Relationship between thyroid function and dietary inflammatory index in Hashimoto thyroiditis patients.

Inflammation is closely related to the changes of thyroid function in Hashimoto thyroiditis patients. Certain nutrients or dietary habits can alter the levels of autoantibodies in Hashimoto thyroiditis. However, it remains unclear whether dietary inflammation affects thyroid function in patients with Hashimoto thyroiditis. The purpose of this study was to assess the relationship between dietary inflammation and thyroid function in Hashimoto thyroiditis patients using data from the National Health and Nutrition Examination Survey. We employed weighted multivariable linear regression, subgroup analyses, and interaction analysis to explore the relationship between thyroid function and dietary inflammatory index. We found that dietary inflammatory index was positively correlated with TSH and total T4. Interaction analysis found an interaction between urinary iodine concentration and FT3, but subgroup analysis for different levels of urinary iodine concentration did not get statistically significant results. Hashimoto thyroiditis patients with more pro-inflammatory diet habits had higher levels of TSH and TT4. In order to prevent hypothyroidism more effectively in patients with Hashimoto thyroiditis, it is essential to control dietary inflammation. However, it is still necessary to design a better prospective cohort study to verify the causal relationship.

Association between serum vitamin D levels and sensitivity to thyroid hormone indices: a cross-sectional observational study in NHANES 2007-2012.

Objective: We designed this study to determine whether there is a link between vitamin D levels and sensitivity to thyroid hormone and to provide a new perspective for studying the relationship between vitamin D and thyroid disease. Methods: Our study included 8,126 participators from the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2012. We used weighted multiple linear regression models to enquire the connection between serum vitamin D levels and thyroid hormone sensitivity indicators, including the following: Thyroid-stimulating hormone index (TSHI), Free Triiodothyronine/Free thyroxine (FT3/FT4), Thyroid Feedback Quantile-based Index (TFQI), and Thyrotroph Thyroxine Resistance Index (TT4RI). Finally, we used constrained cubic splines to explore possible nonlinear relationships. All data cleaning and statistical analyses were performed using R software. Results: The final Results were reached after adjusting for various confounding factors. We found a U-shaped relationship between TFQI and serum vitamin D, and the lowest TFQI appeared when the serum vitamin D concentration was 25.77ng/ml. However, an inverse U-shaped relationship was found between FT3/FT4 and vitamin D levels. When the serum vitamin D concentration was 25.43ng/ml, the ratio of FT3/FT4 was the highest. Conclusion: In the US population, our study concluded that FTQI and FT3/FT4 were U-shaped or inverse-U-shaped with serum vitamin D levels respectively after several adjustments. Therefore, FTQI and FT3/FT4 are considered indicators of the complex relationship between thyroid hormone resistance and vitamin D metabolism. In the future, more complex prospective investigations are needed to confirm these findings and find a causal link between them.

Carfilzomib/pomalidomide single-agent or in combination with other agents for the management of relapsed/refractory multiple myeloma: a meta-analysis of 37 trials.

PURPOSE: The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM). RESULTS: Based on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0.001, I2 = 96.3%), suggesting the overall response rate (ORR) of 66% attained from CFZ/DEX dual combination seemed to be higher than that of 28% from carfilzomib single-agent. And, the same trend favoring CFZ/DEX dual combination was found in ≥VGPR and CBR analysis. The ORR of 31% attained from POM/DEX dual combination was superior to that of 19% from pomalidomide single-agent(P < 0.001, I2 = 94.4%). And, the same trend favoring POM/DEX dual combination was found in ≥VGPR and CBR analysis. However, the ORR of 83% attained from POM/BOR/DEX triplet combination was superior to that of 31% from POM/DEX dual combination(P < 0.001, I2 = 99.1%). And, the same trend favoring POM/BOR/DEX triplet combination was found in ≥VGPR analysis. METHODS: We searched published reports including carfilzomib and (or) pomalidomide therapy for RRMM who had received bortezomib and (or) lenalidomide. CONCLUSION: Pomalidomide/Carfilzomib plus dexamethasone seemed to attain a superior response rate compared with pomalidomide/carfilzomib single-agent. Furthermore, the combination of pomalidomide, bortezomib and dexamethasone resulted in a much higher response rate compared with pomalidomide plus dexamethasone regimen. These results needed more validation in future trials.

Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy after drug-eluting stent implantation in coronary arteries: A meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the long-term clinical efficacy and safety of adding cilostazol (TAT) to conventional dual antiplatelet therapy (DAT) for patients undergoing drug-eluting stent (DES) implantation in coronary arteries. METHODS: We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation with criteria to include trials with a follow-up of more than 6 months. RESULTS: Seven RCTs with a total of 3487 patients were included in this review. The meta-analysis showed that TAT was associated with a significant reduction in major adverse cardiac events (MACEs) (relative risk (RR)=0.66; 95% CI=0.50-0.88), target lesion revascularization (TLR) (RR=0.61, 95% CI=0.43-0.84), target vessel revascularization (TVR) (RR=0.53, 95% CI=0.37-0.75), in-stent restenosis (RR=0.64, 95% CI=0.44-0.85), in-segment restenosis (RR=0.58, 95% CI=0.43-0.79, P<.01), in-stent late loss (LL) (standardized mean difference (SMD)=-0.21, 95% CI=0.32-0.17), and in-segment LL (SMD=-0.27, 95% CI=-0.38-0.16). TAT also did not appear to significantly alter any of the other meta-analysis secondary efficacy outcomes and had similar rates of bleeding, but TAT had significantly higher rates of rash, gastrointestinal side-effects, headache and drug discontinuation. CONCLUSIONS: Compared with standard DAT, the long-term use of TAT in patients after DES implantation gave more benefits in reducing the incidence of MACEs, TLR, TVR, in-stent and in-segment LL and restenosis without increasing bleeding but was associated with an increase in minor adverse events.

Bortezomib and lenalidomide as front-line therapy for multiple myeloma.

The objective of the study was to investigate the effects and safety of novel agents such as bortezomib and lenalidomide in the treatment of newly diagnosed patients with multiple myeloma. We performed a comprehensive meta-analysis of randomized controlled trials (RCTs). An initial search yielded 627 citations, of which 10 RCTs enrolling 4534 patients met the inclusion criteria. The addition of bortezomib to first-line therapy significantly prolonged overall survival (OS) (hazard ratio [HR], 0.75 [0.65, 0.87], p < 0.001). On the other hand, the addition of lenalidomide had no impact on survival (HR, 0.88 [0.65, 1.20], p = 0.42). Both lenalidomide and bortezomib consistently improved progression-free survival (PFS) compared with conventional therapy alone. The corresponding HRs were 0.65, 95% confidence interval (CI) [0.55, 0.77] (p < 0.001) for bortezomib and 0.48, 95% CI [0.42, 0.55]; (p < 0.001) for lenalidomide, respectively. Some of the increased adverse events reported were herpes zoster (relative risk [RR], 3.64 [2.23, 5.94], p < 0.001), peripheral neuropathy (RR, 3.59 [1.89, 6.83], p < 0.001) and gastrointestinal effects (RR, 2.19 [1.37, 3.50], p = 0.001) among patients receiving bortezomib, and gastrointestinal effects (RR, 2.36 [1.33, 4.17], p = 0.003) and thromboembolic events (RR, 2.55 [1.48, 4.38], p < 0.001) among patients receiving lenalidomide. Interestingly, treatment with bortezomib seemed to be associated with a lower rate of treatment related mortality (RR, 0.39 [0.18, 0.85], p = 0.02). An increased incidence of second primary cancers was observed in the lenalidomide group (RR 2.61 [1.60, 4.27], p < 0.001). In summary, bortezomib improved OS, and both lenalidomide and bortezomib consistently improved PFS of patients with newly diagnosed myeloma when it was added to standard therapy.

Continuous treatment with new agents for newly diagnosed multiple myeloma.

To examine the role of novel agents such as bortezomib, lenalidomide, and thalidomide as continuous therapy (induction and consolidation/maintenance) in the treatment of newly diagnosed patients with multiple myeloma, we carried out a meta-analysis of randomized-controlled trials. A comprehensive literature search (Medline, Embase, the Cochrane controlled trials register, and the Science Citation Index) was performed. The initial search yielded 849 citations, of which 11 randomized-controlled trials enrolling 4775 patients fulfilled the inclusion criteria. Continuous addition of bortezomib to conventional therapy before and after autologous stem cell transplantation prolonged overall survival significantly: the summary hazard ratio was 0.80, 95% confidence interval [0.64, 0.99] (P=0.04). Continuous therapy with novel agents consistently improved progression-free survival (PFS) compared with therapy with conventional agents alone. For those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.69 [0.56, 0.85] (P<0.001) for continuous thalidomide therapy and 0.47 [0.33, 0.68] (P<0.001) for continuous lenalidomide therapy; for those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.68 [0.59, 0.79] (P<0.001) for continuous thalidomide therapy and 0.72 [0.61, 0.85] (P<0.001) for continuous lenalidomide therapy. In summary, continuous therapy with novel agents improved PFS consistently, and bortezomib may improve the overall survival of patients with newly diagnosed myeloma when it is added to standard transplantation therapy continuously.

Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma.

Thalidomide (T) and lenalidomide (R) have been used as first-line therapy for previously untreated myeloma. However, direct head-to-head comparison between them is lacking. We performed an indirect meta-analysis to assess the treatment effects of lenalidomide- versus thalidomide-based regimens using common comparators. A comprehensive literature search was undertaken. The initial search yielded 1345 citations, of which 11 randomized controlled trials (RCTs) enrolling 4162 patients met the inclusion criteria. Indirect comparison of lenalidomide versus thalidomide maintenance after autologous stem cell transplant (ASCT) showed a progression-free survival (PFS) benefit (hazard ratio [HR] 0.75, 95% confidence interval [CI] [0.67, 0.85], p < 0.001) but no survival difference (HR 0.83, [0.63, 1.09], p = 0.19) when using observation/placebo as the common comparator. Similarly, the indirect comparison of melphalan-prednisone plus lenalidomide followed by lenalidomide maintenance (MPR-R) versus melphalan-prednisone-thalidomide induction followed by thalidomide maintenance (MPT-T) showed a statistically significant PFS advantage for MPR-R (HR 0.53, 95% CI [0.46, 0.60], p < 0.001), but no difference for overall survival (OS) (HR 0.97, [0.81, 1.17], p = 0.74). Additionally, the significant heterogeneity among pooled studies for the outcome of discontinuation rate due to treatment-related adverse events between MPT-T and MPR-R subgroups (p = 0.007) indicated that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials. In conclusion, lenalidomide seems to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further, a direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted.

Rapid and complete reconstitution of autologous haemopoiesis after cord blood infusion in treatment-naive patients with severe aplastic anemia receiving high-dose cyclophosphamide/ATG therapy.

UNLABELLED: Although high-dose cyclophosphamide seems to achieve durable complete remission, there are still concerns about its too much early toxicity. So, we designed a clinical study to investigate the effects of high-dose cyclophosphamide/ATG combined with cord blood infusion as first-line therapy for patients with severe aplastic anemia. PATIENTS AND METHOD: Between January 2003 and September 2007, we treated 16 treatment-naive patients with severe aplastic anemia with cord blood infusion after high-dose cyclophosphamide (50 mg/kg/d × 2) and rabbit antithymocyte globulin (3 mg/kg/d × 5) therapy. RESULTS: Although only one patient had durable full donor engraftment, 14 of the enrolled 16 patients had rapid autologous hematopoietic recovery. The median recovery time for neutrophils and platelets was only 23 and 37 d after infusion of cord blood. Of the 15 responding patients, all patients achieved treatment-free remission: nine patients met the criteria for a complete remission; six patients achieved a partial remission. CONCLUSION: Infusion of cord blood after high-dose cyclophosphamide/ATG resulted in a rapid autologous hematologic recovery and a high response rate in patients with treatment-naive patients with severe aplastic anemia. These promising results merit further investigation and confirmation on a larger number of patients.