Citations

Marrow adipocytes reprogrammed by myeloma cells induce bone lesions.

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.

PurposeBiomechanical properties can be used as biomarkers to diagnose tumors, monitor tumor development, and evaluate treatment efficacy. The purpose of this preliminary study is to characterize the biomechanical environment of two typical liver tumors, hemangiomas (HEMs) and hepatocellular carcinomas (HCCs), and to investigate the potential of using strain metrics as biomarkers for tumor diagnosis, based on a limited clinical dataset.MethodsMagnetic resonance (MR) tagging was used to quantify the motion and deformation of the two types of liver tumors. Displacements of the tumors arising from a heartbeat were measured over one cardiac cycle. Local biomechanical conditions of the tumors were characterized by estimating two principal strains (ε1 and ε2) and an octahedral shear strain (εsoct) of the tumor and its peripheral region. Biomechanical conditions of the tumors were compared with those of the arbitrarily selected regions from healthy volunteers.ResultsWe observed that the HCCs had significantly smaller strain values compared to their peripheral tissues. However, the HEMs did not have significantly different strains from those of the peripheral tissues, and were similar to healthy liver regions. The sensitivity of using ε1, ε2, and εsoct to diagnose HCC were all 1, while the sensitivity of using ε1, ε2, and εsoct to diagnose HEM were 0.67, 0.17, and 0.67, respectively.ConclusionsLagrangian strain metrics provide insight into the biomechanical conditions of certain liver tumors in the human body and may provide another perspective for tumor characterization and diagnosis.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

AbstractBackgroundCardiac resynchronization therapy (CRT) reverses left ventricular remodeling and improves left ventricular systolic function. However, little is known about whether CRT improves ventricular conduction.ObjectiveTo determine the relationship between CRT response and QRS narrowing.MethodsThe study included consecutive patients who underwent CRT with defibrillator (CRT‐D) implantation between January 2002 and December 2012 and had subsequent generator replacement (GR). At the time of GR, super‐responder was defined as those who had left ventricular ejection fraction (LVEF) of 50% or more; patients who had an LVEF of 36–49% with an increase of more than 5% were considered responders, and the others were nonresponders. All patients were assessed 6 months after CRT‐D implantation and at the time of GR.ResultsOf 114 study patients, 58 (50.9%) were nonresponders, 29 (25.4%) responders, and 27 (23.7%) super‐responders. QRS narrowing at 6 months was significant in super‐responders (175.4 ± 21.4 to 159.7 ± 20.7 ms, P = 0.001) and responders (169.0 ± 21.3 to 157.7 ± 17.6 ms, P = 0.008). At time of GR, only super‐responders had further QRS narrowing (159.7 ± 20.7 to 146.3 ± 19.2 ms, P < 0.001). QRS duration change after 6 months was independently associated with super‐response (hazard ratio: 1.20 for every 5 ms QRS duration narrowing; 95% confidence interval, 1.06–1.38; P = 0.005), and QRS narrowing of 10 ms or more was associated with lower risk of all‐cause mortality after GR.ConclusionContinuous QRS narrowing after CRT, as an electrical marker, is associated with a super‐response to CRT. Further QRS narrowing 6 months after CRT implantation was associated with lower risk of mortality after GR.

Abstract Context Previous epidemiological studies had inconsistent results regarding the relationship between blood lead level (BLL) and adiposity. Objective We aimed to investigate the associations of BLL with body mass index (BMI) particularly using Mendelian randomization analyses and examine the interaction between obesity-predisposing genes and BLL on the associations. Design and Setting A total of 3922 participants were enrolled from 16 sites in East China in 2014 from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic risk score (GRS) based on 29 variants that were identified and validated in East Asians. BLL was measured by atomic absorption spectrometry. Main Outcome Measure BMI was calculated, and BMI ≥25 kg/m2 was defined as overweight. Results Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (β = 0.24; 95% CI, 0.08 to 0.40; P &lt; 0.001) and each 1-point increase in BMI-GRS (β = 0.08; 95% CI, 0.05 to 0.11; P &lt; 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were −0.003 (95% CI, −0.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI ≥25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to 2.05) in the highest quartile of GRS, but no significant associations were found in the lower three quartiles. Conclusions The associations of BLL with BMI and overweight (BMI ≥25 kg/m2) were significantly modulated by BMI genetic susceptibility.