Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

A Retrospective Study on the Efficacy of Trastuzumab in HER2-Positive and Tamoxifen-Refractory Breast Cancer with Brain Metastasis

Background and Objective

The role of trastuzumab in breast cancer with brain metastasis is still in discussion. This study was conducted to investigate the efficacy of trastuzumab in the management of human epidermal growth factor receptor 2 (HER2)–positive, tamoxifen-refractory breast cancer with brain metastasis.

Methods

This retrospective study was conducted between January 2008 and December 2012. A total of 33 patients receiving trastuzumab treatment for HER2-positive, tamoxifen-refractory breast cancer with brain metastasis were assigned to the experimental group, while a matched group of 35 patients who received systemic therapy without trastuzumab were assigned to the control group. Data on the patient characteristics and clinical outcomes were collected and evaluated.

Results

Patients in the trastuzumab group showed a significantly better response to treatment than those in the control group (p = 0.025). Univariate and multivariate Cox proportional regression analyses indicated that progression-free survival was significantly longer in patients receiving trastuzumab therapy than in the control group (hazard ratio [HR] 2.213 [p = 0.003] and HR 3.056 [p < 0.001], respectively) and significantly shorter in patients with two or more extracranial metastases (HR 0.417 [p = 0.002] and HR 0.317 [p < 0.001], respectively). Furthermore, patients on trastuzumab treatment experienced longer overall survival than patients in the control group (HR 2.844 [p < 0.001] and HR 4.017 [p < 0.001], respectively), while shorter overall survival was seen in patients with two or more extracranial metastases (HR 0.524 [p = 0.021] and HR 0.430 [p = 0.005], respectively) and in those receiving capecitabine-based therapy as compared with anthracycline-based therapy (HR 0.558 [p = 0.030] and HR 0.449 [p = 0.011], respectively).

Conclusion

Trastuzumab was found to benefit patients with HER2-positive, tamoxifen-refractory breast cancer with brain metastasis by improving progression-free and overall survival.

     

Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus

Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.     

Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: a meta-analysis

Matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion and metastasis. However, the role of MMP-2 expression in ovarian cancer remains controversial. By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of MMP-2 in ovarian cancer. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Version 11.0 STATA software was used for statistical analysis. Twenty-seven relevant articles were included for this meta-analysis study. The expression of MMP-2 in cancer tissue was significantly higher than that in benign or normal ovarian tissue [cancer vs. benign, OR 10.09 (95 % CI 6.95–14.64); P < 0.001; cancer vs. normal, OR 30.48 (95 % CI 17.19–54.05); P < 0.001; benign vs. normal, OR 1.88 (95 % CI 1.08–3.29); P = 0.025]. The expression of MMP-2 in stage III–IV or lymph node metastasis was significantly higher than that in stage I–II or that without metastasis, respectively [OR 5.83 (95 % CI 4.32–7.85); P < 0.001; OR 7.20 (95 % CI 4.75–10.91); P < 0.001]. MMP-2 was associated with histological types and grade of ovarian cancer [serous vs. mucinous, OR 1.67 (95 % CI 1.17–2.39); P = 0.004; grade 3 vs. 1, 2, OR 3.23 (95 % CI 2.29–4.55); P < 0.001]. However, the age of patients was not associated with MMP-2 expression [OR 1.25 (95 % CI 0.61–2.58); P = 0.546]. In conclusion, MMP-2 is related to the malignant degree, FIGO stage, histological types and grade, and lymph node metastasis of ovarian cancer. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.     

Influence of gaze distance and downward gazing on postural sway in hemiplegic stroke patients

Gaze distance and head flexion suppress postural sway in healthy subjects. However, the effects of these factors on stroke patients have not been fully elucidated. In this study, we aimed to evaluate the effects of gaze distance and downward gazing on postural sway in stroke patients. We examined 15 stroke patients and 14 elderly controls. Postural sway was measured in the subjects under the following 5 conditions: eyes fixed forward on a marker located 600 cm ahead (600-cm condition); eyes fixed forward on a marker located 150 cm ahead (150-cm condition); eyes fixed downward (downward condition); the subject facing straight ahead but with eyes closed (closed-forward condition); and the subject facing downward but with eyes closed (closed-downward condition). The root mean squares of the anteroposterior (A-P RMS) and the mediolateral (M-L RMS) directions were determined. The results showed that the short gaze distance decreased the M-L RMS in both the stroke patients and controls (p < 0.001, r = 0.66; p = 0.024, r = 0.43, respectively). In the control group, the downward condition increased the M-L RMS when compared with the 600-cm condition (p = 0.011, r = 0.48). The downward condition decreased the A-P and M-L RMS in the stroke patients when compared with the 600-cm condition (A-P RMS: p < 0.001; r = 0.66, M-L RMS: p = 0.001; r = 0.59). Our results showed that the short gaze distance decreased postural sway in both groups, and downward gazing decreased it only in the stroke group.     

Secondary Prevention in Younger vs. Older Coronary Heart Disease Patients—Insights from the German Subset of the EUROASPIRE IV Survey

Purpose

Evidence is limited on implementation of secondary prevention guidelines for coronary heart disease (CHD) in clinical practice and variations between younger and elder patients. We investigated the control of cardiovascular risk factors in German patients with CHD enrolled in the European-wide EUROASPIRE IV survey, stratified by younger (18–69 years) and older (70–79 years) age groups.

Method

Eligible subjects were identified via the hospitals’ patient information system and invited to attend a study visit 6 months to 3 years after hospitalization for CHD (myocardial infarction, ischemia, angioplasty/stent, coronary bypass grafting). Information on lifestyle and medication was collected by interview.

Results

Five hundred thirty-six patients were recruited in 2012–2013 (median age 69 years [IQR 62–74 years], 18% female, 44% ≥ 70 years of age, median time between index hospitalization and study visit 1.8 [1.1–2.5] years). Proportion of CHD patients receiving recommended drug therapy was 89% for platelet inhibitors (younger vs. older patients 93 vs. 84%, p < 0.01), 83% for statins (83 vs. 85%, p = 0.9), and 83% for beta-blockers (87 vs. 79%, p = 0.02). Uncontrolled blood pressure was observed in 45% (40 vs. 50%, p = 0.02), LDL cholesterol levels > 2.5 mmol/l in 53% (56 vs. 49%, p = 0.1), and HbA1c levels > 7% in diabetic patients in 39% (45 vs. 32%, p = 0.1). Eighty-five percent were overweight (86 vs. 85%, p = 0.8), 37% were obese (41 vs. 31%, p = 0.01), and 10% reported currently smoking (17 vs. 3%, p < 0.01).

Conclusion

Although most CHD patients received the drug classes recommended by guidelines, treatment goals were frequently not achieved. Elderly subjects had a less favorable pattern, which may reflect multi-morbidity and weaker identification with treatment targets. National CHD prevention strategies should focus not only on enhancing lifestyle modifications and reaching treatment targets, but also on highlighting the different needs in older individuals.

     

Use of adenosine diphosphate receptor inhibitor prior to left ventricular assist device implantation is not associated with increased bleeding

Current guidelines recommend adenosine diphosphate receptor inhibitors (ADPRi) be discontinued 5–7 days prior to cardiac surgery due to increased bleeding events, rates of re-exploration, and transfusions. However, the risks of left ventricular assist device (LVAD) implantation in patients taking an ADPRi have not previously been studied. We retrospectively identified 134 eligible patients with ischemic cardiomyopathy that underwent LVAD implantation between July 2009 and August 2013. The cohorts received an ADPRi ≤5 days of surgery (n = 25) versus >5 days prior or not at all (n = 109). Subgroup analyses adjusted for differences in frequency of redo sternotomy between cohorts, excluded patients that received an ADPRi >1 year prior to surgery, and excluded patients with a redo sternotomy. The ADPRi and control groups did not have significant differences in the primary outcomes, intraoperative PRBC units transfused (3.0 vs. 4.0, p = 0.12) or chest tube output within 24 h of surgery (1.66 L vs. 1.80 L, p = 0.61). After adjusting for differences in frequency of redo sternotomy (ADPRi vs. control, 12 vs. 52%, p ≤ 0.001), no significant difference in PRBC units transfused (3.1 vs. 3.5, p = 0.59) or chest tube output (2.04 L vs. 2.04 L, p = 0.98) was seen. No significant difference in 30-day mortality (8.0 vs. 11.0%, p = 0.63), 90-day mortality (16.4 vs. 23.3%, p = 0.42), or length of stay (29.0 vs. 28.0, p = 0.61) was seen. In this single-center experience, use of an ADPRi ≤5 days prior to LVAD implantation was not associated with increased bleeding, length of stay, or mortality.     

Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early–early systemic sclerosis): a TDI study

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early–early SSc, is a condition characterized by Raynaud’s phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21–70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E _m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E _m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E _t 14 ± 3 vs. 16 ± 2, p = 0.02; E _t/A _t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E _t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S _m 13 ± 3 vs. 15 ± 2 cm/s, p < 0.0003; S _t 14 ± 2 vs. 16 ± 3 cm/s, p < 0.0001) and increased estimated pulmonary artery wedge pressure (9 ± 2 vs. 8 ± 1, p = 0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E′/A′_t, (71% of UCTD-risk-SSc patients vs. 19% of controls; p < 0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.     

Implementing a practice change: early initiation of continuous renal replacement therapy during neonatal extracorporeal life support standardizes care and improves short-term outcomes

Purpose

We hypothesized that a standardized approach to early continuous renal replacement therapy (CRRT) during neonatal extracorporeal life support (ECLS) results in greater homogeneity of CRRT initiation times with improvements in fluid balance and outcomes.

Methods

Retrospective analysis of data (2007–2015) obtained from neonates treated prior to (E1; n?=?32) and after (E2; n?=?31) a 2011 practice change: CRRT initiation within 48 h of ECLS.

Results

Birthweight, gestational age, ECLS mode, and age at ECLS initiation were similar to each epoch. Survival [E1: median 75%, E2: 71%] and length of ECLS [E1: median 221 h, E2: 180 h] were comparable. During E2, 100% of infants received CRRT (vs. E1: 37%; p?<?0.001) and 97% of infants initiated CRRT within 48 h of ECLS (vs. E1: 13%; p?<?0.001). Control charts demonstrate reduced practice variation. Elapsed time from ECLS to CRRT differed between Epochs [E1: median 105 h, E2: 9 h; p?<?0.001] as did weight at CRRT initiation [E1: 4.13 kg (29% above baseline), E2: 3.19 kg (0%); p?<?0.001]. Significant differences in weight change were noted on days 6 and 7 (E1: 14%, E2: 2%; raw data comparison yielded p?<?0.05) and curves were different (p?<?0.05).

Conclusions

We successfully implemented a practice change, initiating CRRT within 48 h of ECLS cannulation, leading to decreased practice variation and improved short-term outcomes including decreased weight gain at CRRT initiation and faster return to baseline weight during the first 7 days of ECLS. We did not demonstrate changes in duration of ECLS, invasive ventilation, or survival.

     

Real-world effectiveness of peginterferon α-2b plus ribavirin in a Canadian cohort of treatment-naïve chronic hepatitis C patients with genotypes 2 or 3: results of the PoWer and RediPEN studies

The purpose of this investigation was to assess the real-life effectiveness of pegylated interferon (peg-IFN) α-2b with ribavirin (RBV) in a cohort of treatment-naïve patients with chronic genotypes 2 (G2) or 3 (G3) hepatitis C virus (HCV) infection. A post-hoc pooled analysis of two Canadian multicenter, observational studies, RediPEN and PoWer, was carried out. A total of 1242 G2- or G3-infected patients were included. The primary outcome was sustained virologic response (SVR). Secondary endpoints included early virologic response (EVR), end-of-treatment (EOT) response, and relapse. Multivariate logistic regression was used to identify independent predictors of treatment response. SVR in G2 and G3 was 74.4 % and 63.6 %, respectively. Relapse occurred in 12.7 % and 19.1 % of G2- and G3-infected patients achieving EOT response, respectively. Overall, G3 was found to independently predict reduced SVR [odds ratio (OR)?=?0.20; p?=?0.007] and increased relapse (OR?=?6.84; p?=?0.022). Among G3-infected patients, increasing fibrosis score was the most important factor predicting reduced SVR [F2 vs. F0/F1 (OR?=?0.41; p?=?0.009); F3 vs. F0/F1 (OR?=?0.72; p?=?0.338); F4 vs. F0/F1 (OR?=?0.27; p?=?0.001)]. Male gender (OR?=?13.16; p?=?0.020) and higher fibrosis score [F2 vs. F0/F1 (OR?=?9.72; p?=?0.016); F3/F4 vs. F0/F1 (OR?=?4.23; p?=?0.113)] were associated with increased relapse in G3 patients. These results support the real-life effectiveness of peg-IFN α-2b plus ribavirin in HCV G2- and G3-infected patients. Overall, genotype was identified as the most significant predictor of treatment outcome. Fibrosis score and gender were key outcome predictors in the G3-infected population. In clinical settings, peg-INF/RBV offers an alternative for patients without access to all oral direct-acting antivirals.     

Oxidative stress levels are correlated with <Emphasis Type="Italic">P15</Emphasis> and <Emphasis Type="Italic">P16</Emphasis> gene promoter methylation in myelodysplastic syndrome patients

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.     

The role of MSCT angiography in early detection of lower limb arterial lesions in patients with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease which is characterized by arterial and venous thromboses, fetal loss, and the presence of antiphospholipid antibodies in the serum. It is characterized by accelerated atherosclerosis. Increased tendency towards thrombosis leads to the occurrence of various vascular events. The objective of our study was to determine if there are subclinical changes on lower limb arteries in APS patients and what the best diagnostic choice for their establishment is. In this study, we analyzed 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients, who have secondary antiphospholipid syndrome (SAPS). The results were compared to 50 controls. The groups were comparable with respect to age, gender, and traditional risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. Study was conducted on 64-multi-slice computed tomography (64-MSCT), where we analyzed quantitative and morphological characteristics of blood vessel-detected lesions. Patients from the control group had statistically very significant elevated cholesterol and triglyceride levels in regard to the patients with SAPS and PAPS (p < 0.001 and p < 0.05). Analyzing percentage of diameter stenosis, we have established that lesions from group with 0–30% diameter stenosis (DS) in patients with PAPS (n = 47) and SAPS (n = 39) are more common than that in control group (n = 3, p < 0.001). The incidence of lesions higher than 70% DS in control group (n = 74) was statistically significant than that in patients with SAPS (n = 74, p < 0.05), while very statistically significant than that in patients with PAPS (n = 48, p < 0.001). Analyzing the qualitative characteristics of plaques, we have established significant higher frequency of soft tissue (n = 32) and mixed lesions (n = 36) in patients with PAPS than the calcified one (n = 7, p < 0.001). Our study showed that the subclinical manifestation of changes on lower extremity arteries is more common in patients with APS. Because of its safety and accuracy, the method of choice is 64-MSCT angiography in monitoring disease progression.     

Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22–57] to 22 % [19–31], p?=?0.05) and NPA (19 % [16–59] to 15 % [11–30], p?=?0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p?=?0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p?=?0.03), and platelet adhesion to collagen (10.2 % [2.5–32.6] to 2.0 % [0.2–9.5], p?=?0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.     

Prognostic accuracy of SIRS criteria,qSOFA score and GYM score for 30-day-mortality in older non-severely dependent infected patients attended in the emergency department

The aim of this study was to determine the accuracy of systemic inflammatory response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA) score and GYM score to predict 30-day mortality in older non-severely dependent patients attended for an episode of infection in the emergency department (ED). We performed an analytical, observational, prospective cohort study including patients 75 years of age or older, without severe functional dependence, attended for an infectious process in 69 Spanish EDs for 2-day three-seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event. We included 1071 patients, with a mean age of 83.6 [standard deviation (SD) 5.6] years; 544 (50.8%) were men. Seventy-two patients (6.5%) died within 30 days. SIRS criteria ≥ 2 had a sensitivity of 65% [95% confidence interval (CI) 53.1–75.9] and a specificity of 49% (95% CI 46.0–52.3), a qSOFA score ≥ 2 had a sensitivity of 28% (95% CI 18.2–39.8) and a specificity of 94% (95% CI 91.9–95.1), and a GYM score ≥ 1 had a sensitivity of 81% (95% CI 69.2–88.6) and a specificity of 45% (95% CI 41.6–47.9). A GYM score ≥ 1 and a qSOFA score ≥ 2 were the cut-offs with the highest sensitivity (p < 0.001) and specificity (p < 0.001), respectively. The area under the curve (AUC) was 0.73 (95% CI 0.66–0.79; p < 0.001) for the GYM score, 0.69 (95% CI 0.61–0.76; p < 0.001) for the qSOFA score and 0.65 (95% CI 0.59–0.72; p < 0.001) for SIRS. A GYM score ≥ 1 may be the most sensitive score and a qSOFA score ≥ 2 the most specific score to predict 30-day mortality in non-severely dependent older patients attended for acute infection in EDs.     

Expression of <Emphasis Type="Italic">MIF</Emphasis> and <Emphasis Type="Italic">TNFA</Emphasis> in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables

Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = ? 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.     

Adverse effects of isolation: a prospective matched cohort study including 90 direct interviews of hospitalized patients in a French University Hospital

Isolation precautions in patients with multi-drug resistant bacteria or other communicable infectious agents can be associated with adverse effects. The aim of this study was to assess satisfaction and psychological impact of patients hospitalized with isolation precautions in comparison with controls. An observational prospective cohort study was performed in five different medical and surgical departments in a 3,000-bed university hospital in Western France between March and July 2012. Different scales were used to assess patient satisfaction (qualitative scale) and anxiety (Spielberger scale), including 30 patients with isolation precautions and 60 matched patients without isolation precautions over 45-hour interviews. Cases were significantly less satisfied than controls for healthcare workers (HCW) assistance in activities of daily life (p?<?0.001), availability and relationships (17 % vs 5 %, p?=?0.05 and 10 % vs 0%, p?=?0.02, respectively). Sixty-seven percent of patients with isolation precautions were not satisfied about the quality of the information related to their infectious status control measures. The median score [range] of anxiety significantly was higher in patients with isolation precautions (52 [20–56] vs 31 [23–73], p <0.001). Isolation precautions may have negative psychological effects, leading to anxiety, and may compromise patient satisfaction according to the availability and relationship with HCW. Professionals should be aware of adverse effects of isolation and inform patients more actively with regard to their infectious status and precautions.     

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis> bacteremia

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.     

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling (“hot spots”), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30–80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a significantly longer disease-free survival (DFS) time compared to type II (p = 0.018) or III (0.010). Also, the WHO G3 group had a significantly shorter DFS time than the WHO G1 (p = 0.020) or G2 (p = 0.007) group. Gastric WDNET is a heterogeneous disease entity encompassing three clinical subtypes—type I, type II, and type III—having their own distinct clinicopathologic characteristics and prognosis. Our results showed that sporadic (type III) WDNET had a significantly higher Ki-67 PI than non-sporadic cases (type I or II); increased PI was associated with higher tumor stage. We also described four type III cases of morphologically WD gastric NET with WHO grade 3 on the basis of Ki-67 PI.     

Changes of FibroScan,APRI, and FIB-4 in chronic hepatitis B patients with significant liver histological changes receiving 3-year entecavir therapy

Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis in patients with chronic hepatitis B (CHB). We aimed to investigate the influence of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with significant liver histological changes (SLHC) defined as inflammatory grade ≥ A2 and/or fibrosis stage ≥ F2. A total of 104 CHB patients with SLHC at the baseline were included. FibroScan, APRI, and FIB-4 values were compared before and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6 to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p = 0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to 0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p < 0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4 decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p < 0.001), while did not decrease significantly in patients with mild fibrosis (from 0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased significantly after 3-year ETV treatment in CHB patients, which indicates that these noninvasive fibrosis tests might be useful for monitoring regression of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.