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2. Versorgungsrealität der stationären vasoaktiven Therapie mit Prostazyklinderivaten bei Patienten mit akralen Durchblutungsstörungen bei systemischer Sklerose in Deutschland

Author

Juche, A., Siegert, E., Mueller-Ladner, U., Riemekasten, G., Günther, C., Kötter, I., Henes, J., Blank, N., Voll, R. E., Ehrchen, J., Schmalzing, M., Susok, L., Schmeiser, T., Sunderkoetter, C., Distler, J., Worm, M., Kreuter, A., Horváth, O. N., Schön, M. P., Korsten, P., Zeidler, G., Pfeiffer, C., Krieg, T., Hunzelmann, N., and Moinzadeh, P.

Published
2020
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5. The metal-insulator transition in amorphous Si_{1-x}Ni_x: Evidence for Mott's minimum metallic conductivity

Author

Mobius, A., Frenzel, C., Thielsch, R., Rosenbaum, R., Adkins, C. J., Schreiber, M., Bauer, H. -D., Grotzschel, R., Hoffmann, V., Krieg, T., Matz, N., Vinzelberg, H., and Witcomb, M.

Subjects
Condensed Matter - Disordered Systems and Neural Networks
Abstract

We study the metal-insulator transition in two sets of amorphous Si_{1-x}Ni_x films. The sets were prepared by different, electron-beam-evaporation-based technologies: evaporation of the alloy, and gradient deposition from separate Ni and Si crucibles. The characterization included electron and scanning tunneling microscopy, glow discharge optical emission spectroscopy, and Rutherford back scattering. Investigating the logarithmic temperature derivative of the conductivity, w = d ln sigma / d ln T, we observe that, for insulating samples, w(T) shows a minimum increasing at both low and high T. Both the minimum value of w and the corresponding temperature seem to tend to zero as the transition is approached. The analysis of this feature of w(T,x) leads to the conclusion that the transition in Si_{1-x}Ni_x is very likely discontinuous at zero temperature in agreement with Mott's original views., Comment: RevTex-file: 25 pages, 17 Postscript figures, 1 GIF figure (original Ps file can be obtained on request). Published version. Changes of v2: Sec. VII completed by two paragraphs on nature of transition, several refs. added

Published
1998
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14. Agreement Between Physician Evaluation and the Composite Response Index in Diffuse Cutaneous Systemic Sclerosis

Author

Zheng, B.Y., Wang, M.B., McKenna, K., Shapiro, L., Silver, R., Csuka, M.E., Hoogen, F. van den, Robinson, D., Pauling, J.D., Hummers, L., Krieg, T., Galdo, F. del, Spiera, R., Jones, N., Khalidi, N., Vacca, A., Vries-Bouwstra, J.K. de, Gordon, J., Baron, M., and Canadian Scleroderma Res Grp

Subjects
Index (economics), Rheumatology, business.industry, Medicine, Nuclear medicine, business
Abstract

Objective Diffuse cutaneous systemic sclerosis (SSc) is a highly heterogeneous disease. A provisionally approved Composite Response Index in diffuse cutaneous SSc (CRISS) was developed as a 1-year outcome measure for clinical trials. Our goal was to further validate the CRISS by examining agreement between CRISS definitions for improved/non-improved with physicians' evaluation of disease. Methods Patient profiles from a large observational cohort were created for 50 random diffuse cutaneous SSc patients of

Published
2022

17. NON-SURGICAL LOCAL TREATMENTS FOR DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW

Author

Campochiaro, C., Suliman, Y. A., Hughes, M., Schoones, J., Giuggioli, D., Moinzadeh, P., Maltez, N., Ross, L., Baron, M., Chung, L., Allanore, Y., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., Alunno, A., Campochiaro, C., Suliman, Y. A., Hughes, M., Schoones, J., Giuggioli, D., Moinzadeh, P., Maltez, N., Ross, L., Baron, M., Chung, L., Allanore, Y., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., and Alunno, A.

Published
2022

18. SYSTEMIC PHARMACOLOGICAL TREATMENT OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW

Author

Maltez, N., Ross, L., Hughes, M., Schoones, J., Baron, M., Chung, L., Campochiaro, C., Suliman, Y. A., Giuggioli, D., Moinzadeh, P., Allanore, Y., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., Alunno, A., Maltez, N., Ross, L., Hughes, M., Schoones, J., Baron, M., Chung, L., Campochiaro, C., Suliman, Y. A., Giuggioli, D., Moinzadeh, P., Allanore, Y., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., and Alunno, A.

Published
2022

19. SURGICAL MANAGEMENT OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW.

Author

Suliman, Y. A., Campochiaro, C., Hughes, M., Schoones, J., Giuggioli, D., Maltez, N., Moinzadeh, P., Ross, L., Chung, L., Allanore, Y., Baron, M., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., Alunno, A., Suliman, Y. A., Campochiaro, C., Hughes, M., Schoones, J., Giuggioli, D., Maltez, N., Moinzadeh, P., Ross, L., Chung, L., Allanore, Y., Baron, M., Denton, C. P., Distler, O., Frech, T., Furst, D., Khanna, D., Krieg, T., Kuwana, M., Matucci-Cerinic, M., Pope, J., and Alunno, A.

Published
2022

20. European dermatology forum S1‐guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis

Author

Knobler, R., Moinzadeh, P., Hunzelmann, N., Kreuter, A., Cozzio, A., Mouthon, L., Cutolo, M., Rongioletti, F., Denton, C.P., Rudnicka, L., Frasin, L.A., Smith, V., Gabrielli, A., Aberer, E., Bagot, M., Bali, G., Bouaziz, J., Braae Olesen, A., Foeldvari, I., Frances, C., Jalili, A., Just, U., Kähäri, V., Kárpáti, S., Kofoed, K., Krasowska, D., Olszewska, M., Orteu, C., Panelius, J., Parodi, A., Petit, A., Quaglino, P., Ranki, A., Sanchez Schmidt, J.M., Seneschal, J., Skrok, A., Sticherling, M., Sunderkötter, C., Taieb, A., Tanew, A., Wolf, P., Worm, M., Wutte, N.J., and Krieg, T.

Published
2017
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21. European Dermatology Forum S1‐guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes

Author

Knobler, R., Moinzadeh, P., Hunzelmann, N., Kreuter, A., Cozzio, A., Mouthon, L., Cutolo, M., Rongioletti, F., Denton, C.P., Rudnicka, L., Frasin, L.A., Smith, V., Gabrielli, A., Aberer, E., Bagot, M., Bali, G., Bouaziz, J., Braae Olesen, A., Foeldvari, I., Frances, C., Jalili, A., Just, U., Kähäri, V., Kárpáti, S., Kofoed, K., Krasowska, D., Olszewska, M., Orteu, C., Panelius, J., Parodi, A., Petit, A., Quaglino, P., Ranki, A., Sanchez Schmidt, J.M., Seneschal, J., Skrok, A., Sticherling, M., Sunderkötter, C., Taieb, A., Tanew, A., Wolf, P., Worm, M., Wutte, N.J., and Krieg, T.

Published
2017
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22. Pharmacology and rationale for imatinib in the treatment of scleroderma

Author

Moinzadeh P, Hunzelmann N, and Krieg T

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Pia Moinzadeh, Nicolas Hunzelmann, Thomas Krieg Department of Dermatology and Venerology, University of Cologne, Germany Abstract: Systemic sclerosis (scleroderma) is a chronic, multisystem, fibrotic disease. Although the pathogenesis is not completely understood, early vascular damage leads to an inflammatory reaction and a severe fibrotic response. Therapy of systemic sclerosis is still not convincing and is mainly restricted to the management of organ complications. A wide choice of immunosuppressive and antifibrotic drugs has been used to try to modify the course of the disease, but significant breakthroughs are still lacking. Imatinib is a tyrosine kinase inhibitor known to regulate growth, proliferation, and differentiation as well as apoptosis of cells and is already widely used for several malignancies, eg, chronic myeloid leukemia and gastrointestinal stromal tumors. It has been used in preclinical as well as clinical studies to modulate the fibrotic process in patients with systemic sclerosis. This is based on its activity to interfere selectively with both the transforming growth factor-ß and platelet-derived growth factor signaling pathway. Preclinical studies in mouse models of scleroderma showed significant anti-inflammatory and antifibrotic effects; however, several clinical, proof-of-concept trials have not yet confirmed these initially promising results. Keywords: scleroderma, systemic sclerosis, SSc, tyrosine kinase inhibitor, imatinib

Published
2013

24. POS0900 SYSTEMIC PHARMACOLOGICAL TREATMENT OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW

Author

Maltez, N., primary, Ross, L., additional, Hughes, M., additional, Schoones, J., additional, Baron, M., additional, Chung, L., additional, Campochiaro, C., additional, Suliman, Y. A., additional, Giuggioli, D., additional, Moinzadeh, P., additional, Allanore, Y., additional, Denton, C. P., additional, Distler, O., additional, Frech, T., additional, Furst, D., additional, Khanna, D., additional, Krieg, T., additional, Kuwana, M., additional, Matucci-Cerinic, M., additional, Pope, J., additional, and Alunno, A., additional

Published
2022
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25. POS0898 SURGICAL MANAGEMENT OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW.

Author

Suliman, Y. A., primary, Campochiaro, C., additional, Hughes, M., additional, Schoones, J., additional, Giuggioli, D., additional, Maltez, N., additional, Moinzadeh, P., additional, Ross, L., additional, Chung, L., additional, Allanore, Y., additional, Baron, M., additional, Denton, C. P., additional, Distler, O., additional, Frech, T., additional, Furst, D., additional, Khanna, D., additional, Krieg, T., additional, Kuwana, M., additional, Matucci-Cerinic, M., additional, Pope, J., additional, and Alunno, A., additional

Published
2022
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26. POS0888 NON-SURGICAL LOCAL TREATMENTS FOR DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW

Author

Campochiaro, C., primary, Suliman, Y. A., additional, Hughes, M., additional, Schoones, J., additional, Giuggioli, D., additional, Moinzadeh, P., additional, Maltez, N., additional, Ross, L., additional, Baron, M., additional, Chung, L., additional, Allanore, Y., additional, Denton, C. P., additional, Distler, O., additional, Frech, T., additional, Furst, D., additional, Khanna, D., additional, Krieg, T., additional, Kuwana, M., additional, Matucci-Cerinic, M., additional, Pope, J., additional, and Alunno, A., additional

Published
2022
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28. The Predict Study: low risk for digital ulcer development in patients with systemic sclerosis with increasing disease duration and lack of topoisomerase-1 antibodies

Author

Hunzelmann, N., Riemekasten, G., Becker, M. O., Moinzadeh, P., Kreuter, A., Melchers, I., Mueller-Ladner, U., Meier, F., Worm, M., Lee, H., Herrgott, I., Pfeiffer, C., Fierlbeck, G., Henes, J., Juche, A., Zeidler, G., Mensing, H., Günther, C., Sárdy, M., Burkhardt, H., Koehm, M., Kuhr, K., Krieg, T., and Sunderkötter, C.

Published
2016
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29. Onkologie III: Grundlagen

Author

Kornfehl, J., Wilfing, A., Hermann, M., Grubeck-Loebenstein, B., Bettinger, B., Lörz, M., Knecht, R., v. Ilberg, C., Klima, A., Bettinger, R., Weber, A., Clasen, B., Kaffenberger, W., v. Beuningen, D., Herold-Mende, C., Ouhayoun, J.-P., Maier, H., Bosch, F. X., Mahran, A., Sinn, H. P., Born, I. A., Weidauer, H., Wustrow, T. P. U., Hein, R., Issing, W. J., Krieg, T., Pettig, C., Jakschies, D., Fibich, C., v. Wussow, P., Deicher, H., Lehnhardt, E., Arndt, O., Bauer, I., Brock, J., Gutmann, R., Feyh, J., Kastenbauer, E., Rolfs, F., Rausch, P. Ch., Schreiber, F., Neu, W., Feldmann, Harald, and Herberhold, Claus

Published
1993
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32. Idiopathic inflammatory myopathies: Narrative review of unmet needs in clinical practice guidelines

Author

Meyer, A, Scire, C, Talarico, R, Alexander, T, Amoura, Z, Avcin, T, Barsotti, S, Beretta, L, Blagojevic, J, Burmester, G, Cavazzana, I, Cherrin, P, Damian, L, Doria, A, Fonseca, J, Furini, F, Galetti, I, Houssiau, F, Krieg, T, Maddalena, L, Launay, D, Campanilho-Marques, R, Martin, T, Matucci-Cerinic, M, Moinzadeh, P, Montecucco, C, Moraes-Fontes, M, Mouthon, L, Neri, R, Paolino, S, Piette, Y, Rednic, S, Tamirou, F, Tincani, A, Toplak, N, Bombardieri, S, Hachulla, E, Mueller-Ladner, U, Schneider, M, Smith, V, Vieira, A, Cutolo, M, Mosca, M, Cavagna, L, Meyer A., Scire C. A., Talarico R., Alexander T., Amoura Z., Avcin T., Barsotti S., Beretta L., Blagojevic J., Burmester G., Cavazzana I., Cherrin P., Damian L., Doria A., Fonseca J. E., Furini F., Galetti I., Houssiau F., Krieg T., Maddalena L., Launay D., Campanilho-Marques R., Martin T., Matucci-Cerinic M., Moinzadeh P., Montecucco C., Moraes-Fontes M. F., Mouthon L., Neri R., Paolino S., Piette Y., Rednic S., Tamirou F., Tincani A., Toplak N., Bombardieri S., Hachulla E., Mueller-Ladner U., Schneider M., Smith V., Vieira A., Cutolo M., Mosca M., Cavagna L., Meyer, A, Scire, C, Talarico, R, Alexander, T, Amoura, Z, Avcin, T, Barsotti, S, Beretta, L, Blagojevic, J, Burmester, G, Cavazzana, I, Cherrin, P, Damian, L, Doria, A, Fonseca, J, Furini, F, Galetti, I, Houssiau, F, Krieg, T, Maddalena, L, Launay, D, Campanilho-Marques, R, Martin, T, Matucci-Cerinic, M, Moinzadeh, P, Montecucco, C, Moraes-Fontes, M, Mouthon, L, Neri, R, Paolino, S, Piette, Y, Rednic, S, Tamirou, F, Tincani, A, Toplak, N, Bombardieri, S, Hachulla, E, Mueller-Ladner, U, Schneider, M, Smith, V, Vieira, A, Cutolo, M, Mosca, M, Cavagna, L, Meyer A., Scire C. A., Talarico R., Alexander T., Amoura Z., Avcin T., Barsotti S., Beretta L., Blagojevic J., Burmester G., Cavazzana I., Cherrin P., Damian L., Doria A., Fonseca J. E., Furini F., Galetti I., Houssiau F., Krieg T., Maddalena L., Launay D., Campanilho-Marques R., Martin T., Matucci-Cerinic M., Moinzadeh P., Montecucco C., Moraes-Fontes M. F., Mouthon L., Neri R., Paolino S., Piette Y., Rednic S., Tamirou F., Tincani A., Toplak N., Bombardieri S., Hachulla E., Mueller-Ladner U., Schneider M., Smith V., Vieira A., Cutolo M., Mosca M., and Cavagna L.

Abstract

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union's Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ' preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.

Published
2019

37. Phlebologie an deutschen Hautkliniken: Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie

Author

Reich-Schupke, S., Alm, J., Altmeyer, P., Bachter, D., Bayerl, C., Beissert, S., Bieber, T., Böhmer, J., Dill, D., Dippel, E., Dücker, P., Effendy, I., El Gammal, S., Elsner, P., Enk, A., Feldmann-Böddeker, I., Frank, H., Gehring, W., Gieler, U., Goebeler, M., Görge, T., Gollnick, H., Grabbe, S., Gross, G., Gudat, W., Happ, A., Herbst, R., Hermes, B., Hoff, N.-P., John, S.M., Jungelhülsing, M., Jünger, M., Kaatz, M., Kapp, A., Kaufmann, R., Klode, J., Knaber, K., König, A., Krieg, T., Kohl, P., Kowalzick, L., Lehmann, P., Löffler, H., Maschke, J., Marsch, W., Mechtel, D., Mohr, P., Moll, I., Müller, M., Nashan, D., Ockenfels, H.M., Peter, R.U., Pillekamp, H., Rompel, R., Ruzicka, T., Salfeld, K., Sander, C., Schaller, J., Scharffetter-Kochanek, K., Schuler, G., Schulze, H.-J., Schwarz, T., Splieth, B., Stege, H., Stolz, W., Strölin, A., Tran, H., Tronnier, M., Ulrich, J., Vogt, T., Wagner, G., Welzel, J., Willgeroth, T., Wollina, U., Zillikens, D., Zouboulis, C.C., Zuberbier, T., Zutt, M., and Stücker, M.

Published
2013
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40. Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition

Author

Bruni, C. Buch, M.H. Furst, D.E. De Luca, G. Djokovic, A. Dumitru, R.B. Giollo, A. Polovina, M. Steelandt, A. Bratis, K. Suliman, Y.A. Milinkovic, I. Baritussio, A. Hasan, G. Xintarakou, A. Isomura, Y. Markousis-Mavrogenis, G. Tofani, L. Mavrogeni, S. Gargani, L. Caforio, A.L.P. Tschöpe, C. Ristic, A. Klingel, K. Plein, S. Behr, E.R. Allanore, Y. Kuwana, M. Denton, C.P. Khanna, D. Krieg, T. Marcolongo, R. Galetti, I. Zanatta, E. Tona, F. Seferovic, P. Matucci-Cerinic, M.

Abstract

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5–300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46–1.00) for the first round and 0.55 (0.44–1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47–1.00)). Criterion validity showed a 78 (73–84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research. © The Author(s) 2021.

Published
2021

41. Targeting methylglyoxal in diabetic kidney disease using the mitochondria-targeted compound mitogamide

Author

Tan, SM, Lindblom, RSJ, Ziemann, Mark, Laskowski, A, Granata, C, Snelson, M, Thallas-Bonke, V, El-Osta, A, Baeza-Garza, CD, Caldwell, ST, Hartley, RC, Krieg, T, Cooper, ME, Murphy, MP, Coughlan, MT, Tan, SM, Lindblom, RSJ, Ziemann, Mark, Laskowski, A, Granata, C, Snelson, M, Thallas-Bonke, V, El-Osta, A, Baeza-Garza, CD, Caldwell, ST, Hartley, RC, Krieg, T, Cooper, ME, Murphy, MP, and Coughlan, MT

Published
2021

42. The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET

Author

Talarico, R, Aguilera, S, Alexander, T, Amoura, Z, Antunes, AMC, Arnaud, L, Avcin, T, Beretta, L, Bombardieri, S, Burmester, GR, Cannizzo, S, Cavagna, L, Chaigne, B, Cornet, A, Costedoat-Chalumeau, N, Doria, A, Ferraris, A, Fischer-Betz, R, Fonseca, JE, Frank, C, Gaglioti, A, Galetti, I, Grunert, J, Guimaraes, V, Hachulla, E, Houssiau, F, Iaccarino, L, Krieg, T, Limper, M, Malfait, F, Mariette, X, Marinello, D, Martin, T, Matthews, L, Matucci-Cerinic, M, Meyer, A, Montecucco, C, Mouthon, L, Muller-Ladner, U, Rednic, S, Romao, VC, Schneider, M, Smith, V, Sulli, A, Tamirou, F, Taruscio, D, Taulaigo, AV, Terol, E, Tincani, A, Ticciati, S, Turchetti, G, van Hagen, P.M., van Laar, JM, Vieira, A, de Vries-Bouwstra, JK, Cutolo, M, Mosca, M, Talarico, R, Aguilera, S, Alexander, T, Amoura, Z, Antunes, AMC, Arnaud, L, Avcin, T, Beretta, L, Bombardieri, S, Burmester, GR, Cannizzo, S, Cavagna, L, Chaigne, B, Cornet, A, Costedoat-Chalumeau, N, Doria, A, Ferraris, A, Fischer-Betz, R, Fonseca, JE, Frank, C, Gaglioti, A, Galetti, I, Grunert, J, Guimaraes, V, Hachulla, E, Houssiau, F, Iaccarino, L, Krieg, T, Limper, M, Malfait, F, Mariette, X, Marinello, D, Martin, T, Matthews, L, Matucci-Cerinic, M, Meyer, A, Montecucco, C, Mouthon, L, Muller-Ladner, U, Rednic, S, Romao, VC, Schneider, M, Smith, V, Sulli, A, Tamirou, F, Taruscio, D, Taulaigo, AV, Terol, E, Tincani, A, Ticciati, S, Turchetti, G, van Hagen, P.M., van Laar, JM, Vieira, A, de Vries-Bouwstra, JK, Cutolo, M, and Mosca, M

Abstract

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Published
2021

48. Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinate accumulation and oxidation is additive

Author

Kohlhauer, M, Pell, VR, Burger, N, Spiroski, AM, Gruszczyk, A, Mulvey, JF, Mottahedin, Amin, Costa, ASH, Frezza, C, Ghaleh, B, Murphy, MP, Tissier, R, Krieg, T, Krieg, T [0000-0002-5192-580X], and Apollo - University of Cambridge Repository

Subjects
Male, Succinate, Succinic Acid, Myocardial Reperfusion Injury, Hypothermia, Malonates, Myocardial infarction, Random Allocation, Ischemia, Hypothermia, Induced, Reperfusion, Animals, cardiovascular diseases, Rabbits, Dimethyl malonate
Abstract

Hypothermia induced at the onset of ischemia is a potent experimental cardioprotective strategy for myocardial infarction. The aim of our study was to determine whether the beneficial effects of hypothermia may be due to decreasing mitochondria-mediated mechanisms of damage that contribute to the pathophysiology of ischemia/reperfusion injury. New Zealand male rabbits were submitted to 30 min of myocardial ischemia with hypothermia (32 °C) induced by total liquid ventilation (TLV). Hypothermia was applied during ischemia alone (TLV group), during ischemia and reperfusion (TLV-IR group) and normothermia (Control group). In all the cases, ischemia was performed by surgical ligation of the left anterior descending coronary artery and was followed by 3 h of reperfusion before assessment of infarct size. In a parallel study, male C57BL6/J mice underwent 30 min myocardial ischemia followed by reperfusion under either normothermia (37 °C) or conventionally induced hypothermia (32 °C). In both the models, the levels of the citric acid cycle intermediate succinate, mitochondrial complex I activity were assessed at various times. The benefit of hypothermia during ischemia on infarct size was compared to inhibition of succinate accumulation and oxidation by the complex II inhibitor malonate, applied as the pro-drug dimethyl malonate under either normothermic or hypothermic conditions. Hypothermia during ischemia was cardioprotective, even when followed by normothermic reperfusion. Hypothermia during ischemia only, or during both, ischemia and reperfusion, significantly reduced infarct size (2.8 ± 0.6%, 24.2 ± 3.0% and 49.6 ± 2.6% of the area at risk, for TLV-IR, TLV and Control groups, respectively). The significant reduction of infarct size by hypothermia was neither associated with a decrease in ischemic myocardial succinate accumulation, nor with a change in its rate of oxidation at reperfusion. Similarly, dimethyl malonate infusion and hypothermia during ischemia additively reduced infarct size (4.8 ± 2.2% of risk zone) as compared to either strategy alone. Hypothermic cardioprotection is neither dependent on the inhibition of succinate accumulation during ischemia, nor of its rapid oxidation at reperfusion. The additive effect of hypothermia and dimethyl malonate on infarct size shows that they are protective by distinct mechanisms and also suggests that combining these different therapeutic approaches could further protect against ischemia/reperfusion injury during acute myocardial infarction.

Published
2019
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