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3. Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation

Author

Polymeris, A. A., Macha, K., Paciaroni, M., Wilson, D., Koga, M., Cappellari, M., Schaedelin, S., Zietz, A., Peters, N., Seiffge, D. J., Haupenthal, D., Gassmann, L., De Marchis, G. M., Wang, R., Gensicke, H., Stoll, S., Thilemann, S., Avramiotis, N. S., Bonetti, B., Tsivgoulis, G., Ambler, G., Alberti, A., Yoshimura, S., Brown, M. M., Shiozawa, M., Lip, G. Y. H., Venti, M., Acciarresi, M., Tanaka, K., Mosconi, M. G., Takagi, M., Jager, R. H., Muir, K., Inoue, M., Schwab, S., Bonati, L. H., Lyrer, P. A., Toyoda, K., Caso, V., Werring, D. J., Kallmunzer, B., Engelter, S. T., Traenka, C., Hert, L., Wagner, B., Schaub, F., Meya, L., Fladt, J., Dittrich, T., Fisch, U., Volbers, B., Siedler, G., Bovi, P., Tomelleri, G., Micheletti, N., Zivelonghi, C., Emiliani, A., Parry-Jones, A., Patterson, C., Price, C., Elmarimi, A., Parry, A., Nallasivam, A., Nor, A. M., Esis, B., Bruce, D., Bhaskaran, B., Roffe, C., Cullen, C., Holmes, C., Cohen, D., Hargroves, D., Mangion, D., Chadha, D., Vahidassr, D., Manawadu, D., Giallombardo, E., Warburton, E., Flossman, E., Gunathilagan, G., Proschel, H., Emsley, H., Anwar, I., Burger, I., Okwera, J., Putterill, J., O'Connell, J., Bamford, J., Corrigan, J., Scott, J., Birns, J., Kee, K., Saastamoinen, K., Pasco, K., Dani, K., Sekaran, L., Choy, L., Iveson, L., Mamun, M., Sajid, M., Cooper, M., Burn, M., Smith, M., Power, M., Davis, M., Smyth, N., Veltkamp, R., Sharma, P., Guyler, P., O'Mahony, P., Wilkinson, P., Datta, P., Aghoram, P., Marsh, R., Luder, R., Meenakishundaram, S., Subramonian, S., Leach, S., Ispoglou, S., Andole, S., England, T., Manoj, A., Harrington, F., Rehman, H., Sword, J., Staals, J., Mahawish, K., Harkness, K., Shaw, L., Mccormich, M., Sprigg, N., Mansoor, S., Krishnamurthy, V., Giustozzi, M., Agnelli, G., Becattini, C., D'Amore, C., Cimini, L. A., Bandini, F., Liantinioti, C., Chondrogianni, M., Yaghi, S., Furie, K. L., Tadi, P., Zedde, M., Abdul-Rahim, A. H., Lees, K. R., Carletti, M., Rigatelli, A., Putaala, J., Tomppo, L., Tatlisumak, T., Marcheselli, S., Pezzini, A., Poli, L., Padovani, A., Vannucchi, V., Masotti, L., Sohn, S. -I., Lorenzini, G., Tassi, R., Guideri, F., Acampa, M., Martini, G., Ntaios, G., Athanasakis, G., Makaritsis, K., Karagkiozi, E., Vadikolias, K., Mumoli, N., Galati, F., Sacco, S., Tiseo, C., Corea, F., Ageno, W., Bellesini, M., Colombo, G., Silvestrelli, G., Ciccone, A., Lanari, A., Scoditti, U., Denti, L., Mancuso, M., Maccarrone, M., Ulivi, L., Orlandi, G., Giannini, N., Tassinari, T., De Lodovici, M. L., Rueckert, C., Baldi, A., Toni, D., Letteri, F., Pieroni, A., Giuntini, M., Lotti, E. M., Flomin, Y., Kargiotis, O., Karapanayiotides, T., Monaco, S., Baronello, M. M., Csiba, L., Szabo, L., Chiti, A., Giorli, E., Del Sette, M., Imberti, D., Zabzuni, D., Doronin, B., Volodina, V., Michel, P., Vanacker, P., Barlinn, K., Pallesen, L. -P., Barlinn, J., Deleu, D., Melikyan, G., Ibrahim, F., Akhtar, N., Gourbali, V., Todo, K., Kimura, K., Shibazaki, K., Yagita, Y., Furui, E., Itabashi, R., Terasaki, T., Shiokawa, Y., Hirano, T., Suzuki, R., Kamiyama, K., Nakagawara, J., Takizawa, S., Homma, K., Okuda, S., Okada, Y., Maeda, K., Kameda, T., Kario, K., Nagakane, Y., Hasegawa, Y., Akiyama, H., Shibuya, S., Mochizuki, H., Ito, Y., Nakashima, T., Matsuoka, H., Takamatsu, K., Nishiyama, K., Endo, K., Miyagi, T., Osaki, M., Kobayashi, J., Okata, T., Tanaka, E., Sakamoto, Y., Tokunaga, K., Takizawa, H., Takasugi, J., Matsubara, S., Higashida, K., Matsuki, T., Kinoshita, N., Ide, T., Yoshimoto, T., Ando, D., Fujita, K., Kumamoto, M., Kamimura, T., Kikuno, M., Mizoguchi, T., and Sato, T.

Subjects
Male, medicine.medical_specialty, Vitamin K, medicine.drug_class, 610 Medicine & health, Aged, 80 and over, Atrial Fibrillation, Factor Xa Inhibitors, Female, Humans, Stroke, Continuous variable, Internal medicine, 80 and over, medicine, Aged, Proportional hazards model, business.industry, Anticoagulant, Confounding, Atrial fibrillation, Patient data, medicine.disease, Oldest old, Neurology, Neurology (clinical), 610 Medizin und Gesundheit, business
Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction = 0.129), adjusted (p interaction = 0.094) or weighted (p interaction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021.

Published
2022

4. Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

Author

Polymeris, A.A. Macha, K. Paciaroni, M. Wilson, D. Koga, M. Cappellari, M. Schaedelin, S. Zietz, A. Peters, N. Seiffge, D.J. Haupenthal, D. Gassmann, L. De Marchis, G.M. Wang, R. Gensicke, H. Stoll, S. Thilemann, S. Avramiotis, N.S. Bonetti, B. Tsivgoulis, G. Ambler, G. Alberti, A. Yoshimura, S. Brown, M.M. Shiozawa, M. Lip, G.Y.H. Venti, M. Acciarresi, M. Tanaka, K. Mosconi, M.G. Takagi, M. Jäger, R.H. Muir, K. Inoue, M. Schwab, S. Bonati, L.H. Lyrer, P.A. Toyoda, K. Caso, V. Werring, D.J. Kallmünzer, B. Engelter, S.T. Engelter, S.T. Lyrer, P.A. Bonati, L.H. Seiffge, D.J. Traenka, C. Polymeris, A.A. Zietz, A. Peters, N. De Marchis, G.M. Thilemann, S. Avramiotis, N.S. Gensicke, H. Hert, L. Wagner, B. Schaub, F. Meya, L. Fladt, J. Dittrich, T. Fisch, U. Macha, K. Haupenthal, D. Gassmann, L. Wang, R. Stoll, S. Schwab, S. Volbers, B. Siedler, G. Kallmünzer, B. Cappellari, M. Bonetti, B. Bovi, P. Tomelleri, G. Micheletti, N. Zivelonghi, C. Emiliani, A. Parry-Jones, A. Patterson, C. Price, C. Elmarimi, A. Parry, A. Nallasivam, A. Nor, A.M. Esis, B. Bruce, D. Bhaskaran, B. Roffe, C. Cullen, C. Holmes, C. Cohen, D. Hargroves, D. Mangion, D. Chadha, D. Vahidassr, D. Manawadu, D. Giallombardo, E. Warburton, E. Flossman, E. Gunathilagan, G. Proschel, H. Emsley, H. Anwar, I. Burger, I. Okwera, J. Putterill, J. O’Connell, J. Bamford, J. Corrigan, J. Scott, J. Birns, J. Kee, K. Saastamoinen, K. Pasco, K. Dani, K. Sekaran, L. Choy, L. Iveson, L. Mamun, M. Sajid, M. Cooper, M. Burn, M. Smith, M. Power, M. Davis, M. Smyth, N. Veltkamp, R. Sharma, P. Guyler, P. O’Mahony, P. Wilkinson, P. Datta, P. Aghoram, P. Marsh, R. Luder, R. Meenakishundaram, S. Subramonian, S. Leach, S. Ispoglou, S. Andole, S. England, T. Manoj, A. Harrington, F. Rehman, H. Sword, J. Staals, J. Mahawish, K. Harkness, K. Shaw, L. McCormich, M. Sprigg, N. Mansoor, S. Krishnamurthy, V. Giustozzi, M. Acciarresi, M. Agnelli, G. Becattini, C. Alberti, A. D’Amore, C. Cimini, L.A. Bandini, F. Tsivgoulis, G. Liantinioti, C. Chondrogianni, M. Yaghi, S. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Vannucchi, V. Masotti, L. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Mumoli, N. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. De Lodovici, M.L. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Pieroni, A. Giuntini, M. Lotti, E.M. Flomin, Y. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Todo, K. Kimura, K. Shibazaki, K. Yagita, Y. Furui, E. Itabashi, R. Terasaki, T. Shiokawa, Y. Hirano, T. Suzuki, R. Kamiyama, K. Nakagawara, J. Takizawa, S. Homma, K. Okuda, S. Okada, Y. Maeda, K. Kameda, T. Kario, K. Nagakane, Y. Hasegawa, Y. Akiyama, H. Shibuya, S. Mochizuki, H. Ito, Y. Nakashima, T. Matsuoka, H. Takamatsu, K. Nishiyama, K. Tanaka, K. Endo, K. Miyagi, T. Osaki, M. Kobayashi, J. Okata, T. Tanaka, E. Sakamoto, Y. Tokunaga, K. Takizawa, H. Takasugi, J. Matsubara, S. Higashida, K. Matsuki, T. Kinoshita, N. Shiozawa, M. Ide, T. Yoshimoto, T. Ando, D. Fujita, K. Kumamoto, M. Kamimura, T. Kikuno, M. Mizoguchi, T. Sato, T. NOACISP-LONGTERM, Erlangen Registry, CROMIS-2, RAF, RAF-DOAC, SAMURAI-NVAF Verona Registry Collaborators

Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (

Published
2022

5. Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis

Author

Siepmann, T; https://orcid.org/0000-0003-2196-5904, Sedghi, A, Simon, E, Winzer, S, Barlinn, J, de With, K, Mirow, L, Wolz, M, Gruenewald, T, Schroettner, P, von Bonin, S, Pallesen, L-P, Rosengarten, B, Schubert, J, Lohmann, T, Machetanz, J, Spieth, P, Koch, T, Bornstein, S, Reichmann, H, Puetz, V, Barlinn, K, Siepmann, T; https://orcid.org/0000-0003-2196-5904, Sedghi, A, Simon, E, Winzer, S, Barlinn, J, de With, K, Mirow, L, Wolz, M, Gruenewald, T, Schroettner, P, von Bonin, S, Pallesen, L-P, Rosengarten, B, Schubert, J, Lohmann, T, Machetanz, J, Spieth, P, Koch, T, Bornstein, S, Reichmann, H, Puetz, V, and Barlinn, K

Abstract

BACKGROUND AND PURPOSE Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I$^{2}$ statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I$^{2}$ = 0%, P = 0.82). CONCLUSIONS Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID

Published
2021

6. Increased risk of acute stroke among patients with severe COVID‐19: a multicenter study and meta‐analysis

Author

Siepmann, T., primary, Sedghi, A., additional, Simon, E., additional, Winzer, S., additional, Barlinn, J., additional, With, K., additional, Mirow, L., additional, Wolz, M., additional, Gruenewald, T., additional, Schroettner, P., additional, Bonin, S., additional, Pallesen, L.‐P., additional, Rosengarten, B., additional, Schubert, J., additional, Lohmann, T., additional, Machetanz, J., additional, Spieth, P., additional, Koch, T., additional, Bornstein, S., additional, Reichmann, H., additional, Puetz, V., additional, and Barlinn, K., additional

Published
2020
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7. Einfluss der Thrombusoberfläche auf die erfolgreiche Revaskularisation nach dem ersten Manöver in der endovaskulären Schlaganfallbehandlung mittels direkter Thrombusaspiration und Stent Retriever

Author

Kaiser, D, additional, Laske, K, additional, Haedrich, K, additional, Mueller, A, additional, Daubner, D, additional, Puetz, V, additional, Pallesen, L, additional, Winzer, R, additional, Kitzler, H, additional, Engellandt, K, additional, Krukowski, P, additional, Abramyuk, A, additional, Linn, J, additional, and Gerber, J, additional

Published
2020
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8. Anticoagulation after Stroke in Patients with Atrial Fibrillation: To Bridge or Not with Low-Molecular-Weight Heparin?

Author

Altavilla, R. Caso, V. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Giulia Mosconi, M. Anna Cimini, L. Fusaro, J. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. MacCarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Paciaroni, M.

Abstract

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P

Published
2019

11. Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes

Author

Paciaroni, M. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Cimini, L.A. Altavilla, R. Volpi, G. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Caso, V.

Abstract

Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.

Published
2018

12. Increased risk of acute stroke among patients with severe COVID‐19: a multicenter study and meta‐analysis.

Author

Siepmann, T., Sedghi, A., Simon, E., Winzer, S., Barlinn, J., With, K., Mirow, L., Wolz, M., Gruenewald, T., Schroettner, P., Bonin, S., Pallesen, L.‐P., Rosengarten, B., Schubert, J., Lohmann, T., Machetanz, J., Spieth, P., Koch, T., Bornstein, S., and Reichmann, H.

Subjects
COVID-19, STROKE patients
Abstract

Background and purpose: Recent observations linked coronavirus disease 2019 (COVID‐19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non‐severe COVID‐19. Methods: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory‐confirmed COVID‐19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines including data from observational studies of acute stroke in COVID‐19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID‐19 severity using a random‐effects model. Between‐study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. Results: Of 165 patients hospitalized for COVID‐19 (49.1% males, median age = 67 years [57–79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9–8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta‐analysis. Amongst 741 pooled COVID‐19 patients, overall stroke rate was 2.9% (95% CI: 1.9–4.5). Risk of acute stroke was increased for patients with severe compared to non‐severe COVID‐19 (RR = 4.18, 95% CI: 1.7–10.25; P = 0.002) with no evidence of heterogeneity (I2 = 0%, P = 0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID‐19 is associated with an increased risk of acute stroke. [ABSTRACT FROM AUTHOR]

Published
2021
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13. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients with Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study

Author

Paciaroni, M. Agnelli, G. Caso, V. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Mosconi, M.G. Cimini, L.A. Procopio, A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S.

Abstract

Background and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Published
2017

14. Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study

Author

Acciarresi, M. Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Morotti, A. Costa, P. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. D'Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R.

Subjects
cardiovascular diseases
Abstract

Background and Purpose The aim of this study was to investigate for a possible association between both prestroke CHA2DS2-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS ≥10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS

Published
2017

15. Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Author

Antonenko, K. Paciaroni, M. Agnelli, G. Falocci, N. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Papageorgiou, S.G. Corea, F. Sette, M.D. Ageno, W. Lodovici, M.L.D. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R. Caso, V.

Subjects
cardiovascular diseases
Abstract

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes. © 2016, © European Stroke Organisation 2016.

Published
2017

17. The option jungle

Author

Pallesen, L. C.

Abstract

Article focused on the conglomeration of options out of which many students never emerge and concentrated on the decisions that students must make in order to become educated. (Editor/RK)

Published
1973

18. Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Lees, K.R.

Subjects
cardiovascular diseases
Abstract

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). The identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06–4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95 % CI 1.04–1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon. © 2015, Springer-Verlag Berlin Heidelberg.

Published
2016

19. Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: Effect of anticoagulation and its timing: The RAF study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Acciarresi, M. D'Amore, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Bubba, V. Silvestri, I. Lees, K.R.

Abstract

Background and Purpose - The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods - The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results - Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions - Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Published
2015

21. Multimodal Computed Tomography Based Definition of Cerebral Imaging Profiles for Acute Stroke Reperfusion Therapy (CT-DEFINE): Results of a Prospective Observational Study

Author

Barlinn, K., primary, Seibt, J., additional, Engellandt, K., additional, Gerber, J., additional, Puetz, V., additional, Kepplinger, J., additional, Wunderlich, O., additional, Pallesen, L.-P., additional, Bodechtel, U., additional, Koch, R., additional, von Kummer, R., additional, and Dzialowski, I., additional

Published
2014
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23. Analgesic efficacy with rapidly absorbed ibuprofen sodium dihydrate in postsurgical dental pain:results from the randomized QUIKK trial

Author

Nørholt, Sven Erik, Hallmer, F, Hartlev, Jens, Pallesen, L, Blomlöf, J, Hansen, E J, Fernandes, N, Eriksson, L, Pinholt, E M, Nørholt, Sven Erik, Hallmer, F, Hartlev, Jens, Pallesen, L, Blomlöf, J, Hansen, E J, Fernandes, N, Eriksson, L, and Pinholt, E M

Abstract

To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid).

Published
2011

24. Epidemiology of European community-associated methicillin-resistant Staphylococcus aureus clonal complex 80 type IV strains isolated in Denmark from 1993 to 2004

Author

Larsen, A R, Böcher, S, Stegger, M, Goering, R, Pallesen, L V, Skov, R, Larsen, A R, Böcher, S, Stegger, M, Goering, R, Pallesen, L V, and Skov, R

Abstract

In Europe, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been caused predominantly by isolates belonging to the "European CA-MRSA" clone (sequence type 80, staphylococcal cassette chromosome mec type IV). In this study, the epidemiology of European CA-MRSA was investigated on a nationwide scale, covering the period from 1993 to 2004. Denmark has been a low-prevalence country regarding MRSA since the mid-1970s but has experienced an increase in the number of new MRSA cases in recent years. Our results show that European CA-MRSA contributed to this increase. The isolates primarily caused skin and soft tissue infections (SSTIs) in patients outside hospitals, and transmission between household members was the predominant mode of spread. Although some of the isolates were found in hospitalized patients, nosocomial transmission seemed likely in only one instance, pointing to endogenous infections as an important factor. Compared to the CA-MRSA clone most common in the United States (USA300), the European CA-MRSA clone seems less well adapted to persist in hospital environments. Patients with a recent history of travel or family relation to the Mediterranean or Middle East were highly overrepresented. The epidemiological data indicated that the European CA-MRSA isolates were introduced into Denmark on multiple occasions, paralleled by an increasing level of genetic diversity of the isolates found during the study period. European CA-MRSA has previously been described as a rather uniform clone. However, we found pronounced, diverse pulsed-field gel electrophoresis subtypes, staphylococcal protein A gene (spa) types, and susceptibility patterns.

Published
2008

28. Influence of particle size of autogenous bone grafts on the early stages of bone regeneration: A histologic and stereologic study in rabbit calvarium

Author

Pallesen, L., Schou, S., Aaboe, Merete, Hjørting-Hansen, E., Nattestad, A., Melsen, F., Pallesen, L., Schou, S., Aaboe, Merete, Hjørting-Hansen, E., Nattestad, A., and Melsen, F.

Abstract

autogenous bone grafts, bone regeneration, calvarial defects, histology, particle size, particulated bone grafts, rabbits, revascularization, stereology

Published
2002

30. A 41-year history of a mandibular subperiosteal implant

Author

Schou, S., Pallesen, L., Hjørting-Hansen, E., Pedersen, C.S., Fibæk, B., Schou, S., Pallesen, L., Hjørting-Hansen, E., Pedersen, C.S., and Fibæk, B.

Abstract

Oral implants, subperiosteal implants, complications

Published
2000

36. Characterization of Human Mucin (MUC15) and Identification of Ovine and Caprine Orthologs. .

Author

Pallesen, L. T., Pedersen, L. R. L., Petersen, T. E., Knudsen, C. R., and Rasmussen, J. T.

Subjects
*MUCINS, *SHEEP, *GOATS, *GLYCOPROTEINS, *MILKFAT, *AMINO acids, *MASS spectrometry
Abstract

The glycoprotein MUC15 (mucin 15) was initially isolated from the bovine milk fat globule membrane. The present work demonstrates the existence of iramunologically similar proteins (∼130 kDa) in ovine, caprine, porcine, and buffalo milk samples. Purification and N-terminal amino acid sequencing confirmed the presence of ovine and caprine MUC15 orthologs in milk fat globule membranes. Expression of MUC15 in human milk was demonstrated by immunostaining (∼150 kDa) as well as by mass spectrometry. Screening of a human multiple tissue expression array showed abundant MUC15 gene expression in placenta, salivary gland, thyroid gland, trachea, esophagus, kidney, testis, and the leukemia K-562 cell line. Furthermore, moderate expression was seen in the pancreas, adult and fetal lung, fetal kidney, lymph node, adult and fetal thymus, and parietal lobe. Structural motifs for interactions (epidermal growth factor receptor and Src homology 2 domains) are identified in the intracellular region. Implication of the mucin in signal transduction and the potential physiological function of MUC15 are discussed. [ABSTRACT FROM AUTHOR]

Published
2008
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37. Characterization of Carbohydrate Structures of Bovine MUC15 and Distribution of the Mucin in Bovine Milk.

Author

Pallesen, L. T., Pedersen, L. R. L., Petersen, T. E., and Rasmussen, J. T.

Subjects
*CARBOHYDRATES, *MUCINS, *GLYCOPROTEINS, *MILKFAT, *DAIRY products, *MOLECULAR weights
Abstract

The present work reports the characterization of carbohydrate structures and the distribution of the newly identified mucin MUC15, a highly glycosylated protein associated with the bovine milk fat globule membrane (MFGM). Distribution of MUC15 was investigated in various fractions of bovine milk by densitometric scanning of Western blots. In raw milk, MUC 15 was shown to constitute 0.08% (wt) of the protein and approximately 1.5% (wt) of the MFGM-associated proteins. Surprisingly, this study showed that in addition to the fat-containing fractions, such as MFGM and buttermilk, MUC15 was present in nonfat-containing fractions as well, such as skim milk and whey. Compositional and structural studies of the carbohydrates of bovine milk MUC15 showed that the glycans are composed of fucose, galactose, mannose, N-acetylgalactosamine, N-acetylglycosamine, and sialic acid. The carbohydrate was shown to constitute 65% of the total molecular weight, and the molar ratios of the individual sugars to protein of the O-linked glycans were determined. The glycan structures of MUC15 were further studied by enzymatic deglycosylation experiments using different endo- and exoglycosidases as well as a panel of lectins. The N-linked glycans were shown to contain mainly hybrid-type N-glycans. In addition, the N-glycans were shown to be sialylated and contain terminal poly-lactosamine structures. The O-linked glycans were found to constitute some unsubstituted Core- 1 structures and a substantial number of sialylated Core-1 O-linked glycans. By comparing the results of peanut agglutinin lectin binding, enzymatic deglycosylation, and monosaccharide composition analysis, we concluded that bovine MUC15 also contains more complex O-glycans containing high amounts N-acetylglucosamine residues. Furthermore, a small subset of the O-linked glycans is decorated with lactosamine on their terminal ends. [ABSTRACT FROM AUTHOR]

Published
2007
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38. The Danish incinerator dioxin study. Part 1

Author

Manscher, O.H., primary, Heidam, N.Z., additional, Vikelsøe, J., additional, Nielsen, P., additional, Blinksbjerg, P., additional, Madsen, H., additional, Pallesen, L., additional, and Tiernan, T.O., additional

Published
1990
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39. Regulation of the phase switch controlling expression of type 1 fimbriae in Escherichia coli.

Author

Pallesen, L., Madsen, O., and Klemm, P.

Subjects
ESCHERICHIA coli, BACTERIAL cell walls, DNA, GENETICS, GENES, PROTEINS
Abstract

The expression of Escherichia coli type 1 fimbriae is phase-variable i.e. the bacterial cell is either fimbriated or non-fimbriated. The transition from one state to the other is caused by the change in configuration of an invertible DNA segment harbouring the promoter of the fimA gene. The position of this phase switch is controlled by two proteins, FimB and FimE, which mediate an ‘on’ or ‘off’ configuration of the switch, respectively. In this study, we have investigated how these proteins control the switch by means of fim-lac fusions on low-copy-number plasmids. It was found, by in trans and cis complementation, that the ratio of fimB to fimE and the total concentration of the gene products determine the configuration of the switch as well as the frequency of phase switching. It was also shown that transcription occurs from the promoter located at the phase switch when this is in the ‘off’ configuration. This suggests a regulatory mechanism, since the resulting transcript would be anti-sense to the fimE transcript. [ABSTRACT FROM AUTHOR]

Published
1989
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40. Epidemiology of European Community-Associated Methicillin-Resistant Staphylococcus aureusClonal Complex 80 Type IV Strains Isolated in Denmark from 1993 to 2004

Author

Larsen, A. R., Bo¨cher, S., Stegger, M., Goering, R., Pallesen, L. V., and Skov, R.

Abstract

ABSTRACTIn Europe, community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) infections have been caused predominantly by isolates belonging to the “European CA-MRSA” clone (sequence type 80, staphylococcal cassette chromosome mectype IV). In this study, the epidemiology of European CA-MRSA was investigated on a nationwide scale, covering the period from 1993 to 2004. Denmark has been a low-prevalence country regarding MRSA since the mid-1970s but has experienced an increase in the number of new MRSA cases in recent years. Our results show that European CA-MRSA contributed to this increase. The isolates primarily caused skin and soft tissue infections (SSTIs) in patients outside hospitals, and transmission between household members was the predominant mode of spread. Although some of the isolates were found in hospitalized patients, nosocomial transmission seemed likely in only one instance, pointing to endogenous infections as an important factor. Compared to the CA-MRSA clone most common in the United States (USA300), the European CA-MRSA clone seems less well adapted to persist in hospital environments. Patients with a recent history of travel or family relation to the Mediterranean or Middle East were highly overrepresented. The epidemiological data indicated that the European CA-MRSA isolates were introduced into Denmark on multiple occasions, paralleled by an increasing level of genetic diversity of the isolates found during the study period. European CA-MRSA has previously been described as a rather uniform clone. However, we found pronounced, diverse pulsed-field gel electrophoresis subtypes, staphylococcal protein A gene (spa) types, and susceptibility patterns.

Published
2008
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41. Cloning and sequencing of a Treponema pallidum gene encoding a 31.3-kilodalton endoflagellar subunit (FlaB2)

Author

Pallesen, L and Hindersson, P

Abstract

A library of Treponema pallidum DNA was established in the direct selection vector pUN121. Six clones carrying a gene coding for a 33-kilodalton T. pallidum flagellum subunit were identified by colony hybridization with an oligodeoxynucleotide probe based on the N-terminal amino acid sequence of this subunit. An open reading frame of 286 amino acids with the expected N-terminal sequence and absence of cysteine residues was identified. The deduced protein had a calculated molecular weight of 31.3 kilodaltons. We propose to name this flagellar subunit FlaB2. FlaB2 shows a significant amino acid homology with flagellins of several remotely related bacterial species. This homology was most pronounced corresponding to the C-terminal and N-terminal parts of the protein, whereas the central region was variable.

Published
1989
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46. A Rubisco-binding protein is required for normal pyrenoid number and starch sheath morphology in Chlamydomonas reinhardtii .

Author

Itakura AK, Chan KX, Atkinson N, Pallesen L, Wang L, Reeves G, Patena W, Caspari O, Roth R, Goodenough U, McCormick AJ, Griffiths H, and Jonikas MC

Subjects
Carbon metabolism, Carbon Cycle, Chlamydomonas metabolism, Chlamydomonas reinhardtii genetics, Mutation, Phenotype, Plant Proteins genetics, Plant Proteins metabolism, Carrier Proteins metabolism, Chlamydomonas reinhardtii metabolism, Plastids metabolism, Ribulose-Bisphosphate Carboxylase metabolism, Starch chemistry
Abstract

A phase-separated, liquid-like organelle called the pyrenoid mediates CO 2 fixation in the chloroplasts of nearly all eukaryotic algae. While most algae have 1 pyrenoid per chloroplast, here we describe a mutant in the model alga Chlamydomonas that has on average 10 pyrenoids per chloroplast. Characterization of the mutant leads us to propose a model where multiple pyrenoids are favored by an increase in the surface area of the starch sheath that surrounds and binds to the liquid-like pyrenoid matrix. We find that the mutant's phenotypes are due to disruption of a gene, which we call StArch Granules Abnormal 1 ( SAGA1 ) because starch sheath granules, or plates, in mutants lacking SAGA1 are more elongated and thinner than those of wild type. SAGA1 contains a starch binding motif, suggesting that it may directly regulate starch sheath morphology. SAGA1 localizes to multiple puncta and streaks in the pyrenoid and physically interacts with the small and large subunits of the carbon-fixing enzyme Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase), a major component of the liquid-like pyrenoid matrix. Our findings suggest a biophysical mechanism by which starch sheath morphology affects pyrenoid number and CO 2 -concentrating mechanism function, advancing our understanding of the structure and function of this biogeochemically important organelle. More broadly, we propose that the number of phase-separated organelles can be regulated by imposing constraints on their surface area., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Published
2019
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47. Contrasting Patterns for Missing Third Molars in the United States and Sweden.

Author

Magraw CBL, Pallesen L, Moss KL, Fisher EL, Offenbacher S, and White RP Jr

Subjects
Adult, Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Nutrition Surveys, Prevalence, Sweden, United States, Molar, Third anatomy & histology
Abstract

Purpose: The purpose of this study was to compare the prevalence of third molars from the US National Health and Nutrition Examination Survey (NHANES) and the Swedish survey., Materials and Methods: This cross-sectional study involved the comparison of the only published data on third molar prevalence. The number of visible third molars in the NHANES of 2011 through 2012 were assessed in nonclinical settings by trained, calibrated dental hygienists and reported by age decade (approximately 5,000 patients). Similar data were reported for the Swedish population with data collected in clinical settings (approximately 700 patients). The primary outcome variable was the number of third molars (0 to 4); the predictor variables were age cohorts (20 to 29 through 70 to 79 yr). Outcome data were reported with descriptive statistics., Results: In the youngest cohort (20 to 29 yr), having no visible third molars was more likely in the US population than in the Swedish population (47 vs 2%, respectively). By 50 to 59 years, outcomes for no third molars were similar in the United States and Sweden (53 and 57%, respectively)., Conclusion: The presence or absence of third molars reported from the US and Swedish populations presented contrasting patterns, particularly in the younger cohorts. More comprehensive and detailed data are required in future surveys as population studies on third molars become more important for clinicians and other stakeholders., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Published
2017
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48. [Organized Post-Stroke Care through Case Management on the Basis of a Standardized Treatment Pathway : Results of a Single-Centre Pilot Study].

Author

Barlinn J, Barlinn K, Helbig U, Siepmann T, Pallesen LP, Urban H, Pütz V, Schmitt J, Reichmann H, and Bodechtel U

Subjects
Aftercare methods, Aftercare standards, Aged, Aged, 80 and over, Case Management standards, Case Management statistics & numerical data, Female, Germany epidemiology, Humans, Male, Middle Aged, Pilot Projects, Practice Guidelines as Topic, Prevalence, Secondary Prevention methods, Secondary Prevention standards, Stroke diagnosis, Stroke Rehabilitation methods, Stroke Rehabilitation standards, Aftercare statistics & numerical data, Critical Pathways standards, Critical Pathways statistics & numerical data, Secondary Prevention statistics & numerical data, Stroke therapy, Stroke Rehabilitation statistics & numerical data
Abstract

Background: Post-stroke care programs based on a standardized treatment pathway supported by case management may prevent secondary stroke and minimize risk factors., Objectives: We aimed to determine the feasibility of a standardized treatment pathway and its impact on risk factor control, life-style changes and adherence to secondary prevention medication., Methods: We conducted a prospective pilot study in consecutive stroke patients. The 12-month post-stroke care program included regular perosnal and phone contact with a certified case manager. Target values for vascular risk factors following current recommendations of stroke guidelines were monitored and treated if necessary. In the case of deviations from the treatment pathway the case manager intervened. Patients were screened for recurrent stroke at the end of the program after 12 months., Results: We enrolled 101 patients: 57.4 % were male, the median age was 72 (IQR, 62-80) years, median baseline NIHSS score was 2(IQR, 1-5), 79.2 % had an ischemic stroke, 3 % a hemorrhagic stroke, and 17.8 % a transient ischemic attack (TIA). Eighty-six (85.1 %) patients completed the program, 12 (11.9 %) withdrew from the program and 3 died of malignant diseases. In total, 628 personal (6.2/patient) and 2,683 phone contacts (26.6/patient) were conducted by the case manager. Three hundred-seventy-nine specific interventions were necessary mostly because of missing medication, non-compliance, and social needs. After 12 months, target goals for blood pressure, body mass index, nicotine use, and cholesterol were more frequently (p < 0.05) achieved than at baseline. No recurrent stroke occurred during the program., Conclusions: Our pilot data demonstrate that case management-based post-stroke care is feasible and may contribute to effective secondary prevention of stroke.

Published
2016
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49. A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle.

Author

Mackinder LC, Meyer MT, Mettler-Altmann T, Chen VK, Mitchell MC, Caspari O, Freeman Rosenzweig ES, Pallesen L, Reeves G, Itakura A, Roth R, Sommer F, Geimer S, Mühlhaus T, Schroda M, Goodenough U, Stitt M, Griffiths H, and Jonikas MC

Subjects
Chlamydomonas reinhardtii genetics, Organelles genetics, Ribulose-Bisphosphate Carboxylase genetics, Carbon Dioxide metabolism, Chlamydomonas reinhardtii enzymology, Organelles enzymology, Ribulose-Bisphosphate Carboxylase metabolism
Abstract

Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

Published
2016
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50. Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin.

Author

Gürgör P, Pallesen LT, Johnsen L, Ulrichsen M, de Jong IE, and Vaegter CB

Subjects
Animals, Ganglia, Spinal metabolism, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons metabolism, Peripheral Nerve Injuries metabolism, Receptor, Nerve Growth Factor metabolism, Sciatic Nerve injuries, Adaptor Proteins, Vesicular Transport biosynthesis, Apoptosis physiology, Ganglia, Spinal pathology, Neurons pathology, Peripheral Nerve Injuries pathology
Abstract

Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75(NTR)) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75(NTR) receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury-induced loss of DRG neurons. This result demonstrates that previous findings linking p75(NTR) and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Published
2016
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