The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis

Objective

To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables.

Methods

Thirty‐seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi‐square, sensitivity, specificity, false‐positive and‐negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions.

Results

The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second‐highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process.

Conclusion

We propose a provisional data‐driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.     

Zur Kenntnis der Netzhautveränderungen bei chronischer Bleivergiftung

Ohne ZusammenfassungNach einem Vortrag, gehalten auf der 41. Tagung der Vereinigung mitteldeutscher Augenärzte in Halle am 1. Dezember 1935.     

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT)

A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistent thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0.005) and an unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.     

Distinct enzyme profiles in patients with cryptogenic cirrhosis reflect heterogeneous causes with different outcomes after liver transplantation (OLT): a long-term documentation before and after OLT

BACKGROUND: Sound information is lacking about the clinical presentation of cryptogenic cirrhosis and its outcome after orthotopic liver transplantation (OLT). METHODS: Among 856 patients who have been transplanted at our center, 40 patients had no evidence of any known etiologies and were therefore defined as suffering from cryptogenic cirrhosis. Their median follow-up period before OLT was 78 months (range, 1-264), and after OLT 97 months (range, 1-132). Laboratory and histological data were evaluated according to features being compatible either with a toxic, hepatitic, or cholestatic condition. RESULTS: The clinical and histological findings differed specifically between these three groups. The toxic-like group (GGT 4-18 x upper limit of normal [ULN]) expressed significantly higher IgA levels, had histologically more often fatty liver changes, and risk factors for non-alcoholic steatohepatitis predominated (56% compared with 3% in the other groups, P=0.01). The hepatitic-like group (ALT 2-18 x ULN) showed histologically features of chronic hepatitis or hepatitic cirrhosis, and only among these patients a median International Autoimmune Hepatitis (IAH) score of 13 was found suggesting autoimmune hepatitis (AiH). In the cholestatic group (AP 2-8 x ULN) histology was compatible with a non-toxic inflammatory process but IAH score excluded AiH in all. After OLT, actuarial graft and patients survival was 90% at 5 years. Mild or moderate graft hepatitis occurred in 9 patients (23%) and was significantly associated with a pre-OLT IAH score >or= 10 (P =0.008). CONCLUSIONS: This study provides arguments that cryptogenic cirrhosis is a heterogeneous disease in which autoimmune mechanisms might be predominately involved and being responsible for recurrence of chronic liver disease observed in some instances after OLT.     

Histological and immunocytochemical findings in a case of fetal choroid plexus papilloma.

Reported in this paper is a case of a fetus delivered in the 24th week of pregnancy whose intracranial space was found to be almost totally filled up by a choroid plexus papilloma. Co-expression of vimentin and cytokeratin 8, 18 of the epithelium was immunocytochemically observed, as had been also described in normal fetal choroid plexus.     

Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines

Cytokines such as tumor necrosis factor alpha (TNF-alpha) are key factors in liver inflammation. Supplementation with essential omega-3 polyunsaturated fatty acids (n-3 PUFA) has been demonstrated to lower TNF-alpha and IL-1 production in mononuclear cells. An inflammation-dampening effect has been observed with increased omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabditis elegans desaturase endogenously forming n-3 PUFA from n-6 PUFA, to analyze the effect of an increased n-3 PUFA tissue status in the macrophage-dependent acute D-galactosamine/lipopolysaccaride (D-GalN/LPS) hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/n-3 PUFA ratio as evidenced by reduced serum alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma TNF-alpha levels and with reduced hepatic gene expression of TNF-alpha, IL-1beta, IFN-gamma and IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by DAPI-staining. CONCLUSION: The results of this study offer evidence for an inflammation dampening effect of omega-3 polyunsaturated fatty acids in the context of liver inflammation.     

Immunohistochemical demonstration of tumor-associated antigens in urinary bladder carcinomas using mono- and polyclonal antisera

Keratin was found in more than 90% of transitional cell carcinomas of the bladder in the cytoplasma with polyclonal antibodies. Intensity increased with dedifferentiation. Cytokeratin was detected with monoclonal antibodies in more than 80%. Squamous cell carcinoma of the urinary bladder was always strongly positive for keratin and cytokeratin. CEA was found in 20% of G1 and 40% of G2 and G3 carcinomas of the urinary bladder. The prostatic epithelium markers PSA and PAP were always negative also Ca1.     

Gelenkflächenverhalten der Articulatio radioulnaris distalis bei fehlgestelltem distalem Radius

Pathological changes of wrist bones and ligaments after radial fracture loco typico induce permanent functional restriction and pain. In this paper the effects of malunion on the distal radioulnar joint are investigated and osteotomic therapy of Kinenböck's disease gets a new evaluation. By simulating radial malunions on anatomic forearm specimen the effects of these malunions on the contact area during supination, neutral position and pronation are measured. Isolated posttraumatic radial shortening as well as epiphyseal inclination and torsion cause a reduction of radioulnar contact. During supination and pronatijon the loss of radioulnar contact increases. Most significant reduction of contact takes place at a lower graduation of radial malunion. Pronatory torsion of distal radius compensates for a radioulnar contact reduction from combining dorsal inclination with radial shortening. One conclusion of this paper is an exact restitution of anatomical relations between ulnar head and radial notch after fracture of the distal radius.     

Interrater and Intrarrater Reliability of the Exeter Dysphagia Assessment Technique Applied to Healthy Elderly Adults

The purpose of this study was to evaluate the inter- and intrarater reliabilities of the Exeter Dysphagia Assessment Technique in a sample of elderly adults. This procedure uses noninvasive methods to record aspects of oral motor efficiency and synchronization of respiration during swallowing with the aid of specially developed equipment. Changes in the direction of nasal air flow, time of lip or tongue/spoon contact, and the time/frequency of swallow sounds are monitored and analyzed. Seventy records were evaluated independently by three trained assessors on three consecutive occasions. Interrater reliability was found to be good to very good for five of the respiratory variables assessed and moderate for the sixth. Interrater agreement was also very good for three of the timed oropharyngeal events assessed and moderate for the fourth. Intrarater reliability was very good for the same five respiratory variables and moderate for the sixth. Intrarater agreement was also very good for three of the timed oropharyngeal events and moderate for the fourth. Repeat evaluations of these records showed that agreement between and within raters concerning the sixth respiratory variable was improved substantially when the charts were examined in an enlarged form that provided improved resolution. We conclude that the majority of variables monitored by the Exeter Dysphagia Assessment Technique can be evaluated very reliably.