Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (hαCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of hαCGRP (2 μg/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (Vmean) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% ± 1.7 with hαCGRP, vs. −1.6% ± 3.1 with placebo (mean ± SD)] (P = 0.43). Vmean in MCA decreased to 13.5% ± 3.6 with hαCGRP versus 0.6% ± 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. hαCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine

Clinical, biochemical and endoscopic disease activity of Inflammatory Bowel Diseases are not associated with the severity or long-term outcomes of COVID-19-A Danish prospective population-based cohort study

BACKGROUND: Whether the disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) is correlated with the severity of coronavirus disease 2019 (COVID-19) remains poorly investigated with only few selected cohort studies having addressed this in the past. METHODS: We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Clinical disease activity was measured by simple clinical colitis index and Harvey-Bradshaw Index in UC and CD, respectively. The biochemical activity was defined as C-reactive protein higher than 5 mg/L or fecal calprotectin higher than 250 μg/g. The endoscopic activity was defined as Mayo Endoscopic Subscore of at least 2 in UC, or Simple Endoscopic Score Crohn’s Disease of at least 3 for CD. Sequelae following COVID-19 were defined as symptoms that (i) developed during or after an infection consistent with COVID-19, (ii) and were present for more than 12 weeks, (iii) and were not attributable to alternative diagnoses. RESULTS: During the inclusion period between January 28(th), 2020, to April 1(st), 2021, the study included 319 patients with UC and 197 patients with CD who developed laboratory confirmed COVID-19. Of these, data on clinical, biochemical, and endoscopic activity were available among 265/319 (83.1%), 319/319 (100.0%), and 66/319 (20.7%) of patients with UC, respectively, and 140/197 (71.1%), 131/197 (66.5%), and 42/197 (21.3%) of patients with CD. Figures 1–2 outlines the outcomes of COVID-19 according to the degree of clinical, biochemical and endoscopic disease activity. In both UC and CD, clinical, biochemical, and endoscopic activity were not associated with adverse or severe COVID-19, nor long-term outcomes, in unadjusted nor adjusted analysis (Table 1). [Image: see text] [Image: see text] [Image: see text] CONCLUSION: In this population-based study, we found no association between disease activity of UC or CD and severity of COVID-19. These findings have implications for the risk stratification of patients with IBD acquiring COVID-19

Long-term health consequences of COVID-19 in patients with Inflammatory Bowel Diseases - A Danish prospective population-based cohort study

BACKGROUND: The vast majority of patients with ulcerative colitis (UC) and Crohn’s disease (CD) who acquire coronavirus disease 2019 (COVID-19) survive the infection. Still, the long-term health consequences of COVID-19 are not well described in patients with underlying inflammatory bowel disease (IBD). METHODS: We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Sequelae following COVID-19 were defined as symptoms that developed during or after an infection consistent with COVID-19, were present for more than 12 weeks, and were not attributable to alternative diagnoses. RESULTS: The study included 319 patients with UC and 197 patients with CD from January 28(th), 2020, to April 1(st), 2021. Of these, a total of 137 (42.9%) and 85 (43.1%), respectively, participated in a subsequent investigation of post-COVID-19 sequelae after a median of 5.1 months (IQR 4.5–7.9) after infection (Table 1). An equal proportion of patients with UC (58 (42.3%)) and CD (39 (45.9%), p=0.60) reported persisting symptoms of COVID-19 for at least 12 weeks, consistent with the development of post-COVID-19 syndrome. The most common persisting patient-reported symptoms included fatigue (UC: 49 (35.8%), CD: 31 (36.5%), p=0.92), anosmia (UC: 37 (27.0%), CD: 25 (29.4%), p=0.70), ageusia (UC: 26 (19.0%), CD: 24 (28.2%), p=0.11), headache (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), dyspnea (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), and arthralgia (UC: 17 (12.4%), CD: 14 (16.5%), p=0.40) (Figure 1). Only discontinuation of immunosuppressive therapies for UC during COVID-19 (OR=1.50 (95% CI 1.07–10.22), p=0.01) and the severity of COVID-19 among patients with CD were independently associated with the long-term effects of COVID-19 (OR=2.76 (95% CI 1.05–3.90), p=0.04) (Tables 2–3). [Image: see text] [Image: see text] [Image: see text] [Image: see text] CONCLUSION: This Danish population-based study found a high occurrence of patient-reported persisting symptoms following the acute phase of COVID-19 infection, which were associated with the discontinuation of immunosuppressive therapies for UC during COVID-19 and the severity of COVID-19 among patients with CD. These findings might have implications for planning the healthcare of patients with inflammatory bowel diseases in the post-COVID-19 era

Outcomes of COVID-19 among patients with inflammatory bowel diseases and the influence of IBD-related medications- A Danish prospective population-based cohort study

BACKGROUND: Population-based data regarding outcomes of coronavirus disease 2019 (COVID-19) among patients with ulcerative colitis (UC) and Crohn’s disease (CD) remain limited. METHODS: We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Regression analysis was adjusted for age, sex, disease type, disease activity, cardiovascular disease, and corticosteroids. Outcomes of COVID-19 among patients with UC and CD were compared with those among the background population covering all incidents of COVID-19 in Denmark. RESULTS: The study included 319 patients with UC and 197 patients with CD from January 28(th), 2020, to April 1(st), 2021. Baseline characteristics are presented in Table 1. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N=46(14.4%), RR=2.49 (95%CI 1.91–3.26)) and CD (N=24(12.2%), RR=2.11 (95%CI 1.45–3.07)) as compared with the background population (N=13,306 (5.8%)). A similar pattern was observed for admission to intensive care (UC: N=8(2.51%), RR=27.88 (95%CI 13.88–56.00); CD: N=3 (1.52%), RR=16.92 (95%CI 5.46–52.46)) (Figure 1). The association between these outcomes and IBD-related clinical characteristics and treatments is presented in Tables 2–3. As shown, none of the IBD-related medications were associated with severe COVID-19 in univariate and multivariable analysis. However, systemic steroids were found to be associated with an increased risk of adverse COVID-19 among patients with CD (adjusted odds ratio (aOR)=13.62 (95% CI 1.98–17.77)). [Image: see text] [Image: see text] [Image: see text] [Image: see text] CONCLUSION: This Danish population-based study on COVID-19 outcomes among patients with UC and CD demonstrated severe COVID-19 among only a minority of patients, which was not associated with IBD-related medications. Apart from systemic steroids, this study encourages continued use of IBD therapy to prevent IBD relapse and complications

Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn’s Disease

BACKGROUND: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated. AIM: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. METHODS: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. RESULTS: There was a significant increase in bone formation markers osteocalcin (P CONCLUSIONS: This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.</p