Clinical Implications of the Coexistence of Anemia and Diabetes Mellitus in the Elderly Population.

Diabetes mellitus (DM) and also anemia are common in the elderly and have a negative impact on the clinical outcomes of patients. The coexistence of anemia and DM seems to be insufficiently recognized; therefore, the aim of our study is to analyze the incidence and clinical consequences of this coexistence, including mortality, in the population of people aged ≥60. A retrospective study was conducted on 981 primary care clinic patients aged ≥60 during 2013-2014. The prevalence of coexistence of DM and anemia (defined in accordance with WHO) and data on the incidence of comorbidities, hospitalization, medical procedures, and all-cause mortality were analyzed. In the study population, 25% had DM, while 5.4% had both DM and anemia. Peripheral artery disease (PAD) was found in 48 patients (4.89%) of the entire study population, more often in men (p < 0.001). Diabetic patients with anemia compared to nonanemic diabetics had more comorbidities (median 4 (4, 5) vs. 3 (2-4); p < 0.001)-PAD more often (p = 0.004), more hospitalization (median 2 (0-11) vs. 0 (0-11); p < 0.001), and more frequent medical procedures (e.g., percutaneous coronary intervention (p < 0.001), coronary artery bypass surgery (p = 0.027), arteriography (p < 0.001), and bypass surgery or endovascular treatments of lower limb ischemia (p < 0.001)). The cumulative survival of patients with both DM and anemia vs. nonanemic diabetics at 36 months was 86.4% vs. 99.3% (p < 0.001). A multivariate logistic regression model showed anemia to be a significant risk factor for death in diabetic patients (p = 0.013). Patients with both DM and anemia have more comorbidities than nonanemic diabetic patients; they are more often hospitalized, require medical procedures more frequently, and are at a higher risk of death. Effective treatment of anemia in patients with DM is advisable and may well improve the prognosis of patients.

[Malignant acanthosis nigricans associated with cholangiocarcinoma]. / Acanthosis nigricans malin révélant un cholangiocarcinome.

INTRODUCTION: Acanthosis nigricans is a dermatosis characterized by the presence of a hyperpigmented, velvety cutaneous thickening in the flexural areas, especially axillary and inguinal fossas, and lateral faces of the neck. AN is usually a benign condition but can sometimes reveal an internal malignancy corresponds to a cutaneous paraneoplasic syndrome. Literature shows a predominant association with gastric adenocarcinoma. Here, we report a rare association between AN and cholangiocarcinoma. CASE REPORT: We report a 43-year-old woman who presented an extensive AN associated to a tripe palms syndrome and florid cutaneous papillomatosis. She consulted in dermatology because of the itchiness of the lesions as well as for esthetics reasons. Complementary investigations enabled to diagnose a cholangiocarcinoma without visceral metastasis and she was treated by tumor resection and chemotherapy. Consequently, a slight improvement of the skin condition and the disappearance of pruritus were observed. CONCLUSION: AN should be considered as cutaneous sign either of malignancy or endocrinopathy and therefore requires further investigations. The existence of extensive lesions, pruritus, tripe palms syndrome, florid cutaneous papillomatosis or mucous lesions, associated to an AN is a sign of malignancy should be investigated urgently the early diagnosis of which can lead to a better prognosis.

Erythrocyte transketolase deficiency in patients suffering from Crohn's disease.

OBJECTIVE: Aim of the study was to assess the possible vitamin B1 deficiency in relation to the exacerbation of Crohn's disease (CD) in adult patients. PATIENTS AND METHODS: Forty-nine Crohn's disease (CD) patients with different disease activity (The Crohn's Disease Activity Index-CDAI) were included in the study. Anthropometrical and biochemical parameters, i.e., high sensitive C-reactive protein, were assessed. The spectrophotometric method was used to measure the transketolase activity (TK) in erythrocytes. The normalized transketolase activity ratio (NTKZ) and the percentage of activation with thiamine pyrophosphate (%TPP) were also evaluated. RESULTS: The mean values of BMI were close to cut-off: 18.5 kg/m2, indicating a poor nutritional status in CD patients. The patients with moderate-to-severe active CD had a statistically significant higher value of CDAI and hsCRP concentrations compared to those being in the asymptomatic remission or at the mildly active stage of the disease. The level of NTKZ and %TPP were statistically different between the analyzed groups, showing the deficit of vitamin B1 in the group of moderate-to-severe active CD patients (Mean ± SD; NTKZ: 1.99 ± 0.87 vs. 1.54 ± 0.62 U/g Hb; % of TPP: 0.15 ± 0.78 vs. 54.90 ± 38.80). CONCLUSIONS: Vitamin B1 deficiency is part of the Crohn's disease manifestation in moderate-to-severe active patients.

Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients.

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25-75, with BMI 19.0-53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C-reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1-act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA-negative and OSA-positive patients (p < 0.05). Increased PON1-act was observed in the LL-genotype versus the LM + MM-genotype in the study population (p < 0.05). PON1-act was higher in the OSA-negative compared with OSA-positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1-act and LDL-cholesterol in the entire study population. The OSA-positive group presented an inverse relationship between PON1-act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.

Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

Suspicious liver nodule in chronic liver disease: Usefulness of a second biopsy.

PURPOSE: To assess the usefulness of a second biopsy when the first one was inconclusive in patients with a liver nodule found during the follow-up for chronic liver disease. MATERIALS AND METHODS: Among 381 patients (544 nodules) included in a prospective study designed to evaluate the accuracy of imaging for the diagnosis of small hepatocellular carcinoma (HCC) in chronic liver disease, 254 nodules were biopsied. The following histological results were considered as conclusive: HCC, dysplastic or regenerative nodule, and other identified tumors (benign or malignant). For nodules with inconclusive results (e.g. fibrosis or no definite focal lesion), a second biopsy was suggested, but was not mandatory. RESULTS: A total of 242 patients (194 men, 48 women; mean age, 61.9±9.5 [SD]; range: 40.2-89.0years) with 254 nodules underwent a first biopsy. Mean nodule diameter was 19.2±5.4mm (range: 10-33mm). The first biopsy was conclusive in 189/254 nodules (74.4%): 157 HCCs (83.1%), 11 regenerative nodules (5.8%), 10 dysplastic nodules (5.3%), 3 cholangiocarcinomas (1.6%), and 8 other tumors (4.2%). Among the 65 nodules for which the first biopsy was inconclusive, a second biopsy was performed for 17 nodules in 16 patients within 6 months of the first one. It was conclusive in 13/17 nodules (76.5%): 10 HCCs (76.9%), 2 dysplastic nodules (15.4%), and 1 other tumor (7.7%). In 4/17 nodules (23.5%), no definitive diagnosis could be provided. CONCLUSION: The diagnostic yield of a second biopsy of a suspicious lesion suggestive of HCC in chronic liver disease is not decreased compared to the first one. Repeated biopsy after a first negative one could be an alternative option to the follow-up of patients with chronic liver disease.

Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest. METHODS: Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. RESULTS: The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. CONCLUSION: The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Circadian rhythms of melatonin and cortisol in manifest Huntington's disease and in acute cortical ischemic stroke.

Recent studies indicate disruptions to the circadian system in brain injury and neurodegeneration. The results, however, are often not consistent and limited by measurement of only one circadian marker and by infrequent sampling rates. In this study, we examined diurnal rhythmicity in different stages of Huntington (HD) disease and in patients with acute moderate ischemic stroke (AIS) outside the retinohypothalamic pathway by evaluating serum concentrations of melatonin and cortisol at twelve timepoints. All study participants were subjected to the same study protocol of 12-hour light/dark cycle and controlled room conditions. Using cosinor analysis of data and comparing the results with the controls we found melatonin phase delay with lowered amplitude and mesor in stage III HD patients. These changes coexisted with phase advanced rhythm and elevated values of mesor and amplitude for cortisol. Early and mid-stages of HD showed only a phase advance in cortisol secretion. In AIS the circadian rhythm of serum melatonin was sustained without any phase shift and exhibited more flattened profile (lowered mesor and amplitude values), while advanced rhythm with higher mesor for cortisol was present. In conclusion, 1) abnormal pattern of melatonin release in the late stages of HD and in moderate AIS occurs in conjunction with phase-advanced rhythm of cortisol; 2) changes observed in late stages of HD are similar to those that occur with ageing; 3) brain regions other than the presumptive retinopineal neural pathway may play an important role in the pineal production of melatonin in humans; 4) lesion in extrahypothalamic region is related to the strong adrenal stimulation in response to AIS.

Human papillomavirus does not play a role in the Barrett esophagus: a French cohort.

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).

The Effect on Cognition of Mitochondrial Respiratory System Proteins in Peripheral Blood Mononuclear Cells in the Course of Lung Cancer.

Peripheral blood mononuclear cells (PBMC) represent an easily available population of cells for the studies on remote effects of lung cancer. NADH dehydrogenase (ubiquinone) Fe-S protein-1 (Ndufs1), a marker of mitochondrial complex I, and mitochondrially encoded cytochrome c oxidase 1 (MTCO1), a marker of complex IV, may participate in cognitive decline during the course of lung cancer. In this study, Ndufs1 and MTCO1 expression in PBMC was evaluated by means of ELISA in 80 lung cancer patients. Mini-Mental State Examination (MMSE) were conducted Trail Making Tests (TMT-A and TMT-B) at baseline and after the 6 months' follow-up. Autoantibodies were identified by means of indirect immunofluorescence and line blot. We found that enhanced levels of Ndufs1 in PBMC were related to impaired cognitive performance; TMT-A of 13.6 ± 3.1 s and TMT-B of 162.5 ± 46.4 s compared with 8.6 ± 4.5 s (p = 0.003) and 124.8 ± 51.8 s (p < 0.05), respectively, in the case of low Ndufs-1 levels. The Ndufs1 expression at baseline was associated with MMSE - τb (Kendall's tau-b) = -0.31; p = 0.024; TMT-A - τb = 0.30; p = 0.001), and TMT-B - τb = 0.199; p = 0.012) after the 6 months' follow-up. Higher MTCO1 expression was accompanied by worse TMT-A results than in case of inhibited MTCO1; 11.1 ± 5.8 s vs. 8.5 ± 4.1 s; respectively; p = 0.048. MTCO1 expression was correlated with TMT-A results (τb = 0.17; p = 0.034) at baseline. We conclude that stimulation of PBMC mitochondrial function in lung cancer patients is associated with cognitive impairment. Mitochondrial dysfunction in PBMC may reflect cytotoxicity responsible for neurological deficits.

Humoral Immune Response against Neural Antigens and Its Effects on Cognition in Lung Cancer Patients.

Cognitive impairment develops as a clinical manifestation of immune-mediated indirect effects of malignancy in lung cancer patients. This study aimed to evaluate the effects of humoral immune response on cognition in lung cancer patients. Fifty-one lung cancer patients were subjected to neurological examination: Mini Mental State Examination (MMSE), Trail Making Test (TMT), and Hamilton scale. The Psychology Experiment Building Language software was used for the evaluation of digit span, simple reaction time (SRT), and choice reaction time (CRT) tests. Serum samples were tested for the presence of onconeuronal antibodies and antineural antibodies. The results demonstrate that autoantibodies were found in 31 % patients. MMSE scores were lower (26.7 ± 2.7) in seropositive patients than in seronegative subjects (28.7 ± 1.2; p = 0.013). Executive functions were also influenced by the presence of autoantibodies. The humoral immune response in lung cancer patients affected both SRT and CRT. We conclude that the humoral immune response in lung cancer patients is associated with cognitive impairment. Cognitive impairment is associated with both specific reactions against onconeuronal or antineural antigens and non-organ specific reactions against nucleosome antigens.

Efficacy of cerebral thrombolysis in an extended 'time window'.

WHAT IS KNOWN AND OBJECTIVE: Cerebral systemic thrombolysis (i.v. thrombolysis) with tissue-type plasminogen activator (rt-PA) is the only proven medical therapy for ischaemic stroke. The use of i.v. thrombolysis up to 4·5 h from stroke onset was approved in certain countries in 2008, but its safety and efficacy have not been fully determined to date. OBJECTIVE: To assess the long-term outcome and complication rate of i.v. thrombolysis performed in the extended 'time window'. METHODS: The study included 403 ischaemic stroke patients consecutively treated with i.v. thrombolysis from 2006 to 2012 at three comprehensive stroke centres in Poland. The long-term outcome and the haemorrhagic complications' (HC) rate were compared between subgroups of patients treated within 3 vs. 3-4·5 h from stroke onset. RESULTS AND DISCUSSION: About 132 (32·75%) patients were treated between 3 and 4·5 h from stroke onset. Neurological deficits tended to be more severe in patients treated ≤3 than in those treated 3-4·5 h (National Institutes of Health Stroke Scale, NIHSS 12 vs.10 points; P = 0·053); however, the ratio of patients with a favourable outcome (mRS 0-2 points) and mortality did not differ between the two groups (53·9 vs. 58·3, P = 0·39 and 17·7 vs. 21·2, P = 0·39, respectively). The rate of HC also did not differ between the two groups (18·8% vs. 15·1%, P = 0·46). WHAT IS NEW AND CONCLUSION: The efficacy of i.v. thrombolysis routinely performed in an extended 'time window' is not reduced when compared to procedures performed within 3 h from symptom onset.

MRI versus histological methods for time course monitoring of steatosis amount in a murine model of NAFLD.

PURPOSE: Hepatic steatosis is an increasingly frequent disease with potentially severe complications. A simple quantification method is required for pretherapeutic studies to allow steatosis monitoring. This study aimed at evaluating steatosis quantification via a standard 1.5T MRI machine in a murine model. MATERIALS AND METHODS: Eleven groups of two rats received a choline methionine deficient diet. MRI was performed at days 0, 2, 4, 5, 6, 7 and 8, and weeks 2, 3, 4 and 5. A phased array surface coil system was used to acquire a GE T1 in- and out-of-phase multi-echo sequence, with neither cardiac nor respiratory synchronization. Steatosis was calculated with the 3-echoes method. Histological quantifications were performed both by optical analysis (percentage of fatty hepatocytes) and by automated measurement of the area of steatosis (AOS). The reference was total intrahepatic triglycerides (TIT). Protocol was approved by the ethic committee. RESULTS: Steatosis without inflammation, increasing with diet duration, was obtained. MRI provided better agreement (intraclass correlation coefficient) with TIT (0.889, p<0.001) than did AOS (0.629, p=0.001) or optical analysis (0.280, p=0.098). MRI permitted closer monitoring of TIT over time than did AOS or optical analysis. By multivariate analysis, MRI was an independent predictor of TIT on first step and ALT on second step. A model combining these 2 variables provided excellent agreement with TIT (0.953, p<0.001) and permitted excellent monitoring of steatosis over time. CONCLUSION: MRI is reliable, easy, fast and superior to histological techniques for the assessment of hepatic steatosis in a murine model.

Water-enema multidetector computed tomography for planning surgery.

PURPOSE: Water-enema multidetector computed tomography (WE-MDCT) is a technique for the localization and preoperative T- and N-stage assessments of colon cancer. It may be a useful tool for planning surgery. The primary aim of this study was to evaluate the diagnostic accuracy of WE-MDCT for T-staging and its ability to locate tumors for laparoscopy planning. The secondary aim was to assess reading reproducibility and diagnostic accuracy for the preoperative determination of N-stage. METHODS: We performed a study to evaluate preoperative WE-MDCT for surgical planning in patients with symptomatic colon adenocarcinomas who underwent surgery between June 2010 and January 2014. A radiologist and a surgeon read the WE-MDCTs separately. Results were compared with colonoscopy and the surgical specimen. RESULTS: Seventy-one patients (42 men (59.1%); mean age 73.1 years (range 45 to 95)) were included. Seventy-six tumors were assessed. The intraclass correlation coefficient (ICC) for location as determined by surgery and that determined by WE-MDCT was 1, and the ICC for location between colonoscopy and WE-MDCT was 0.85 (95% CI 0.75-0.91). For T-stage determination, sensitivity was 96 and 94% and specificity 83 and 88% for readers 1 and 2, respectively. The T-stage assessment allowed for the programing of surgical access and showed good sensitivity and specificity for the assessment of invasion in adjacent organs. CONCLUSION: WE-MDCT is relatively easy to perform, and its results can be read effectively by radiologists and surgeons. WE-MDCT indicated the location of tumors perfectly and permitted a good determination of their T-stage. The technique is thus pertinent for the planning of laparoscopic surgery for colon cancer.

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C.

BACKGROUND: Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. AIM: To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). METHODS: A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). RESULTS: During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. CONCLUSIONS: Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis.

Substantia nigra hyperechogenicity in Polish patients with Parkinson's disease.

BACKGROUND: Hyperechogenicity of the substantia nigra (SN) measured by transcranial sonography (TCS) is a characteristic feature observed in patients with Parkinson's disease (PD). To our knowledge, no SN hyperechogenicity data are available for Polish population. Moreover most of studies come from few centres, which used the one type of ultrasound device. The main aim of the study was to investigate the association between PD and SN hyperechogenicity measured by sonographic machine, not assessed so far. MATERIALS AND METHODS: In this study cross-sectional study SN hyperechogenicity was evaluated in 102 PD patients and 95 control subjects. Midbrain was visualised by Aloka Prosound 7 ultrasound device. SN area measurement, the relation to the clinical features of PD, inter- and intra-observer reliability were evaluated. RESULTS: We confirmed that SN echogenicity is significantly increased in PD patients compared to control subjects (p < 0.001). The area under curve for PD patients vs. controls was 0.93. Receiver operating characteristic analysis indicated a cut-offs for SN echogenicity at 0.19 cm² with accuracy equal to 90%, specificity - 86% and sensitivity - 93.7%. The SN hyperechogenicity was not related to PD clinical findings. Reliability was good if an experienced sonographer performed the SN measurements. CONCLUSIONS: This study shows that the SN abnormality observed by TCS isa specific feature, which can be helpful in the process of PD diagnosing.

Intravenous rt-PA in patients with ischaemic stroke and renal dysfunction.

OBJECTIVE: Renal dysfunction (RD) increases risk for ischaemic stroke (IS). The impact of RD on the effects of iv-thrombolysis in the Caucasian population has not been fully determined. AIMS: To evaluate the associations between RD and the outcome of iv-thrombolysis in Caucasian patients with IS. METHODS: The observational, multicentre study included 404 patients with IS who were treated with iv-thrombolysis. RD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m(2). Outcome was assessed with modified Rankin Score at 3 months after the stroke onset. RESULTS: Medians baseline NIHSS score did not differ between groups of patients with and without RD (12.0 vs. 11.0 pts, p=0.33). Unfavourable outcome was found in 52.1% of patients with and in 41.2% of patients without RD (p=0.05), mortality was higher in patients with RD (29.9% vs. 14.3%, p<0.001), and the presence of haemorrhagic transformation (HT) did not differ between the groups (17.1% vs. 17.1% respectively, p=0.996). A multivariate analysis showed no impact of RD on the unfavourable outcome (OR 0.98; 95%CI 0.88-1.10), mortality (OR 0.92; 95%CI 0.81-1.05) or presence of HT (OR 1.03; 95%CI 0.90-1.18). CONCLUSIONS: We found no impact of RD on the safety and efficacy of iv-thrombolysis in Caucasian patients with IS.