Bmc Med
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Obesity usually is accompanied by inflammation of fat tissue, with a prominent role of visceral fat. Chronic inflammation in obese fat tissue is of a lower grade than acute immune activation for clearing the tissue from an infectious agent. It is the loss of adipocyte metabolic homeostasis that causes activation of resident immune cells for supporting tissue functions and regaining homeostasis. ⋯ Matrix remodeling and angiogenesis is further intensified as well as possibly detrimental fibrosis. The accumulation of senescent cells also may be detrimental via eventual spread of senescence state from affected to neighboring cells by the release of microRNA-containing vesicles. Obese visceral fat inflammation can be viewed as an initially protective response in order to cope with excess ambient nutrients and restore tissue homeostasis but may contribute to tissue damage at a later stage.
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Regenerative medicine has the potential to treat genetic disorders and replace damaged or missing tissue. The use of donor or animal tissue raises many well-known issues, including limited tissue availability, the possibility of rejection and patient infection. Stem cell therapy raised hope of overcoming these issues, but created new risks including tumour formation and limited benefit if the desired target tissue does not form. The recent development of 3-dimensional tissues, including organoids, allows the creation of more complex tissues for personalised regenerative medicine. ⋯ The potential use of 3-dimensional organoid and tissue therapy may deliver greater patient benefits than other regenerative medicine approaches, but raises new health and ethical risks. Preclinical testing of these therapies will not mitigate some of their risks; they may only be understood after first-in-human trials. The potential irreversibility and high risk of these therapies affects how clinical trials should be structured, including post-trial care for participants.
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Randomized Controlled Trial Multicenter Study
Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial.
Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine has survival benefits and acceptable tolerability in patients with HER2-positive metastatic breast cancer. We further assessed addition of pyrotinib to trastuzumab and docetaxel in the neoadjuvant setting. ⋯ The primary endpoint of the study was met. Neoadjuvant pyrotinib, trastuzumab, and docetaxel significantly improved the tpCR rate compared with placebo, trastuzumab, and docetaxel, with manageable toxicity, providing a new option for HER2-positive early or locally advanced breast cancer.
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Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behavior.
Obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity and even fewer that have examined its relationship to eating behaviors. ⋯ By finding peculiar gut microbiome profiles associated with eating patterns, we laid the foundation for elucidating gut-brain axis communication in the obese phenotype. Subject to confirmation of the hypotheses herein generated, our work could help guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.
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Approximately half of all women suffer from heartburn at some stage during pregnancy. The most effective treatment is proton pump inhibitors, but the safety of use during pregnancy cannot be guaranteed. This study aimed to elucidate the effect of proton pump inhibitors on the risk of pre-eclampsia, gestational diabetes mellitus, preterm birth, an Apgar score at 5 min below 7, and a child being small or large for its gestational age. ⋯ Proton pump inhibitor use was associated with a higher risk of pre-eclampsia, gestational diabetes, preterm birth, and being born small for gestational age.