Validation of the non-alcoholic fatty liver disease activity score.

BACKGROUND: The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is a scoring system designed by the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) to encompass the spectrum of NAFLD and evaluate histological changes. However, the NAS and the correlation between the NAS and a diagnosis of NASH have not been validated outside the NASH CRN. AIM: To validate the NAS outside the NASH CRN. METHODS: This study retrospectively examined liver biopsies from adults with NAFLD or steatohepatitis obtained from January 2003 to May 2010. Biopsy specimens were evaluated twice in a blinded manner by a single hepatopathologist, once to determine a diagnosis (steatohepatitis or steatosis/not-steatohepatitis), and a second time to determine the NAS. RESULTS: A total of 386 liver biopsies were evaluated. Mean age of patients at time of biopsy was 49.9±10.2years. NASH was found in 51% of the patients. For NAS ≥5 as a diagnosis of steatohepatitis and NAS <5 for not-steatohepatitis, the sensitivity was 57%, specificity: 95%, negative predictive value (NPV): 68% and positive predictive value (PPV): 93%. Lowering the NAS to ≥4 as a diagnosis of steatohepatitis increased the sensitivity to 85% with a decrease in specificity to 81%; NPV: 84%, PPV: 82% and Cohen's kappa 0.658. CONCLUSIONS: The NAFLD activity score is a valid scoring system encompassing the spectrum of NAFLD with an excellent level of agreement between the histological diagnosis and the NAFLD activity score. A NAFLD activity score ≥4 has optimal sensitivity and specificity for predicting steatohepatitis, and is the recommended value for admission into an interventional trial for NASH.

Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative versus qualitative IgM analysis.

BACKGROUND: Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS). OBJECTIVE: To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS. METHODS: Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4-22.8 years) were studied. The two subgroups with (n=44) or without (n=26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data. RESULTS: The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p=0.04, p=0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis. CONCLUSION: Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of 'oligoclonal' IgM or linear IgM index.

Detection of diastolic dysfunction: acoustic quantification (AQ) in comparison to Doppler echocardiography.

OBJECTIVES: To evaluate the potential of acoustic quantification (AQ) in detection of diastolic dysfunction in comparison to Doppler analysis, we investigated, as a model of restrictive filling pattern, nonrejecting heart transplant recipients early postoperatively. BACKGROUND: AQ, an ultrasonic backscatter imaging system, enables instantaneous calculation of cavity areas and thus provides a new approach to diastolic function. METHODS: Of 27 pts who have undergone heart transplantation, echocardiography has been performed at the day of biopsy. During a time course of 8 weeks echocardiographic data have been analysed at 3 different time points (early, mid and late) in 16 nonrejecting pts. Indexes of the area-change waveform and its 1. derivative (dA/dt) obtained by AQ were opposed to usual Doppler indexes. RESULTS: In comparing data of the early and late time point of investigation, significant changes of early diastolic filling were detectable by AQ as well as by Doppler: End-diastolic areas have increased (p < 0.001), while peak filling rate (p < 0.0001), slope of area change during rapid filling (p < 0.001) and amount of relative area change during rapid filling (p < 0.001) have decreased. Complementary, Doppler derived pressure half-time (p < 0.0001) and isovolumic relaxation time (p < 0.0001) have increased while the peak early filling velocity (p < 0.0001) and its time velocity integral (p < 0.001) have decreased. CONCLUSION: An initial restrictive filling pattern has improved 8 weeks postoperatively. Since multiple indexes, obtained from the area change waveforms, in particular the for end-diastolic area normalized peak filling rate, seem to be highly sensitive in detecting changes of diastolic function, AQ may play an important complementary role in non-invasive evaluation of restrictive filling pattern.

Psychosocial, neuropsychological and neurological status in a sample of heart transplant recipients.

The sample for this psychosocial follow-up study was formed using the 71 surviving patients from a total of 100 who underwent heart transplantation up until March 1990 at Kiel University Hospital. Forty of these could be investigated comprehensively. The neurological investigation comprised EEG and auditory and visually evoked potentials. The psychological investigation started with several neuropsychological tests; additionally all patients were interviewed and they completed questionnaires concerning anxiety, depression, ways of coping, personality characteristics and life satisfaction. Within the entire sample, there were few indications for specific psychological impairment. The psychosocial status of the patients was not significantly related to the time which had elapsed since they underwent transplantation. There were few associations between neuropsychological and psychosocial data, and several indicators of early postoperative complications which are described in the literature (e.g., length of stay in the intensive care unit). Clinically relevant subgroups (formed on the basis of neuropsychological test results, anxiety and depression) did not differ in terms of these indicators. Nevertheless, a considerable proportion of the patients (25%) were characterized by having a higher level of affective and neuropsychological impairment. Although based upon retrospective investigations, the results of this follow-up generally correlate with those gained from Anglo-American countries. In interpreting the results one needs to consider the possible influence of premorbid personality characteristics as well as denial which may be typical for patients undergoing heart transplantation.

[Polyneuropathy and central nervous system diseases before and after heart transplantation. Is cyclosporin neurotoxic?]. / Polyneuropathie und zentralnervöse Störungen vor und nach Herztransplantation. Wirkt Ciclosporin neurotoxisch?

In a cross-sectional study, 52 patients (44 men, 8 women, mean age 50.6 [19-68] years) were investigated clinically and electrophysiologically for evidence of peripheral and central nervous system damage before and after heart transplantation. 20 patients were investigated before heart transplantation (group 1), 16 at 7 days to 5 months after transplantation (early post-operative group; group 2) and 16 at 6 to 32 months after transplantation (late post-operative group; group 3). Nerve conduction studies (median, peroneal and sural nerves) revealed polyneuropathy in 14 out of 16 patients in group 2, significantly more than in group 1 (11 out of 19) and group 3 (9 out of 16). The mean blood cyclosporin concentration was 656 ng/ml in group 2 and 409 ng/ml in group 3 (P less than 0.001). Patients in group 3 with polyneuropathy had significantly higher cyclosporin concentrations than patients without polyneuropathy (505 vs 284 ng/ml; P less than 0.01). Among patients who had undergone operations, there were no noteworthy differences between the mean cyclosporin concentrations and clinical data in those with or without central nervous system lesions. There is preliminary evidence of a neurotoxic effect of cyclosporin on the peripheral but not the central nervous system.