Patients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on ...the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE‐anti‐TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.
On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also ...known as a clinically isolated syndrome) to multiple sclerosis.
During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T
-weighted MRI, cumulative number of new lesions enhanced on T
-weighted MRI "enhancing lesions", and cumulative combined number of unique lesions new enhancing lesions on T
-weighted MRI plus new and newly enlarged lesions on T
-weighted MRI).
A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval CI, 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo.
The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).
Prevention of pathogen colonization of medical implants is a major medical and financial issue since infection by microorganisms constitutes one of the most serious complications after surgery or ...critical care. Immobilization of antimicrobial molecules on biomaterials surfaces is an efficient approach to prevent biofilm formation. Herein, the first self‐defensive coating against both bacteria and yeasts is reported, where the release of the antimicrobial peptide is triggered by enzymatic degradation of the film due to the pathogens themselves. Biocompatible and biodegradable polysaccharide multilayer films based on functionalized hyaluronic acid by cateslytin (CTL), an endogenous host‐defensive antimicrobial peptide, and chitosan (HA‐CTL‐C/CHI) are deposited on a planar surface with the aim of designing both antibacterial and antifungal coating. After 24 h of incubation, HA‐CTL‐C/CHI films fully inhibit the development of Gram‐positive Staphylococcus aureus bacteria and Candida albicans yeasts, which are common and virulent pathogens agents encountered in care‐associated diseases. Hyaluronidase, secreted by the pathogens, leads to the film degradation and the antimicrobial action of the peptide. Furthermore, the limited fibroblasts adhesion, without cytotoxicity, on HA‐CTL‐C/CHI films highlights a medically relevant application to prevent infections on catheters or tracheal tubes where fibrous tissue encapsulation is undesirable.
Polysaccharide multilayer films, based on antimicrobial peptide functionalized hyaluronic acid as polyanion and chitosan as polycation, are deposited on planar surfaces with the aim of designing a self‐defensive coating against both bacteria and yeasts.
Chromogranin A (CgA) belongs to the granin family of uniquely acidic secretory proteins co-stored and co-secreted with other hormones and peptides in elements of the diffuse neuroendocrine system. ...The granins arise from different genes and are characterized by numerous sites for post-translational cleavage into shorter peptides with postulated regulatory properties. This review is directed towards endocrine aspects of CgA and its biologically active peptides. There is ample evidence from in vitro studies of distinct effects and targets for three CgA-derived peptides, vasostatin-I, pancreastatin and catestatin. Endocrine regulations are indicated from in vivo studies, consistent with the postulated prohormone function of CgA for peptides with regulatory properties. Most of the effects fit into patterns of direct or indirect, inhibitory modulations of major functions, implicating CgA peptides in regulation of calcium and glucose metabolism, cardiovascular functions, gastrointestinal motility and nociception, tissue repair, inflammatory responses and as host defense peptides in the first phase of microbial invasions.
Summary
Chronic spontaneous urticaria (CSU) is a mast cell‐driven disease that is defined as the recurrence of weals, angioedema or both for > 6 weeks due to known or unknown causes. As of yet, ...disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease‐related biomarkers. Here, we reviewed available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroup allocation or response to treatment. We performed a PubMed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between patients with CSU and healthy controls in blood levels or values of D‐dimer, C‐reactive protein (CRP), matrix metalloproteinase‐9 (MMP‐9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1 + 2 (F1 + 2), tumour necrosis factor, dehydroepiandrosterone sulphate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D‐dimer, F1 + 2, CRP, IL‐6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti‐FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non‐existent. Taken together, we identified 10 biomarkers that are supported by strong evidence for distinguishing patients with CSU from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers that predict outcome or treatment response in CSU.
A seismic swarm affected the 53.3°–54.3° Latitude North section of the Mid‐Atlantic Ridge from 26 September to 10 December 2022. We rely on regional, teleseismic and array data to relocate 61 ...hypocenters and derive 77 moment tensors. The 2022 swarm released a cumulative moment equivalent to Mw 6.3. Seismicity was shallow (7 ± 3 km depth). Most earthquakes are located along the ridge axis with typical, NS oriented normal faulting mechanisms, but a few among the largest and latest earthquakes have unusual thrust mechanisms and locations as far as ∼25 km from the ridge. We attribute the swarm to a shallow magmatic intrusion, with a vertical dike first propagating ∼60 km along axis, accompanied by shallow normal faulting, and then thickening and triggering thrust earthquakes off the ridge, in response to compressive stress buildup. The unrest provides a rare example of an energetic, magmatic driven swarm episode at the mid‐ocean ridge.
Plain Language Summary
The largest plate boundary systems on Earth are Mid‐ocean ridges (MOR), where the plates continuously drift apart and new lithosphere is constantly being formed. Although the process is well understood, we rarely detect spreading events at MOR, mainly because these regions are remote and local monitoring is rarely possible. In September–November 2022 a large, unusual seismic swarm occurred along a spreading center ridge segment of the North Mid‐Atlantic Ridge. Despite the remoteness of the region, we managed to model regional and teleseismic data to perform earthquake relocation, depth estimation and moment tensor inversion. In this way, we could reconstruct the geometry and the evolution of the seismicity. We found that in the early days of the swarm, seismicity migrated unilaterally over ∼60 km along the ridge axis, from North to South, triggering normal faulting earthquakes, which are typical at MOR. Later, large thrust mechanisms, anomalous in an extensional environment, appeared and quickly became predominant. We explain seismological observations by a magmatic intrusion, which first propagated southward, producing shallow normal faulting earthquakes above the vertical magma dike, and later thickened, increasing compressional stresses on its sides, and triggering large thrust earthquakes.
Key Points
Analysis of a short, intense seismic swarm at the Mid‐Atlantic Ridge
Identification of unusual, thrust focal mechanisms in an extensional environment
Swarm triggered by dike intrusion at the mid‐ocean ridge
Background
Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add‐on therapy for CSU patients; ...however, its effect on patients who are double‐positive for wheals and angioedema has not been systematically studied.
Objective
The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU‐Q2oL) questionnaire. Number of angioedema‐burdened days, time interval between successive angioedema episodes, disease activity, angioedema‐specific and overall QoL impairment were secondary objectives.
Methods
X‐ACT was a phase III, randomized, double‐blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072).
Results
Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28‐week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU‐Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema‐burdened days/week with omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57–63 days with omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema‐specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of omalizumab.
Conclusion
Omalizumab was an effective treatment option for patients with moderate‐to‐severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.
Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host–defense responses in certain bacterial ...infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6–deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.
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