2 Minute Medicine Rewind August 26, 2019

Evaluation of the Central Vein Sign as a Diagnostic Imaging Biomarker in Multiple Sclerosis

Diagnosing multiple sclerosis (MS) is challenging, in part because imaging findings in MS partially overlap with MS mimics such as vascular disease, migraine, and neuromyelitis optica spectrum disorder (NMOSD). The central vein sign has been shown to be a highly sensitive and specific biomarker for MS based on results from ultrahigh-field MRI studies, but as ultrahigh-field MRI is not widely available, MRI protocols using 3 Tesla (T) have been proposed. However, only small studies have examined the 3T central vein sign as a biomarker for MS to date. In this multicenter, cross-sectional study, 606 patients with relapsing-remitting MS (RRMS) or an MS-mimicking disease (including clinically isolated syndrome, NMOSD, systemic lupus erythematosus (SLE), cerebral vasculitis, episodic migraine, cluster headache, and small vessel disease) were studied to investigate the sensitivity and specificity of various central vein sign lesion criteria using 3T brain MRI. At baseline, 38.9% of patients had RRMS, 23.4% had cerebral small vessel disease, 19.3% of patients had clinically isolated syndrome, 5.3% had aquaporin-4 antibody-positive NMOSD, 4.8% had migraine, 4.1% had SLE, 3.3% had diabetes mellitus, and 0.8% had cluster headaches. Researchers found that a positive central vein sign was found in 47.4% of RRMS lesions, 54.2% of clinically isolated syndrome lesions, and 15.7% of all other non-MS lesions. For the 35% central vein sign proportion threshold, the specificity for differentiation between MS and clinically isolated syndrome and patients without MS was 82.9%, and the sensitivity was 68.1%. The criteria of three or more central vein sign lesions had a sensitivity of 61.9% and specificity of 89.0%. Finally, the use of optimized T2*-weighted imaging increased the sensitivity and specificity of the 35% central vein sign proportion threshold to 100% and 86.7%, respectively. Overall, this study illustrates that the central vein sign on 3T MRI has a high specificity and moderate sensitivity in differentiating MS from MS-mimicking diseases, however, future prospective studies will be necessary to support the use of this diagnostic test in clinical practice.

Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt

Childhood-onset inflammatory bowel disease (IBD) typically has a more severe course than adult-onset IBD, and has been found to be associated with psychiatric morbidity in previous studies. However, these studies have failed to account for familial confounding. In this population-based cohort study, 6,464 patients with childhood-onset IBD were compared with 323,200 matched controls and 6,999 siblings of patients with IBD to examine the risk of psychiatric morbidity, including any psychiatric disorder and suicide attempt. At baseline, 3,228 patients had ulcerative colitis, 2,536 had Crohn’s disease, and 700 had IBD-unclassified. Patients were followed for a median of 9 years (IQR 4 to 15 years), and the median age at the end of follow-up was 23 years (IQR 18 to 29 years). Researchers found that, during the follow-up period, more patients with childhood-onset IBD received a diagnosis of any psychiatric disorder (incidence rate (IR) 17.1 per 1,000 person-years) than matched controls (IR 11.2 per 1,000 person-years, HR 1.6, 95% CI 1.5 to 1.7). Moreover, more patients with childhood-onset IBD attempted suicide (IR 1.6 per 1,000 person-years) than matched controls (IR 1.2 per 1,000 person years, HR 1.4, 95% CI 1.2 to 1.7). Childhood-onset IBD was also associated with mood disorders (HR 1.6, 95% CI 1.4 to 1.7), anxiety disorders (HR 1.9, 95% CI 1.7 to 2.0), eating disorders (HR 1.6, 95% CI 1.3 to 2.0), personality disorders (HR 1.4, 95% CI 1.1 to 1.8), attention-deficit/hyperactivity disorder (HR 1.2, 95% CI 1.1 to 1.4), and autism spectrum disorders (HR 1.4, 95% CI 1.1 to 1.7). The sibling comparison confirmed the observed associations, and results were similar between girls and boys. The risk of any psychiatric disorder was tripled in the first year after IBD diagnosis (HR 3.5, 95% CI 3.0 to 4.0) and remained statistically significant after 5 or more years of follow-up (HR 1.3, 95% CI 1.2 to 1.5). Finally, there was a particularly increased risk of any psychiatric disorder among patients with very early-onset IBD (<6 years of age, HR 2.4, 95% CI 1.9 to 3.1), as well as those with extra-intestinal manifestations (HR 2.0, 95% CI 1.7 to 2.4), bowel surgery (HR 1.9, 95% CI 1.6 to 2.2), perianal surgery (HR 2.0, 95% CI 1.7 to 2.4), and parental psychiatric history (HR 3.4, 95% CI 1.7 to 6.7) as compared to matched controls. This study was limited by a lack direct measurement of IBD severity. In summary, this study emphasizes the increased risk of psychiatric morbidity in patients with childhood-onset IBD, and thus, the critical importance of mental health surveillance in this patient group.

Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial

Maintenance inhaled corticosteroid therapy is effective for preventing severe asthma exacerbations in patients with mild to moderate asthma at baseline. However, adherence to these agents in clinical practice is poor. A proposed alternative approach is to use a combination of a long-acting beta-agonist (LABA), such as formoterol, and an inhaled corticosteroid, such as budesonide, as a reliever monotherapy, which would enable the titration of use according to symptom severity. In this open-label, randomized controlled trial, 885 patients with a self-reported doctor’s diagnosis of asthma who were using a short-acting beta-agonist (SABA) for symptom relief with or without low to moderate doses of inhaled corticosteroids in the previous 12 weeks were assigned to receive either reliever (as-needed) therapy with inhaled budesonide-formoterol, or maintenance budesonide plus as-needed terbutaline (a SABA), to assess the number of severe exacerbations per patient per year. A severe exacerbation was defined as the use of systemic corticosteroids for at least 3 days because of an asthma exacerbation, admission to hospital, or emergency department visit because of asthma requiring systemic corticosteroids. Patients were followed for 52 weeks. At baseline, 30% of patients were taking SABA reliever therapy alone, and 70% of patients were taking an inhaled corticosteroid in addition to a SABA. Researchers found that the rate of severe asthma exacerbations was lower with as-needed budesonide-formoterol than maintenance budesonide and as-needed terbutaline (RR 0.69, 95% CI 0.48 to 1.00, p=0.049). Furthermore, time to first severe exacerbation was longer with budesonide-formoterol than maintenance budesonide plus as-needed terbutaline. Nasopharyngitis was the most common adverse event in both groups, occurring in 35% of patients receiving as-needed budesonide-formoterol, and 32% of patients receiving maintenance budesonide plus terbutaline. This study was limited by its open-label design. These findings support the use of an as-needed corticosteroid-formoterol inhaler over maintenance therapy for the prevention of severe asthma exacerbations in patients with mild to moderate asthma.

Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases

With the large and growing population of cancer survivors over the last several decades, there exists significant concern that these patients may be at an increased risk of cardiovascular disease. However, few studies have examined risks of multiple specific outcomes of cardiovascular disease in survivors of a wide range of cancers. In this population-based cohort study, 108,215 cancer survivors of the 20 most common cancers, alive 12 months after diagnosis, and 523,541 matched controls were studied to compare the risks of a range of long-term cardiovascular disease outcomes. Primary care, hospital, and cancer registry data were obtained through the UK Clinical Practice Research Datalink. At 10 years after cancer diagnosis, 15.2% of cancer survivors and 19.0% of controls were still under follow-up. At baseline, smoking, hypertension, previous history of cardiovascular disease, and chronic kidney disease were slightly more prevalent in cancer survivors than matched controls, whereas heavy drinking was slightly less prevalent in cancer survivors than matched controls at baseline. Researchers found that cancer survivors were at an increased risk of venous thromboembolism (in 18 of 20 cancers), heart failure or cardiomyopathy (10 of 20 cancers), arrhythmia (8 of 20 cancers), pericarditis (8 of 15 cancers), coronary artery disease (5 of 20 cancers), stroke (5 of 20 cancers), and valvular heart disease (3 of 18 cancers) (by adjusted HRs, p<0.01 for all). Survivors of hematological malignancies were at increased risk of all cardiovascular outcomes, whereas the risk pattern was more varied for survivors of other types of cancers. Furthermore, there was an increased risk of heart failure or cardiomyopathy and venous thromboembolism in younger patients and patients without previous cardiovascular disease in a variety of cancers; this risk was most pronounced in patients who had received chemotherapy. Overall, results from this study suggest that cancer survivors are at an increased risk of multiple cardiovascular disease as compared to the general population, underlining a need for more intensive cardiovascular disease screening, prevention, and management strategies in this patient population.

Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor

In patients with Crohn’s disease (CD), endoscopic evidence of healing after treatment is associated with favorable outcomes. Anti-tumor necrosis factor (TNF) agents have been shown to induce ileocolonic healing in CD, however the impact of these agents on gross small bowel healing as indicated by endoscopy has not been studied. In this case series, 116 patients with ileal or ileocolonic CD treated with anti-TNF agents at a single center in Japan were evaluated using balloon-assisted enteroscopy (BAE) to assess endoscopic healing (EH) in the small bowel and colon before and after anti-TNF therapy. Secondary outcomes included the rate of complete ulcer healing and endoscopic response (defined as a reduction in the Simple Endoscopy Score for CD by 50% or more). At baseline, 40% of patients had only ileal involvement, and 60% of patients had ileocolonic involvement; 75% of patients were male, and 63% of patients were anti-TNF naïve. In total, 46 patients received infliximab and 70 patients received adalimumab. Researchers found that 35% of patients achieved small bowel EH and 79% of patients achieved colonic EH during anti-TNF maintenance therapy; the rate of small bowel EH was significantly lower than that of colonic EH (p<0.001). Failure to achieve small bowel EH was found to be significantly associated with stricturing or penetrating disease (p=0.014), lack of concomitant treatment with immunomodulators (p=0.015), and having received previous treatment with an anti-TNF agent (p=0.018). Prognostically, small bowel EH was associated with better disease outcomes than non-small bowel EH (relapse, p<0.001; hospitalization, p=0.001; surgery, p=0.035). In summary, this study indicates that small bowel Crohn’s disease is less likely to demonstrate endoscopic healing after anti-TNF therapy than colonic Crohn’s disease. The findings of this study also indicate that patients that achieve small bowel healing have a more favorable prognosis compared to those that achieve non-small bowel healing.

Image: PD

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