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1. Improved clinical effectiveness of adalimumab when initiated with clindamycin and rifampicin in hidradenitis suppurativa

Author

Aarts, P., van Huijstee, J. C., van Der Zee, H. H., van Straalen, K. R., Prens, E. P., Aarts, P., van Huijstee, J. C., van Der Zee, H. H., van Straalen, K. R., and Prens, E. P.

Abstract

Background: Adalimumab monotherapy for hidradenitis suppurativa (HS) is often insufficient with a maximum clinical efficacy of 60% in Hidradenitis Suppurativa Clinical Response (HiSCR) and limited effect on draining tunnels. Data suggest that adalimumab therapy could be improved by concomitant antibiotics. Objective: To compare the clinical effectiveness of adalimumab with clindamycin and rifampicin versus adalimumab monotherapy after 12 weeks. Methods: This retrospective study included patients who started adalimumab with additional clindamycin and rifampicin and patients treated with adalimumab monotherapy, matched on sex and refined Hurley score. The primary outcome measure was the difference in change in the International Hidradenitis Suppurativa Severity Score System (IHS4) at 12 weeks. Results: In total, 62 patients were included in the combination therapy group (n = 31) and adalimumab monotherapy group (n = 31), showing comparable IHS4 scores; 32.5 versus 29, p = 0.87 at baseline respectively. The combination therapy demonstrated greater clinical effectiveness expressed in median IHS4 improvement (−20 vs. −9, p < 0.001), IHS4-55 (74% vs. 36%, p = 0.002), median draining tunnel reduction (−4 vs. −2, p < 0.001) and pain response (47% vs. 27%, p = 0.02). Conclusion: Adalimumab initiated with clindamycin and rifampicin shows greater clinical effectiveness than adalimumab monotherapy. An important difference in effect was observed in the decrease of draining tunnels, addressing a serious limitation of adalimumab monotherapy.

Published
2024

3. The inter‐rater reliability of IHS4 corroborates its aptitude as primary outcome measurement instrument for large clinical studies in hidradenitis suppurativa

Author

Zouboulis, C. C., primary, Hrvatin Stancic, B., additional, Abaitancei, A., additional, Guimarães, M. J., additional, Lobo, I. L., additional, Massa, A. F., additional, Nikolakis, G., additional, Nogueira, M. O., additional, Özdemir, A. O., additional, Pirogova, A., additional, Prens, E. P., additional, Szepietowski, J. C., additional, Tusheva, I., additional, Tzellos, T., additional, and Zouboulis, V. A.., additional

Published
2023
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7. The inter‐rater reliability of IHS4 corroborates its aptitude as primary outcome measurement instrument for large clinical studies in hidradenitis suppurativa.

Author

Zouboulis, C. C., Hrvatin Stancic, B., Abaitancei, A., Guimarães, M. J., Lobo, I. L., Massa, A. F., Nikolakis, G., Nogueira, M. O., Özdemir, A. O., Pirogova, A., Prens, E. P., Szepietowski, J. C., Tusheva, I., Tzellos, T., and Zouboulis, V. A.

Subjects
HIDRADENITIS suppurativa, MEDICAL ethics
Abstract

The article discusses the inter-rater reliability of the International Hidradenitis Suppurativa Severity Scoring System (IHS4) as a primary outcome measurement instrument for large clinical studies in hidradenitis suppurativa (HS). The study involved 31 dermatology residents from 16 countries who evaluated 10 HS patients with varying disease severity. The results showed that the IHS4 had excellent inter-rater reliability among the raters, indicating its suitability for use in large clinical studies. However, the evaluation of HS lesions without weighting and the evaluation of inflammatory nodules and abscesses only led to reduced reliability. The article concludes that the IHS4 is a reliable instrument for assessing HS in clinical studies. [Extracted from the article]

Published
2024
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10. Primary alterations during the development of hidradenitis suppurativa

Author

Dajnoki, Z., Somogyi, O., Medgyesi, B., Jenei, A., Szabó, L., Gáspár, K., Hendrik, Z., Gergely, P., Imre, D., Póliska, S., Törőcsik, D., Zouboulis, C. C., Prens, E. P., Kapitány, A., Szegedi, A., and Dermatology

Subjects
SDG 3 - Good Health and Well-being
Abstract

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. Objectives: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. Methods: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. Results: Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1β, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1β expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. Conclusions: Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1β but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.

Published
2022

11. Complement activation in Hidradenitis suppurativa:Covert low-grade inflammation or innocent bystander?

Author

van Straalen, K. R., Dudink, K., Aarts, P., van der Zee, H. H., van den Bosch, T. P.P., Giang, J., Prens, E. P., Damman, J., van Straalen, K. R., Dudink, K., Aarts, P., van der Zee, H. H., van den Bosch, T. P.P., Giang, J., Prens, E. P., and Damman, J.

Abstract

Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disease with a complex and multifactorial pathogenesis involving both the innate and adaptive immune system. Despite limited evidence for local complement activation, conflicting results have been published on the role of systemic complement activation in HS. It was hypothesized that complement was consumed in highly inflamed HS skin, trapping complement from the circulation. Therefore, the aim of this study was to evaluate this local complement deposition in HS skin lesions using routine and commonly used complement antibodies.Direct immunofluorescence for C1q, C3c, C4d, C5b-9, and properdin was performed on frozen tissue sections of 19 HS patients and 6 controls. C5a receptor 1 (C5aR1) was visualized using immunohistochemistry. Overall, we found no significant local complement deposition in HS patients versus controls regarding C1q, C3c, C4d, C5b-9, or properdin on either vessels or immune cells. C5aR1 expression was exclusively found on immune cells, predominantly neutrophilic granulocytes, but not significantly different relatively to the total infiltrate in HS lesions compared with controls. In conclusion, despite not being able to confirm local complement depositions of C1q, C3c, C4d, or properdin using highly sensitive and widely accepted techniques, the increased presence of C5aR1 positive immune cells in HS suggests the importance of complement in the pathogenesis of HS and supports emerging therapies targeting this pathway.

Published
2022

20. Hidradenitis suppurativa severity score system (HS4): preliminary results: O08–5

Author

Zouboulis, C. C., Alavi, A., Bettoli, V., Boer, J., Danby, F. W., De Haes, P., Delli, F. S., Dessinioti, C., Emtestam, L., Garcovich, S., Giammarellos-Bourboulis, E., Guillem, P., Gulliver, W., Hunger, R. E., Ingram, J., Ingvarsson, G., Jemec, G. B. E., Martorell-Calatayud, A., Mrowietz, U., Nassif, A., Nikolakis, G., Patsatsi, A., Pinter, A., Prens, E. P., Puig, L., Sabat, R., Sinclair, R., Szepietowski, J. C., Trigoni, A., Tympanidis, P., van der Zee, H. H., Zisimou, C., and Tzellos, T.

Published
2016

25. Diagnostic delay in hidradenitis suppurativa is a global problem

Author

Saunte, D. M., Boer, J., Stratigos, A., Szepietowski, J. C., Hamzavi, I., Kim, K. H., Zarchi, K., Antoniou, C., Matusiak, L., Lim, H. W., Williams, M., Kwon, H. H., Gurer, M. A., Mammadova, F., Kaminsky, A., Prens, E., van der Zee, H. H., Bettoli, V., Zauli, S., Hafner, J., Lauchli, S., French, L. E., Riad, H., El-Domyati, M., Abdel-Wahab, H., Kirby, B., Kelly, G., Calderon, P., del Marmol, V., Benhadou, F., Revuz, J., Zouboulis, C. C., Karagiannidis, I., Sartorius, K., Hagstromer, L., McMeniman, E., Ong, N., Dolenc-Voljc, M., Mokos, Z. B., Borradori, L., Hunger, R. E., Sladden, C., Scheinfeld, N., Moftah, N., Emtestam, L., Lapins, J., Doss, N., Kurokawa, I., and Jemec, G. B.E.

Published
2015
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34. Quantitative intracellular oxygen availability before and after 5-aminole-vulinic acid skin photodynamic therapy

Author

Ubbink, R., Prens, E. P., Mik, E. G., Ubbink, R., Prens, E. P., and Mik, E. G.

Abstract

Background: During photodynamic therapy (PDT) oxygen is transformed into reactive oxygen species (ROS) to induce cellular apoptosis in (pre)malignant cells. Real time oxygen availability measurement is clinically available with the Cellular Oxygen Metabolism (COMET) monitor. Methods: Primary objective is to show that mitochondrial oxygen availability (mitoPO2) measurement is possible during clinical ALA-PDT. The secondary aim was to determine the pain sensation, because it is the most commonly reported side effect of PDT. Before and after the two fraction PDT treatment, with a 2-hour dark period, mitoPO2 was measured and reported pain was documented with a visual analog scale (VAS) 0–100. Results: Nine patients were included. Before the first PDT session the median signal quality was [IQR] 55.0% [34.2–68.0], which decreased after session one to 0% [0.0–10.0]. MitoPO2 was 40.0 [17.7–53.8] mmHg and increased afterwards to 61.8 [38.2–64.8] mmHg. This likely the result of the delay time between the illumination stop and the mitoPO2 measurements in a vasodilated, visibly red lesion. Before session two signal quality was 10.4% [0–20.15], 40% lower than at the start. In 5 patients the signal quality after session 2 was too low because of photobleaching and insufficient regeneration of PpIX, median 0% [0–10]. Subjects reported low median VAS scores, all below 3, directly after the mitoPO2 measurements. Conclusion: With COMET we were able to reliably measure mitochondrial oxygen concentrations during photodynamic therapy. Signal quality drastically decreases after a PDT session because of PpIX deterioration during the illumination phase.

Published
2021

38. Evaluating patients' unmet needs in hidradenitis suppurativa: Results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project

Author

Garg, A. Neuren, E. Cha, D. Kirby, J.S. Ingram, J.R. Jemec, G.B.E. Esmann, S. Thorlacius, L. Villumsen, B. Marmol, V.D. Nassif, A. Delage, M. Tzellos, T. Moseng, D. Grimstad, Ø. Naik, H. Micheletti, R. Guilbault, S. Miller, A.P. Hamzavi, I. van der Zee, H. Prens, E. Kappe, N. Ardon, C. Kirby, B. Hughes, R. Zouboulis, C.C. Nikolakis, G. Bechara, F.G. Matusiak, L. Szepietowski, J. Glowaczewska, A. Smith, S.D. Goldfarb, N. Daveluy, S. Avgoustou, C. Giamarellos-Bourboulis, E. Cohen, S. Soliman, Y. Brant, E.G. Akilov, O. Sayed, C. Tan, J. Alavi, A. Lowes, M.A. Pascual, J.C. Riad, H. Fisher, S. Cohen, A. Paek, S.Y. Resnik, B. Ju, Q. Wang, L. Strunk, A.

Abstract

Background: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. Objective: To evaluate unmet needs from the perspective of HS patients. Methods: Prospective multinational survey of patients between October 2017 and July 2018. Results: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. Limitations: Data were self-reported. Patients with more severe disease may have been selected. Conclusion: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address. © 2019 American Academy of Dermatology, Inc.

Published
2020

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