Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection

BackgroundHBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection.ObjectivesWe explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250 IU/ml (Abbott Diagnostics).Study designTwo hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution.Results and conclusionsHBsAg (log 10 IU/ml) was established for immune tolerance (4.50 ± 0.43), HBeAg-positive CHB (4.17 ± 0.66), inactive HBV carrier (3.32 ± 0.44), and HBeAg-negative CHB (3.23 ± 0.40); (p = 4.92 × 10⁻³⁵). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p = 0.247). The proportions of HBsAg <2000 IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p = 0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p = 1.23 × 10⁻⁴) and HBeAg-positive CHB (p = 0.003), but not for HBeAg-negative CHB (p = 0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p = 0.030), HBeAg-positive CHB (p = 0.016), and inactive HBV carrier (p = 0.001), but not in HBeAg-negative CHB (p = 0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p = 0.338) or HBeAg-negative CHB (p = 0.564) were observed. For patients with HBsAg quantitation >250 IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state.     

Effects of supervised whole body vibration exercise on fall risk factors,functional dependence and health-related quality of life in nursing home residents aged 80+

ObjectiveTo test the feasibility and effectiveness of whole-body vibration (WBV) therapy on fall risk, functional dependence and health-related quality of life in nursing home residents aged 80+ years.DesignTwenty-nine 80–95 years old volunteers, nursing home residents were randomized to an eight-week WBV intervention group) (n = 15) or control group (n = 14). Functional mobility was assessed using the timed up and go (TUG) test. Lower limb performance was evaluated using the 30-s Chair Sit to Stand (30-s CSTS) test. Postural stability was measured using a force platform. The Barthel Index was used to assess functional dependence and the EuroQol (EQ-5D) was used to evaluate Health-Related Quality of Life. All outcome measures were assessed at baseline and at a follow-up after 8 weeks.ResultsAt the 8-week follow up, TUG test (p < 0.001), 30-s CSTS number of times (p = 0.006), EQ-5Dmobility (p < 0.001), EQ-5DVAS (p < 0.014), EQ-5Dutility (p < 0.001) and Barthel index (p = 0.003) improved in the WBV intervention group when compared to the control group.ConclusionsAn 8-week WBV-based intervention in a nursing home setting is effective in reducing fall risk factors and quality of life in nursing home residents aged 80+.     

Telbivudine in the treatment of hepatitis B-associated cryoglobulinemia

BackgroundHepatitis C virus (HCV) infection is often associated to extrahepatic manifestations while these are less common in HBV infections. Reported cases of mixed cryoglobulinemia (MC) related to HBV infection are very rare: the exact prevalence of this extrahepatic manifestation has not yet been established and the optimal treatment is unclear (no guideline indications are available).ObjectivesWe propose an explorative evaluation of treatment of MC HBV-related with telbivudine (LdT) in a small group of patients affected by chronic hepatitis B (CHB).Study designWe included 7 patients affected by CHB naive for previous treatment. We administered a single dose of 600 mg/day of LdT. ALT levels, HBV-DNA, CD4+/CD8+ ratio and cryocrit were monthly measured. We evaluated the efficacy of 1 year-treatment with LdT on the cryocrit and MC-related symptoms.ResultsWe observed a significant decrease of cryocrit (p = 0.002) and HBV-DNA (p = 0.001) during the treatment; CD4+/CD8+ ratio increased (p = 0.002) after 1 year. Five patients did not show symptoms and two patients with necrotizing vasculitis have reported a significant clinical improvement with only residual paresthesias. No exacerbations were observed.ConclusionsWe consider LdT a suitable option for the treatment of MC HBV-related.     

Circulating osteoprotegerin and asymptomatic carotid atherosclerosis in postmenopausal non diabetic women

PurposeOsteoprotegerin (OPG) is a bone metabolism regulator but it is also involved in vascular calcification. Its role in the development of atherosclerosis is still a subject of debate. Postmenopausal women seem to have an increased risk for cardiovascular disease. The aim of the study is to evaluate the relationship between serum OPG and asymptomatic carotid atherosclerosis in postmenopausal non-diabetic women.Material/methodsCarotid artery examination was performed in 100 postmenopausal women without diabetes mellitus and overt cardiovascular disease, using B-mode ultrasonography to determine the carotid intima-media thickness (CIMT) and the presence of plaques. Serum OPG was measured in all study participants and its relationship with clinical, biochemical and vascular parameters was evaluated.ResultsCIMT correlated with age (r = 0.45, p < 0.001), years since menopause (r = 0.30, p = 0.003), abdominal circumference (r = 0.25, p = 0.01) and OPG (r = 0.23, p = 0.02). Carotid plaques correlated with age (p < 0.001), obesity (p = 0.03), abdominal circumference (p = 0.03) and CIMT (p < 0.001), but not with serum OPG (p = 0.86). In regression analyses the independent predictors for CIMT were age (β = 0.717, p < 0.001), OPG (β = 0.214, p = 0.02), and years since menopause (β = −0.334, p = 0.04) and for the presence of carotid plaques were obesity (p = 0.04, OR = 3.90), CIMT (p < 0.001, OR = 6408.86) and smoking (p = 0.02, OR = 687.93).ConclusionOPG is associated with cardiovascular risk factors, CIMT, but not with the presence of asymptomatic carotid plaques in non diabetic postmenopausal women. OPG may be a marker of cardiovascular risk.     

Serologic evidence for hepatitis E virus infection among patients with undifferentiated acute febrile illness in Kibera,Kenya

BackgroundHepatitis E (HEV) is an emerging cause of viral hepatitis mainly transmitted through the fecal-oral route. Residents of the Kibera slum of Nairobi, Kenya are at risk for fecal-orally transmitted infections.ObjectiveTo quantify the incidence and prevalence of HEV infection among acute febrile illness (AFI) cases using a population-based infectious disease surveillance network.Study designCross-sectional serum samples from AFI case-patients between 2009 and 2012 were matched to the age and gender distribution of the Kibera population and tested by IgM and IgG enzyme immunoassays (EIA) and nucleic acid testing (NAT). Serum from healthy residents was also tested by EIA.ResultsOf the 482 AFI serum samples tested, 124 (25.7%) and 182 (37.8%) were IgM and IgG reactive, respectively. On multivariate analysis, IgM reactivity was associated with HIV (RR 1.66, 95%CI 1.07, 2.60; p = 0.024) while IgG reactivity was associated with increasing age (p < 0.001) and HIV (RR 1.93, 95%CI 1.52, 2.46; p < 0.001). AFI case-patients were more likely to be IgM (p = 0.002) and IgG (p<0.001) reactive compared to healthy residents. The seroincidence by HEV-specific IgM was 84.0 per 1000 person years, however, all 482 samples were negative by NAT.ConclusionsSerologic evidence for HEV in Kibera suggests a high burden of infection, but NAT did not confirm HEV viremia. Additional testing is needed to determine whether EIAs are susceptible to false positivity in undifferentiated AFI populations before their widespread use.     

Specifying the effects of physician's communication on patients’ outcomes: A randomised controlled trial

ObjectiveTo experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain.MethodsUsing a 2 × 2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants’ outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed.ResultsPositive affect-oriented communication reduced anxiety (p < 0.001), negative mood (p = 0.001), and increased satisfaction (p < 0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p < 0.001) and outcome expectancies (p < 0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p = 0.02), increased outcome expectancies (p = 0.01) and satisfaction (p = 0.001).ConclusionBeing empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients’ outcomes for the best.Practice implicationsContinued medical training is needed to harness placebo-effects of medical communication into practice.     

Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians

BackgroundMolecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL).MethodsGenotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls.ResultsWe observed an increased incidence of activating KIRs namely; 2DS2 (OR = 2.23, p = <0.001), 2DS3 (OR = 1.74, p = 0.011), 3DS1 (OR = 2.22, p = <0.001), 2DS5 (OR = 2.10, p = 0.001), 2DS1 (OR = 4.42, p = <0.001) and 2DS4 (OR = 2.88, p = <0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2–6 activating KIR genes was predominant in cases compared to controls (OR = 2.55, p = <0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases.ConclusionOur data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.     

Hepatitis B virus infection among pregnant women in Haiti: A cross-sectional serosurvey

BackgroundHepatitis B vaccine administered shortly after birth is highly effective in preventing mother to child transmission (MTCT) of infection. While hepatitis B vaccine was introduced in Haiti as part of a combined pentavalent vaccine in 2012, a birth dose is not yet included in the immunization schedule.ObjectivesDetermine the seroprevalence of hepatitis B virus (HBV) infection among pregnant women to evaluate the risk of MTCT.Study designWe selected 1364 residual serum specimens collected during a 2012 human immunodeficiency virus (HIV) sentinel serosurvey among pregnant women attending antenatal care clinics. Haiti was stratified into two regions: West, which includes metropolitan Port-au-Prince, and non-West, which includes all other departments. We evaluated the association between demographic and socioeconomic characteristics and HIV infection with HBV infection.ResultsOf 1364 selected specimens, 1307 (96%) were available for testing. A total of 422 specimens (32.7%) tested positive for total anti-HBc (38.2% in West vs. 27% in non-West, p < 0.001), and 33 specimens (2.5%) were HBsAg positive (2.1% in West vs. 3% in non-West, p = 0.4). Of HBsAg positive specimens, 79% had detectable HBV DNA. Women aged 30 and older had more than double the odds of positive total anti-HBc than women aged 15–19 years (p < 0.001). Women with secondary (adjusted odds ratio (aOR) = 0.54; 95% CI: 0.36–0.81) and post-secondary education (aOR = 0.40, 95% CI: 0.19–0.79) had lower odds of total anti-HBc positivity compared with women with no education. HIV-status was not associated with HBV infection.ConclusionsHaiti has an intermediate endemicity of chronic HBV infection with high prevalence of positive HBV DNA among chronically infected women. Introduction of a universal birth dose of hepatitis B vaccine might help prevent perinatal HBV transmission.     

Rate and predictors of serum HCV-RNA >6 million IU/mL in patients with chronic hepatitis C

BackgroundBaseline serum HCV-RNA predicts sustained virological response in chronic hepatitis C patients treated with antiviral therapy. A threshold at 6 million IU/mL has been proposed to best discriminate treatment outcomes on sofosbuvir-based regimens. In comparison with the general population, immunosuppressed individuals exhibit greater viral load values.ObjectivesTo estimate the rate and predictors of serum HCV-RNA above 6 million IU/mL in chronic hepatitis C patients on care outside clinical trials.Study designSerum HCV-RNA values recorded from all chronic hepatitis C patients consecutively attended at our clinic during the last decade were analyzed. Testing had been performed using the COBAS TaqMan HCV test v2.0.ResultsA total of 816 individuals with detectable serum HCV-RNA were identified. The main characteristics of this population were as follows: mean age 48.6 years-old; 73.4% males; mean ALT 82.6 IU/L; mean HCV-RNA 6.02 log IU/mL; 80.6% HCV genotypes 1 or 4; 34.9% advanced liver fibrosis; 35.4% IL28B-CC alleles. HIV coinfection in 78.7%, of whom 91% were on antiretroviral therapy.Overall, 127 (15.6%) had serum HCV-RNA values >6 million IU/mL. This high viremia was found in 18.2% of HIV-positive versus 5.7% of HIV-negative subjects (p < 0.001). In multivariate analysis, serum HCV-RNA >6 million IU/mL was only significantly associated with HIV coinfection (OR: 4.03; 95% CI: 1.98–8.19, p < 0.01) and HCV genotypes 1 or 4 (OR: 1.88; 95% CI: 1.05–3.37, p = 0.03).ConclusionsSerum HCV-RNA >6 million IU/mL is roughly seen in 6% of chronic hepatitis C monoinfected patients, and increases up to 18% in HIV coinfection.     

An investigation on physicians’ acceptance of hospital information systems: A case study

PurposeInformation technology is used to support a wide range of highly specified healthcare tasks and services. There is, therefore, a need to understand the factors affecting the acceptance of this technology by healthcare professionals. Physicians are key providers of healthcare services and are among the principal users of hospital information systems. Their acceptance of hospital information systems is hence of great significance when evaluating the success of those systems.MethodThe survey methodology was employed to targeted physicians in the selected case hospital for investigating factors affecting physicians’ acceptance of hospital information systems. A total of 202 questionnaires were sent out, with 124 completed copies returned, indicating a valid response rate of 61.4%. We used structural equation modeling to analyze the data.ResultsThe results indicated that top management support (γ = 0.431, p < 0.001) had a significant impact on perceived usefulness. Project team competency (γ = 0.381, p < 0.001) and system quality (γ = 0.369, p < 0.001) had a significant impact on physicians’ perceived ease of use of hospital information systems. Physicians’ perceptions of the usefulness (β = 0.132, p < 0.05, R² = 0.296) and ease of use (β = 0.952, p < 0.001, R² = 0.784) of hospital information systems had a significant impact on the acceptance of the systems, accounting for 81.4% of total explained variance.ConclusionsThrough the understanding of the identified critical factors affecting physicians’ HIS acceptance, the planners and managers should ensure that hospital information systems to be introduced into a hospital are useful and ease to use. Effort should be focuses on providing sufficient top management support, selecting qualified project team members, and delivering higher system quality in addressing physicians’ clinical needs. Thus, our research results can help planners and managers understand key considerations affecting HIS development and use, and may be used as a reference for system design, development and implementation.     

Low-dose 17-β-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling

ObjectivesDescribe the effect of 50 mcg vaginal 17-β-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse.MethodsSeventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-β), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP).ResultsSerum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p = 0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p < 0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p = 0.03) and itching (p = 0.02) improved. Tissue biomarker levels did not change (TGF-β p = 0.35, NFKB p = 0.74, eNOS p = 0.80, iNOS p = 0.24, TSP p = 0.80).DiscussionVaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.     

Early postoperative predictors of satisfaction following total knee arthroplasty

BackgroundDespite the excellent total knee arthroplasty (TKA) results reported using traditional outcome measures, dissatisfaction rates of up to 30% are reported following surgery. Although several preoperative factors have been identified as possible predictors of satisfaction, there is conflicting evidence. Identification of dissatisfaction in the early postoperative assessment may therefore be an alternative consideration.MethodsWe examined the relationship between 12-month satisfaction, and early post-operative outcomes in a cohort of 486 TKA patients. Preoperative, and postoperative outcome measures at 3- and 12-months (Oxford knee score, pain score, SF12, and knee motion), were analysed and compared between patients who were satisfied and dissatisfied at 12-months following TKA. Mean scores, and postoperative change in scores were calculated. Postoperative outcomes were examined for correlation with satisfaction, and multivariate logistic regression models used to identify potential predictors of dissatisfaction.ResultsOverall satisfaction was 77.0%. No preoperative differences were observed between groups. Dissatisfaction was associated with worse postoperative status across all outcome measures (p < 0.001), except the 3-month SF12-physical component (p = 0.052). Dissatisfied patients demonstrated minimal further improvement or even worsening of outcome scores between 3- and 12-months postoperatively (p < 0.02). Both the 3-month OKS (OR = 1.15, p < 0.001), and knee flexion (OR = 1.03, p = 0.009) were significant predictors of subsequent 12-month satisfaction.ConclusionsDissatisfaction following TKA is associated with worse outcomes as early as 3 months following surgery, with minimal further improvement subsequently achieved at 12-months. Early postoperative assessment following TKA should therefore be considered, including clinical assessment, to identify those patients at risk of dissatisfaction.     

Inflammatory predictors of ongoing pain 2 years following knee replacement surgery

IntroductionThe prevalence of unrelieved pain following total knee arthroplasty (TKA) is substantial.ObjectiveWe asked if cytokine markers of inflammation in preoperative serum or knee synovial fluid (SF) would predict pain 2 years following TKA.MethodsDemographic data and functional outcomes were recorded at baseline and 2 years with the WOMAC index. Serum and SF tissue samples were collected at the time of surgery. Linear regression modeling was used to determine the relationship between SF/serum inflammatory markers and a lesser improvement in self reported pain at two years follow-up.ResultsOf our 28 patient cohort, significant correlations between serum and SF levels were found for IL-1β (p < 0.002), MIP-1β (p < 0.001), adiponectin (p < 0.001) and leptin (p < 0.001). Adjusted analysis showed that greater SF concentrations of TNF-α, MMP-13 and IL-6 were independent predictors of less pain improvement at two years follow-up (p < 0.05).ConclusionsThose patients, having ongoing pain despite no clinical or radiological cause, may have an inflammatory profile characterizing a predisposition to ongoing pain after TKA.Level of EvidencePrognosis study, Level 2.     

Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients

BackgroundEnterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization.ObjectivesTo assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM.Study designObservational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A = no PCR or negative PCR (n = 17), group B = positive real-time PCR (n = 20), and group C = positive GXEA (n = 22). Clinical, laboratory and health-care costs data were compared.ResultsClinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60 h (IQR (interquartile range) 44–87) in group B to 5 h (IQR 4–11) in group C (p < 0.0001). Median duration of antibiotics was 1 (IQR 0–6), 1 (0–1.9), and 0.5 days (single dose) in groups A, B, and C, respectively (p < 0.001). Median length of hospitalization was 4 days (2.5–7.5), 2 (1–3.7), and 0.5 (0.3–0.7), respectively (p < 0.001). Median hospitalization costs were $5458 (2676–6274) in group A, $2796 (2062–5726) in group B, and $921 (765–1230) in group C (p < 0.0001).ConclusionsRapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs.     

Effect of Foeniculum vulgare (fennel) vaginal cream on vaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled trial

ObjectiveVaginal atrophy is one of the main concerns of postmenopausal women. The aim of the present study was to investigate the effect of fennel vaginal cream on vaginal atrophy in postmenopausal women in Ahvaz, Iran.Materials and methodsThis double-blind randomized controlled trial was conducted on 60 postmenopausal women (45–65 years of age) in Ahvaz, Iran. The study participants were randomly divided into one of two groups, receiving either a placebo (n = 30) or fennel 5% vaginal cream (n = 30) administered as one application per day (5 g/day) for 8 weeks.Main outcomeThe vaginal pH and maturation vaginal index (MVI) were measured at baseline and 8 weeks after the intervention, while the vaginal atrophy symptoms was measured at baseline and at 2, 4, and 8 weeks after the intervention. The data were analyzed using the independent t-test, chi-square test, paired sample t-test, and the generalized estimating equation.ResultsThe number of superficial cells increased significantly in the fennel group after 8 weeks compared to the control group (76.1 ± 15.3 vs. 11.8 ± 8, p < 0.001). The number of intermediate and parabasal cells decreased significantly in the fennel group compared to the control group (p < 0.001). The vaginal pH decreased significantly at the 8-week follow-up in the fennel group compared to the control group (100% vs. 7.4%, p < 0.001). All women in the fennel group had an MVI of 65–100 at the 8-week follow-up, whereas almost half (40.7%) of the women in the control group had an MVI of 50–64 (p < 0.001).ConclusionAccording to results of this study, fennel is an effective means to manage the symptoms of vaginal atrophy in postmenopausal women and is devoid of side effects. Larger studies are necessary to confirm the positive impact of fennel for vaginal conditions occurring among postmenopausal women.     

L’âge des culots globulaires transfusés influence-t-il toujours le pronostic des patients en réanimation ?

ObjectiveFew studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients.DesignRetrospective, observational, cohort study in a Medical Intensive Care Unit.PatientsConsecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient's demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay.ResultsFive hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3–14) and SAPS II 48 (35–62). RBC equaling to 5.9 were transfused per patients (22.7% < 14 days and 57.3% < 21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p = 0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR = 1.02 per point, p < 0.001), number of RBC (OR = 1.08 per RBC, p < 0.001), length of stay in ICU (p < 0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox's model.ConclusionsRBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age.     

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.     

The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

Background and ObjectiveHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in patients with HAE-C1-INH.MethodsThe serum concentrations of ficolin-2, ficolin-3, MBL, MASP-2, MASP-3, and MAP-1 were measured during symptom-free periods in 91 patients with HAE-C1-INH, and in 100 healthy controls using sandwich ELISAs.ResultsCompared with controls, the levels of ficolin-2 (p < 0.0001) and MASP-2 (p = 0.0238) were reduced, while the levels of MBL and MASP-3 were elevated (p = 0.0028 and p < 0.0001, respectively) in HAE-C1-INH patients. Ficolin-3 and MAP-1 levels did not differ significantly between the two groups. Ficolin-2 correlated with MASP-3 in patients (r = 0.3443, p = 0.0008), while these parameters showed an opposite relationship in controls (r = −0.4625, p < 0.0001). In the patients, ficolin-3 correlated with MASP-2 (r = 0.3698, p = 0.001). Ficolin-2, -3, and MAP-1 correlated negatively with the annual requirement of plasma derived C1-INH concentrate (r = −0.2863, p = 0.0059; r = −0.2654, p = 0.0110 and r = −0.2501, p = 0.0168, respectively). Ficolin-3 showed a negative correlation with the annual number of attacks (r = −0.2478, p = 0.0179).ConclusionsWe found significant differences between patients and controls in the levels of some of the molecules belonging to the lectin complement pathway. Low concentrations of particularly ficolin-2 and -3 were inversely correlated with the severity of HAE-C1-INH, while this was not observed for MBL. This suggests a previously unrecognized involvement of the ficolin-dependent lectin complement pathway in the pathophysiology of HAE-C1-INH.     

Walking shoes and laterally wedged orthoses in the clinical management of medial tibiofemoral osteoarthritis: A one-year prospective controlled trial

The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospective, single-blind, block-randomized controlled design.Sixty-six subjects (29 males, 37 females, mean age 62.4 years, mean BMI 33.0 kg/m²) were block-randomized to a lateral wedge (treatment) or neutral (control) orthotic group. Both groups were issued a standardized walking shoe for use with the orthoses. Primary outcome measures included the pain, stiffness, and functional limitations subscales of the Western Ontario and McMaster Universities index. Secondary outcome measures included the 6-minute walk distance and pain change, and stair negotiation time and pain change.A significant interaction (p = 0.039) favoring the treatment group was observed for pain change during the 6-minute walk. The treatment group demonstrated significant improvements at both 1 month (p < 0.001) and 1 year (p < 0.001) compared to baseline. The control group only demonstrated significant improvements at 1 year (p = 0.017). No other interactions were observed. Both groups were improved at each follow-up in the WOMAC subscales for pain (p < 0.001), stiffness (p < 0.001), and physical function (p < 0.001). Both groups also improved in 6-minute walk test distance (p < 0.001), stair negotiation test time (p = 0.004), and stair negotiation test pain change (p < 0.001).The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes. However, the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group.     

Anti-Tax antibody levels in asymptomatic carriers,oligosymptomatic carriers,patients with rheumatologic disease or with HAM/TSP do not correlate with HTLV-1 proviral load

BackgroundHTLV-1 infects millions of people around the world and induces myelopathy (HAM/TSP), adult T-cell leukemia (ATL) or other inflammatory or rheumatologic diseases. The host–virus interaction causes asymptomatic carriers to develop HAM/TSP. Biomarkers are needed to predict patients who are at risk for HAM/TSP. Tax is highly immunogenic and is a major target protein recognized by cytotoxic T lymphocytes. Anti-Tax antibodies are involved in HAM/TSP pathogenesis.ObjectivesTo assess anti-Tax IgG reactivity with a flow cytometry assay (FCA) using an infection/transfection system with Vaccinia virus and pLW44/Tax-expressing Tax and to correlate the anti-Tax response and the HTLV-1 proviral load.Study design: We enrolled 81 individuals: 9 HTLV-1 seronegative (NP) and 72 HTLV-1 positive (23 HTLV-1 asymptomatic carriers (AC), 12 oligosymptomatic patients (OL), 7 with rheumatologic diseases (DR) and 30 with HAM/TSP (HT)). Anti-Tax reactivity was assessed by FCA, and HTLV-1 proviral load was measured with real time PCR.ResultsThe HT and DR groups showed greater anti-Tax IgG reactivity (p < 0.001 and p < 0.05 comparing HT to the OL and AC group, respectively; p < 0.05 comparing DR to the OL group), and the reactivity in the DR + HT group was significantly different when compared to the AC group (p < 0.05) and to the OL group (p < 0.001). The proviral load was higher in the HT group compared to the OL (p < 0.001) and in the HT + DR group compared to OL (p < 0.001). There was no correlation between anti-Tax IgG reactivity and proviral load in any of the HTLV-1-infected groups.ConclusionThese findings suggest that although anti-Tax IgG reactivity and the HTLV-1 proviral load are important markers of the development of HTLV-1-associated diseases, their levels are not correlated.