Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated. METHODS: We analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP

A Retrospective Observational Single-Centre Study on the Burden of Immune Thrombocytopenia (ITP)

Background: German data on economic consequences of immune thrombocytopenia (ITP) are limited. Patients and Methods: A retrospective, observational study based on chart review of adult patients with a confirmed diagnosis of ITP was conducted at a German university hospital. Costs are presented from the hospital perspective. Results: Of 50 eligible patients, 45 could be classified by disease duration: 19 patients = 3 to = 12 months (38%, chronic ITP). Complications included 85 bleeding events in 43 patients, including 3 intracranial haemorrhages. Documented were 955 outpatient visits in 43 patients (86%) and 92 inpatient hospital admissions in 45 patients (90%). Of the 46 patients (92%) treated, all received corticosteroids, 25 (50%) intravenous immunoglobulin, and 7 (14%) further therapies. 12 patients (24%) underwent splenectomy. Average total direct medical costs (mean (standard deviation)) were (sic) 17,091 ((sic) 18,859) per patient, (sic) 12,749 ((sic) 11,663) in 17 newly diagnosed ITP patients with a 0.88-month (0.65 months) average disease duration, and (sic) 29,868 ((sic) 29,397) in 13 chronic ITP patients with a 33.5-month (16.8 months) average disease duration. Inpatient stays were the main cost drivers. Conclusion: These data concerning current healthcare provision for ITP patients in Germany indicate considerable resource consumption and the need for more effective treatment options in individual patients

Bedside differentiation of vestibular neuritis from central "vestibular pseudoneuritis".

Acute unilateral peripheral and central vestibular lesions can cause similar signs and symptoms, but they require different diagnostics and management. We therefore correlated clinical signs to differentiate vestibular neuritis (40 patients) from central ‘‘vestibular pseudoneuritis’’ (43 patients) in the acute situation with the final diagnosis assessed by neuroimaging. Skew deviation was the only specific but non-sensitive (40%) sign for pseudoneuritis. None of the other isolated signs (head thrust test, saccadic pursuit, gaze evoked nystagmus, subjective visual vertical) were reliable; however, multivariate logistic regression increased their sensitivity and specificity to 92%

Diagnosis and Treatment of Tracheal or Bronchuotracheal Adenoid Cystic Carcinoma

Background and objective Adenoid cystic carcinoma is primary bronchopulmonary carcinoma with low malignancy, and 43 patients treated in the past 50 years in our hospital were retrospectively studied. The aim of this study is to discuss the clinical symptoms, pathologic characteristic and therapeutic method of primary tracheal or bronchuotracheal adenoid cystic carcinoma. Methods This study summarized total 43 patients of primary tracheal or bronchus adenoid cystic carcinoma treated in our hospital from Jan. 1958 to Dec. 2007. Among them, 40 patients were treated by surgical resection, and 3 patients were treated by fiberoptic bronchoscope’s interventional treatment. Results The 1-yr, 3-yr, 5-yr survival rates of the 43 patients above were 100% (41/41), 89.5% (34/38), 87.1% (27/31), respectively. Conclusion Primary tracheal or bronchus adenoid cystic carcinoma are rare and low malignancy carcinoma. The clinical symptoms of them are not typical. The best treatment is early detection and taking measures of operation plus radiotherapy. The other palliative treatment is fiberoptic bronchoscope’s interventional treatment

Effects of focal frontal lesions on response inhibition

This study examined the performance of 38 normal subjects and 43 patients with focal lesions of the frontal lobes on a simple go-nogo task where the probability of the nogo stimulus was either 75% or 25%. Patients with lesions to the superior medial parts of the frontal lobes, in particular to the left superior portion of Brodmann area 6 (which includes the supplementary motor areas and the premotor areas for the right hand) had an increased number of false alarms (incorrect responses to the nogo stimulus). These results indicate that area 6 is specifically involved in the inhibition of response. Patients with lesions to the right anterior cingulate (areas 24 and 32) were slower and more variable in their reaction time. These findings could be explained by an inability to sustain stimulus-response contingencies. Lesions to the right ventrolateral prefrontal cortex (Brodmann areas 44, 45, 47) also increased the variability of response, perhaps by disrupting monitoring performance

Reliability of perceptions of voice quality: evidence from a problem asthma clinic population

&lt;p&gt;Introduction: Methods of perceptual voice evaluation have yet to achieve satisfactory consistency; complete acceptance of a recognised clinical protocol is still some way off.&lt;/p&gt; &lt;p&gt;Materials and methods: Three speech and language therapists rated the voices of 43 patients attending the problem asthma clinic of a teaching hospital, according to the grade-roughness-breathiness-asthenicity-strain (GRBAS) scale and other perceptual categories.&lt;/p&gt; &lt;p&gt;Results and analysis: Use of the GRBAS scale achieved only a 64.7 per cent inter-rater reliability and a 69.6 per cent intra-rater reliability for the grade component. One rater achieved a higher degree of consistency. Improved concordance on the GRBAS scale was observed for subjects with laryngeal abnormalities. Raters failed to reach any useful level of agreement in the other categories employed, except for perceived gender.&lt;/p&gt; &lt;p&gt;Discussion: These results should sound a note of caution regarding routine adoption of the GRBAS scale for characterising voice quality for clinical purposes. The importance of training and the use of perceptual anchors for reliable perceptual rating need to be further investigated.&lt;/p&gt

Surgical treatment of the osteoporotic spine with bone cement-injectable cannulated pedicle screw fixation: technical description and preliminary application in 43 patients

OBJECTIVES: To describe a new approach for the application of polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws. METHODS: Between June 2010 and February 2013, 43 patients with degenerative spinal disease and osteoporosis (T-scor

Patients with anorectal malformation and upper limb anomalies:genetic evaluation is warranted

Abstract The objective of this study was to compare the prevalence of genetic disorders in anorectal malformation (ARM) patients with upper limb anomalies to that in ARM patients with other associated anomalies. A retrospective case study was performed in two pediatric surgery centers. All patients born between 1990 and 2012 were included. VACTERL (vertebral defects (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula with esophageal atresia (TE), renal dysplasia (R), and limb anomalies (L)) was defined as at least three components present. We included 700 ARM patients: 219 patients (31 %) had isolated ARM, 43 patients (6 %) had a major upper limb anomaly, and 438 patients (63 %) had other associated anomalies. The most prevalent upper limb anomalies were radial dysplasia (n=12) and hypoplastic thumb (n= 11). Ten of the 43 patients (23 %) with an upper limb anomaly were diagnosed with a genetic disorder—nine also met the V

Vibrio fluvialis in Patients with Diarrhea, Kolkata, India

We identified 131 strains of Vibrio fluvialis among 400 nonagglutinating Vibrio spp. isolated from patients with diarrhea in Kolkata, India. For 43 patients, V. fluvialis was the sole pathogen identified. Most strains harbored genes encoding hemolysin and metalloprotease; this finding may contribute to understanding of the pathogenicity of V. fluvialis

Dermal C4d Deposition and Neutrophil Alignment Along the Dermal-Epidermal Junction as a Diagnostic Adjunct for Hypocomplementemic Urticarial Vasculitis (Anti-C1q Vasculitis) and Underlying Systemic Disease

Urticarial vasculitis (UV) is a clinicopathologic entity characterized by persistent urticarial lesions with biopsy features of vasculitis. Currently, only certain clinical features such as arthralgia and serum complement concentrations are used to identify UV patients at risk for an underlying systemic disease. Hypocomplementemic urticarial vasculitis (HUV) is in contrast to normocomplementemic urticarial vasculitis (NUV), strongly associated with underlying systemic disease, especially systemic lupus erythematosus (SLE). The aim of this study was to find specific histopathological features associated with HUV and underlying systemic disease in UV. In addition, the use of complement C4d deposition in skin biopsies was evaluated as a diagnostic adjunct for HUVand UV-associated systemic disease. In this retrospective study, the clinical, histopathological, and immunohistological (C4d) features of 43 patients with UV were compared between HUV and NUV and analyzed for association with UV-associated systemic disease. Eight of 43 patients with UV (19%) had hypocomplementemia