Conversion of the bronchial tree into a conforming electrode to ablate the lung nodule in a porcine model.

BACKGROUND: Radiofrequency ablation (RFA) is one of the treatment options for lung nodules. However, the need for exact delivery of the rigid metal electrode into the center of the target mass often leads to complications or suboptimal results. To overcome these limitations, a concept of conforming electrodes using a flexible material has been tested in this study. METHODS: A bronchoscopy-guided RFA (CAROL) under a temperature-controlled mode was tested in in-vivo and ex-vivo porcine lungs. Gallium-based liquid metal was used for turning the bronchial tree into temporary RF electrodes. A customized bronchoscopy-guided balloon-tipped guiding catheter (CAROL catheter) was used to make the procedure feasible under fluoroscopy imaging guidance. The computer simulation was also performed to gain further insight into the ablation results. Safety was also assessed including the liquid metal remaining in the body. RESULTS: The bronchial electrode injected from the CAROL catheter was able to turn the target site bronchial air pipe into a temporally multi-tined RF electrode. The mean volume of Gallium for each effective CAROL was 0.46 ± 0.47 ml. The ablation results showed highly efficacious and consistent results, especially in the peripheral lung. Most bronchial electrodes were also retrieved by either bronchoscopic suction immediately after the procedure or by natural expectoration thereafter. The liquid metal used in these experiments did not have any significant safety issues. Computer simulation also supports these results. CONCLUSION: The CAROL ablation was very effective and safe in porcine lungs showing encouraging potential to overcome the conventional approaches.

Lung cancer can be treated by inserting a metal device into the lung via the throat and using this to send radio waves into the cancer. However, using a rigid metal device can cause damage to other areas of the lung and can only treat small cancers. Here, we describe an alternative method to treat lung cancers in which liquid metal is used to fill the spaces within the lung closest to the cancer. We demonstrate that this method can be used to treat cancer in a swine model of lung cancer. Given the positive results we obtained, we think this approach should be tested in a clinical trial in human patients with lung cancer, as it might improve cancer treatment.

Gut-associated IgA+ immune cells regulate obesity-related insulin resistance.

The intestinal immune system is emerging as an important contributor to obesity-related insulin resistance, but the role of intestinal B cells in this context is unclear. Here, we show that high fat diet (HFD) feeding alters intestinal IgA+ immune cells and that IgA is a critical immune regulator of glucose homeostasis. Obese mice have fewer IgA+ immune cells and less secretory IgA and IgA-promoting immune mediators. HFD-fed IgA-deficient mice have dysfunctional glucose metabolism, a phenotype that can be recapitulated by adoptive transfer of intestinal-associated pan-B cells. Mechanistically, IgA is a crucial link that controls intestinal and adipose tissue inflammation, intestinal permeability, microbial encroachment and the composition of the intestinal microbiome during HFD. Current glucose-lowering therapies, including metformin, affect intestinal-related IgA+ B cell populations in mice, while bariatric surgery regimen alters the level of fecal secretory IgA in humans. These findings identify intestinal IgA+ immune cells as mucosal mediators of whole-body glucose regulation in diet-induced metabolic disease.

Nucleic Acid-Targeting Pathways Promote Inflammation in Obesity-Related Insulin Resistance.

Obesity-related inflammation of metabolic tissues, including visceral adipose tissue (VAT) and liver, are key factors in the development of insulin resistance (IR), though many of the contributing mechanisms remain unclear. We show that nucleic-acid-targeting pathways downstream of extracellular trap (ET) formation, unmethylated CpG DNA, or ribonucleic acids drive inflammation in IR. High-fat diet (HFD)-fed mice show increased release of ETs in VAT, decreased systemic clearance of ETs, and increased autoantibodies against conserved nuclear antigens. In HFD-fed mice, this excess of nucleic acids and related protein antigens worsens metabolic parameters through a number of mechanisms, including activation of VAT macrophages and expansion of plasmacytoid dendritic cells (pDCs) in the liver. Consistently, HFD-fed mice lacking critical responders of nucleic acid pathways, Toll-like receptors (TLR)7 and TLR9, show reduced metabolic inflammation and improved glucose homeostasis. Treatment of HFD-fed mice with inhibitors of ET formation or a TLR7/9 antagonist improves metabolic disease. These findings reveal a pathogenic role for nucleic acid targeting as a driver of metabolic inflammation in IR.