BackgroundImmune checkpoint inhibitors (ICPIs) are increasingly being used in the treatment of a variety of malignancies. The original studies that demonstrated the efficacy of ICPIs excluded patients actively being treated for autoimmune conditions, and there is only limited evidence that these treatments are safe and effective in this population of patients.Case presentationWe present a case of a man with Crohn’s disease actively requiring immunosuppressive therapy who subsequently received pembrolizumab for metastatic melanoma. He had no further progression of metastatic disease and had resolution of his pulmonary nodule while he experienced no Crohn’s disease flares or immune related adverse events. We surveyed the existing literature for studies examining the use of ICPIs in patients with autoimmune disorders and reviewed the unique mechanism of action of the α4β7 inhibitor, vedolizumab.ConclusionPatients with autoimmune conditions should be considered candidates for immune checkpoint inhibition even in the setting of active immunosuppressive therapy. The mechanism of action of immunosuppressive therapy should be considered with the most targeted form of treatment being used when possible. Further prospective studies investigating immunotherapy in patients with autoimmune conditions are warranted.
Background Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients. Methods We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Clinical trials.gov until Nov 3, 2020, including studies with two or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each combination. Effectiveness was reported as pooled rates of clinical, endoscopic and/or radiographic response and remission. The certainty of evidence was rated according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Results Of the 3,688 publications identified, 13 studies (1 clinical trial, 12 observational studies) involving 266 patients on seven different combinations were included. Median number of prior biologics ranged from 0-4, and median duration of follow-up was 16-68 weeks. Most common DBT and SBT were vedolizumab (VDZ) with anti-Tumor Necrosis Factor (aTNF, n=56) or tofacitinib (Tofa, n=57), respectively. Pooled rates of SAE for these were 9.6% (95% CI, 1.5–21.4) for VDZ-aTNF and 1.0% (95% CI, 0.0–7.6) for Tofa-VDZ. The overall certainty of evidence was very low due to the observational nature of the studies, and very serious imprecision and inconsistency. Conclusions DBT or SBT appears to be generally safe and may be effective in IBD patients, but the evidence is very uncertain.
We sought to review the epidemiological features and clinical implications of normal-weight obesity. The concept of normal-weight obesity has been recently reported as an important risk factor for cardiovascular disease, metabolic dysregulation, and poor functional outcomes. However, in clinical practice, normal-weight obesity is not commonly recognized. In this review, we examine the clinical significance and important epidemiological outcomes of normal-weight obesity and describe other variants of adiposity and adiposity-related metabolic status. The incorporation of measures of body fat content and distribution in the clinical setting could allow more accurate identification of adiposity-related long-term risk. This could in turn lead to early lifestyle changes and behavioral modifications that are essential to the treatment of obesity.
Obesity is an epidemic that threatens the health of millions of people worldwide and is a major risk factor for cardiovascular diseases, hypertension, diabetes, and dyslipidemia. There are multiple and complex mechanisms to explain how obesity can cause cardiovascular disease. In recent years, studies have shown some limitations in the way we currently define obesity and assess adiposity. This review focuses on the mechanisms involved in the cardiometabolic consequences of obesity and on the relationship between obesity and cardiovascular comorbidities, and provides a brief review of the latest studies focused on normal weight obesity and the obesity paradox.
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