Annals of medicine
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Probabilistic graphical modelling (PGM) can be used to predict risk at the individual patient level and show multiple outcomes and exposures in a single model. ⋯ The causal predictors of surgical outcome for DCM were sex, dementia and PreJOA score. Therefore, PGM may be a useful personalized medicine tool for predicting the outcome of patients with DCM.
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Antimicrobial resistance is a global health threat. Among Gram-negative bacteria, resistance to carbapenems, a class of β-lactam antibiotics, is usually a proxy for difficult-to-treat resistance, since carbapenem-resistant organisms are often resistant to many classes of antibiotics. ⋯ In this perspective, we discuss how the treatment of severe KPC-Kp infections has evolved over the last decades, guided by the accumulating evidence from clinical studies, and how recent advances in diagnostics have allowed to anticipate identification of KPC-Kp in infected patients. KEY MESSAGESIn the last decade, the management of severe infections due to KPC-Kp has presented many peculiar challenges to clinicians worldwideFollowing the introduction in clinical practice of novel β-lactam/β-lactamase inhibitor combinations and novel β-lactams active against KPC-producing bacteria, the management of severe KPC-Kp infections has witnessed a remarkable evolutionTreatment of severe KPC-Kp infections is a highly dynamic process, in which the wise use of novel antimicrobials should be accompanied by a continuous refinement based on evolving clinical evidence and laboratory diagnostics.
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Proton pump inhibitor (PPI) use has been associated with reduced diversity of the gut microbiome and may lead to worse clinical outcomes in inflammatory bowel disease (IBD). We aimed to evaluate whether PPI use affects clinical outcomes in a real-world setting. ⋯ PPI use was associated with worse clinical outcomes in patients with IBD in the real-world setting. Further studies are warranted to validate these findings, but caution may be needed when prescribing a PPI to IBD patients.Study highlights WHAT IS KNOWNProton pump inhibitors (PPIs) are one of the most prescribed therapies in the United States (US).Reduction of gastric acid secretion by PPI use increases the risk of imbalance in gut microbiota composition and may increase the risk of enteric infections.Recent studies have reported that the use of PPI was associated with development of inflammatory bowel disease (IBD) and reduced rates of remission in patients on infliximab therapy, which may be due to alterations of intestinal microbiota.WHAT IS NEW HEREIn a large real-world US healthcare database study, IBD patients with PPI use were more likely to have a new biologic medication started, have an IBD-related surgery, and have an IBD-related hospitalization, which remained significant after adjusting for confounders by multivariable analysis, propensity-score matched analysis, and subgroup analysis.Appropriate clinical review of PPI necessity may need to be performed in patients with IBD when considering prescribing a PPI or who are already on PPI therapy.
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Blood-based biomarkers provide a crucial information in the progress of neurodegenerative diseases with a minimally invasive sampling method. Validated blood-based biomarker application in people with amyotrophic lateral sclerosis would derive numerous benefits. Canine degenerative myelopathy is a naturally occurring animal disease model to study the biology of human amyotrophic lateral sclerosis. Serum derived exosomes are potential carriers for cell-specific cargoes making them ideal venue to study biomarkers for a variety of diseases and biological processes. This study assessed the exosomal proteins that may be assigned as surrogate biomarker that may reflect biochemical changes in the central nervous system. ⋯ Serum-derived exosomal biomolecules can serve as surrogate biomarkers in neurodegenerative diseases.KEY MESSAGESA canine with degenerative myelopathy can serve as a model animal to study human amyotrophic lateral sclerosis.Serum-derived exosomes contain Transactive Response DNA Binding Protein 43 (TDP-43), a potential biomarker candidate.The levels of spinal cord TDP-43 proteins and that of serum-derived exosomes exhibited similar profiling. Therefore, serum derived exosomes may be used as a venue for establishing blood-based biomarkers for neurodegenerative diseases.
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With high recurrence and metastatic rates, triple-negative breast cancer (TNBC) has few therapy choices. The innate immune stimulator of interferon genes protein (STING) pathway has emerged as a critical foundation for improving anticancer immunotherapy. Although 2',3'-cGAMP has been shown to have therapeutic potential as a STING agonist in subcutaneous solid tumour treatments in mice, the effect of cGAMP in metastatic malignancies has received less attention. ⋯ The findings suggest that cGAMP could be useful in the immunotherapy of immune-insensitive metastatic breast cancer.