A novel therapeutic option in Cogan diseases? TNF-α blockers

Cogan's syndrome is characterized by non-infectious, interstitial keratitis combined with a vestibulo-auditory deficit. Despite therapy with corticosteroids in combination with immunosuppressive agents, relapses occurred in two subjects and the clinical course suggested a progression of the disease. Treatment with anti-TNF-α was started leading to a rapid and sustained clinical remission for over 2 respectively 3year

A Randomized Prospective Study of Cefepime Plus Metronidazole with Imipenem-Cilastatin in the Treatment of Intra-abdominal Infections

Abstract : Background: : Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections. Together with surgery, antimicrobial combinations are still widely used to achieve the required spectrum of activity. The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenemcilastatin for the treatment of intra-abdominal infections in adult patients. Methods: : Patients with a clinically confirmed diagnosis of intra-abdominal infection were randomized to one of two treatment regimens: cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection. The duration of follow-up was 30 days. Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection. Surgical management of the infection was determined by the surgeon-in-charge. Results: : Of the 122 intended-to-treat patients included in the study, 60 patients (33 men) were randomized to cefepime + metronidazole and 61 (27 men) to imipenemcilastatin. Cefepime + metronidazole treatment was successful in 52 (87%) patients and imipenem-cilastatin in 44 (72%) patients (p = 0.004). Microbiological eradication was established in similar proportions in both groups (cefepime + metronidazole, 43; imipenem-cilastatin, 38). Conclusion: : Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infection

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (l000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa×V>7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6±5.1 versus 50.9±5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6±3.2 to 60.6±5.4 pg/ml, P=0.182) and fell in normocalciuric stone formers (from 45.9±2.6 to 38.1±3.3 pg/ml, P=0.011). The total amount of urinary calcium excreted after OCL was 2.50±0.20 mmol in controls, 2.27±0.27 mmol in normocalciuric and 3.62±0.32 mmol in hypercalciuric stone formers (P=0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r=0.392, P=0.024). Maximum increase in urinary calcium excretion rate, δCa-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of δ calcitriol/δPTHmax after calcium load (r=−0.653, P=0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria. Finally, late absorption of calcium as suggested by maximum urinary calcium excretion beyond 4 h after oral calcium load was as rare in hypercalciuric stone formers (2 of 12) as in controls (1 of 13) and did not occur in normocalciuric stone former

Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures

Objective. The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. Methods. Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. Results. Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. Conclusion. The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marke

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

Aims/hypothesis: Structural and functional imaging of the islets of Langerhans and the insulin-secreting beta cells represents a significant challenge and a long-lasting objective in diabetes research. In vivo microscopy offers a valuable insight into beta cell function but has severe limitations regarding sample labelling, imaging speed and depth, and was primarily performed on isolated islets lacking native innervations and vascularisation. This article introduces extended-focus optical coherence microscopy (xfOCM) to image murine pancreatic islets in their natural environment in situ, i.e. in vivo and in a label-free condition. Methods: Ex vivo measurements on excised pancreases were performed and validated by standard immunohistochemistry to investigate the structures that can be observed with xfOCM. The influence of streptozotocin on the signature of the islets was investigated in a second step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo. Results: xfOCM circumvents the fundamental physical limit that trades lateral resolution for depth of field, and achieves fast volumetric imaging with high resolution in all three dimensions. It allows label-free visualisation of pancreatic lobules, ducts, blood vessels and individual islets of Langerhans ex vivo and in vivo, and detects streptozotocin-induced islet destruction. Conclusions/interpretation: Our results demonstrate the potential value of xfOCM in high-resolution in vivo studies to assess islet structure and function in animal models of diabetes, aiming towards its use in longitudinal studies of diabetes progression and islet transplant

[Musculoskeletal puncture, injection and infiltration: swiss rheumatologists' point of view]

Arthrocentesis, injection and infiltration of joints and soft tissues belong to the basic procedures in rheumatology. The indications and the practical performance are based on experience and tradition. Nowadays, a crucial reappraisal and adaption of indications and technical aspects appear important in the light of new evidence and technical developments. The main indications for puncture remain the search of an infectious arthritis and reduction of intra-articular pressure due to effusion. Good indications for the injection of glucocorticoids are inflammation in sterile joints and activated osteoarthritis. The local infiltration with corticosteroids in mechanically induced enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia have to be questioned in the light of recent publications which show that this common practice is associated with a poorer outcome than without injection

Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS).

BACKGROUND In patients with multiple sclerosis (MS), relapses and disability progression have been associated with decreased health-related quality of life (HRQoL). METHODS PROTYS, a prospective, multicentre, single-arm, observational study in seven Swiss MS centres, evaluated correlations between change in disability status (measured through the Expanded Disability Status Scale (EDSS)) and HRQoL changes (measured through the global Multiple Sclerosis International Quality of Life (MusiQoL) index questionnaire) in 35 patients with relapsing remitting MS on natalizumab for 1 year. In addition, several other scales were also used, such as: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19, EuroQoL-5 Dimension, and Fatigue Scale of Motor and Cognitive Function. A post hoc analysis further assessed the association between HRQoL changes after 1 year and the MusiQoL subscores and other patient-reported outcome (PRO) measures. RESULTS At 1 year, patients were categorised into 'EDSS improved' (6/35), 'EDSS stable' (28/35) and 'EDSS worsened' (1/35). Mean disability scores decreased for 'EDSS improved' and 'EDSS stable' but increased for 'EDSS worsened'. Mean MusiQoL index score for 'EDSS improved' increased from 61.2 at baseline to 66.3 at 1 year, while the 'EDSS stable' group increased from 67.9 to 70.8. No meaningful statistical relationship was observed between EDSS group and changes in MusiQoL score. For the post hoc analysis, patients were categorised in 'MusiQoL improved' (n=21) and 'MusiQoL worsened' (n=14) groups. MusiQoL subscores for 'symptoms,' 'psychological well-being' and 'activities of daily living', as well as scores for several related PRO measures, correlated with improvement of the MusiQoL global index. There was no correlation between the changes in MusiQoL global index and EDSS score. CONCLUSIONS Natalizumab treatment for 1 year resulted in either improved or stable EDSS status in most patients, and although no significant relationship was observed between global HRQoL change and EDSS change, several domains of HRQoL seemed to improve with natalizumab treatment. TRIAL REGISTRATION NUMBER NCT02386566

Virtual reality rehabilitation system for neuropathic pain and motor dysfunction in spinal cord injury patients

Spinal cord injury (SCI) causes both lower limb motor dysfunction and associated neuropathic pain. Although these two conditions share related cortical mechanisms, different interventions are currently used to treat each condition. With intensive training using entertaining virtual reality (VR) scenarios, it may be possible to reshape cortical networks thereby reducing neuropathic pain and improving motor function. We have created the first VR training system combining action observation and execution addressing lower limb function in incomplete SCI (iSCI) patients. A particular feature of the system is the use of size-adjustable shoes with integrated motion sensors. A pilot single-case clinical study is currently being conducted on six iSCI patients. Two patients tested to date were highly motivated to perform and reported improved physical well-being. They improved in playing skill and in controlling the virtual lower limbs. There were post-intervention indications of neuropathic pain decrease, muscle strength increase, faster walking speed and improved performance on items relevant for ambulation. In addition functional MRI before and after treatment revealed a decreased activation pattern. We interpret this result as an improvement of neuronal synergies for this task. These results suggest that our VR system may be beneficial for both reducing neuropathic pain and improving motor function in iSCI patients

Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures

OBJECTIVE: The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. METHODS: Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. RESULTS: Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. CONCLUSION: The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker