Lichen planus and other cutaneous manifestations in chronic hepatitis C: pre- and post-interferon-based treatment prevalence vary in a cohort of patients from low hepatitis C virus endemic area

Background Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. Objectives To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)‐based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV‐seropositive patients and 171 HCV‐seronegative age‐ and gender‐matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN‐based therapy were assessed. Results Overall presence of LP in HCV‐seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN‐based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN‐based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post‐treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85–53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44–12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. Conclusions LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post‐compared with pre‐treated patients. The role of IFN in post‐treatment persistence of skin manifestations needs to be assessed.     

Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis.

BACKGROUND CONTEXT: The publication of several recent studies showing minimal benefit for radiofrequency (RF) lumbar zygapophysial (l-z) joint denervation have led many investigators to reevaluate selection criteria. One controversial explanation for these findings is that the most commonly used cutoff value for selecting patients for l-z (facet) joint RF denervation, greater than 50% pain relief after diagnostic blocks, is too low and hence responsible for the high failure rate. PURPOSE: To compare l-z joint RF denervation success rates between the conventional greater than or equal to 50% pain relief threshold and the more stringently proposed greater than or equal to 80% cutoff for diagnostic medial branch blocks (MBB). STUDY DESIGN/SETTING: Multicenter, retrospective clinical data analysis. PATIENT SAMPLE: Two hundred and sixty-two patients with chronic low back pain who underwent l-z RF denervation at three pain clinics. OUTCOME MEASURES: Outcome measures were greater than 50% pain relief based on visual analog scale or numerical pain rating score after RF denervation persisting at least 6 months postprocedure, and global perceived effect (GPE), which considered pain relief, satisfaction and functional improvement. METHODS: Data were garnered at three centers on 262 patients who underwent l-z RF denervation after obtaining greater than or equal to 50% pain relief after diagnostic MBB. Subjects were separated into those who received partial (greater than or equal to 50% but less than 80%) and near-complete (greater than or equal to 80%) pain relief from the MBB. Outcomes between groups were compared with multivariate analysis after controlling for 14 demographic and clinical variables. RESULTS: One hundred and forty-five patients obtained greater than or equal to 50% but less than 80% pain relief after diagnostic MBB, and 117 patients obtained greater than or equal to 80% relief. In the greater than or equal to 50% group, success rates were 52% and 67% based on pain relief and GPE, respectively. Among patients who experienced greater than 80% relief from diagnostic blocks, 56% obtained greater than or equal to 50% relief from RF denervation and 66% had a positive GPE. CONCLUSIONS: Using more stringent pain relief criteria when selecting patients for l-z joint RF denervation is unlikely to improve success rates, and may lead to misdiagnosis and withholding a potentially valuable treatment from good candidates.     

Oxidative stress,NOx/l-arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic ‘sterile inflammation’. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.     

Clinical predictors of success and failure for lumbar facet radiofrequency denervation

OBJECTIVE: To determine the clinical factors associated with the success and failure of radiofrequency denervation of the lumbar facet joints. METHODS: Clinical data were garnered from 3 academic medical centers on 192 patients with low back pain who underwent radiofrequency denervation after a positive response to diagnostic blocks. Success was defined as >/=50% pain relief lasting at least 6 months. Factors evaluated for their association with outcome included duration of pain, opioid use, symptom location, paraspinal tenderness, pain exacerbated by extension/rotation (ie, facet loading), MRI abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery and levels treated. RESULTS: The only factor associated with a successful outcome was paraspinal tenderness. Variables that correlated with treatment failure were 'facet loading,' long duration of pain, and previous back surgery. CONCLUSIONS: It is counterproductive to use 'facet loading' as the sole basis for choosing patients for facet interventions. In patients at high risk for treatment failure, taking additional steps to reduce the rate of false-positive screening blocks may improve outcomes.     

The Validation Study of Neurofilament Heavy Chain and 8-hydroxy-2′-deoxyguanosine as Plasma Biomarkers of Clinical/Paraclinical Activity in First and Relapsing-Remitting Demyelination Acute Attacks

Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T₁-Gd-enhancing lesion volume) activities of disease. Both parameters were increased in CIS and RRMS compared to control subjects (p < 0.05). The positive correlations were observed between 8-OHdG values and index of BBB permeability, clinical severity of disease, and demyelinated brain lesion volume, in CIS group (r > 0.50; p < 0.05). Similar correlations were obtained between pNF-H values and the above parameters, as well as the index of disease progression, in RRMS group (r > 0.30; p < 0.05). There was a significant correlation between values of 8-OHdG and pNF-H only in CIS group, r = 0.52, p < 0.05. While the plasma values of 8-OHdG reflect the degree of acute demyelination in CIS, pNF-H values reflect that in RRMS. The obtained results must be reevaluated in similar prospective studies related to their prognostic values.     

Enhancing memory for lists by grouped presentation and rehearsal: A pilot study in healthy subjects with unexpected results

List learning is probably the most established paradigm for the psychometric evaluation of episodic memory deficits in different neuropsychiatric conditions including epilepsy. Strategies which are capable of increasing the test performance might be promising candidates for a therapeutic improvement of daily memory performance. Based on the classical ‘temporal grouping effect’ we wanted to evaluate the memory-enhancing potential of disentangling perceiving, rehearsing and encoding by temporally grouped presentation and group-wise reproduction during acquisition. According to the ethical principle of subsidiary the study was performed in healthy adolescents (N = 126) before setting-up a patient study. Subjects had to learn a list of 12 semantically unrelated nouns and a list of 12 figures during two acquisition trials under one of four experimental conditions defined by the size of presented item groups (GS): GS = 1 (single items, i.e., 12 × 1 item), GS = 3 (4 × 3 items), GS = 6 (2 × 6 items), and GS = 12 (standard presentation mode, i.e., 1 × 12 items). Repeated measures MANOVA confirmed a positive effect of smaller GS on acquisition performance but the grouping condition obtained no effect on immediate and delayed free recall or on yes/no recognition. For verbal retention, GS = 12 even showed a tendency toward an advantage as compared to GS = 3. Although appearing reasonable and promising, facilitating acquisition during list learning by temporal grouping and grouped overt rehearsal turned out to be ineffective with regard to long-term memory encoding and retrieval. A strategy however which fails in healthy subjects is unlikely to obtain a therapeutic potential in patients with memory deficits.     

Divergent Squamous Differentiation in Upper Urothelial Carcinoma—Comparative Clinicopathological and Molecular Study

Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p < 0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p < 0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p = 0.007), Ki-67 activity (p = 0.016) and growth (p = 0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.