Baseline diabetic knowledge after 5-day teaching program is an independent predictor of subclinical macroangiopathy in patients with type 1 diabetes (Poznan Prospective Study)

PurposeThe cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (DM1). Carotid intima-media thickness (IMT) has been approved as a marker of subclinical atherosclerosis. The aim of this prospective study was to evaluate the relationship between baseline diabetic knowledge after five-day teaching program and IMT in patients with (DM1) treated with intensive functional insulin therapy (IFIT) from the onset of the disease.Material/methodsThe analysis included 79 subjects aged 23.4 ± 5.1 years with newly diagnosed DM1, participating in Poznan Prospective Study (PoProStu). The patients attended a five-day structured training program in IFIT at diagnosis, followed by a test consisting of 20 questions. After follow-up period of 11 years we evaluated the presence of microangiopathy and subclinical macroangiopathy. IMT of the right common carotid artery was determined using high resolution ultrasonography and calculated automatically with the Carotid Analyzer for Research program.ResultsAfter 11-year follow-up median intima-media thickness was 560 (IQR: 520–630) μm. We found a negative correlation between diabetes knowledge at baseline and IMT at the end of follow-up (r = −0.27, p = 0.017). In multivariate linear regression model baseline diabetic knowledge test result was associated with IMT at follow-up, independently from sex, age, smoking status, presence of hypertension and diabetic kidney disease (all at follow-up) and from mean follow-up LDL-cholesterol concentrations and HbA_1c results (β = −8, 95% CI −16, −1, p = 0.037).ConclusionsBaseline diabetic knowledge after 5-day teaching program is an independent predictor of subclinical macroangiopathy in patients with DM1.     

Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: Associations with organ manifestations,immunolaboratory markers and disease activity indices

BackgroundSome tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis.ObjectivesWe assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement.MethodsTAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively.ResultsThere were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p < 0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p < 0.05). The mean absolute serum levels of CEA (6.6 ± 1.7 vs 1.8 ± 1.4 mg/l) and CA15-3 (22.9 ± 1.8 vs 18.6 ± 2.2 kU/l) were also significantly higher in SSc compared to controls (p < 0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p < 0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls.ConclusionThe concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.     

A meta-analysis of P2X7 gene-1513A/C polymorphism and pulmonary tuberculosis susceptibility

ObjectiveA meta-analysis was performed to determine the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.MethodsBased on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.ResultsA total of 1916 cases and 2194 controls in 10 studies were pooled together for evaluation of the overall association between P2X7-1513A/C polymorphism and susceptibility of pulmonary tuberculosis. Allele model (A vs. C: p = 0.15; OR = 0.86, 95% CI = 0.69–1.06), homozygous model (AA vs. CC: p = 0.22; OR = 0.78, 95% CI = 0.53–1.16), and heterozygous model (AC vs. CC: p = 0.23; OR = 0.80, 95% CI = 0.56–1.15) did not show decreased risk of developing pulmonary tuberculosis. Similarly, dominant model (AA + AC vs. CC: p = 0.19; OR = 0.80, 95% CI = 0.56–1.12) and recessive model (AA vs. AC + CC: p = 0.21; OR = 0.85, 95% CI = 0.66–1.10) failed to show decreased risk of developing pulmonary tuberculosis. In Indians, allele model (A vs. C: p = 0.0006; OR = 0.69, 95% CI = 0.55–0.85), and recessive model (AA vs. AC + CC: p = 0.0003; OR = 0.62, 95% CI = 0.48–0.80) indicated significant association between P2X7-1513A/C polymorphism and susceptibility to pulmonary tuberculosis.ConclusionsOur pooled data suggest a association between P2X7-1513A/C polymorphism and the prevalence of pulmonary tuberculosis among Indian populations.     

Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment

BackgroundAnaemia is a common side-effect of ribavirin (RBV) use that overwhelms management of hepatitis C when protease inhibitors are added.AimTo assess the pharmacogenomic impact of candidate genes SLC28A2, SLC28A3 and ITPA on anaemia in patients receiving triple therapy.MethodsPatients (n = 161) with chronic hepatitis C genotype 1 treated with telaprevir (n = 95) or boceprevir (n = 66) were included. Using RT-PCR we genotyped ITPA (rs1127354, rs7270101) and SLC28A3 (rs56350726, rs10868138) and SLC28A2 (rs11854484). Clinically significant anaemia (CSA) was diagnosed when at least one of the following criteria was observed: (a) haemoglobin <8.5 g/dL during treatment; (b) blood transfusion required; (c) erythropoietin administered.ResultsCSA occurred in 44% (69/157) of patients and was associated with SLC28A2 rs11854484 [CC/CT genotypes: 33% (26/78) vs. TT genotype: 56% (36/64); p = 0.006]. Further, the needed for blood transfusion was related to genotype [CC: 0% (0/18) vs. CT: 13% (8/61) vs. TT: 27% (17/64); p = 0.016]. Similarly, ITPA rs1127354 genotypes [AA/AC: 19% (3/16) vs. CC: 45% (61/135; p = 0.060] were linked to CSA. In multivariate analysis, SLC28A2 rs11854484 TT genotype (OR:2.33;95%CI:1.10–4.95; p = 0.027), female sex (OR:2.54;95% CI:1.13–5.71;p = 0.024) and Hb drop at week 4) OR: 1.36; 95CI%: 1.11–1.67; p = 0.003) were independently associated with CSA. Similarly, ITPA rs1127354 genotypes [AA/AC: 16% (3/19) vs. CC: 63% (85/134); p = 0.0001] and ITPA rs6051702 genotypes [CC/CA: 46% (26/57) vs. CC: 65% (60/93); p = 0.023] were related to Hb drop of >3g/dL at week 4.ConclusionsIn patients receiving first generation protease inhibitors, genotype SLC28A2 rs11854484 predicts CSA, and helps to identify a subgroup of patients with better tolerance of triple therapy.     

Endothelial function,antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes

PurposeThis pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection.Patients/methodsUntreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies.ResultsTen patients were recruited (M = 8, F = 2, mean age = 51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p = 0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 μmol/L vs. 0.51 μmol/L, p = 0.45, 427.4 ng/ml vs. 307.22 ng/ml, p = 0.54, 517.70 ng/ml vs. 377.50 ng/ml, p = 0.51 and 290.75 μg/dL vs. 224.26 μg/dL, p = 0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p = 0.34).ConclusionsVenesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further.     

Radiographic outcome of limb-based versus knee-based patient specific guides in total knee arthroplasty

BackgroundPatient specific guides (PSG's) were developed to improve overall component alignment in total knee arthroplasty (TKA). The aim of this study was to undertake a comparative radiographic study of two commonly used PSG and determine whether the radiographic technique used to construct the PSG had a significant effect on overall alignment.MethodsThis prospective cohort study examined the accuracy of limb-based (n = 112) versus knee-based (n = 105) MR PSG in restoring the mechanical axis in three planes according to post-operative Perth CT scan protocol.ResultsLimb-based MR and knee-based MR PSG systems both restored overall hip–knee–ankle angle (HKAA), femoral coronal alignment, tibial coronal alignment, femoral sagittal alignment, tibial sagittal alignment and femoral rotation alignment to within 3° of a neutral mechanical axis with similar precision (91.1% vs. 86.7% p = 0.30, 97.3% vs. 96.2% p = 0.63, 97.3% vs. 97.1% p = 0.94, 94.6% vs. 89.4% p = 0.16, 90.2% vs. 81.0% p = 0.05, 91.1% vs. 86.7% p = 0.30, respectively). However, when the secondary outcome measure of alignment within 2° was assessed, limb-based MR PSG restored HKAA, femoral coronal and tibial sagittal alignment with greater precision than knee-based MR PSG (73.2% vs. 64.8% p = 0.016, 93.8% vs. 80.8% p = 0.004 and 82.1% vs. 62.9% p = 0.001, respectively).ConclusionsThe findings of this study recommend the use of limb-based MR PSG for improved precision in the restoration of neutral mechanical alignment over knee-based MR PSG in TKA.Level of EvidenceTherapeutic level III     

Serological markers of rheumatoid arthritis in patients with primary biliary cholangitis and the vice versa: A Tunisian study

BackgroundPrimary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destructive lymphocytic cholangitis and anti-mitochondrial antibodies (AMA). Anti-gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients. Patients with PBC have a propensity to have an extrahepatic manifestation which is especially autoimmune.ObjectiveWe aimed to determine the frequency of serological markers of rheumatoid arthritis (RA) (CCP-Ab or RF) in PBC patients and to do the vice versa.MethodsOur PBC study included 70 patients with PBC and 80 healthy blood donors (HBD) and our RA study included 75 patients with RA and 75 HBD. Anti-cyclic citrullinated peptide antibodies (CCP-Ab) and rheumatoid factor (RF) were performed by indirect ELISA. AMA, anti-Sp100 and anti-gp210 were determined by indirect immunofluorescence.ResultsRA autoantibodies (CCP-Ab or RF) were more frequent in PBC patients than in HBD (65.7% vs. 8.7% p 〈1 0 ⁻⁶). CCP-Ab were significantly more frequent in patients than in controls (15.7% vs. 2.5%; p = 0.004). Nine patients had both CCP-Ab and RF vs. none of controls (12.8% vs. 0%; p = 0.001). RF were detected in 45 patients with PBC and in 5 HBD (64.3% vs. 6.2%; p 〈1 0 ⁻⁶). In PBC patients, RF were more frequent than CCP-Ab (64.3% vs. 15.7%; p 〈1 0 ⁻⁶). RF-IgG were present in 18.5% of patients; RF-immunoglobulin (Ig) A in 34.3% and RF-IgM in 54.3%. These frequencies were significantly higher than those found in control group (1.2% for RF-IgG (p 〈1 0 ⁻³); 0% for RF-IgA (p 〈1 0 ⁻⁶); and 6.2% for RF-IgM (p 〈1 0 ⁻⁶)). In our PBC patients, RF-IgA were more frequent than RF-IgG (34.3% vs. 18.5%; p = 0.03) and than CCP-Ab (34.3% vs. 15.7%; p = 0.01). Six patients had only RF-IgA versus none of the control group (8.6% vs. 0%; p = 0.01). AMA, anti-Sp100 and anti-gp 210 were absent in all RA patients.ConclusionsSerological markers of RA were more frequent in PBC patients than in HBD and the vice versa was not true.     

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

ObjectivesStudies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg).MethodsA total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima–media thickness (IMT) and stiffness index (β); blood total cholesterol, HDL and triglycerides were assessed.ResultsAll three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 ± 36.31 mg/dL vs. 250.59 ± 38.37 mg/dL vs. 245.09 ± 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01—ANOVA), the highest triglycerides (139.34 ± 41.82 mg/dL vs. 111.35 ± 28.22 mg/dL vs. 122.09 ± 33.42 mg/dL; p < 0.01), the highest FMD (6.32 ± 2.33% vs. 4.10 ± 2.06% vs. 4.66 ± 2.52%; p < 0.01) and the lowest stiffness index (β) (5.08 ± 1.68 vs. 6.28 ± 1.75 vs. 5.99 ± 1.86; p = 0.01). LTZg did not differ significantly from NETg on any evaluated parameter.ConclusionsWe did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (β) and FMD between women receiving tamoxifen and letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole.     

Separate may not be equal: A preliminary investigation of clinical correlates of electronic psychiatric record accessibility in academic medical centers

ObjectivesElectronic Medical Records (EMR) have the potential to improve the coordination of healthcare in this country, yet the field of psychiatry has lagged behind other medical disciplines in its adoption of EMR.MethodsPsychiatrists at 18 of the top US hospitals completed an electronic survey detailing whether their psychiatric records were stored electronically and accessible to non-psychiatric physicians. Electronic hospital records and accessibility statuses were correlated with patient care outcomes obtained from the University Health System Consortium Clinical Database available for 13 of the 18 top US hospitals.Results44% of hospitals surveyed maintained most or all of their psychiatric records electronically and 28% made psychiatric records accessible to non-psychiatric physicians; only 22% did both. Compared with hospitals where psychiatric records were not stored electronically, the average 7-day readmission rate of psychiatric patients was significantly lower at hospitals with psychiatric EMR (5.1% vs. 7.0%, p = .040). Similarly, the 14 and 30-day readmission rates at hospitals where psychiatric records were accessible to non-psychiatric physicians were lower than those of their counterparts with non-accessible records (5.8% vs. 9.5%, p = .019, 8.6% vs. 13.6%, p = .013, respectively). The 7, 14, and 30-day readmission rates were significantly lower in hospitals where psychiatric records were both stored electronically and made accessible than at hospitals where records were either not electronic or not accessible (4% vs 6.6%, 5.8% vs 9.1%, 8.9 vs 13%, respectively, all with p = 0.045).ConclusionsHaving psychiatric EMR that were accessible to non-psychiatric physicians correlated with improved clinical care as measured by lower readmission rates specific for psychiatric patients.     

Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection

BackgroundThe differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis.ObjectivesWe investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB.Study designA total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n = 21), patients with HBeAg-negative hepatitis (n = 95), HBeAg-positive hepatitis (n = 141) and liver cirrhosis (n = 82).ResultsSerum M30-antigen levels were correlated significantly not only with AST (r = 0.544, p < 0.001) and ALT (r = 0.315, p < 0.001) and but also inflammatory grading score on liver biopsy (r = 0.240, p < 0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78 U/L vs 148.90 U/L, p < 0.001). Multivariate analysis showed that AST (p < 0.001), albumin (p = 0.009) and M30-antigen (p = 0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344 U/L) and AST (>78 IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value.ConclusionsSerum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.     

Aortic elastic properties and cognitive function in elderly individuals: The Ikaria Study

BackgroundThe aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island.MethodsIn 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE).Results88% of the elders had normal values of MMSE score (i.e., ≥24). Elders who achieved MMSE score ≥24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg^?1 = 1.25, 95%CI 0.99–1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (>70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made.ConclusionArterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.     

Chemokine receptor V Δ32 deletion in multiple sclerosis patients in Csongrád County in Hungary and the North-Bácska region in Serbia

The roles of chemokine receptor V (CCR5) and its polymorphism, rs333 in multiple sclerosis (MS) are controversial. We investigated the receptor and its deletion in a large MS (428) and a numerous control (831) population in Csongrád County (Hungary) and North-Bácska (Serbia). Taqman probes firstly were used for the allele discrimination. There was no significant difference in genotype (OR = 1.092, 95% CI = 0.807–1.478, p = 0.568 for wt/wt (wt = wild type allele) vs wt/Δ32, Δ32/Δ32 (Δ32 = Δ32 base pair deletion allele)) or allele frequency (OR = 0.914, 95% CI = 0.692–1.207, p = 0.525). Neither the deletion nor the wt allele affected the Expanded Disability Status Scale score or the age at onset. Our results indicate no association between the CCR5 Δ32 allele and MS.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.     

Clinical characteristics and outcomes of severe rhinovirus-associated pneumonia identified by bronchoscopic bronchoalveolar lavage in adults: Comparison with severe influenza virus-associated pneumonia

BackgroundRhinoviruses (RVs) may cause pneumonia, but the characteristics of RV-associated pneumonia have not been adequately evaluated.ObjectiveWe aimed to compare characteristics, complications, and outcomes between severe RV- and influenza virus (IFV)-associated pneumonia in adults.Study designWe used prospective cohort data of adult patients with severe pneumonia who had been admitted to the medical intensive care unit of a tertiary care hospital over a 4-year period. The clinical features and outcomes of 27 patients with RV-positive bronchoscopic bronchoalveolar lavage (BAL) fluid were compared to those of 51 pneumonia patients with IFV-positive BAL fluid or IFV-positive nasopharyngeal specimens.ResultsOf 356 patients who underwent bronchoscopic BAL and respiratory virus polymerase chain reaction (PCR), RV was the most commonly identified virus (8.1%) from BAL fluid. Patients with RV-associated pneumonia were more likely to be immunocompromised than patients with IFV-associated pneumonia (81.5% vs. 33.3%, p < 0.001). Bacterial coinfection tended to be less common in the RV group (18.5% vs. 37.3%, p = 0.09). Although septic shock was less common in the RV group (29.6% vs. 54.9%, p = 0.03), other clinical manifestations, laboratory findings, and radiologic patterns were similar between the groups. The 28-day mortality of patients with severe RV- and IFV-associated pneumonia was similarly high (29.6% vs. 35.3% respectively, p = 0.61).ConclusionsSevere RV-associated pneumonia patients were more likely to be immunocompromised and less likely to present septic shock. Overall clinical features were similar and mortalities of both groups were comparably high. Studies of larger cohorts encompassing mild to moderate pneumonia patients are needed.     

Peginterferon alfa-2a and peginterferon alfa-2b combined with ribavirin in patients with genotype 1 chronic hepatitis C: Results of a prospective single-centre study

PurposeThis prospective, randomized, single-centre study compared peginterferons alfa-2a and alfa-2b, combined with ribavirin, in treating patients infected with hepatitis C virus (HCV) genotype 1.Material/methodsHundred-and-one patients received 48 weeks of open-label treatment with peginterferon alfa-2a (180 μg/week) and 111 patients received peginterferon alfa-2b (1.5 μg/kg/week). All patients received the same dose of ribavirin 1000/1200 mg/day, depending on weight. The primary efficacy endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) 24 weeks after the end of treatment.ResultsEarly virologic response (EVR), defined as at least 2 log₁₀ IU/mL reduction of viral load at 12 weeks, was more common in patients treated with peginterferon alfa-2a (88% vs. 74.8%; p = 0.04). However, the difference in SVR was not statistically significant (49.5% vs. 44.1%; p = 0.43).ConclusionsPeginterferon alfa-2a treated patients were also more likely to be HCV RNA negative at the end of treatment (67.3% vs. 57.7%), but this difference did not reach statistical significance. Multivariate logistic regression analysis found that SVR was associated with low fibrosis stage (F1–2 by Scheuer; p = 0.001) and low serum HCV RNA level (<400,000 IU/L; p = 0.023). While both forms of peginterferon showed similar efficacy as measured by SVR, use of peginterferon alfa-2b could lower the number of patients receiving unnecessary treatment beyond 12 weeks.     

TNF-α -238, -308, -863 polymorphisms,and brucellosis infection

BackgroundBrucella abortus is an intracellular bacterium that affects humans and domestic animals. Tumor necrosis factor-alpha (TNF-α) has been shown as a key player in the induction of cell-mediated resistance against Brucella infection. We aimed to evaluate the possible influence of the TNF-α promoter polymorphisms (-308 G/A, -238 G/A, and -863 C/A) on the susceptibility of human brucellosis.MethodologyA total of 153 patients with active brucellosis and 128 healthy individuals were recruited. All subjects were genotyped for the polymorphisms in the TNF-α gene by Allele-Specific polymerase chain reaction analysis.ResultsOur results showed that the TNF-α -308 GG genotype was significantly more frequently present in controls than in brucellosis patients (91% vs. 75%), thus was a protective factor against developing brucellosis (OR = 0.313, p = 0.001). In contrast, the -308 GA genotype (OR = 3.026, p = 0.002) and minor allele (A) (OR = 3.058, p = 0.001) as well as AAG haplotype (OR = 4.014, p = 0.001) conferred an increased risk of brucellosis. However, the -238 G/A and -863 C/A polymorphisms were not associated with the risk of brucellosis at both allelic and genotypic levels (p > 0.05).ConclusionOur study revealed that the TNF-α -308 A allele or GA heterozygosity or AAG haplotype were associated with an increased risk of brucellosis in our population.     

Role of left atrial speckle tracking echocardiography in predicting persistent atrial fibrillation electrical cardioversion success and sinus rhythm maintenance at 6 months

PurposeWe assessed the value of left atrium speckle tracking imaging (STI) indices, and clinical and other echocardiographic parameters in persistent atrial fibrillation (AF) patients to predict the efficacy of electrical cardioversion (EC) and sinus rhythm (SR) maintenance at 6 months.Material/methodsEighty persistent AF patients planned to receive EC, underwent echocardiography including STI. After 24 h, patients with successful EC were examined to predict SR maintenance. After 6 months patients with no AF recurrence in electrocardiogram (ECG) underwent 7-day ECG to exclude silent AF. Every AF > 1 min was a recurrence.ResultsSR restored in 61 patients, 19 unsuccessful. Prior use of statins (68.8% vs. 42.1%, p = 0.03) was the only factor, determined later by univariate analysis to be a significant EC success predictor (OR = 1.09, CL ± 95% 1.001–1.019, p < 0.03). Both groups received similar antiarrhythmics and had similar echocardiographic parameters. After 6 months, SR was maintained in 19 patients (31.1%, Group I); AF recurrences were registered in 42 patients (68.8%, Group II). In Group I, only the mitral valve deceleration time (MVDT) 224.18 ± 88.13 vs. 181.6 ± 60.6 in Group II, p = 0.04) and the dispersion of time to peak longitudinal strain (dTPLS) (86.0 ± 68.3 vs. 151.8 ± 89.6, p = 0.03) differed significantly. The univariate analysis revealed dTPLS as a significant predictor of SR maintenance.ConclusionHigh EC efficacy and frequent AF recurrences were observed. The dispersion of time to the maximal longitudinal strain (LS) of left atrial segments facilitated prediction of SR maintenance. The value of 7-day ECG monitoring for detection of arrhythmia after 6 months was limited.     

Efficacy and safety of paliperidone extended-release in schizophrenia patients with prominent affective symptoms

BackgroundThis post-hoc analysis evaluated the effects of paliperidone extended-release (ER) in patients with schizophrenia and prominent affective symptoms.MethodsPooled data from three 6-week, randomized, double-blind, placebo-controlled studies were analyzed. Subjects received fixed doses of paliperidone ER 3–12 mg/day or placebo. Prominent affective symptoms were defined as depressive (Positive and Negative Syndrome Scale [PANSS] depression item score of ≥ 5 [moderately severe]) and/or manic (PANSS grandiosity score of ≥ 4 [moderate], plus a score of ≥ 4 [moderate] on at least 1 PANSS item for excitement, hostility, uncooperativeness, or poor impulse control). Assessments included PANSS, Clinical Global Impressions-Severity (CGI-S), Personal and Social Performance (PSP) scale, and adverse events (AEs).ResultsAmong 193 patients with prominent affective symptoms, 140 received paliperidone ER and 53 received placebo. Paliperidone ER showed significant mean (SD) improvements vs. placebo in PANSS total (? 20.5 [23.8] vs. ? 6.3 [27.2]; p < 0.001, respectively) and all factor scores (p < 0.01). Significant mean (SD) improvements were observed in PSP (7.2 [15.8] vs. 0.4 [14.6]; p = 0.004) and CGI-S (? 0.9 [1.2] vs. ? 0.3 [1.2]; p < 0.001) scores. Most common AEs with paliperidone ER vs. placebo: headache (16.4% vs. 13.2%), insomnia (7.9% vs. 9.4%), akathisia (7.1% vs. 1.9%), sedation (7.1% vs. 3.8%).LimitationsThese studies were not designed to examine patients with prominent affective symptoms. Authors' clinical judgment was used to define prominent affective symptoms, using relevant PANSS items.ConclusionsPaliperidone ER was well tolerated and associated with significantly greater improvements in symptomatology, functioning, and overall clinical status vs. placebo in patients with schizophrenia and prominent affective symptoms.     

Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension

PurposeAlthough many studies have described various features of neuroimaging tests associated with intracranial hypotension, few have examined their validity and reliability. We evaluated the association between CSF leaks detected by radionuclide cisternography and abnormal MRI findings in the accurate diagnosis of intracranial hypotension.Patients/methodsWe retrospectively assessed 250 patients who were suspected of intracranial hypotension and underwent subsequent radionuclide cisternography. We obtained 159 sagittal and 153 coronal T2-weighted MRI images and 101 gadolinium-enhanced T1-weighted MRI images. We assessed the CSF leaks in relation to a sagging brain, the maximum subdural space in sagittal and coronal images, and dural enhancement.ResultsOverall, 186 (74%) patients showed CSF leaks on radionuclide cisternography. A sagging brain was observed in 21 (13%) of the 159 patients with sagittal MRIs. A sagging brain was not associated with CSF leaks (14% vs. 10%; p = 0.49). Compared to patients without CSF leaks, those with CSF leaks tended to have a larger maximum subdural space in both the sagittal (3.7 vs. 4.1 mm) and coronal (2.5 vs. 2.8 mm) images; however, the differences were not significant (p = 0.18 and p = 0.53, respectively). Dural enhancement was observed only in one patient, who presented with CSF leaks on radionuclide cisternography.ConclusionsOur study, which included a relatively large population, did not find any association between the findings of radionuclide cisternography and MRI. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately.