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Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions: Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Keywords: allergy; aspergillosis; diabetes; rhino-orbital cerebral mucormycosis; serum ferritin EN allergy aspergillosis diabetes rhino-orbital cerebral mucormycosis serum ferritin 715 720 6 06/14/23 20230701 NES 230701 Key points COVID-19 pandemic led to the rise in cases of mucormycosis in India. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? All patients admitted with suspect mucormycosis were also subjected to RT-PCR for COVID-19 at the time of admission (previous status of COVID-19 was also recorded). The role of high ferritin levels in post-COVID patients cannot be disregarded as ferritin takes longer to clear from circulation in these patients, a factor favourable for I Mucorales i to survive. [Extracted from the article]

Summary: Background: Interleukin‐23 inhibitors are effective and safe for treating moderate‐to‐severe plaque psoriasis. Objectives: To evaluate the efficacy and safety of mirikizumab in adult patients with moderate‐to‐severe plaque psoriasis through 52 weeks in a phase III randomized controlled trial. Methods: OASIS‐1 (NCT03482011) was a double‐blind, placebo‐controlled, randomized withdrawal, phase III trial. Patients (n = 530, randomized 4 : 1) received subcutaneous mirikizumab 250 mg or placebo every 4 weeks (Q4W) through week 16. Coprimary endpoints were superiority of mirikizumab vs. placebo on static Physician's Global Assessment (sPGA; score of 0 or 1 with ≥ 2‐point improvement) and ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90, responders) at week 16. Mirikizumab responders were rerandomized (1 : 1 : 1) to mirikizumab 250 mg every 8 weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W through week 52. Secondary endpoints were evaluated at weeks 16 and 52. Safety was monitored in all patients. Results: All primary and key secondary endpoints were met. At week 16, sPGA(0,1) responses were significantly greater with mirikizumab (293 of 423, 69·3%) than placebo (seven of 107, 6·5%) (P < 0·001). PASI 90 response was also greater with mirikizumab (272 of 423, 64·3%) than placebo (seven of 107, 6·5%) (P < 0·001). Significantly more patients in the mirikizumab arms achieved PASI 75 and PASI 100 (mirikizumab 349, 82·5% and 137, 32·4%; placebo 10, 9·3% and 1, 0·9%, respectively; all P < 0·001). At week 52, PASI 90, PASI 100 and sPGA(0,1) responses were mirikizumab 250Q4W/placeboQ8W (N = 91; 19%, 10%, 18%), mirikizumab 250Q4W/125Q8W (N = 90; 86%, 59%, 86%) and mirikizumab 250Q4W/250Q8W (N = 91; 86%, 60%, 82%; all P < 0·001), respectively. Rates of serious adverse events were similar across treatments (induction: mirikizumab 1·2% vs. placebo 1·9%; maintenance: mirikizumab 250Q4W/125Q8W 1%, mirikizumab 250Q4W/250Q8W 3% vs. placebo 3%). No deaths occurred. Conclusions: Mirikizumab was superior to placebo at week 16 and maintained efficacy through week 52, with no new safety signals. What is already known about this topic?Interleukin (IL)‐23 is a key cytokine in the pathogenesis of psoriasis. Drugs targeting the p19 subunit of IL‐23 have recently been approved for the treatment of adult patients with moderate‐to‐severe plaque psoriasis.Patients with moderate‐to‐severe plaque psoriasis achieved significantly greater improvements in skin measures and patient‐reported quality‐of‐life measures after 16 weeks when treated every 8 weeks with mirikizumab compared with placebo in a phase II clinical trial. What does this study add?Compared with placebo, mirikizumab demonstrated high levels of efficacy at week 16 in a large phase III trial; safety profiles were similar between the mirikizumab and placebo arms.After week 16, patients maintained on doses of mirikizumab 250 mg every 8 weeks (Q8W) or 125 mg Q8W showed similar efficacy and favourable safety profiles over 52 weeks, whereas patients switched to placebo gradually lost efficacy over time. [ABSTRACT FROM AUTHOR]

Background Computed tomography perfusion (CTp), a useful technique in oncology, is not widely utilized due to the high radiation dose delivered from it. It involves scanning the region of interest every second for 50 seconds following intravenous contrast administration. Doubling sampling interval (SI) to 2 seconds will half the radiation dose, but may impact its effectiveness, which needs to be evaluated. Objectives To evaluate a dose reduction strategy in CTp by determining agreement between standard dose (SD) CTp (acquisition with SI 1 second) and low-dose CTp techniques with SI of 2 seconds (achieved either by reconstruction only or true low-dose acquisition). Materials and methods This cross-sectional study was conducted on histopathology-proven head and neck squamous cell carcinoma (HNSCC) patients who underwent CTp on 64 slice multidetector CT. A total of 56 patients had SD and 24 patients underwent true low dose (LD) acquisition. SD data were also reconstructed at SI 2 seconds to obtain a dataset simulating low dose (low-dose reconstruction [LDr]). Paired t -test was applied to compare CTp in SD and LDr groups and the Bland–Altman plot drawn to calculate 95% confidence limit of agreement. The Kolmogorov–Smirnov test compared CTp parameters for LDr and LD groups. Results There was no statistical difference in CTp parameters (except blood flow in malignant) in SD and LDr groups for both malignant and normal tissues. CTp of malignant tissue was not statistically different in LDr and LD groups but the radiation dose was half in the LD group. Conclusion Reduction of radiation dose to half achieved by doubling the SI does not affect the CTp parameters significantly. So LD acquisitions will increase the use of CTp in HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: Capsaicin is a specific agonist of transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptors. Capsaicin not only produces acute pain but also leads to long-lasting analgesia in patients with chronic pain. Although capsaicin-induced TRPV1 and Ca 2+ /calpain-dependent ablation of axonal terminals is necessary for long-lasting analgesia, the mechanisms underlying capsaicin-induced ablation of axonal terminals and its association with analgesia are not fully understood. Microtubules are composed of tubulin polymers and serve as a main axonal cytoskeleton maintaining axonal integrity. In this study, we hypothesized that capsaicin would increase the depolymerization of microtubules and lead to axonal ablation and analgesia for trigeminal neuropathic pain. Paclitaxel, a microtubule stabilizer, decreased capsaicin-induced ablation of axonal terminals in time-lapsed imaging in vitro. Capsaicin increases free tubulin in dissociated sensory neurons, which was inhibited by paclitaxel. Consistently, subcutaneous injection of paclitaxel prevented capsaicin-induced axonal ablation in the hind paw skin. Capsaicin administration to the facial skin produced analgesia for mechanical hyperalgesia in mice with chronic constriction injury of the infraorbital nerve, which was prevented by the coadministration of paclitaxel and capsaicin. Whole-mount staining of facial skin showed that paclitaxel reduced capsaicin-induced ablation of peptidergic afferent terminals. Despite the suggested involvement of TRPV1 Ser801 phosphorylation on microtubule integrity, capsaicin-induced analgesia was not affected in TRPV1 S801A knock-in mice. In conclusion, capsaicin-induced depolymerization of axonal microtubules determined capsaicin-induced ablation of nociceptive terminals and the extent of analgesia. Further understanding of TRPV1/Ca 2+ -dependent mechanisms of capsaicin-induced ablation and analgesia may help to improve the management of chronic pain. [ABSTRACT FROM AUTHOR]