Incidence of anxiety disorder in adults with hidradenitis suppurativa.

BACKGROUND: There are limited data on the risk of new-onset anxiety disorders in patients with hidradenitis suppurativa (HS). OBJECTIVES: To compare the risk of new-onset anxiety disorder in patients with HS and controls, and to describe risk factors for the development of anxiety in patients with HS. METHODS: We carried out a retrospective cohort analysis of a US electronic health records database between 2011 and 2020. Adults newly diagnosed with HS at a dermatology or primary care visit and control participants were included. The primary outcome was a new diagnosis of generalized anxiety disorder, phobic disorders, panic disorder or unspecified anxiety. Cox proportional hazards regression was used to compare the crude risk of any anxiety disorder between groups and to assess the independent association with HS while controlling for potential demographic, clinical and healthcare-related confounders. RESULTS: Among 9597 patients with HS and 959 493 controls, the incidence rate (IR) of anxiety was 5.74 and 3.86 per 100 person-years (PY), respectively. The crude risk among all patients was 48% higher for those with HS vs. controls [hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.40-1.55]. When stratified by index encounter type, patients with HS had 2.43 (95% CI 2.13-2.77) times the risk of anxiety disorder than dermatology controls and 1.46 (95%CI 1.38-1.55) times the risk than primary care controls. The adjusted HR for patients with HS vs. controls was 1.11 (95% CI 1.05-1.17) overall, 1.26 (95% CI 1.07-1.48) in the dermatology subgroup and 1.07 (95% CI 1.01-1.13) in the primary care subgroup. Risk factors for an incident anxiety diagnosis among patients with HS included depression (HR 1.69, 95% CI 1.48-1.93), female sex (HR 1.41, 95% CI 1.23-1.60), younger age (HR 0.87 per 10-year increase, 95% CI 0.84-0.90), White race, in the Medicaid insurance programme (HR 1.22, 95% CI 1.07-1.40), tobacco smoking (HR 1.16, 95% CI 1.03-1.31) and having one or more emergency department visits in the year before a HS diagnosis. Absolute IRs of anxiety disorders were highest among patients with HS who were aged 18-29 years (7.10 per 100 PY), female (6.34 per 100 PY) and White (6.79 per 100 PY). CONCLUSIONS: HS is independently associated with an increased risk of anxiety disorders. An increased risk remains but is attenuated when confounders are controlled for. The relative risk may be particularly high in patients managed by dermatologists.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful skin lesions that often leak pus from sensitive areas of the body, including the arm pits, breasts, groin and perineum. The disease can flare in severity without notice. Due to the sensitive nature of the affected areas, unpredictability of the disease course and scarring that may occur because of chronic inflammation, HS is known to severely affect a person's quality of life. Some studies have linked HS to depression and anxiety. However, there is limited evidence describing which condition comes first, and the relationship is less well established among people from the USA with HS. This study aimed to investigate how many people with HS go on to develop a diagnosis of an anxiety disorder in the USA. We found that anxiety is more likely to develop in people with HS than in people without the disease. We also found that certain risk factors make a person with HS more likely to be diagnosed with anxiety, such as a history of depression, being female, being younger, being White, being an active cigarette smoker, being in the Medicaid insurance programme and making one or more visits to the emergency department in the year before their HS diagnosis. Overall, our study findings provide information on the association between HS and the development of anxiety, which is important to guide the clinical management of patients diagnosed with this skin condition.

Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn's disease and regulate Th1/Th17 cell responses.

Increased T helper (Th)1/Th17 immune responses are a hallmark of Crohn's disease (CD) immunopathogenesis. CD90+ (myo-)fibroblasts (MFs) are abundant cells in the normal (N) intestinal mucosa contributing to mucosal tolerance via suppression of Th1 cell activity through cell surface membrane-bound PD-L1 (mPD-L1). CD-MFs have a decreased level of mPD-L1. Consequently, mPD-L1-mediated suppression of Th1 cells by CD-MFs is decreased, yet the mechanism responsible for the reduction in mPDL-1 is unknown. Increased expression of matrix metalloproteinases (MMPs) has been reported in CD. Herein we observed that when compared to N- and ulcerative colitis (UC)-MFs, CD-MFs increase in LPS-inducible levels of MMP-7 and -9 with a significant increase in both basal and inducible MMP-10. A similar pattern of MMP expression was observed in the CD-inflamed mucosa. Treatment of N-MFs with a combination of recombinant human MMP-7, -9 and -10 significantly decreased mPD-L1. In contrast, inhibition of MMP activity with MMP inhibitors or anti-MMP-10 neutralizing antibodies restores mPD-L1 on CD-MFs. CD-MFs demonstrated reduced capacity to suppress Th1 and Th17 responses from activated CD4+ T cells. By contrast, supplementation of the CD-MF:T-cell co-cultures with MMP inhibitors or anti-MMP neutralizing antibodies restored the CD-MF-mediated suppression. Our data suggest that (i) increased MMP-10 expression by CD-MFs and concomitant cleavage of PD-L1 from the surface of CD-MFs are likely to be one of the factors contributing to the decrease of mPD-L1-mediated suppression of Th1/Th17 cells in CD; and (ii) MMPs are likely to have a significant role in the intestinal mucosal immune responses.

Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes.

Cancers harboring mutations in the Kirsten rat sarcoma homolog (KRAS) gene have been associated with poor prognosis and lack of targeted therapies. KRAS mutations occur in approximately one in four patients diagnosed with non-small cell lung cancer (NSCLC) with KRAS G12C mutations harbored at approximately 11-16%. Research into KRAS-driven tumors and analytical chemistry have borne a new class of selective small molecules against the KRAS G12C isoform. Phase II data for sotorasib (AMG510) has demonstrated a 37.1% overall response rate (ORR). Adagrasib (MRTX849) has demonstrated a 45% ORR in an early study. While single agent efficacy has been seen, initial data suggest combination approaches are an opportunity to improve outcomes. Here, we present perspectives on the initial progress in targeting KRAS G12C, examine co-mutations evident in KRAS G12C NSCLC, and comment on potential future combinatorial approaches including SHP2, SOS1, MEK, EGFR, mTOR, CDK, and checkpoint blockade which are currently being evaluated in clinical trials. As of May 28, 2021, sotorasib has achieved US FDA approval for patients with KRAS G12C mutant lung cancer after one line of a prior therapy.