Complications and results of the arthrodesis after total ankle arthroplasty failure: a retrospective monocentric study of 12 cases.

INTRODUCTION: Total ankle arthroplasty (TAA) has the objective to maintain the range of motion of the tibiotarsal joint and to preserve the nearby joints. However, the complication rate and failures remain quite high after TAA. The main objective of the study was to evaluate the improvement in the functional scores of the tibiotarsal arthrodesis after TAA failure. The secondary objective was to assess the specific complications. MATERIALS AND METHODS: This monocentric retrospective series includes 12 patients (nine men, three women, average age 52.5 years) operated between 2003 and 2018. An iliac graft was used in all cases. The arthrodesis was stabilized either by screws or by retrograde nailing. RESULTS: The reoperation was due to painful malleolar conflicts or loosening. The AOFAS score increased from 38/100 to 67/100 (51-86) post-operatively. The fusion was acquired at 3.7 months (3-6) except in two cases. DISCUSSION AND CONCLUSION: The 83% primary fusion rate is in the low average of the literature and 92% fusion rate in the high average after reoperation. All patients were improved even in two non-unions. The results of this study confirm that the arthrodesis after TAA failure is a reliable alternative to the TAA replacement. However, they are lower than those after a first-line arthrodesis.

[Genetic methods for analysis of autoinflammatory diseases]. / Genetische Methoden für die Analyse autoinflammatorischer Erkrankungen.

Over the past years the phenotypic and genetic spectrum of autoinflammatory diseases has continuously increased. Moreover, several monogenic autoinflammatory disorders have now been identified where febrile episodes are not among the leading symptoms and which can be accompanied by autoimmune phenomena and susceptibility to infections. Autoinflammatory conditions that are characterized by uncontrolled activity of cytokines, such as interleukin-1 beta (IL1ß), tumor necrosis factor alpha (TNF-α) and type 1 interferons (1-IFN), are amenable to specific therapeutic interventions. Thus, identification of the underlying genetic cause is important. During diagnostic work-up, genetic testing of a patient with autoinflammation should be carried out depending on the clinical presentation. If a distinct disorder is suspected, sequencing of the causative gene should be performed. Genetic tests using next generation sequencing (NGS), such as panel sequencing, exome sequencing and array comparative genomic hybridization (CGH) can be carried out if symptoms cannot be assigned to a specific disease entity.

Inter-rater Agreement in Three Perfusion-Computed Tomography Evaluation Methods before Endovascular Therapy for Acute Ischemic Stroke.

PURPOSE: There is ongoing debate on which method of perfusion computed tomography (PCT) evaluation in ischemic stroke is the most appropriate for improved selection of patients for endovascular treatment. We sought to test different assessment methods for inter-rater reliability. METHODS: Twenty-six patients were enrolled prospectively before endovascular therapy for acute anterior circulation ischemic stroke. Three raters experienced in stroke imaging and blinded to other imaging and clinical information independently analyzed 22 technically successful PCT scans according to 3 prespecified assessment methods applied to cerebral blood flow (CBF)/cerebral blood volume (CBV) and time-to-peak (TTP) maps: (1) visual mismatch estimate (VME), (2) Alberta Stroke Program Early CT Score perfusion method (ASPECTS-PCT), and (3) quantitative perfusion ratios (qPRs): RCBF, RCBV, RTTP. Inter-rater agreement was assessed with Cohen's kappa, intraclass correlation coefficients (ICC), Bland-Altman plots, and global and descriptive statistics. RESULTS: Significant differences between raters were found with VME and ASPECTS-PCT (P < .001) but with qPRs only for CBV (P = .03). Inter-rater agreement for VME was at best moderate by kappa statistics (.51); moderate by ICC for all parametric maps of ASPECTS-PCT (.56-.62), strong for RTTP (.76), and excellent for RCBF (.92) and RCBV (.86). Pairwise comparisons revealed less scattering of individual values with qPRs and less deviation of mean differences from 0, suggesting minor systematic deviation by any 1 rater as compared with VME or ASPECTS-PCT. CONCLUSION: PCT evaluation methods used before endovascular therapy for acute anterior circulation stroke are subject to substantial inter-rater disagreement. QPRs in PCT evaluation had better inter-rater reliability than the often used VME and ASPECTS-PCT assessment.

[Type I interferonopathies. Systemic inflammatory diseases triggered by type I interferons]. / Typ-I-Interferonopathien. Durch Typ-1-Interferone bedingte entzündliche Systemerkrankungen.

Type I interferons mediate immune defense against viral infections. The induction of type I interferons has stimulating and modulating effects on the innate and adaptive immune systems thereby reducing tolerance against self-antigens. Genetic defects that result in an inadequate activation of the type I interferon system can cause a group of inflammatory disorders, which are collectively referred to as type I interferonopathies. While the clinical spectrum of type I interferonopathies is broad and heterogeneous, neurological and cutaneous symptoms are the most frequent manifestations. Some clinical and genetic features of type I interferonopathies are shared by multifactorial diseases, such as systemic lupus erythematosus and systemic vasculitis. Advances in understanding the disease mechanisms underlying type I interferonopathies have pinpointed novel targets for therapeutic interventions.

Comparing perfusion CT evaluation algorithms for predicting outcome after endovascular treatment in anterior circulation ischaemic stroke.

AIM: To analyse perfusion CT (PCT) evaluation algorithms for their predictive value for outcome after endovascular therapy (ET) in acute ischaemic stroke. MATERIALS AND METHODS: Twenty-six patients were prospectively enrolled to undergo endovascular therapy for moderate to severe [National Institute of Health Stroke Scale (NIHSS) score of ≥5] anterior circulation stroke ≤6 h of onset. PCT datasets were evaluated according to three algorithms: visual mismatch estimate (VME), Alberta Stroke Programme Early CT Score (ASPECTS) perfusion, and quantitative perfusion ratios (QPRs: RCBF, RCBV) of cerebral blood flow (CBF) and volume (CBV). Results were correlated with outcome measures [NIHSS score at discharge, NIHSS score change until discharge (ΔNIHSSA/D), mRS at 90 days (mRS90d)] and compared with a matched control group. RESULTS: Recanalization was achieved in 73%, median NIHSS score decreased from 14 to 5 at discharge. The treatment and control group did not differ by VME and ASPECTS perfusion, nor did VME correlate with any of the three outcome measures. ASPECTS perfusion was not predictive of any outcome measure in the ET group. RCBF and RCBV were associated with ΔNIHSSA/D in controls and, inversely, the ET group, but not with mRS90d. Receiver operating characteristic (ROC) analysis of RCBF (and RCBV) showed a positive predictive and negative predictive value of 87% (78%) and 74% (73%), respectively, for discriminating major neurological improvement (ΔNIHSSA/D <7 versus ≥7). CONCLUSIONS: Implementation of QPRs for CBF and CBV are superior to clinically used VME and ASPECTS perfusion evaluation methods for predicting early outcome after ET for anterior circulation stroke.

Aicardi-Goutières syndrome: a model disease for systemic autoimmunity.

Systemic autoimmunity is a complex disease process that results from a loss of immunological tolerance characterized by the inability of the immune system to discriminate self from non-self. In patients with the prototypic autoimmune disease systemic lupus erythematosus (SLE), formation of autoantibodies targeting ubiquitous nuclear antigens and subsequent deposition of immune complexes in the vascular bed induces inflammatory tissue injury that can affect virtually any organ system. Given the extraordinary genetic and phenotypic heterogeneity of SLE, one approach to the genetic dissection of complex SLE is to study monogenic diseases, for which a single gene defect is responsible. Considerable success has been achieved from the analysis of the rare monogenic disorder Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that clinically resembles in-utero-acquired viral infection and that also shares features with SLE. Progress in understanding the cellular and molecular functions of the AGS causing genes has revealed novel pathways of the metabolism of intracellular nucleic acids, the major targets of the autoimmune attack in patients with SLE. Induction of autoimmunity initiated by immune recognition of endogenous nucleic acids originating from processes such as DNA replication/repair or endogenous retro-elements represents novel paradigms of SLE pathogenesis. These findings illustrate how investigating rare monogenic diseases can also fuel discoveries that advance our understanding of complex disease. This will not only aid the development of improved tools for SLE diagnosis and disease classification, but also the development of novel targeted therapeutic approaches.

Nurses' practice patterns in relation to adherence-enhancing interventions in stem cell transplant care: a survey from the Nurses Group of the European Group for Blood and Marrow Transplantation.

Recipients of stem cell transplants (SCT) must accurately manage multiple medications as non-adherence jeopardises treatment benefits. There is an evidence base for the efficacy of adherence-enhancing interventions; however, level of clinical implementation is unknown. This study aimed to identify patterns of practice in assessing medication adherence, screening for risk factors of non-adherence, interventions used in SCT to improve adherence and how nurses perceive the effectiveness of such interventions. A convenience sample of 143 European nurses completed a 29-item questionnaire measuring the frequency and perceived effectiveness of assessment/screening methods for adherence and three types of intervention (educational/cognitive, counselling/behavioural and psychological/affective). Questioning patients about adherence was the most regularly used assessment method (51.5%). Nurses used a median of seven interventions (interquartile range: six) 'frequently', the most popular being provision of reading materials (79%). The interventions perceived as most effective were; providing individual patient/family with teaching and reading materials. This is the first study exploring patterns of practice relating to adherence in SCT. Educational interventions were the most frequently employed style of intervention, which is at odds with recent data suggesting limited efficacy with this style of intervention. Combining educational, behavioural and psychological interventions would more accurately embrace current understanding.

Perfluorodecalin-soluble fluorescent dyes for the monitoring of circulating nanocapsules with intravital fluorescence microscopy.

Perfluorodecalin (PFD) is an established artificial oxygen carrier due to its physical capability to solve the respiratory gases oxygen and carbon dioxide. PFD-filled poly(n-butyl-cyanoacrylate) (PACA) nanocapsules are already discussed as effective artificial oxygen carriers, and their principal suitability for intravenous administration had been shown. To further elucidate their action in vivo, it is imperative to characterise their preclinical safety and particularly their biodistribution. For these purposes, intravital fluorescence microscopy would display an attractive technique in order to monitor the PACA nanocapsules in vivo, but unfortunately, it is impossible to stain the PACA nanocapsules with a fluorescent dye fulfilling special criteria required for in vivo microscopy. In order to develop such a dye, a long-chained fluorinated thiol was used to modify a BODIPY derivative that is a highly fluorescent organic compound belonging to the difluoro-boraindacene family, as well as to functionalise mesoscopic systems, such as CdSe/ZnS-quantum dots and gold nanoparticles. Furthermore, a functionalisation of porphyrin derivatives was investigated by placing divalent ions in the centre of these systems. Due to the high solubility of all synthesised dyes in PFD, it should be possible to stain PFD-filled particles in general. However, only the functionalised BODIPY derivative was suitable for in vivo monitoring of the PFD-filled PACA nanocapsules.

Endovascular management of spinal dural arteriovenous fistulas in 78 patients.

INTRODUCTION: The purpose of this study was the evaluation of the safety and efficiency of the endovascular treatment of spinal dural arteriovenous fistulas (SDAVFs). METHODS: Between May 1992 and August 2012, 78 patients (59 men) with an angiographically proven SDAVF with pial venous drainage were treated by endovascular embolization (n = 61) and/or surgery (n = 31) at three German hospitals by a single team of physicians and according to a uniform therapeutic concept. RESULTS: Endovascular treatment resulted in a complete occlusion of the fistula in 47 cases (77 %). After failed embolization with residual shunt, 14 DAVFs were surgically cured (23 % failure rate). We had one permanent and two minor complications after endovascular therapy. Within a postoperative period of 2 weeks, 73.6 % of patients improved in gait disability, 51.1 % in micturition function, and 70.5 % in paresthesia of the lower extremities. Long-term follow-up data showed further improvement of clinical symptoms confirmed by normalization or resolution of spinal changes on MRI. CONCLUSIONS: An interdisciplinary approach to the management of SDAVFs is mandatory. Patients without a common origin of arteries supplying the spinal cord and the dural fistula, and without a stenosis or occlusion of the concerning segmental artery are potential candidates for endovascular treatment (diluted n-butyl-2-cyanoacrylate). Only occlusion of the "nidus" and the proximal segment of the draining vein can lead to clinical improvement.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

BACKGROUND: We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. PATIENTS AND METHODS: From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. RESULTS: Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. CONCLUSIONS: Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

The necessity for the coating of perfluorodecalin-filled poly(lactide-co-glycolide) microcapsules in the presence of physiological cholate concentrations: Tetronic-908 as an exemplary polymeric surfactant.

Recently, we demonstrated that biodegradable poly(lactide-co-glycolide) (PLGA) micro- and nanocapsules with a liquid content of perfluorodecalin are principally useful for the development of artificial oxygen carriers. In order to solve a decisive and well-known problem with PLGA microcapsules, i.e. the spontaneous agglomeration of the capsules after depletion of the emulsifying agent (i.e. cholate), coating with the ABA block copolymer, Tetronic-908 was studied. After Tetronic-908 treatment at concentrations that were harmless to cultured cells, the clustering of the microcapsules was prevented, the adsorption of opsonins was decreased and the attachment to cells was inhibited, but the oxygen transport capacity of PLGA microcapsules was even increased. The present data clearly show that perfluorodecalin-filled PLGA microcapsules must be coated before decreasing the emulsifying agent cholate to physiological concentrations, in order to develop a solution that has the capabilities to function as a potential artificial oxygen carrier suspension.

CT-angiographic collateralization predicts final infarct volume after intra-arterial thrombolysis for acute anterior circulation ischemic stroke.

BACKGROUND: Final infarct volume after thrombolysis for acute ischemic stroke depends on time to, and degree of reperfusion and residual blood flow, which is influenced by leptomeningeal collateralization. We evaluated the role of collateralization in the ischemic territory as a predictor of infarct size. METHODS: Twenty-five patients (17 women, 8 men, mean age: 67.6 ± 12.4 years) selected by non-contrast-enhanced CT and CT angiography (CTA) underwent intra-arterial thrombolysis (iaT) within 6 h after symptom onset (mean 4.1 ± 1.3 h) for middle cerebral and terminal internal carotid artery (MCA/ICA) stroke. CTA was evaluated for collateralization using thick-slice coronal and axial maximum-intensity projection reconstructions according to a simple score, the CTA collateralization score (CTA-cs): 0 = no collateral filling, 1 = ≤50%, 2 = >50% but <100%, and 3 = 100% collateral filling. We analyzed the association between the final infarct volume on CT 5 days after the intervention and the CTA-cs, successful reperfusion (Thrombolysis in Myocardial Infarction, TIMI, grades 2 and 3) and time to treatment in a prospective study approved by our institutional review board, with informed consent from all patients. RESULTS: Reperfusion was achieved in 72%. Asymptomatic and symptomatic parenchymal hemorrhage occurred in 2 patients (8%) each and hemorrhagic transformation in 4 (16%). CTA-cs (r = -0.63; p < 0.001) and postinterventional TIMI grade (r = -0.403; p = 0.046) were inversely associated with final infarct volume. After multiple regression analysis, CTA-cs and reperfusion remained as independent predictors of final infarct volume whereas time to treatment and initial stroke severity did not. CONCLUSION: The extent of collateralization and reperfusion are independent predictors of final infarct volume in acute MCA/ICA stroke treated with iaT. Time to treatment and stroke severity had no independent effect on final infarct volume.

A ruptured intraorbital ophthalmic artery aneurysm, associated with a dural arteriovenous fistula: combined transarterial and transvenous endovascular treatment.

BACKGROUND: True aneurysms of the ophthalmic artery (OA) are extremely rare and most often arise at the origin of this artery. We present the endovascular management of a ruptured intraorbital OA aneurysm and of an associated dural arteriovenous fistula (dAVF). PATIENT: A patient with a ruptured intraorbital ophthalmic artery aneurysm, associated with a dAVF with cortical drainage presented with acute visual loss and intra- and periorbital hematoma. The aneurysm was treated by endovascular coil occlusion. The dAVF was occluded by transvenous obliteration of the draining basal vein of Rosenthal. Both intraorbital ophthalmic artery aneurysms and their rupture are extremely rare. CONCLUSION: Transvenous treatment of dAVFs is well feasible even with very far going catheterization, in this case to the origin of the basal vein of Rosenthal.

Virtual angioscopy and 3D navigation: a new technique for analysis of the aortic arch after vascular surgery.

PURPOSE: Anatomy of the aortic arch is highly variable and can be drastically altered by surgical or endovascular procedures. Detailed analysis of computed tomography (CT) scans is facilitated by reconstruction techniques such as virtual angioscopy (VA). In the present study, we have evaluated the benefit of VA for the assessment of aortic arch abnormalities in patients with prior surgical or endovascular procedures. MATERIAL AND METHODS: We analysed post-procedural CT scans available in 103 patients who underwent thoracic aortic procedures between 2006 and 2009 at our institution. Patients were classified into three groups: surgical (group A, n = 26), hybrid (group B, n = 27) and endovascular (group C, n = 50), procedures. A 64 LightSpeed volume computed tomography (VCT) multidetector-row computed tomography was used, allowing maximal intensity projection, maximal projection rendering imaging and three-dimensional (3D) rendering of images. VA reconstruction was performed by applying volume-rendered thresholds and spatial rendering to generate endoluminal views. RESULTS: Multiplanar reformations (MPRs) detected 46 abnormalities in 39 patients: inadequate apposition of the proximal rim of a stent-graft (n = 21), abnormalities of the stent-graft itself (n = 11), aortic aneurysm (n = 6), residual intimal tears (n = 5) and secondary dissection (n = 3). VA provided additional information in 76% of cases (35/46) and was more contributive after endovascular repair than after open repair (group A: 54% (7/14), group B: 75% (9/12), group C: 95% (19/20)). VA improved localisation of abnormalities with respect to supra-aortic vessels, measured inadequate stent-graft apposition in relation to the aortic wall and precisely analysed kinking or inadequate apposition of overlapping stent grafts. VA diagnosed three additional abnormalities: two false aneurysms and one retrograde dissection developed on a suture line. CONCLUSIONS: VA conceptualises planar images by 3D reconstruction. It provides additional information in comparison with conventional CT scans by allowing precise localisation of abnormalities with respect to the aortic wall itself and supra-aortic vessels. Furthermore, it facilitates analysis of abnormalities in case of overlapping stent grafts.

Validity of the sonographic measurement of the diameters of the ascending aorta in rats.

PURPOSE: The objective of this investigation was to compare transthoracic ultrasound (US) determinations of ascending aortic diameters in rats with video microscopy (VM), the current standard for measuring aortic diameters in rats. MATERIALS AND METHODS: The diameter of the ascending aorta was measured in 111 adult Lewis male rats, by VM and US, with a 9 MHz probe, before and after intervention for induction of experimental aneurysm of the ascending aorta. RESULTS: The Bland-Altman test showed a high degree of agreement between the two methods, with a bias of only 0.23 mm (95 % confidence limits - 0.86 - 0.39 mm). Also, the measurements obtained by US correlated highly (r = 0.83, p < 0.0001) with those obtained by VM. Rat ascending aortic diameters obtained both by VM and US correlated significantly with the weight (r = 0.62 and r = 0.39, respectively), and with the age of the animals (r = 0.74 and r = 0.49, respectively). CONCLUSION: This study demonstrates that noninvasive US ascending aortic measurements are a reliable supplement to VM for the development of an ascending aortic aneurysm model, and for monitoring the efficiency of novel therapeutic agents.

Perfluorocarbon-filled poly(lactide-co-gylcolide) nano- and microcapsules as artificial oxygen carriers for blood substitutes: a physico-chemical assessment.

The physico-chemical suitability of perfluorocarbon-filled capsules as artificial oxygen carriers for blood substitutes is assessed on the example of biodegradable poly(lactide-co-gylcolide) micro- and nanocapsules with a liquid content of perfluorodecalin. The morphology of the capsules is studied by confocal laser scanning microscopy using Nile red as a fluorescent marker. The mechanical stability and the wall flexibility of the capsules are examined by atomic force microscopy. The permeability of the capsule walls in connection with the oxygen uptake is detected by nuclear magnetic resonance. It is shown that the preparation in fact leads to nanocapsules with a mechanical stability which compares well with the one of red blood cells. The capsule walls exhibit sufficient permeability to allow for the exchange of oxygen in aqueous environment. In the fully saturated state, the amount of oxygen dissolved within the encapsulated perfluorodecalin in aqueous dispersion is as large as for bulk perfluorodecalin. Simple kinetic studies are presently restricted to the time scale of minutes, but so far indicate that the permeability of the capsule walls could be sufficient to allow for rapid gas exchange.

Comparison between two intraoperative intravenous loading doses of paracetamol on pain after minor hand surgery: two grams versus one gram.

BACKGROUND: Paracetamol (acetaminophen) is widely used for postoperative analgesia at a recommended dose of 1 g every six hours in adult patients. Increasing the loading dose to 2 g was suggested to improve immediate postoperative analgesia without increased toxicity in healthy adult patients. We tested the hypothesis that a loading dose of 2 g of intravenous paracetamol results in better postoperative analgesia after surgery as compared with a dose of 1 g. METHODS: Sixty adult patients scheduled for minor hand surgery under intravenous regional anaesthesia were randomized into two groups. The first group received 1 g of intravenous paracetamol before surgery while the second group received 2 g. Verbal numeric pain score, analgesic consumption, first night sleep quality, and patient's satisfaction were recorded during the first 24 hours. RESULTS: Verbal numeric pain scores during the first 24 hours after surgery were significantly lower in the 2 g paracetamol group as compared to the 1 g paracetamol group. No differences were found between the two groups with regard to rescue analgesic consumption, sleep quality and patient's satisfaction. CONCLUSIONS: An intraoperative loading dose of 2 g paracetamol improves postoperative analgesia after minor hand surgery as compared to 1 g paracetamol.