Serum adiponectin and markers of endothelial dysfunction in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG)

PurposeIt has been established that endothelial dysfunction (ED) occurs after coronary artery bypass grafting (CABG). The aim of the study was to assess whether adiponectin may act as a novel marker of ED and its potential relations with new markers of ED: novel cell adhesion molecule CD146, a natural anti-thrombin glycoprotein – thrombomodulin (TM) and the well-established ED marker – Von Willebrand factor (VWF) in coronary artery disease (CAD) patients undergoing CABG.Material/methods45 CAD patients undergoing elective CABG were included in the study.ResultsIn the study group the concentration of adiponectin and CD146 before the surgery were significantly lower than in the control group – 6.06 μg/ml ± 3.06 vs. 19.0 μg/ml ± 6.4 and 303.2 ng/ml ± 28.7 vs. 328.1 ng/ml ± 22.6 (p < 0.05). Significant increase of adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. Adiponectin concentration 3 months after CABG correlated with VWF, TM, CD146, and a number of grafts. CD146 before and 3 months after CABG correlated significantly with adiponectin, VWF activity as well as the statins therapy after the surgery.ConclusionsIn CAD patients undergoing CABG new markers of endothelial cell dysfunction as adiponectin and CD146 are significantly lower compared to healthy volunteers. Significant increase in adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. However adiponectin concentrations 3 months after CABG were still significantly lower compared to healthy individuals, whereas CD146 concentration returned to the values comparable to the control.     

Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease

PurposeLeft main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3–5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD.Material/methodsWe enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups – with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes.ResultsWe observed more complications with wound healing (40.5% vs. 12.8%, p < 0.001) and sternal dehiscence (23.8% vs. 4.0%, p < 0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p = 0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p = 0.014).ConclusionsPatients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.     

Nonclassical human leukocyte antigen (HLA-G,HLA-E,and HLA-F) in coronary artery disease

AimsSeveral evidences suggest the association between the evolution of coronary artery disease (CAD) and the development of coronary syndrome that is often associated with disrupted plaque and partial or complete thrombosis of the related artery. Because of the inflammatory nature of CAD, we investigated the human leukocyte antigen (HLA)-G, HLA-E, and HLA-F genetic polymorphisms within CAD patients and evaluated their potential association with this disease in Tunisian population.MethodsDifferent polymorphisms in HLA-G (14-bp Insertion/Deletion, +3142C/G), HLA-E (HLA-E*01:01/01:03 A/G), HLA-F (HLA-F*01:02 T/C, 01:03 C/T, 01:04 A/C) genes were typed using different laboratory techniques in a cohort of 89 CAD patients and 84 controls.ResultsA significant association was reported between the HLA-G +3142 G allele (OR = 1.64, 95% CI = 1.05–2.56, p = 0.02) and increased risk of CAD. No association was found for the other studied polymorphisms. When we considered the haplotypes, we found TDELCA and TDELGG haplotypes associated to CAD with p = 0.008 and p = 0.030, respectively, suggesting the potential interaction between HLA-G and HLA-E genes.ConclusionsOur findings indicated that the HLA-G +3142C/G polymorphism and TDELCA and TDELGG haplotypes can harbour a reliable diagnosis value for the risk of CAD development suggesting that HLA-G, -E and -F molecules might be involved in the pathogenesis of the disease. However, further studies are necessary to confirm our results.     

Postprandial ghrelin responses are associated with the intermeal interval in time-blinded normal weight men,but not in obese men

ObjectiveTo investigate the relation between ghrelin responses and meal initiation and the effects of BMI and energy status on this.DesignThe experiment had a randomised, cross-over design.Setting and subjectsNine normal-weight (age: 33.2 ± 4.8 y, BMI: 23.2 ± 0.5 kg/m²) and eleven obese (age: 40.8 ±4.7 y, BMI: 33.2 ± 0.8 kg/m²) healthy men were recruited from a pool of volunteers and by advertisements.InterventionsSubjects followed a three-day energy restrictive and a three-day energy balanced diet separated by one month. Each diet was followed by a time-blinded (overnight) stay at the research facility. Subjects received a breakfast (preload) and were instructed to ask for lunch when they felt hungry. Ghrelin, insulin, glucose, free fatty acids, appetite, IMI and energy intake during lunch were assessed.ResultsPostprandial decreases in ghrelin (r = ? 0.54; p < 0.05) and the AUC of the ghrelin response (r = ? 0.57, p = 0.01) were associated with the intermeal interval, independent of diet, but in normal weight subjects only. Lunch request was preceded by an increase in ghrelin, reaching at least 93% of fasting values. These preprandial increases in ghrelin were correlated with IMI, after energy restriction only. Ghrelin concentrations but not changes in ghrelin were correlated with appetite.ConclusionMeal-related changes in ghrelin are correlated with the IMI in normal weight subjects only, independent of diet. Ghrelin concentrations may need to reach a certain threshold level before the next meal is initiated.SponsorshipSupported by Dutch Ministry of Education, Culture and Science, Dutch Ministry of Health, Welfare and Sport and Danone Research.     

A comparison of alignment using patient specific guides,computer navigation and conventional instrumentation in total knee arthroplasty

BackgroundPatient specific guides (PSG) have been introduced as a tool in total knee arthroplasty (TKA) in an attempt to improve limb alignment and reduce operative time compared to other established surgical techniques. The purpose of this study was to compare the post-operative radiographic alignment and operative time in patients who underwent TKA surgery with PSG, conventional instrumentation or computer-assisted navigation surgery using fully cemented components.MethodsA cohort of 260 patients who underwent TKA surgery using PSG (PSG group, n = 115) was compared to patients who underwent TKA using either conventional instrumentation (CON group, n = 92) or computer-assisted navigation (CAS group, n = 53). Post-operative CT imaging using the Perth CT protocol was used to compare alignment between the three groups.ResultsIn the PSG and CAS groups, the post-operative hip–knee angle (HKA) was within 3° of neutral alignment in 91.3% and 90.7% of patients, respectively. This compared to 80.4% of patients in the CON group (p = 0.02). There were no significant differences with respect to alignment when comparing individual component positioning between the PSG and CAS groups apart from tibial slope (Table 3). Total operative time was found to be significantly reduced in the PSG group (80.2 min) compared to both the CON group (86 min, p = 0.002) and the CAS group (110.2 min, p < 0.0001).ConclusionsThe use of PSG resulted in similar alignment accuracy to CAS and superior alignment to CON with significantly shorter operative times.     

Impact of telephone counseling on the quality of life of patients discharged after coronary artery bypass grafts

BackgroundThis study aimed to assess the impact of telephone counseling on quality of life in patients with coronary artery bypass graft.MethodsA quasi-experimental study was conducted with 71 discharged patients after coronary artery bypass graft surgery at Ekbatan Edcuational hospital in Hamadan, Iran, in 2014. The patients were randomly allocated into intervention (n = 36) and control group (n = 35). The intervention group received education and counseling about therapeutic plan via telephone after discharge. Patients in the control group received only routines. All patients completed the quality of life questionnaire before and after the intervention period of five weeks.ResultsThere was no significant difference between intervention and control group about quality of life before intervention (p = 0.696). However, there was significant and positive deference between the two groups in favor of the telephone counseling after the intervention (P = 0.01) and control group (P = 0.04). Quality of life in the intervention group was significantly better compared to control group (P = 0.01).ConclusionsTelephone counseling could be a cost-effective patient counseling plan for therapeutic adherence after coronary artery bypass surgery in order to improve the patients’ quality of life.Practice implicationsTelephone counseling is feasible to implement and well accepted for patient counseling for many diseases.     

Impact of Tele-nursing on adherence to treatment plan in discharged patients after coronary artery bypass graft surgery: A quasi-experimental study in Iran

Background and aimsCoronary artery bypass graft is a major surgery and has complications that require professional and long term follow-up and nursing care that if do not properly handled, could reduce the quality of life and increase post-operative complications. On the other hand Tele-nursing is a cost-effective way to educate and follow-up of patients. This study aimed to assess the impact of Tele-nursing on adherence to treatment plan in discharged patients after coronary artery bypass graft.Materials and methodsA quasi-experimental study was carried out at Ekbatan Therapeutic and Educational Center of Hamadan University of Medical Sciences at Hamadan, Iran, in 2013. In this study, 71 patients who had undergone coronary artery bypass graft surgery and had inclusion criteria were randomly divided into two experimental group (n = 36), and control group (n = 35). They completed questionnaire before discharging from Therapeutic and Educational Center. In the experimental group on days 2, 4, 7, second week (day 11), third week (day 18) and fourth week (day 25) after discharge, follow-up interventions and nursing education with Tele-nursing was done, but in the in the control groups, patients received only routine interventions. After completion of the intervention period, both groups completed the questionnaire and the results were compared.ResultsAdherence of treatment plan in both groups did not have significant difference before intervention (P = 0.696), but had a significant difference with regard to baseline after intervention in aromatherapy group (P <  0.01) and with control group after intervention (P < 0.01). Adherence to treatment plan in the aromatherapy group was better in compared to control group (P < 0.01).ConclusionTele-nursing is a convenient way, cost effective training and follow-up care for patients after coronary artery bypass surgery, which can improve patients’ adherence to treatment plan in developing countries such as Iran.     

TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients

BackgroundToll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response.ObjectivesTo analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients.Study designWe performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate^® assay with VeraCode^®. The outcome variables were early virologic response (EVR) and sustained virologic response (SVR).ResultsIn a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039).ConclusionsOur study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.     

Preliminary investigation of rate of torque development deficits following total knee arthroplasty

BackgroundTo assess changes in maximal strength and rate of torque development (RTD) following TKA, and examine the relationships between these measures and physical function.MethodsThirty-five TKA patients and 23 controls completed isometric knee extensor torque testing preoperatively, 1, and 6 months after surgery. Maximal strength was calculated as the peak torque during a maximal voluntary isometric contraction (MVIC) of the knee extensor muscles, peak RTD (RTD_peak) was calculated as the maximum value from the 1st derivative of the isometric knee extension torque data, RTD_25% and RTD _50% were calculated as the change in force over the change in time from force onset to 25% and 50% MVIC. Physical function was measured using a timed-up-and-go (TUG) and stair climbing test (SCT).ResultsRTD was significantly lower in the TKA group, at all-time points, compared to the Controls. MVIC and RTD significantly decreased 1-month following surgery (p = 0.000 for all measures). RTD_peak measures added to linear regressions with strength improved the prediction of TUG scores (p = 0.006) and the SCT scores (p = 0.015) 1-month post-surgery. Adding RTD_50% to the regression model, following MVIC, improved predicting both TUG (p = 0.033) and SCT (p = 0.024). At 6-months, the addition of RTD_25% to the regression model, following MVIC, improved the prediction of TUG (p = 0.037) and SCT (p = 0.036).ConclusionFollowing TKA, physical function is influenced by both the maximal strength and the rate of torque development of the knee extensors, and the prediction of function is improved with the addition of RTD compared to that of maximal strength alone.     

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.     

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.     

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.     

Support system for decision making in the identification of risk for body dysmorphic disorder: A fuzzy model

PurposeTo develop a fuzzy linguistic model to quantify the level of distress of patients seeking cosmetic surgery. Body dysmorphic disorder (BDD) is a mental condition related to body image relatively common among cosmetic surgery patients; it is difficult to diagnose and is a significant cause of morbidity and mortality. Fuzzy cognitive maps are an efficient tool based on human knowledge and experience that can handle uncertainty in identifying or grading BDD symptoms and the degree of body image dissatisfaction. Individuals who seek cosmetic procedures suffer from some degree of dissatisfaction with appearance.MethodsA fuzzy model was developed to measure distress levels in cosmetic surgery patients based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostic criterion B for BDD. We studied 288 patients of both sexes seeking abdominoplasty, rhinoplasty, or rhytidoplasty in a university hospital.ResultsPatient distress ranged from “none” to “severe” (range = 7.5–31.6; cutoff point = 18; area under the ROC curve = 0.923). There was a significant agreement between the fuzzy model and DSM-IV criterion B (kappa = 0.805; p < 0.001).ConclusionThe fuzzy model measured distress levels with good accuracy, indicating that it can be used as a screening tool in cosmetic surgery and psychiatric practice.     

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.     

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.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

BackgroundAlloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization.Study designTwo-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT–HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression.ResultsWhile only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status.ConclusionOur data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.     

Patient knowledge and information-seeking about personalized cancer therapy

BackgroundUnderstanding patients’ knowledge and prior information-seeking regarding personalized cancer therapy (PCT) may inform future patient information systems, consent for molecular testing and PCT protocols. We evaluated breast cancer patients’ knowledge and information-seeking behaviors regarding PCT.MethodsNewly registered female breast cancer patients (n = 100) at a comprehensive cancer center completed a self-administered questionnaire prior to their first clinic visit.ResultsKnowledge regarding cancer genetics and PCT was moderate (mean 8.7 ± 3.8 questions correct out of 16). A minority of patients (27%) indicated that they had sought information regarding PCT. Higher education (p = 0.009) and income levels (p = 0.04) were associated with higher knowledge scores and with seeking PCT information (p = 0.04). Knowledge was not associated with willingness to participate in PCT research.ConclusionEducational background and financial status impact patient knowledge as well as information-seeking behavior. For most patients, clinicians are likely to be patients’ initial source of information about PCT. Understanding patients’ knowledge deficits at presentation may help inform patient education efforts.     

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 prospective double blinded randomized study of anterior cruciate ligament reconstruction with hamstrings tendon and spinal anesthesia with or without femoral nerve block

BackgroundCurrent literature supports the thought that anesthesia and analgesia administered perioperatively for an anterior cruciate ligament (ACL) reconstruction have a great influence on time to effective rehabilitation during the first week after hospital discharge.PurposeThe aim of this study is to answer the research question is there a difference in clinical outcomes between the use of a femoral nerve block with spinal anesthesia versus spinal analgesia alone for people undergoing ACL reconstruction?MethodsACL reconstruction with spinal anesthesia and patient sedation (Group one); and spinal anesthesia with patient sedation and an additional femoral nerve block (Group two). Patients were re-evaluated for pain, range of motion (ROM), active contraction of the quadriceps, and a Functional Independence Measure (FIM) scoring scale.ResultsSpinal anesthesia with a femoral nerve block demonstrates pain relief 6 h after surgery (VAS 0.37; p = 0.007). From the third (VAS = 4.56; p = 0.028) to the seventh (VAS = 2.87; p = 0.05) days after surgery, this same nerve blockage delivered higher pain scores. Patients had a similar progressive improvement on knee joint range of motion with or without femoral nerve block (p < 0.002). Group one and two had 23.75 and 24.29° 6 h after surgery and 87.81 and 85.36° of knee flexion after 48 h post op.ConclusionSpinal anesthesia associated with a femoral nerve block had no additional benefits on pain control after the third postoperative day. There were no differences between groups concerning ability for knee flexion and to complete daily activities during postoperative period.Level of EvidenceRandomized Clinical Trial Level I.