cohorts, they also suggest that amyloid deposition is not related to the early stages of the dementia process in the oldest old.

Anti-beta2 glycoprotein I antibodies cause inflammation and recruit dendritic cells in platelet clearance.

Scavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite proinflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the beta2 Glycoprotein I (beta2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se intemalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1beta, TNF-alpha, or IL-10, beta2GPI bound to activated platelets and was required for their recognition by anti-beta2GPI antibodies. DCs internalised platelets opsonised by anti-beta2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-alpha and IL-1beta by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-10. We conclude that anti-beta2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

[Learning to die/practice means learning about life with an awareness of death]. / Sterben lernen/üben heisst Leben lernen in Abschiedlichkeit.

Living with the understanding that one must take leave of life means being able to restore the past. Living with the understanding that one must take leave of life means new insight into the present. Living with the understanding that one must take leave of life means creating an inspiring future. These three theorems are discussed in detail based on conversations with elderly persons.

The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells.

Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1 beta, and tumor necrosis factor-alpha, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 cross-linking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues. (Blood. 2000;96:4300-4306)

Anti-beta2 glycoprotein I antibodies prevent the De-activation of platelets and sustain their phagocytic clearance.

Exposure to phosphatidylserine (PS) tags dying and senescent cells for removal and identifies activated platelets. In this study we followed the fate of PS-exposing platelets in the presence of antibodies purified from Systemic Lupus Erythematosus (SLE) and primary Anti-phospholipid Syndrome (APS) patients' sera by beta2GPI affinity chromatography. Thrombin-activated platelets exposed PS and associated to beta2GPI. Both events were required for recognition by antibodies. Human monocyte-derived macrophages phagocytosed activated platelets only. Each macrophage internalized an average of 3.16+/-0.2 platelets after 60 min at 37 degrees C. Phagocytosis did not increase after longer incubations (4.65+/-0.26 platelets internalized by each macrophage after 300 min). Recognition of platelets by anti-beta2GPI antibodies significantly increased phagocytosis (P< 0.01). Upon withdrawal of thrombin, platelets downregulated PS (PS exposure t(1/2): 242 min) and the ability to be recognized by macrophages. Purified beta2GPI bound to PS-exposing platelets (association t(1/2): 250 min). Phosphatidyl serine exposure and beta2GPI association had virtually identical kinetics. Antibody binding prolonged the exposure of the beta2GPI/PS complex (t(1/2): >1200 min). The ability to phagocytose opsonized platelets was accordingly sustained (5.3+/-0.2 opsonized platelets were internalized by each macrophage after 60 min and 9.4+/-0.3 after 300 min). Anti-beta2GPI antibodies therefore poise activated platelets in a PS-exposing status, preventing the recycling of their function and favoring their phagocytic clearance.

Clinical evidence for correlation of insufficient tissue oxygen supply (hypoxia) and tumor-associated proteolysis in squamous cell carcinoma of the head and neck.

Hypoxic tumors of patients with squamous cell carcinoma of the head and neck show a consistent trend towards poor treatment outcome. We now report that tumor hypoxia in these patients is correlated with elevated antigen content of the tumor-associated serine protease uPA (urokinase-type plasminogen activator), a marker of tumor cell invasion and metastasis.