Comorbid Inducible Urticaria Is Linked to Non-Autoimmune Chronic Spontaneous Urticaria: CURE Insights.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) can have comorbid inducible urticaria (CIndU). How comorbid CIndU affects patients and their CSU is largely unclear. OBJECTIVE: To compare patients with CSU with and without comorbid CIndUs for differences in demographic features, clinical characteristics, and laboratory markers. METHODS: We analyzed 708 patients with CSU of our Urticaria Center of Reference and Excellence enrolled in CURE, the chronic urticaria registry. CURE data collected until October 2022 were used to compare patients with and without comorbid CIndU for their demographic characteristics, disease onset, activity, impact, and control, as well as concomitant allergic and autoimmune diseases and laboratory parameters associated with autoimmune CSU. RESULTS: Of 708 patients with CSU, 247 (35%) had comorbid CIndU. Compared with patients with standalone CSU, patients with CSU with comorbid CIndU were significantly younger, had earlier disease onset, longer disease duration, higher impact on quality of life, and a higher rate of concomitant allergic diseases. Moreover, patients with CSU with comorbid CIndU less often had features linked to autoimmune CSU such as angioedema, concomitant autoimmune diseases, eosinopenia, low levels of total IgE, and low total IgE combined with elevated anti-thyroid peroxidase IgG. CONCLUSIONS: Autoimmune CSU may be less common in patients with comorbid CIndU than without, and comorbid CIndU may point to autoallergic CSU.

Real-world clinical effectiveness of Tixagevimab/Cilgavimab and Regdanvimab monoclonal antibodies for COVID-19 treatment in Omicron variant-dominant period.

Several virus-neutralizing monoclonal antibodies (mAbs) have become new tools in the treatment of the coronavirus disease (COVID-19), but their effectiveness against the rapidly mutating virus is questionable. The present study investigated the effectiveness of Tixagevimab/Cilgavimab and Regdanvimab for mild and moderate COVID-19 treatment in real-world clinical practice during the Omicron variant-dominant period. Patients with known risk factors for disease progression and increasing disease severity were enrolled in the study within the first 7 days of symptom onset. Seventy-seven patients were divided into four groups: first 15 patients received 300 mg Tixagevimab/Cilgavimab intravenously (IV) and 23 patients got the same drug 300 mg intramuscularly (IM), the next 15 patients was on the same combination in dose of 600 mg IV, and 24 patients were on Regdanvimab at a dose of 40 mg/kg IV. By Day 4, 100% of Tixagevimab/Cilgavimab IV patients showed negative polymerase chain reaction results for SARS-CoV-2 Ribonucleic acid (RNA) regardless of the mAbs dose while in the Regdanvimab group 29% of the patients were positive for SARS-CoV-2 virus RNA. The testing for virus neutralizing antibodies (nAbs) to various Omicron sublineages (BA.1, BA.2, and BA.5) showed that an increase in nAb levels was detected in blood serum immediately after the drug administration only in Tixagevimab/Cilgavimab 300 mg and 600 mg IV groups. In the group of intravenous Regdanvimab, a significant increase in the level of nAbs to the Wuhan variant was detected immediately after the drug administration, while no increase in nAbs to different Omicron sublineages was observed. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05982704.

The Features of Martensitic Transformation in 12% Chromium Ferritic-Martensitic Steels.

An anomaly in martensitic transformation (the effect of martensitic two-peak splitting in the temperature-dependent thermal expansion coefficient) in complex alloyed 12% chromium steels Fe-12%Cr-Ni-Mo-W-Nb-V-B (ChS-139), Fe-12%Cr-Mo-W-Si-Nb-V (EP-823) and Fe-12%Cr-2%W-V-Ta-B (EK-181) was investigated in this study. This effect is manifested in steels with a higher degree of alloying (ChS-139). During varying temperature regimes in dilatometric analysis, it was found that the splitting of the martensitic peak was associated with the superposition of two martensitic transformations of austenite depleted and enriched with alloying elements. The anomaly was subsequently eliminated by homogenization of the steel composition due to high-temperature aging in the γ-region. It was shown that if steel is heated to 900 °C, which lies in the (α + γ) phase region or slightly higher during cooling, then the decomposition of austenite proceeds in two stages: during the first stage, austenite is diffused into ferrite with carbides; during the second stage, shear transformation of austenite to martensite occurs.

Autoimmune Chronic Spontaneous Urticaria Detection with IgG Anti-TPO and Total IgE.

BACKGROUND: Autoimmune chronic spontaneous urticaria (aiCSU) comes with high disease activity and poor response to treatment. Recently, elevated levels of IgG anti-thyroid peroxidase (aTPO) and low levels of total IgE were reported to be common in aiCSU. OBJECTIVE: To investigate how high aTPO and low IgE individually and combined are linked to features of aiCSU, including treatment responses. METHODS: We analyzed records of patients with CSU from 2 independent cohorts (n = 1120) for demographic, clinical, and laboratory parameters and treatment responses. Total IgE and aTPO were measured, and 4 markers of aiCSU were analyzed: autologous serum skin test, basophil activation test (BAT), and blood eosinophil and basophil counts. Cutoff values were greater than or equal to 34 kU/L (high aTPO) and less than 40 IU/mL (low total IgE). RESULTS: One of 10 patients with CSU had both high aTPO and low IgE (aTPO↑IgE↓, 11%, n = 123). aTPO↑IgE↓ was linked to higher age at CSU onset, being female, angioedema, and shorter CSU duration. aTPO↑IgE↓ was associated with markers of aiCSU, that is, BAT and autologous serum skin test positivity, basopenia, and eosinopenia (P < .01 for all). Almost half the patients with aTPO↑IgE↓ (44%, 19 of 43) had a positive BAT result, the best single marker for aiCSU, versus 12% (43 of 344) of patients without aTPO↑IgE↓ (P < .001). Relative risk of showing BAT positivity for a patient with aTPO↑IgE↓ is 3.636 (95% CI, 2.382-5.551). Patients with aTPO↑IgE↓ showed low response rates to antihistamine treatment as compared with patients without aTPO↑IgE↓ (30% vs 47%; P = .01). CONCLUSIONS: Our findings suggest that aTPO↑IgE↓ is a useful diagnostic marker for aiCSU in everyday clinical practice.

Temporal Clinical and Laboratory Response to Interleukin-6 Receptor Blockade With Tocilizumab in 89 Hospitalized Patients With COVID-19 Pneumonia.

BACKGROUND: Pandemic COVID-19 pneumonia due to SARS-2 is an important cause of morbidity and mortality. Emerging evidence links poor outcomes to an inflammatory cytokine storm. METHODS: We treated 89 hospitalized patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) with an infusion of tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor. RESULTS: Clinical and laboratory evidence of improvement was evident when baseline and 1-2-day post-infusion indices were compared. Among the 72 patients receiving supplemental oxygen without mechanical ventilation, severity of condition on the NEWS2 scale scores fell from 5 to 2 (P<0.001), C reactive protein levels fell from 95 to 14 mg/L (P<0.001), and lymphocyte counts rose from 900 to 1000/uL (P=0.036). Sixty-three of 72 patients were discharged from the hospital, one patient died, and eight patients remained in the hospital at the time of this writing. Among the 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (P=0.014) and early improvements in NEWS2 scores in 10 of 17 patients, 10 patients ultimately died and the other seven remain in the hospital at the time of this writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (<1000/uL) before TCZ administration. CONCLUSIONS: Inflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of tocilizumab, an anti-IL-6 receptor antibody, is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.