A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Left atrial thrombus two years after placement of a left atrial appendage closure device: Unexplored area of the Watchman

A 72‐year‐old man who underwent a left atrial appendage (LAA) closure device 2 years ago presented with atrial flutter with rapid ventricular rate and was referred for cardioversion. Precardioversion transesophageal echocardiogram showed left atrial thrombus and therefore the procedure was aborted. Currently, there is no guideline on imaging surveillance or anticoagulation in patients with LAA closure device who develop intracardiac thrombus after the initial 6‐month surveillance period.     

Dietary factors associated with hyperuricemia in adults

OBJECTIVES: Although diet has long been assumed to be associated with hyperuricemia, the association between diet and hyperuricemia remains to be verified. METHODS: The Nutrition and Health Survey in Taiwan (NAHSIT) implemented between 1993 and 1996 was a nationwide survey using a stratified multistage sampling design. A food frequency questionnaire (FFQ), 24-hour diet recall, and blood samples were utilized. Hyperuricemia was defined as serum urate >7.7 mg/dL for men and >6.6 mg/dL for women. RESULTS: In total, 2176 adults, 987 (45%) men and 1189 (55%) women, were recruited. Mean serum urate was 6.81 +/- 1.66 mg/dL (range, 2.5-16.8 mg/dL) and 5.47 +/- 1.55 mg/dL (range, 1.4-11.5 mg/dL) for men and women, respectively. Multiple logistic regression analysis indicated that beer consumption in both the FFQ and the 24-hour diet recall were significantly associated with hyperuricemia in men after adjusting for age, total caloric intake, body mass index, and geographic area. In FFQ, the adjusted odds ratio was 1.49 for men who imbibed 0.1 to 11.6 g ethanol (<1 standard drink) daily and 1.56 for men who imbibed > or =11.7 g ethanol (> or =1 standard drink) daily, when compared with that for men who did not drink beer (P = 0.035). In the 24-hour diet recall, the adjusted odds ratio for men who drank <5 cans of beer daily was 1.13, and for men who drank > or =5 cans daily was 1.28 when compared with that for men who did not drink beer (P = 0.003). CONCLUSIONS: This cross-sectional survey demonstrated that beer intake is independently associated with increased risk of hyperuricemia in men. Restricted beer intake may help prevent hyperuricemia in the population. The finding of elevated mean serum urate levels over recent decades warrants further study.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

The Effect of Mass Azithromycin Distribution on Childhood Mortality: Beliefs and Estimates of Efficacy

A cluster-randomized trial demonstrated that mass oral azithromycin distribution reduced childhood mortality 49.6% (Trachoma Amelioration in Northern Amhara [TANA]). The relative risk of childhood mortality was then estimated using two approaches: an expert survey and a Bayesian analysis. The survey asked public health experts to estimate the true effect of mass azithromycin distribution on childhood mortality. The Bayesian estimation used the TANA study''s results and prior estimates of the efficacy of other effective population-level interventions. The experts believed mass azithromycin reduces childhood mortality (relative risk = 0.83, 95% credible intervals [CrI] = 0.70–1.00). The Bayesian analysis estimated a relative risk of 0.71 (95% CrI = 0.39–0.93). Both estimates suggest that azithromycin may have a true mortality benefit, though of a smaller magnitude than found in the single available trial. Prior information about nonantibiotic, population-level interventions may have informed the expert''s opinions. Additional trials are needed to confirm a mortality benefit from mass azithromycin.