Respiratory variation in the inferior vena cava (ΔIVC) has been extensively studied with respect to its value in predicting fluid responsiveness, but the results are conflicting. This systematic review was aimed at investigating the diagnostic accuracy of ΔIVC in predicting fluid responsiveness. Databases including Medline, Embase, Scopus and Web of Knowledge were searched from inception to May 2013. Studies exploring the diagnostic performance of ΔIVC in predicting fluid responsiveness were included. To allow for more between- and within-study variance, a hierarchical summary receiver operating characteristic model was used to pool the results. Subgroup analyses were performed for patients on mechanical ventilation, spontaneously breathing patients and those challenged with colloids and crystalloids. A total of 8 studies involving 235 patients were eligible for analysis. Cutoff values of ΔIVC varied across studies, ranging from 12% to 40%. The pooled sensitivity and specificity in the overall population were 0.76 (95% confidence interval [CI]: 0.61-0.86) and 0.86 (95% CI: 0.69-0.95), respectively. The pooled diagnostic odds ratio (DOR) was 20.2 (95% CI: 6.1-67.1). The diagnostic performance of ΔIVC appeared to be better in patients on mechanical ventilation than in spontaneously breathing patients (DOR: 30.8 vs. 13.2). The pooled area under the receiver operating characteristic curve was 0.84 (95% CI: 0.79-0.89). Our study indicates that ΔIVC measured with point-of-care ultrasonography is of great value in predicting fluid responsiveness, particularly in patients on controlled mechanical ventilation and those resuscitated with colloids.

BackgroundBaseline clinical variables are prognostic for overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Their prognostic and predictive value with agents targeting bone metastases, such as radium-223, is not established.Patients and methodsThe radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. Percentage changes in biomarker levels from baseline were evaluated during the trial period; changes from baseline to week 12 were evaluated for association with OS and surrogacy.ResultsEastern Cooperative Oncology Group performance status, total alkaline phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) at baseline were associated with OS (P ≤ 0.0003) in the intent-to-treat population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium-223 and 23% of placebo patients (P < 0.001). LDH declined in 51% and 34% (P = 0.003), whereas PSA declined in 27% and 14% (P = 0.160). Mean tALP change from baseline was 32.2% decrease with radium-223 and 37.2% increase with placebo. Radium-223 patients with tALP decline from baseline to week 12 (confirmed ≥3 weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34–0.61) versus those with no confirmed tALP decline. Proportional treatment effect (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 (95% CI: 0–0.746), 0.07 (95% CI: 0–0.211), and 0 (95% CI: 0–0.082), respectively.ConclusionsSignificant tALP declines (versus placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or LDH declines at 12 weeks correlated with longer OS, but did not meet statistical surrogacy requirements. Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor, but do not serve as surrogates for survival.

Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223.

412 Background: Skin toxicity is a known adverse effect of multikinase inhibitors, and was shown to be a predictor of OS in patients (pts) with HCC treated with sorafenib (Reig M, 2014). In the RESORCE trial, regorafenib improved OS versus placebo in pts with HCC progressing on sorafenib (HR 0.62, 95% CI 0.50, 0.78; Bruix J, 2017). This retrospective analysis explored whether HFSR with regorafenib was associated with OS in RESORCE. Methods: Pts in RESORCE who were randomized to regorafenib 160 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether or not they had HFSR. Estimates of OS (95% CI) were calculated using the Kaplan–Meier method. Pts who were randomized, but not treated, were included in the no HFSR group for the analysis of survival. Results: Of 379 pts randomized, 374 received at least one dose of regorafenib. Of the treated pts, 53% (n = 199) had HFSR of any grade and 13% (n = 47) had grade 3 HFSR. Among pts with HFSR at any time during the study, 77% (n = 153) had the first HFSR event (any grade) during Cycle 1. Subgroups of pts with and without HFSR at any time had some imbalances in baseline characteristics (Table). OS was improved in pts who had HFSR at any time versus those who did not (Table). Pts who had a HFSR event during Cycle 1 also had improved OS versus those who did not (median OS 13.2 vs 8.5 months; HR 0.66, 95% CI 0.51, 0.86). Conclusions: In this post-hoc exploratory analysis, HFSR with regorafenib was associated with improved OS, as was previously shown for sorafenib. The potential confounding influence of baseline factors requires further investigation. Clinical trial information: NCT01774344. [Table: see text]

Vitamin D deficiency is associated with an increased risk of subclinical atherosclerosis. To explore the potential link of the serum vitamin D level with carotid atherosclerosis, this meta-analysis assessed the correlation between vitamin D and carotid intima-media thickness as well as carotid atherosclerotic plaque. PubMed, Embase, Web of Science, and Cochrane Library databases were searched until the end of March 2017. Clinical studies investigating the relationship between vitamin D and carotid atherosclerosis were included. The outcome data were extracted according to the inclusion criteria and pooled for an effect estimate by a random-effects model. Of the 506 initially retrieved studies, 11 studies involving a total of 16,434 participants were included in the meta-analysis. Newcastle-Ottawa Quality Assessment Scale scores suggested that the included studies were of high quality. The pooled effects estimate showed that the serum vitamin D level was negatively associated with carotid atherosclerosis (odds ratio, 0.95; 95% confidence interval [CI], 0.93-0.96), with substantial heterogeneity among the individual studies (I = 54%). Furthermore, a subgroup analysis suggested that hypovitaminosis D was associated with an 0.85-fold decrease in the odds of having a higher carotid intima-media thickness (95% CI, 0.76-0.96; P < .05; I = 69%). Additionally, the pooled analysis also indicated that the serum vitamin D level was a protective factor against increased carotid plaque (odds ratio, 0.95; 95% CI, 0.93-0.97; P < .05; I = 29%). Funnel plots and the Egger regression test showed the absence of a publication bias. In this meta-analysis, we comprehensively revealed a close link between vitamin D deficiency and carotid atherosclerosis. Patients with hypovitaminosis D might have extra requirements for preventive and therapeutic measures against early atherosclerosis, thus reducing the cardiovascular disease risk in the long term.

Background:Whether the diagnosis value of computed tomography angiography (CTA) for intracranial aneurysm is in accordance with magnetic resonance angiography (MRA) remains inconclusive. This meta-analysis aims to synthesize relevant studies to compare the diagnostic efficacies of the 2 methods.Methods:Potentially relevant studies were selected through PubMed, Embase, Wanfang, Chongqing VIP, and China National Knowledge Infrastructure databases by using the core terms “computer tomography angiography” (CTA) and “magnetic resonance angiography” (MRA) and “intracranial aneurysm∗” in the titles, abstracts, and keywords of the articles. Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2) was utilized to evaluate the quality. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were count. Summary receiver operating characteristic curves (SROC) and area under the curve (AUC) were used to summarize the overall diagnostic performance. Statistical analyses were performed by Stata version 12.0 and MetaDisc 1.4 software.Results:Ten articles were identified in this current paper. For CTA, the pooled estimates of diagnostic parameters for intracranial aneurysm were as follows: sensitivity, 0.84 (95%CI = 0.81–0.86); specificity, 0.85 (95%CI = 0.79–0.89); PLR, 4.09 (95%CI = 2.45–6.81); NLR, 0.18 (95%CI = 0.11–0.28); DOR, 23.74 (95%CI = 10.49–53.74); AUC, 0.90, respectively. For MRA, the pooled estimates of diagnostic parameters for intracranial aneurysm were as follows: sensitivity, 0.80 (95%CI = 0.77–0.83); specificity, 0.87 (95%CI = 0.82–0.91); PLR, 3.61 (95%CI = 1.72–7.55); NLR; 0.27 (95%CI = 0.21–0.35); DOR, 16.77 (95%CI = 7.38–38.11); AUC, 0.87, respectively. No significant difference was found the AUC value between CTA and MRA for intracranial aneurysm (Z = 0.828, P > .05).Conclusion:This comprehensive meta-analysis demonstrated that the diagnosis value of CTA was in accordance with MRA for intracranial aneurysm. However, considering the limitation of sample size, the results should be treated with caution.

We aimed to explore the potential link of serum vitamin D level with nonalcoholic fatty liver disease (NAFLD). PubMed, Embase and the Cochrane Library database were searched until the end of February 2018. Clinical studies with sufficient data investigating the relationship between serum vitamin D and NAFLD were included. The outcome data were processed to make an overall estimate of combined standardized mean differences (SMD) and pooled odds ratio (OR)/hazard ratios with 95% confidence intervals (CIs). Of the 309 initially retrieved studies, 15 studies of high quality involving a total of 20 096 participants (including 7803 NAFLD patients) were included in this meta-analysis. Meta-analysis of continuous data indicated that NAFLD patients had averagely 0.90 ng/ml lower levels of 25-hydroxyvitamin D compared with the non-NAFLD subjects (SMD −0.90; 95% CI: −1.29 to −0.52). Parallelly, pooled dichotomous data revealed that serum vitamin D level is negatively associated with NAFLD (OR = 0.64, 95% CI = 0.54–0.77), albeit with substantial heterogeneity. Next, subgroup analysis showed that Western NAFLD patients were more likely to be vitamin D deficient (OR = 0.60, 95% CI = 0.46–0.78). Finally, meta-regression showed that sample size, ethnic background, and diagnosis of NAFLD were possible sources of heterogeneity in the meta-analysis. Our results revealed that serum vitamin D level was inversely associated with an increased risk of NAFLD. Patients with hypovitaminosis D might benefit from extra supplement of vitamin D against the risk of NAFLD.

The aim of this study was to assess associations between ER, Ki67, Her-2 phenotypes, molecular subtypes of breast cancer and circulating levels of lymphocyte subsets (CD4+, CD8+, NK, CD19+, CD20+) and the ratio of CD4+ to CD8+ prior to treatment. Cells from peripheral blood were counted by flow cytometry, ER, Her-2, and Ki67 expressions were detected by pathological examination, and Her-2 was also detected by FISH. We conducted a case-case comparison of 494 women with newly diagnosed breast cancer to evaluate association between levels of lymphocyte subsets in peripheral blood and breast cancer phenotypes [ER- vs. ER+; Ki67 ≥ 14 % vs. Ki67 < 14 %; Her-2+ vs. Her-2-; triple-negative breast cancer (TNBC) vs. luminal A]. Women with the highest levels of CD3+ (OR 0.45, 95 % CI 0.22-0.94), CD4+ (OR 0.22, 95 % CI 0.08-0.59), and the ratio of CD4+/CD8+ (OR 0.17, 95 % CI 0.06-0.47) were least likely to have TNBCs compared with luminal A cancers. The highest tertile of CD8+ (OR 3.67, 95 % CI 1.06-12.72) and NK (OR 2.64, 95 % CI 1.12-6.24) was significantly associated with TNBC compared with luminal A cancer. ER-, Ki67 ≥ 14 %, Her-2+ were associated with low levels of CD4+ and CD4+/CD8+ compared with ER+, Ki67 < 14 %, Her-2-. Women in the highest level of CD8+ had more likelihood to have ER- and Her-2+ compared with ER+ and Her-2-. High levels of NK cells were associated with increased risk of ER- compared with ER+ cancers. Highest levels of CD19+ and CD20+ were associated with low risk of ER-, compared with ER+ cancers. These findings show that immune function differs among different breast cancer phenotypes or subtypes and is associated with ER-, Her-2+, Ki67 ≥ 14 %, and TNBC which are likely to be aggressive phenotypes.