Prognostic Performance of SOFA, qSOFA, and SIRS in Kidney Transplant Recipients Suffering from Infection: A Retrospective Observational Study.

INTRODUCTION: The prognostic performance of scoring systems for illness severity in infectious kidney transplant recipients (KTRs) is rarely reported. We investigated the ability of the scores for the quick Sequential Organ Failure Assessment (qSOFA), Sequential Organ Failure Assessment (SOFA) and Systemic Inflammatory Response Syndrome (SIRS) to predict in-hospital mortality, intensive care unit (ICU) admission and mechanical ventilation (MV) requirement. METHODS: This was a second analysis of a retrospective observational study. Scores for SIRS, SOFA and qSOFA were calculated upon hospitalization (infection onset was before hospitalization) or on the day of infection onset (infection episodes were during hospitalization). The primary outcome was in-hospital mortality. The secondary outcomes were ICU admission and MV requirement. Binary logistic regression and area under the receiver operating characteristic curve (AUC) were employed to assess prognostic performance. RESULTS: A total of 161 infectious episodes occurred in 97 KTRs. Forty patients (41%) experienced more than one episode. The SOFA score was available in 161 infections, and scores for qSOFA and SIRS were available in 160 infections. The SIRS score was not different between KTRs with opposite outcomes. The qSOFA score was higher in infections necessitating MV. The SOFA score was significantly higher in the deceased, those needing ICU admission, MV, and for those with positive etiology results. The SOFA score was the only independent predictor of in-hospital mortality, ICU admission, and MV requirement, and the AUCs were 0.879, 0.815, and 0.784, respectively. The optimum cutoff value of predicting the three outcomes was SOFA score ≥ 3. CONCLUSIONS: The SOFA score (but not those for SIRS and qSOFA) independently predicted in-hospital mortality, ICU admission, and MV requirement in infectious KTRs.

Risk factors and etiology of repeat infection in kidney transplant recipients.

Kidney transplantation (KT) is the best therapy available for patients with end-stage renal disease, but postoperative infections are a significant cause of mortality.In this retrospective study the frequency, risk factors, causative pathogens, and clinical manifestations of infection in KT recipients from Beijing Chao-Yang Hospital, Capital Medical University were investigated. Ninety-seven KT recipients who were hospitalized with infection between January 2010 and December 2016 were included. Clinical characteristics, surgery details, laboratory results, and etiology were compared in patients who developed single infection and patients who developed repeated infection (2 or more) after KT.A total of 161 infections were adequately documented in a total of 97 patients, of which 57 patients (58.8%) had 1 infection, 24 (24.7%) had 2, 11 (11.3%) had 3; 3 (3.1%) had 4, and 2 (2.1%) had 5 or more. The most common infection site was the urinary tract (90 infections; 56%), both overall and in the repeated infection group. The most frequently isolated pathogen was Pseudomonas aeruginosa. In the repeated infection patients, in most cases of P. aeruginosa infection (54%) it was cultured from urine. For first infections, a time between KT and infection of ≤ 21 days (area under receiver operating characteristic curve [AUC] 0.636) and a tacrolimus level ≥ 8 ng/mL (AUC 0.663) independently predicted repeat infection. The combination of these two predictive factors yielded an AUC of 0.716, which did not differ statistically significantly from either predictor alone.With regard to first infections after KT, a time between KT and infection of ≤ 21 days, and a tacrolimus level ≥ 8 ng/mL each independently predicted repeated infection in KT recipients.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting.

AIM: To assess the efficacy and safety of combined directly acting antivirals (DAAs) for the treatment of Chinese chronic hepatitis C (CHC) patients in a real-world setting. METHODS: Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS: Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3% (45/54) achieved rapid virological response at 2 wk after treatment initiation (RVR 2) and 94.4% (51/54) achieved sustained virological response at 24 wk after the end of treatment (SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels (83.6 ± 17.9 vs 88.8 ± 19.4, P01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P01 < 0.001), and no significant improvements were observed at 24w after the end of treatment (83.6 ± 17.9 vs 86.8 ± 19.1, P02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P02 = 0.001). The total frequency of adverse events (AEs) during treatment was 33.3% (18/54), with major AEs being fatigue (16.7%), headache (7.4%), anorexia (7.4%), and insomnia (5.6%). CONCLUSION: Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.

Dynamic mitral annular motion after posterior mitral annuloplasty: Use of a strip that is designed for placement in the posterior annulus.

BACKGROUND: Most annuloplasty rings and bands used for mitral valve repair restrict annular motion due to their fixation to the posterior annulus, the commissures, and the trigones. OBJECTIVE: Annular motion was evaluated after posterior mitral annuloplasty (PMA) for correction of mitral valve regurgitation (MR) using a strip that is designed for placement in the posterior annulus only, sparing the anterior annulus and both commissural angles. METHODS: Valve annular dynamics were analyzed in 51 patients who underwent PMA for MR. In 37 patients (72.5%), additional associated procedures were performed: new chord placement (n = 35), patch valvuloplasty (n = 4), and posterior leaflet augmentation (n = 12). Patients received serial echocardiographic follow-up. RESULTS: After PMA, the MR grade was nil or mild (0 and 1+) in 47 patients (92.1%), moderate (2+) in 3 patients (5.9%), and moderate to severe (3+) in 1 patient (2.0%). The maximum and minimum septo-lateral dimensions during the cardiac cycle were 21.7 ± 4.8 mm and 18.1 ± 4.1 mm (p < 0.0001), respectively, and the change ratios were 19.8 ± 9.3%. While the septo-lateral dimensions exhibited dynamic changes, the aorto-mitral dimensions remained constant throughout the cardiac cycle. CONCLUSIONS: PMA preserves dynamic septo-lateral motion of the mitral valve annulus during the cardiac cycle.

Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy.

BACKGROUND: The ultimate goal of hepatitis B treatment is hepatitis B surface antigen (HBsAg) seroclearance. Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts. However, there are few studies evaluating the factors during long-term entecavir (ETV) therapy. In the present study, we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years. METHODS: A total of 47 chronic hepatitis B (CHB) patients treated with ETV monotherapy were included in this study. Liver biochemistry, hepatitis B virus (HBV) serological markers, serum HBV DNA, and HBsAg titers were tested at baseline, 3 months, 6 months, and yearly from 1 to 7. The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance. RESULTS: At baseline, serum HBsAg levels showed a positive correlation with baseline HBV DNA levels (r = 0.625, P < 0.001). The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers (P ranges from 0.025 to 0.000,000,6). The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment (P < 0.05). Multivariate test showed that hepatitis B e antigen (HBeAg) seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value (96.77%) for HBsAg seroclearance (P = 0.002, P = 0.012, respectively). CONCLUSIONS: The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment. Further, HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.

Dynamics of Genotypic Mutations of the Hepatitis B Virus Associated With Long-Term Entecavir Treatment Determined With Ultradeep Pyrosequencing: A Retrospective Observational Study.

The aim of the study is to explore the evolution of genotypic mutations within the reverse transcriptase region in partial virological responders (PVRs) receiving long-term entecavir (ETV) treatment. A total of 32 patients were classified as completely virological responders (CVRs) (n = 12) or PVRs (n = 20). Five partial responders were hepatitis B virus (HBV)-DNA positive after long-term therapy, which lasted for >3 years. A total of 71 serum samples from these 32 patients were assayed by ultra-deep pyrosequencing (UDPS): 32 samples were from all patients at baseline, and 39 were from PVRs with sequential inter-treatment. Approximately 84,708 sequences were generated per sample. At baseline, the quasispecies heterogeneity did not significantly differ between the 2 groups. The frequencies of substitutions indicating pre-existence of nucleos(t)ide analog resistant (NAr) mutants ranged from 0.10% to 6.70%, which did not statistically differ between groups either. However, the substitutions associated with the NAr mutants were significantly different from those associated with the non-NAr mutants in 13 patients; 6 of these patients were PVRs and the others were CVRs. Five patients were HBV DNA positive after regular ETV monotherapy for >3 years, and 4 of these patients underwent mild NAr substitution fluctuations (<20%). One patient developed virological breakthrough while bearing single, double, and triple (rtL180 M, rtM204 V, rtS202G) substitutions. In addition to the common substitutions, unknown amino acid substitutions, such as rtL145 M/S, rtF151Y/L, rtR153Q, rtI224 V, rtN248H, rtS223A, rtS256C, need to be further verified. NAr substitutions are observed at frequencies of 0.10% to 6.7% before therapy. Long-term ETV therapy generally results in virological responses, as long as the proportion of resistance mutations remains at a relatively low level. Genotypic resistance to ETV is detected in all PVRs receiving long-term ETV therapy.

Dysregulation of non-coding RNAs in gastric cancer.

Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC.

Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10.

AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients. METHODS: One hundred and thirty-nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNα-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline. RESULTS: The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNα-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 ± 244.2 pg/mL vs 310.0 ± 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non-TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014). CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.

Role of C6ORF120, an N-glycosylated protein, is implicated in apoptosis of CD4⁺ T lymphocytes.

BACKGROUND: Although CD4(+) T cell apoptosis and CD8(+) T cell responses have been extensively studied during HIV infection, how apoptosis signals being initiated in CD4(+) T cells still need to be elucidated. The present study was designed to characterize the function-unknown gene, C6orf120, and elucidates its primary role in tunicamycin-induced CD4(+) T apoptosis. METHODS: The C6orf120 coding sequence was amplified from peripheral blood mononuclear cells (PBMCs) total RNA of AIDS patients. The DNA fragment was inserted into the pET-32a expression system, transformed into Escherichia coli, and preparation of C6ORF120 recombinant protein. The magnetic cell separation technology was used to prepare primary CD4(+) T cells and CD8(+) T cells. The primary T cells were cultured at 1 × 10(6) cells/ml, treated with 0, 0.1, 1, 10, 100, and 200 ng/ml of C6orf120 recombinant protein for 48 hours, then harvested for cell cycle and apoptosis analysis. Tunicamycin (0.5 µmol/L) was used to induce endoplasmic reticulum stress in Jurkat cells. The biomarker 78 KDa glucose-regulated protein (GRp78) and growth arrest and DNA damage (GADD) were used to evaluate endoplasmic reticulum stress of Jurkat cells. RESULTS: We prepared C6ORF120 recombinant protein and its polyclonal antibody. Immunohistochemical analysis showed that C6orf120 mainly expressed in hepatocytes and cells in germinal center of lymph node. At concentration of 0.1, 1, 10, 100, and 200 ng/ml, C6orf120 recombinant protein could induce apoptosis of Jurkat cells and primary CD4(+) T cells, and promoting G2 phase of its cell cycle. Western blotting analysis showed that C6ORF120 recombinant protein increased the expression of GRp78 and GADD in Jurkat cells in vitro. CONCLUSION: Our results suggested that C6ORF120 could induce apoptosis of CD4(+) T cells, at least in part, mediated with endoplasmic reticulum stress.