Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUND: Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients. AIM: To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas. METHODS: This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events. RESULTS: The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) µg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) µg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations. CONCLUSION: We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Metabolic syndrome and endocrine status in HIV-infected transwomen.

BACKGROUND: HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. METHODS: A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. RESULTS: A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. CONCLUSION: In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.

Airway smooth muscle enlargement is associated with protease-activated receptor 2/ligand overexpression in patients with difficult-to-control severe asthma.

BACKGROUND: Asthma is a complex disease with heterogeneous features of airway inflammation and remodeling. The increase in airway smooth muscle (ASM) mass is an essential component of airway remodeling in patients with severe asthma, yet the pathobiological mechanisms and clinical outcomes associated with ASM enlargement remain elusive. OBJECTIVE: We sought to compare ASM area in control subjects and patients with mild-to-moderate or severe asthma and to identify specific clinical and pathobiological characteristics associated with ASM enlargement. METHODS: Bronchial biopsy specimens from 12 control subjects, 24 patients with mild-to-moderate asthma, and 105 patients with severe asthma were analyzed for ASM area, basement membrane thickness, vessels, eosinophils, neutrophils, T lymphocytes, mast cells, and protease-activated receptor 2 (PAR-2). In parallel, the levels of several ASM mitogenic factors, including the PAR-2 ligands, mast cell tryptase, trypsin, tissue factor, and kallikrein (KLK) 5 and KLK14, were assessed in bronchoalveolar lavage fluid. Data were correlated with asthma severity and control both at inclusion and after 12 to 18 months of optimal management and therapy. RESULTS: Analyses across ASM quartiles in patients with severe asthma demonstrated that patients with the highest ASM quartile (median value of ASM area, 26.3%) were younger (42.5 vs ≥50 years old in the other groups, P ≤ .04) and had lower asthma control after 1 year of optimal management (P ≤ .006). ASM enlargement occurred independently of features of airway inflammation and remodeling, whereas it was associated with PAR-2 overexpression and higher alveolar tryptase (P ≤ .02) and KLK14 (P ≤ .03) levels. CONCLUSION: Increase in ASM mass, possibly involving aberrant expression and activation of PAR-2-mediated pathways, characterizes younger patients with severe asthma with poor asthma control.