Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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The advent of checkpoint blockade-based immunotherapy is rapidly changing the management of lung cancer. Whereas past anticancer drugs' primary toxicity was hematologic, the newer agents have primarily autoimmune toxicity. ⋯ They must also understand management of autoimmune conditions, leveraging the skills of the rheumatologist, endocrinologist and gastroenterologist in the process. Herein we describe the mechanism of action and toxicities associated with immune checkpoint blockade in patients with lung cancer and provide a framework for management of adverse events.
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Asthma is the most common life-threatening chronic disease in children. Although guidelines exist for the diagnosis and treatment of asthma, treatment of severe, pediatric asthma remains difficult. Limited studies in the pediatric population on new asthma therapies, complex issues with adolescence and adherence, health disparities, and unequal access to guideline-based care complicate the care of children with severe, persistent asthma. ⋯ An improved understanding of asthma heterogeneity, clinical characteristics, inflammatory patterns, and pathobiology can help further guide the management of severe asthma in children. More studies are needed in the pediatric population to understand emerging therapeutics application in children. Effective multimodal strategies tailored to individual characteristics and a commitment to address risk factors, modifiers, and health disparities may help reduce the burden of asthma in the USA.
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Randomized Controlled Trial
Serum high-molecular-weight adiponectin and response to dapagliflozin in patients with type 2 diabetes and non-alcoholic fatty liver disease.
A better baseline renal function is associated with a better response to sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes. Low serum adiponectin is associated with visceral fat accumulation and hepatic steatosis. We investigated the relationship between baseline serum adiponectin and glycemic response to dapagliflozin in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). ⋯ In the dapagliflozin group, the change in HbA1c was positively correlated with the changes of CAP, but negatively correlated with the change in serum HMW adiponectin. In conclusion, a lower serum level of HMW adiponectin was associated with a better response to dapagliflozin in patients with type 2 diabetes and NAFLD. Trial registration numberUMIN000022155.
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The management of pulmonary arterial hypertension (PAH) has significantly evolved over the last decades in the wake of more sensitive diagnostics and specialized clinical programs that can provide focused medical care. In the current era of PAH care, 1-year survival rates have increased to 86%-90% from 65% in the 1980s, and average long-term survival has increased to 6 years from 2.8 years. The heterogeneity in the etiology and disease course has opened doors to focusing research in phenotyping the disease and understanding the pathophysiology at a cellular and genetic level. ⋯ With more insight, clinical trial designs and primary end-points may change to identify the true survival benefit of pharmacotherapy. Identifying responders from non-responders to therapy may help provide individualized patient-centered care rather than an algorithm-based approach. The purpose of this review is to highlight the latest advances in screening, diagnosis, and management of PAH.
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Cystic fibrosis (CF) is a chronic lung disease characterized by acute pulmonary exacerbations (PExs) that are frequently treated with antibiotics. The impact of antibiotics on airway microbial diversity remains a critical knowledge gap. We sought to define the association between beta-lactam pharmacokinetic (PK) and pharmacodynamic target attainment on richness and alpha diversity. ⋯ However, alpha diversity remained decreased at FU compared with PEx in those with sufficient fT>MIC but increased in those with insufficient fT>MIC (Shannon -0.222 vs +0.452, p=0.031, and inverse Simpson -1.376 vs +1.388, p=0.032). Fluoroquinolone resistance was also more frequently detected in those with insufficient fT>MIC (log2 fold change (log2FC) 2.29, p=0.025). These findings suggest sufficient beta-lactam fT>MIC is associated with suppressed recovery of alpha diversity following the antibiotic exposure period.