Umeclidinium plus vilanterol versus fluticasone propionate plus salmeterol for chronic obstructive pulmonary disease: a meta-analysis of randomized, controlled trials.

PURPOSE: Umeclidinium plus vilanterol (UMEC/VI) is an inhaled long-acting muscarinic antagonist/long-acting beta2-agonist (LAMA/LABA), recently approved as once-daily maintenance therapy for chronic obstructive pulmonary disease (COPD). This meta-analysis aims to assess the efficacy and safety of UMEC/VI compared with fluticasone propionate plus salmeterol (FP/SAL). METHODS: A systematic search was conducted by a trained medical research librarian across MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese Biomedical Literature Database (CBM) for randomized controlled trials comparing UMEC/VI with FP/SAL in COPD patients. Two reviewers independently assessed the risk of bias and extracted data. The primary outcome was 0-24 h weighted mean (wm) forced expiratory volume in the first second (FEV1), trough FEV1. The secondary outcomes were other lung functions, symptoms, quality of life, and safety. RESULTS: Three studies with 2119 patients were included in the meta-analysis. UMEC/VI showed improvement in 0-24 h wm FEV1 (mean difference (MD) 0.08 L, 95% confidence interval (CI) 0.06 to 0.10, P < 0.01, moderate quality) and trough FEV1 (MD 0.09 L, 95% CI 0.07 to 0.11, P < 0.01, moderate quality) in comparison with FP/SAL. UMEC/VI statistically significantly improved all other lung functions compared with FP/SAL. However, there were no significant differences between UMEC/VI and FP/SAL in rescue-medication use, symptomatic endpoints, and health outcomes. UMEC/VI also demonstrated fewer drug-related adverse effects (risk ratio 0.47, 95% CI 0.27 to 0.82, P = 0.01, low quality). CONCLUSIONS: UMEC/VI, when compared with FP/SAL, demonstrated significant improvements in lung functions with fewer drug-related adverse effects. However, the conclusion was limited by the scarcity of studies and long-term trials.

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia.

Rituximab (RTX) is a monoclonal antibody commonly used to treat PLA2R-associated membranous nephropathy (MN). This report presents a case of refractory MN in a patient who experienced severe hypokalemia, a rare but clinically significant condition, after the 5th RTX infusion. Clinicians should be aware of the potential for hypokalemia and its management during or after RTX infusion. After the onset of hypokalemia, the patient received treatment with obinutuzumab and achieved partial remission of renal disease without experiencing further hypokalemia. Obinutuzumab may be a viable alternative therapy for refractory membranous nephropathy that develops side effects after rituximab therapy or is refractory to it, but further studies are necessary to determine its efficacy and safety.

Systemic corticosteroids in fibrotic lung disease: a systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched Embase, Medline, Cochrane CENTRAL and Web of Science databases from inception to April 17 2023. ELIGIBILITY CRITERIA: We included studies that compared corticosteroids with standard care, placebo or no treatment in adult patients with fILD. DATA EXTRACTION AND SYNTHESIS: We report on the change in forced vital capacity (FVC) and mortality. We used random-effects meta-analysis to estimate relative risk (RR) for dichotomous outcomes, and mean difference (MD) and standardised MDs for continuous outcomes, with 95% CIs. RESULTS: Of the 13 229 unique citations identified, we included 10 observational studies comprising 1639 patients. Corticosteroids had an uncertain effect on mortality compared with no treatment (RR 1.03 (95% CI 0.85 to 1.25); very low certainty evidence). The effect of corticosteroids on the rate of decline in FVC (% predicted) was uncertain when compared with no treatment (MD 4.29% (95% CI -8.26% to 16.83%); very low certainty evidence). However, corticosteroids might reduce the rate of decline in FVC in patients with non-idiopathic pulmonary fibrosis (IPF) fILD (MD 10.89% (95% CI 5.25% to 16.53%); low certainty evidence), while an uncertain effect was observed in patients with IPF (MD -3.80% (95% CI -8.94% to 1.34%); very low certainty evidence). CONCLUSIONS: The current evidence on the efficacy and safety of corticosteroids in fILD is limited and of low certainty. Randomised trials are needed to address this significant research gap.

Effect of roxadustat on red blood cell lifespan in patients with long-term haemodialysis: a single-centre, prospective, single-arm study.

Background: Reduced survival of red blood cells (RBCs) in patients with chronic kidney disease (CKD) is thought to contribute to renal anaemia. Although renal anaemia improved greatly because of the wide use of erythropoiesis-stimulating agents (ESAs) and the advancement of dialysis techniques, RBC longevity seems not to be obviously ameliorated. Methods: In this single-centre, single-arm trial, patients who had been undergoing haemodialysis and ESA therapy with epoetin alfa for at least 12 weeks changed their anti-anaemia drugs from epoetin alfa to oral roxadustat three times per week for 24 weeks. The primary endpoint was the change in RBC lifespan from baseline at week 24. The change in the circulating percentage of eryptotic RBCs, RBC deformability and RBC oxygen transport ability were also assessed. Results: A total of 27 patients were enrolled, with 26 completing the full course of intervention. At baseline, the average RBC lifespan was 60.1 days [standard deviation (SD) 14.4; n = 27]. At the end of the study period, 26 patients had an RBC lifespan measurement (83.9 days on average; SD 21.9). The RBC lifespan increased by 22.8 days on average [95% confidence interval (CI) 15.5-30.0, P < .001]. This equated to an average RBC lifespan increase of 39.2% (95% CI 27.8-50.6). The percentage of circulating eryptotic RBCs, erythrocyte filtration index and the pressure at which haemoglobin is 50% saturated decreased significantly from baseline to week 24 (1.39 ± 0.44% versus 0.89 ± 0.25%, P < .0001; 0.29 ± 0.12 versus 0.16 ± 0.08, P < .0001 and 32.54 ± 4.83 versus 28.40 ± 2.29, P < .001, respectively). Conclusion: Roxadustat prolonged RBC lifespan in patients with long-term haemodialysis.

Association of circulating proprotein convertase subtilisin/kexin type 9 concentration with coagulation abnormalities in patients with primary membranous nephropathy.

OBJECTIVES: The aims of the study were to explore the potential associations between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and coagulation indexes in patients with primary membranous nephropathy (PMN). METHODS: A total of 87 patients diagnosed with PMN were enrolled in our study. 30 healthy participants were recruited to match PMN participants. Plasma PCSK9 concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Correlations between PCSK9 and coagulation abnormalities in patients with PMN were analyzed using univariate and multiple linear regression analysis. RESULTS: Plasma PCSK9 levels in patients with PMN were significantly higher than that in healthy controls [232.0 (143.5, 359.5) ng/mL vs. 166.8 (129.7, 199.7) ng/mL; p = 0.001]. Plasma levels of PCSK9 were positively correlated with factor VIII, factor IX, factor XI, log-transformed tissue factor, protein C and protein S (r = 0.267, p = 0.013; r = 0.496, p < 0.001; r = 0.217, p = 0.045; r = 0.584, p < 0.001; r = 0.372, p = 0.001; r = 0.282, p = 0.011). In multiple linear regression analysis, PCSK9 concentration was independently and positively correlated with factor VIII, factor IX, and tissue factor (ß = 0.186, p = 0.047; ß = 0.325, p = 0.001; ß = 0.531, p < 0.001; respectively). PCSK9 concentration was independently and negatively correlated with PT (ß= -0.343, p = 0.011). CONCLUSION: Plasma PCSK9 levels had good positive correlations with procoagulant clotting factors and negative correlations with PT in PMN, which might provide novel information with regard to PCSK9 and hypercoagulability in PMN.

Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.

Association between adverse oral conditions and cognitive impairment: A literature review.

Oral environment deterioration results from a lack of self-cleaning ability in patients with cognitive dysfunction but is also a risk factor for cognitive dysfunction. Adverse oral conditions can be alleviated and improved through a self-management and medical examination. In this review, the epidemiological evidence of previous studies is integrated to highlight the relationship between periodontitis, tooth loss, oral flora, oral dysfunction and cognitive dysfunction, emphasizing the importance of oral health for cognition. The results show that poor oral condition is associated with cognitive impairment. Although many previous studies have been conducted, there is a lack of higher-level research evidence, different judgment criteria, and conflicting research results. There is a bidirectional relationship between oral health and cognitive dysfunction. A comprehensive analysis of the relationship between oral health and cognitive dysfunction that explores the relationship and takes measures to prevent cognitive dysfunction and control the progression of such diseases is warranted in the future.

Associations of left renal vein entrapment with IgA nephropathy and Henoch-Schönlein purpura nephritis.

OBJECTIVES: The aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition. METHODS: A total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens. RESULTS: LRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01). CONCLUSIONS: LRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

Anti-PLA2R antibody measured by ELISA predicts the risk of vein thrombosis in patients with primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) is associated with the highest risk for developing venous thrombosis compared with other nephrotic diseases. The aim of the study was to assess the predictive value of the pathognomonic anti-phospholipase A2 receptor (PLA2R) antibody with regard to incidence of venous thrombosis in PMN. METHODS: A total of 365 in-hospital patients diagnosed with PMN were enrolled in the study. Anti-PLA2R antibody was detected by commercial enzyme-linked immunosorbent assay. Multivariate logistic regression was used to detect the independent risk factors for venous thrombosis. RESULTS: Thirty-seven patients (10.14%) had venous thrombosis. Patients with venous thrombosis had higher levels of cholesterol (CHOL), low-density lipoprotein (LDL), and D-dimer than those without venous thrombosis (p < .05). Patients with venous thrombosis had significantly lower levels of albumin (23.95 ± 5.53 vs. 26.18 ± 6.59 g/L, p = .049). No significant differences were found in proteinuria, serum creatinine, estimated glomerular filtration rate, platelets, and fibrinogen between patients with and without thrombosis. Anti-PLA2R antibody levels in patients with venous thrombosis were significantly higher than in patients without it (p = .002). In the univariate logistic regression, Ln anti-PLA2R antibody (OR: 1.340; p = .004), albumin (OR: 0.945; p = .050), CHOL (OR: 1.191; p = .006), and LDL (OR: 1.271, p = .006) were associated with venous thrombosis. Ln anti-PLA2R antibody (OR = 1.269; 95%CI: 1.032-1.561), and LDL (OR = 1.213; 95%CI: 1.017-1.448) were the independent risk factors for venous thrombosis (p < .05) in multivariate analysis. CONCLUSIONS: Anti-PLA2R antibody was the independent risk factor for venous thrombosis in PMN. Larger prospective studies were warranted to verify the results in future.

Clinical utility of intravascular ultrasonography-guided therapy in a small-vessel coronary lesion associated with Type 2 diabetes mellitus.

OBJECTIVE: It is unknown whether the intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI) should be routinely used in small-vessel coronary lesions in patients affected by Type 2 diabetes mellitus (T2DM). This study aimed to assess the clinical significance of the IVUS-guided PCI treatment for small-vessel coronary lesions in T2DM. METHODS: This was a prospective interventional trial. A total of 228 patients affected by T2DM with stable angina and a positive stress test in the presence of coronary arteriography (CAG) involving small vessels [online measurement reference vessel diameter ≤3.0 mm by means of quantitative coronary angiography (QCA)] were recruited and divided into two groups: an IVUS-guided group (n=120) and a CAG-guided group (n=108). Follow-up PCIs were performed via CAG or IVUS criteria, respectively. Between-group comparisons were made for the number of stents implanted, length, diameter, and high-pressure balloons used post-dilatation. Major adverse cardiac events (MACEs) defined as cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR) were the primary endpoint. The value of late lumen loss and proportion of in-stent restenosis (ISR) were the secondary endpoint, all of which were also evaluated during the follow-up period. RESULTS: There was an increased lesion length observed using the IVUS measurement when compared with QCA measurements in the IVUS-guided group (p≤0.001). The number of implanted stents, diameter, length, percentage of high-pressure balloons used during post-dilatation, value of late lumen loss, and proportion of ISR decreased in the IVUS-guided group when compared with the CAG-guided group (p=0.002, p=0.001, p=0.003, p=0.004, p=0.007, p=0.001, respectively). After a 2-year follow-up, the Kaplan-Meier curves indicated that the incidence of MACEs was significantly lower in the IVUS-guided group (log-rank p=0.029), mainly because of the TLR reduction (log-rank p=0.037). CONCLUSION: The IVUS-guided PCI treatment improved the event-free survival in small-vessel coronary lesions in patients affected by T2DM.

TUSC3: a novel tumour suppressor gene and its functional implications.

The tumour suppressor candidate 3 (TUSC3) gene is located on chromosome region 8p22 and encodes the 34 kD TUSC3 protein, which is a subunit of the oligosaccharyl transferase responsible for the N-glycosylation of nascent proteins. Known to be related to autosomal recessive mental retardation for several years, TUSC3 has only recently been identified as a potential tumour suppressor gene. Based on the structure and function of TUSC3, specific mechanisms in various diseases have been investigated. Several studies have demonstrated that TUSC3 is an Mg2+ -transporter involved in magnesium transport and homeostasis, which is important for learning and memory, embryonic development and testis maturation. Moreover, dysfunction or deletion of TUSC3 exerts its oncological effects as a modulator by inhibiting glycosylation efficiency and consequently inducing endoplasmic reticulum stress and malignant cell transformation. In this study, we summarize the advances in the studies of TUSC3 and comment on the potential roles of TUSC3 in diagnosis and treatment of TUSC3-related diseases, especially cancer.

Umeclidinium Plus Vilanterol Versus Placebo, Umeclidinium, or Vilanterol Monotherapies for Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of umeclidinium plus vilanterol as a combination therapy for chronic obstructive pulmonary disease (COPD) has not yet been clearly defined. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of umeclidinium plus vilanterol, in contrast to either monotherapy or placebo. METHODS: Systematic searches were conducted in Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Chinese Biomedical Literature Database (CBM). Randomized clinical trials pertaining to the treatment of COPD with the combination of umeclidinium and vilanterol, versus umeclidinium, vilanterol or placebo, were reviewed. Studies were pooled to mean differences (MDs), with 95 % confidence intervals (CIs). RESULTS: Six studies were included in our meta-analysis. The application of umeclidinium plus vilanterol compared with umeclidinium alone showed increases in trough forced expiratory volume in 1 s [FEV1] (MD 0.05 L, 95 % CI 0.04-0.07; p < 0.00001) and forced vital capacity [FVC] (MD 0.07 L, 95 % CI 0.04-0.10; p < 0.00001). Similarly, versus vilanterol alone, the application of umeclidinium plus vilanterol showed increases in trough FEV1 (MD 0.10, 95 % CI 0.08-0.12; p < 0.00001) and FVC (MD 0.16 L, 95 % CI 0.13-0.20; p < 0.00001). Compared with placebo, umeclidinium plus vilanterol also showed increases in trough FEV1 (MD 0.21 L, 95 % CI 0.19-0.22; p < 0.00001) and FVC (MD 0.31 L, 95 % CI 0.26-0.35; p < 0.00001). In addition, umeclidinium plus vilanterol has beneficial effects on dyspnea, albuterol use, and health-related quality of life compared with the other three groups. CONCLUSIONS: Compared with the other three groups, i.e. placebo, umeclidinium and vilanterol, umeclidinium plus vilanterol improves lung function and quality of life in patients with COPD, reduces the use of albuterol, and does not increase the incidence of adverse events and serious adverse events.

Long-term outcome of intravascular ultrasound application in patients with moderate coronary lesions and grey-zone fractional flow reserve.

OBJECTIVE: This study aimed to assess the long-term outcome of intravascular ultrasound (IVUS) application in patients with a fractional flow reserve (FFR) of 0.75-0.80. BACKGROUND: Scientifically evaluating anatomical structures is vital because structure influences both physiological function and decision-making in moderate coronary lesions, especially for those with an FFR of 0.75-0.80. MATERIALS AND METHODS: Patients (n=128) were divided into three groups based on treatment: the drug control group (n=40), the IVUS-percutaneous coronary intervention (PCI) group (n=40) and the IVUS-drug group (n=48). A PCI was performed when a patient had a minimum lumen area less than 4 mm(2) and a plaque burden of 70% or greater. Major adverse clinical events were defined as cardiac death, nonfatal myocardial infarction, target vessel revascularization, including PCI or coronary artery bypass grafting, and unstable angina, all of which were also evaluated during follow-up. RESULTS: Kaplan-Meier curves indicated that the incidence of major adverse clinical events did not differ between the IVUS-PCI and IVUS-drug groups (5 vs. 6.3%, P=0.810), but the levels in both of these groups significantly decreased compared with the drug control group (5 vs. 22.5%, P=0.024, and 6.5 vs. 22.5%, P=0.026, respectively). CONCLUSION: The long-term outcome of the application of IVUS in patients with a grey-zone FFR of 0.75-0.80 was superior to that of patients who were treated only with drugs without IVUS measurement. Patients with a grey-zone FFR should receive an individualized treatment strategy according to their IVUS parameters. Patients with the same FFR values may require different treatment strategies.

Tumor suppressor candidate 3 as a novel predictor for lymph node metastasis in lung cancer patients.

Tumor suppressor candidate 3 (TUSC3) was recently identified as a potential tumor suppressor gene in several cancer types. However, no data are currently available regarding the expression of TUSC3 in lung cancer. The present study investigated the expression of TUSC3 in patients with lung cancer and determined its association with the clinicopathological parameters of the disease. Cytoplasmic TUSC3 expression was evaluated by immunohistochemistry on tissue microarray slides, which included 35 small cell lung cancer (SCLC) specimens, 80 squamous cell lung cancer specimens (SCC), 80 adenocarcinoma lung cancer (ADC) specimens and 37 normal lung tissue specimens. Analysis showed significantly reduced TUSC3 expression in the SCLC patients, but not in the ADC and SCC patients, as compared with the normal controls. Additionally, TUSC3 expression in the patients with a degree of differentiation of 1-2 (well-moderately differentiated) was significantly higher than that in patients with a differentiation degree of 3-4 (poorly differentiated-undifferentiated). Further analysis showed that TUSC3 expression levels were negatively correlated with the degree of differentiation in the ADC and SCC patients. Notably, a marked decrease in TUSC3 expression was identified in the patients who were lymph node metastasis-positive (LNM+) compared with patients who were LNM-. Further analysis showed that significant differences in TUSC3 expression were identified among the different N stages (LNM status) in the SCLC, ADC and SCC patients. Correlation analysis also identified a negative correlation between TUSC3 expression and LNM in all three pathological types of lung cancer tested. Overall, these results indicated that a reduction in TUSC3 may be associated with a poorly-differentiated grade of lung cancer. Importantly, TUSC3 expression may be a useful predictor of LNM in lung cancer patients. A combined analysis of TUSC3 expression and the clinical variables will aid in predicting the incidence of LNM.

Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis.

AIM: To assess the effects and safety of iron-based phosphate binders in adult patients receiving dialysis. METHODS: We electronically searched MEDLINE, EMBASE, CENTRAL, and CBM for randomized controlled trials about iron-based phosphate binders in adult dialysis patients. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by RevMan 5.3. RESULTS: Eight studies with 2018 participants were eligible for our meta-analysis. Iron-based phosphate binders were superior to placebo (MD = -2.43 mg/dL, 95% CI: -3.18 to -1.68, p < 0.00001) and as efficient as sevelamer (MD = 0.04 mg/dL, 95% CI: -0.29 to 0.36, p = 0.83) in reducing serum phosphorus in dialysis patients. No significant differences were found in all adverse events (OR = 1.30, 95% CI: 0.77 to 2.20, p = 0.32) between iron-based phosphate binders and placebo. Iron-based phosphate binders were associated with significant higher serum iron (MD = 9.39 ng/mL, 95% CI 1.48 to 17.30, p = 0.02), higher serum transferring saturation (MD = 6.29%, 95% CI 2.72 to 9.87, p = 0.0006) and lower serum total iron binding capacity (MD = -23.13 µg/dL, 95% CI -35.69 to -10.58, p = 0.0003) in comparison to placebo. CONCLUSION: Iron-based phosphate binders are as effective as sevelamer and well tolerated for hyperphosphatemia in dialysis patients. Iron-based phosphate binders appear to have a beneficial effect on renal anemia in patients receiving dialysis. Therefore, iron-based phosphate binders may represent a new treatment option for dialysis patients.

Efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders in patients with chronic kidney disease: a systematic review and meta-analysis.

PURPOSE: We conducted this review to assess the relative efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders in chronic kidney disease. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials and Chinese Biological Medical Database for randomized controlled trials comparing lanthanum carbonate with calcium-based phosphate binders in adult patients with chronic kidney disease. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by reviewer manager software, version 5.3. RESULTS: Eleven trials with 1,501 participants were included. Lanthanum carbonate appeared to be associated with a significant reduction in progression of vascular calcification and a beneficial effect on bone outcomes without aluminum-like toxicity. Lanthanum carbonate achieved similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27-1.44) with lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05-0.35) in comparison with calcium-based phosphate binders. Lanthanum carbonate was associated with significantly lower serum calcium, similar serum Ca × P product and higher serum iPTH compared with calcium salts in patients with chronic kidney disease. CONCLUSION: Lanthanum carbonate could delay the progression of vascular calcification and benefit chronic kidney disease patients on bone outcomes. Lanthanum carbonate could achieve similar proportion of phosphate-controlled patients as calcium-based phosphate binders with lower incidence of hypercalcemia.

Effect of lanthanum carbonate versus calcium-based phosphate binders in dialysis patients: a meta-analysis.

BACKGROUND: The effects of lanthanum carbonate (LC) vs. calciumbased phosphate binders in dialysis patients have been a matter of debate. METHODS: We electronically searched PubMed, Embase, CENTRAL, and CBM for all randomized controlled trials comparing LC with calcium-based phosphate binders in adult dialysis patients. Quality assessment was performed using the Cochrane risk of bias tool. Metaanalysis was conducted by RevMan 5.2. RESULTS: Nine studies were eligible for our meta-analysis. There was no significant difference in all-cause mortality (RR 0.84, 95% CI 0.25 - 2.83) and cardiovascular events (RR 0.84, 95% CI 0.55 - 1.29) between LC and calcium-based phosphate binders. LC was associated with similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27 - 1.44) and lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05 - 0.35) in comparison to calcium-based phosphate binders. Compared with calcium salts, LC was associated with significantly lower serum calcium, similar serum Ca x P product and higher serum iPTH. CONCLUSION: Despite the trends observed, we found no statistically significant differences in all-cause mortality and cardiovascular events between LC and calcium-based phosphate binders in dialysis patients. The conclusion was limited by lack of large sample and long-term trials. LC could reduce the incidence of hypercalcemia while comparable with calcium-based phosphate binders in reducing serum phosphorus level.

Clinical significance of serum soluble death receptor 5 concentration in locally advanced non-small cell lung cancer patients.

There is an urgent requirement for the identification of suitable biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in patients with locally advanced stage III NSCLC, and to evaluate its diagnostic and prognostic significance in these patients. The sDR5 concentrations were evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls and 122 patients with locally advanced stage III NSCLC [including 57 adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and after concurrent chemoradiotherapy. It was found that the pretreatment sDR5 levels in patients with NSCLC were higher than the sDR5 levels of healthy controls (P<0.001). However, no significant difference in the sDR5 levels was observed between the ADC and SCC subgroups (P=0.874). According to multiple clinical classifications, a significant increase in the pretreatment serum sDR5 levels could be observed in IIIB-stage patients compared with IIIA-stage patients (P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5 concentration than those with a tumor burden ≤3 cm (P=0.026). Additionally, T4-stage patients had significantly higher pretreatment sDR5 levels compared with those of T1-stage patients (P<0.001). There were no significant differences between pre- and post-treatment sDR5 concentrations in the total NSCLC patient group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore, when patients were divided according to therapeutic response, the pretreatment sDR5 levels in the responder patients were significantly lower compared with those of the non-responders (P<0.001). Further survival analysis showed that the patients whose pretreatment sDR5 levels were ≤14 pg/ml (cutoff value, 14 pg/ml) had a longer progression-free survival (PFS) time than patients with sDR5 levels >14 pg/ml. However, no correlation was observed between the post-treatment sDR5 levels and therapeutic response or PFS time. To the best of our knowledge, the present study results provide the first evidence that the pretreatment serum levels of sDR5 may be a useful biomarker for the diagnosis, prediction and prognosis of patients with locally advanced stage III NSCLC.