1,540 research outputs found

    Adalimumab in conjunction with surgery compared with adalimumab monotherapy for Hidradenitis suppurativa: A Randomized Controlled Trial in a real-world setting

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    Background: Adalimumab, the only biologic registered for hidradenitis suppurativa, shows clinical response in up to 60% of patients, leaving many patients in need for other treatment options such as surgery. Objective: To compare the clinical effectiveness of adalimumab combined with surgery vs adalimumab monotherapy in patients with moderate to severe hidradenitis suppurativa. Methods: A pragmatic Randomized Controlled Trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean International Hidradenitis Suppurativa Severity Score System reduction after 12 months of treatment with the difference in mean Dermatology Life Quality Index reduction as a key secondary outcome. Results: Thirty-one patients were included per arm. The mean International Hidradenitis Suppurativa Severity Score System at baseline was 23.9 ± 10.7 in the surgery group and 20.9 ± 16.4, in the monotherapy group. After 12 months of treatment the surgery group had a significantly greater reduction in International Hidradenitis Suppurativa Severity Score System compared with the monotherapy group (−19.1 ± 11.3 vs −7.8 ± 11.8, P < .001). Moreover, the surgery group showed a greater reduction in Dermatology Life Quality Index after treatment compared with the monotherapy group (−8.2 ± 6.2 vs −4 ± 7.7, P = .02). Limitations: The study follow-up was too short to assess surgical recurrence rates. Discussion: Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa

    Fibromyalgia in Patients With Hidradenitis Suppurativa

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    Pain is a paramount and debilitating symptom of hidradenitis suppurativa (HS). However, clinical experience reveals that pain intensity is not always consistent with disease severity, and pain can persist after disease remission.1 In other HS-associated inflammatory diseases in which this phenomenon was previously observed, an increased prevalence of fibromyalgia (characterized by generalized entheseal pain) was described.2 In HS, more than half of patients exhibit tenderness of the entheses.3 Therefore, we conducted this study to assess fibromyalgia prevalence using the 2016 Fibromyalgia Diagnostic Criteria in patients with HS compared with age- and sex-matched controls.4Methods:We performed a cross-sectional, survey-based, case-control study at the Department of Dermatology, Erasmus University Medical Center Rotterdam, between February and November 2020. The Erasmus University Medical Center Rotterdam Ethical Committee confirmed that the Medical Research Involving Human Subjects Act did not apply to this research. All patients provided written informed consent. We followed the STROBE reporting guideline.All consecutive patients with HS 18 years or older were included during routine clinic visits. Age- and sex-matched controls (with non–pain-related conditions) were recruited from the same outpatient clinic. Fibromyalgia was diagnosed according to the 2016 Fibromyalgia Diagnostic Criteria.4 Univariate and multivariate logistic regression models were constructed to assess the outcomes of variables associated with fibromyalgia.Two-sided P ≤ .05 was considered statistically significant. Statistical analyses were performed from December 2022 to January 2023, using SPSS Statistics 26.0 (IBM Corporation). The eMethods in Supplement 1 provide more details.Results:The study included 100 patients with HS (median [IQR] age, 34.5 [27.3-47.0] years) and 100 controls (median [IQR] age, 33.5 [27.0-48.8] years), and both groups comprised 71 females (71%) and 29 males (29%). Table 1 shows characteristics of each group. No significant difference in self-reported fibromyalgia diagnosis was found between the groups. However, significantly more patients with HS than controls were diagnosed with fibromyalgia when the diagnostic criteria were used (13 [13%] vs 4 [4%]; P = .02).Univariate logistic regression of all participants identified a significantly increased odds ratio (OR) for fibromyalgia in patients with HS (3.56; 95% CI, 1.13-11.41; P = .03), rheumatoid arthritis (5.97; 95% CI, 1.01-35.29; P &lt; .05), and previously diagnosed depression (7.75; 95% CI, 2.68-22.39; P &lt; .001) (Table 2). Rheumatoid arthritis, another possible risk factor for fibromyalgia, was included in the multivariate logistic regression. The OR for fibromyalgia among patients with HS remained significantly increased at 3.45 (95% CI, 1.08-11.09; P = .04). Within the HS group, both the International Hidradenitis Suppurativa Severity Score System (OR, 1.11; 95% CI, 1.03-1.20; P = .01) and pain (OR, 1.47; 95% CI, 1.15-1.87; P = .002) scores showed an association with fibromyalgia and hence increased odds.Discussion:Two studies have described fibromyalgia prevalence in patients with HS.5,6 The first was a cross-sectional population-based study with 56 084 patients that found increased fibromyalgia odds (1.51) in patients with HS. The second study was a retrospective medical records review with 1356 patients that found the fibromyalgia prevalence in the HS population was lower than the overall US estimated prevalence (3.2% vs 6.0%).5,6 However, both studies relied on self-reported fibromyalgia diagnoses. In the present cohort, the actual odds for fibromyalgia were 3 times higher than the self-diagnosed reports, highlighting the limitations and underestimation associated with self-reported fibromyalgia diagnoses in research settings.Proinflammatory cytokines, which are elevated in HS, such as tumor necrosis factor and interleukin 17 are also increased in plasma of patients with fibromyalgia. This mechanism suggests that elevated levels of proinflammatory cytokines might be associated with increased fibromyalgia prevalence, strengthening the hypothesis that local and systemic inflammation could drive the alteration in neurotransmission.A study limitation was the single-center design, which could have created a homogeneous population and may limit generalizability. However, a study strength was use of the 2016 Fibromyalgia Diagnostic Criteria vs self-reported diagnosis. Antidepressants and antiepileptics, such as gabapentin and pregabalin, could be beneficial in treatment of chronic pain for patients with HS and comorbid fibromyalgia. This case-control study found that patients with HS had over 3 times the odds of having fibromyalgia compared with controls according to the 2016 Fibromyalgia Diagnostic Criteria

    Maternal exposure to polystyrene nanoparticles retarded fetal growth and triggered metabolic disorders of placenta and fetus in mice

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    Microplastics can enter the human body via direct body contact or the food chain, increasing the likelihood of adverse impacts on pregnancy and fetal development. We investigated the potential effects and modes of action of polystyrene nanoplastics (PS-NPs) in placenta and fetus using mice as a model species. Maternal PS-NP exposure (100 nm; 1 and 10 mg/L) via drinking water induced a significant decline in fetal weights at the higher exposure concentration. Abnormal morphologies of cells in the placenta and fetus were observed after exposure. For the placenta, transcriptomic analyses indicated that PS-NPs significantly disturbed cholesterol metabolism and complement and coagulation cascades pathways. Metabolomics showed appreciable metabolic disorders, particularly affecting sucrose and daidzein concentrations. For the fetal skeletal muscle, transcriptomics identified many significantly regulated genes, involving muscle tissue development, lipid metabolism, and skin formation. Transcriptomic analysis of the placenta and fetal skeletal muscle at the high PS-NP concentration showed that APOA4 and its transcriptional factors, facilitating cholesterol transportation, were significantly regulated in both tissues. Our study revealed that PS-NPs caused fetal growth restriction and significantly disturbed cholesterol metabolism in both placenta and fetus, offering new insights into the mechanisms underlying the placental and fetal effects in mice exposed to PS-NPs

    Guselkumab for hidradenitis suppurativa:a phase II, open-label, mode-of-action study

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    BACKGROUND: The effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are needed. OBJECTIVES: To investigate the efficacy and mode of action of guselkumab [an anti-interleukin (IL)-23p19 monoclonal antibody] 200 mg subcutaneously every 4 weeks for 16 weeks in patients with HS. METHODS: An open-label, multicentre, phase IIa trial in patients with moderate-to-severe HS was carried out (NCT04061395). The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. The protocol was reviewed and approved by the local institutional review board (METC 2018/694), and the study was conducted in accordance with good clinical practice guidelines and applicable regulatory requirements. RESULTS: Thirteen of 20 patients (65%) achieved HiSCR with a statistically significant decrease in median IHS4 score (from 8.5 to 5.0; P = 0.002) and median AN count (from 6.5 to 4.0; P = 0.002). The overall patient-reported outcomes did not show a similar trend. One serious adverse event, likely to be unrelated to guselkumab treatment, was observed. In lesional skin, transcriptomic analysis revealed the upregulation of various genes associated with inflammation, including immunoglobulins, S100, matrix metalloproteinases, keratin, B-cell and complement genes, which decreased in clinical responders after treatment. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. CONCLUSIONS: Sixty-five per cent of patients with moderate-to-severe HS achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study were the small sample size and absence of a placebo arm. The large placebo-controlled phase IIb NOVA trial for guselkumab in patients with HS reported a lower HiSCR response of 45.0-50.8% in the treatment group and 38.7% in the placebo group. Guselkumab seems only to be of benefit in a subgroup of patients with HS, indicating that the IL-23/T helper 17 axis is not central to the pathophysiology of HS.</p

    The association between echogenicity and progression of Dupuytren's disease (DD):Birth of an imaging biomarker?

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    BACKGROUND: The shift of focus towards disease-controlling treatments to prevent DD progression at an early stage underlines the need for objective and reliable measurements that can monitor and predict the course of disease. Ultrasound has been studied as a potential tool for this purpose. This study examined to what extent echogenicity of early DD nodules predicts clinical progression.METHODS: Sonographic assessments of Dupuytren's nodules were performed by the same observer on 151 participants as part of an ongoing prospective cohort study on the course of DD. Echogenicity was assessed by determining the greyness of a nodule relative to the surrounding tissue, using ImageJ software. Progression of disease was defined as 1) an increase in total passive extension deficit (TPED) of ≥15 degrees and 2) surgical intervention of the examined ray, both occurring after the sonographic assessment. The associations between echogenicity and time to progression were estimated using Cox-regression models.RESULTS: The association between echogenicity and time to TPED progression showed that for every additional decrease of 1% in relative greyness (darker image) of a nodule, the risk of TPED progression during follow-up increases by 3.4% (hazard ratio [HR] = 0.966, 95% confidence interval [CI]: 0.935-0.966). Similarly, echogenicity was also associated with time to surgical intervention (HR = 0.967, 95% CI: 0.938-0.997), which indicates a higher risk for surgery during follow-up for darker nodules.CONCLUSIONS: These results suggest that echogenicity is predictive of the prognosis of the early stages of DD and might potentially be used as a prognostic imaging biomarker in the future.</p

    Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa

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    Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, high levels of IL-17 were discovered in skin lesions of HS patients. In the following years, translational and clinical research led to a better understanding of the pathogenesis of HS. In June 2023, more than 12 years after the initial note, secukinumab, an anti-IL-17A monoclonal antibody, was approved for the treatment of moderate to severe HS. This is the next milestone in improving the treatment of these patients after the approval of the anti-TNF-α monoclonal antibody adalimumab in 2015. In this review article, we present the IL-17 pathway in HS and discuss the use of secukinumab as a therapeutic option for this disease. Our review starts with a description of the epidemiology, clinical features, etiology, and pathogenesis of HS. An overview of the IL-17/IL-17 receptor system in general and a detailed description of the known facts about the expression and action of IL-17 in HS follow. Afterward, we consider the results of clinical trials evaluating the safety and efficacy of IL-17 inhibitors in HS. Finally, a comparison is made between secukinumab and adalimumab and the characteristics of the patients that may be particularly suitable for each of these biologics are described.</p

    Outcome measures for the evaluation of treatment response in hidradenitis suppurativa for clinical practice

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    Importance Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting

    Expected Risk as basis for assessment of safe use of chemicals

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    This paper describes a straightforward modeling procedure to derive ‘expected risk’ (ER) of chemical substances. Starting from proposed use volumes, intended uses, physical and chemical substance properties and toxicity information, the procedure combines multimedia environmental fate modeling with species sensitivity modeling to derive the probability that exposure concentrations exceed critical effect concentrations. The procedure was tested on 1977 so-called mono-constituent organic chemicals that had been registered to be marketed in the EU, after ‘possibility to be used safely’ had been demonstrated by showing that the possible Risk Quotients (RQ) defined as PEC/PNEC ratios (Predicted Exposure Concentration & Predicted No Effect Concentration) were expected to remain below the value of 1, as required by REACH. It appears from this study that (i) RQ and ER of chemicals can be calculated readily, reliably, transparently and reproducibly, that (ii) both RQ and ER can be used to assess whether a new chemical may exceed a chosen acceptability level, but that (iii) in addition ER can be straightforwardly used to rank chemicals according to expected environmental safety. In conclusion, the paper states that modeling ER of chemicals (instead of estimating RQ values), could strengthen the scientific basis of environmental risk assessment for use in REACH. The paper further recommends that more robust environmental risk calculation can be done by using acute EC50, instead of chronic NOEC as critical effect concentration
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