164 results on '"Alexandrovska University Hospital"'
Search Results
2. Cataract surgery in toxoplasmosis-associated panuveitis: a case report
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Markov, Georgi, Department of Ophthalmology, Alexandrovska Hospital, Zdravkov, Yani, Clinic of Ophthalmology, Department of Ophthalmology, Alexandrovska University Hospital, Medical University of Sofia, and Oscar, Alexander
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toxoplasmosis, phacoemulsification, corticosteroids, trimethoprim/sulfamethoxazole - Abstract
Introduction: Cataract is one of the most frequent complications of uveitis. In the cases with toxoplasmosis, it is more common in the congenital form. Cataract surgery in the setting of uveitis is associated with a higher risk of postoperative complications and of reactivation of uveitis.Aim: Our aim is to present a clinical case of successful cataract surgery in toxoplasmosis-associated panuveitis.Case Report: A 74-year-old Caucasian man presented to our clinic with complaints of decreased vision in his left eye (OS). He had been treated for toxoplasmosis-associated panuveitis. The diagnosis was based on the clinical exam and ancillary serologic tests. On admission to the hospital, best-corrected visual acuity of OS (BCVA) was 0.4. He had posterior subcapsular cataract in OS. There were no signs of inflammation in the anterior and posterior segments. We did phacoemulsification with implantation of a foldable, hydrophobic acrylic intraocular lens. There were no intraoperative complications. Postoperatively, BCVA was 0.9. He was treated for 1.5 months with oral trimethoprim/sulfamethoxazole 2 x 960 mg and frequent topical tobramycin/dexamethasone. We did not observe reactivation of the uveitis. Three years following surgery, he developed a secondary cataract.Conclusion: We demonstrated a case of successful surgical therapy of complicated cataract in toxoplasmosis-associated panuveitis. In the setting of postoperative therapy with trimethoprim/sulfamethoxazole, reactivation of uveitis was not observed. The only late complication was secondary cataract.
- Published
- 2022
3. Cardiopoietic cell therapy for advanced ischemic heart failure : results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial
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Bartunek, Jozef, Terzic, Andre, Davison, Beth A, Filippatos, Gerasimos S, Radovanovic, Slavica, Beleslin, Branko, Merkely, Bela, Musialek, Piotr, Wojakowski, Wojciech, Andreka, Peter, Horvath, Ivan G, Katz, Amos, Dolatabadi, Dariouch, El Nakadi, Badih, Arandjelovic, Aleksandra, Edes, Istvan, Seferovic, Petar M, Obradovic, Slobodan, Vanderheyden, Marc, Jagic, Nikola, Petrov, Ivo, Atar, Shaul, Halabi, Majdi, Gelev, Valeri L, Shochat, Michael K, Kasprzak, Jaroslaw D, Sanz Ruiz, Ricardo, Heyndrickx, Guy R, Nyolczas, Noémi, Legrand, Victor, Guédès, Antoine, Heyse, Alex, Moccetti, Tiziano, Fernandez Aviles, Francisco, Jimenez Quevedo, Pilar, Bayes Genis, Antoni, Hernandez Garcia, Jose Maria, Ribichini, Flavio, Gruchala, Marcin, Waldman, Scott A, Teerlink, John R, Gersh, Bernard J, Povsic, Thomas J, Henry, Timothy D, Metra, Marco, Hajjar, Roger J, Tendera, Michal, Behfar, Atta, Alexandre, Bertrand, Seron, Aymeric, Stough, Wendy Gattis, Sherman, Warren, Cotter, Gad, Wijns, W. i. l. l. i. a. m. Collaborators Clinical investigators, Dens, sites Belgium: Ziekenhuis Oost Limburg: J., Dupont, M., Mullens, W., Janssens, M., Dolatabadi, Hoˆpital Civil de Charleroi: D., De Bruyne, Y., Lalmand, J., Dubois, P., El Nakadi, B., Aminian, A., De Vuyst, E., Gurnet, P., Gujic, M., Blankoff, I., Guedes, CHU Mont Godinne UCL: A., Gabriel, L., Seldrum, S., Doyen, C., Andre´, M., Heyse, AZ Glorieux: A., Van Durme, F., Verschuere, J., Legrand, Domaine Universitaire du Sart Tilman: V., Gach, O., D’Orio, V., Davin, L., Lancellotti, P., Baudoux, E., Ancion, A., Dulgheru, R., Vanderheyden, OLV Ziekenhuis Aalst – Cardiologie: M., Bartunek, J., Wijns, W., Verstreken, S., Penicka, . M., Gelev, P. Meeus Bulgaria: Tokuda Hospital Sofia: V., Zheleva Kichukova, I., Parapunova, R., Melamed, R., Sardovski, S., Radev, O., Yordanov, A., Radinov, A., Nenov, D., Amine, I., Petrov, City Hospital Clinic Cardiology Center: I., Kichukov, K., Nikitasov, L., Stankov, Z., Stoyanov, H., Tasheva Dimitrova, I., Angelova, M., Dimitrov, E., Minchev, M., Garvanski, I., Botev, C., Polomski, P., Alexandrovska University Hospital, Vassilev, Sofia: D., Karamfiloff, K., Tarnovska Kadreva, R., Vladimirova, L., Dimitrov, G., Hadzhiev, E., Tzvetkova, G., Andreka, . M. Atanasova Hungary: Gottsegen Gyo¨ rgy Orszagos Kardiologiai Inte´zet: P., Fontos, G., Fabian, J., Csepregi, A., Uzonyi, G., Gelei, A., Edes, Debreceni Egyetem Orvos e´s Ege´szse´gtudomanyi Centrum Altalanos Orvostudomanyi Kar Kardiologia Inte´zet: I., Balogh, L., Vajda, G., Darago, A., Gergely, S., Fulop, T., Jenei, C., Horvath, Pe´csi Tudomanyegyetem Klinikai Ko¨zpont Szıvgyogyaszati Klinika: I., Magyari, B., Nagy, A., Cziraki, A., Faludi, R., Kittka, B., Alizadeh, H., Merkely, Semmelweis Egyetem Varosmajori Szıv e´s Ergyogyaszati Klinika: B., Geller, L., Farkas, P., Szombath, G., Foldes, G., Skopal, J., Kovacs, A., Kosztin, A., Gara, E., Sydo, N., Nyolczas, MH Ege´szse´gu¨gyi Ko¨zpont Kardiologiai Osztaly: N., Kerecsen, G., Korda, A., Kiss, . M., Borsanyi, T., Polgar, B., Muk, B., Sharif, Z. Bari Ireland: HRB Clinical Research Facility: F., Atar, Y. M. Smyth Israel:Western Galilee Hospital: S., Shturman, A., Akria, L., Kilimnik, M., Brezins, M., Halabi, Ziv Medical Center: M., Dally, N., Goldberg, A., Aehab, K., Rosenfeld, I., Levinas, T., Saleem, D., Katz, Barzilai Medical Center: A., Plaev, T., Drogenikov, T., Nemetz, A., Barshay, Y., Jafari, J., Orlov, I., Nazareth Hospital EMMS: M. Omory, N. Kogan Nielsen, Shochat, Hillel Yaffe Medical Center: M., Shotan, A., Frimerman, A., Meisel, S., Asif, A., Sofer, O., Blondheim, D. S., Vazan, A., Metra, L. Arobov Italy: A. O. Spedali Civili di Brescia: M., Bonadei, I., Inama, L., Chiari, E., Lombardi, C., Magatelli, M., Russo, D., Lazzarini, V., Carubelli, V., Vassanelli, AOUI Verona – Borgo Trento Hospital: C., Ribichini, Flavio Luciano, Bergamini, C., Krampera, Mauro, Cicoria, M. A., Zanolla, L., Dalla Mura, D., Gambaro, A., Rossi, A., Pesarini Poland: Jagiellonian University Department of Cardiac, G., Musialek, Vascular Diseases at John Paul II Hospital in Krakow: P., Mazurek, A., Drabik, L., Ka˛dzielski, A., Walter, Z., Dzieciuch Rojek, M., Rubis, P., Plazak, . W., Tekieli, L., Podolec, J., Orczyk, W., Sutor, U., Zmudka, K., Olszowska, M., Podolec, P., Gruchala, Uniwersyteckie Centrum Kliniczne: M., Ciecwierz, D., Mielczarek, M., Burakowski, S., Chmielecki, M., Zielinska, M., Frankiewicz, A., Wdowczyk, J., Stopczynska, I., Bellwon, J., Mosakowska, K., Nadolna, R., Wroblewska, J., Rozmyslowska, M., Rynkiewicz, M., Marciniak, I., Raczak, G., Tarnawska, M., Taszner, M., Kasprzak, Bieganski Hospital: J., Plewka, M., Fiutowska, D., Rechcinski, T., Lipiec, P., Sobczak, M., Weijner Mik, P., Wraga, M., Krecki, R., Markiewicz, M., Haval Qawoq, D., Wojakowski, Gornosla˛skie Centrum Medyczne Sla˛skie j. Akademii Medycznej: W., Ciosek, J., Dworowy, S., Gaszewska Zurek, E., Ochala, A., Cybulski, W., Jadczyk, T., Wanha, W., Parma, Z., Kozlowski, M., Dzierzak, M., Markiewicz Serbia: Clinical Hospital Center Zvezdara, M., Arandjelovic, Cardiology Clinic: A., Sekularac, N., Boljevic, D., Bogdanovic, A., Zivkovic, S., Cvetinovic, N., Loncar, G., Clinical Centre of Serbia, Beleslin, Cardiology Clinic: B., Nedeljkovic, M., Trifunovic, D., Giga, V., Banovic, M., Nedeljkovic, I., Stepanovic, J., Vukcevic, V., Djordjevic Dikic, A., Dobric, M., Obrenovic Kircanski, B., Seferovic, Cardiology Clinic: P., Orlic, D., Tesic, M., Petrovic, O., Milinkovic, I., Simeunovic, D., Jagic, Clinical Center of Kragujevac: N., Tasic, M., Nikolic, D., Miloradovic, V., Djurdjevic, P., Sreckovic, M., Zornic, N., Clinical Hospital Center Bezanijska Kosa, Radovanovic, Cardiology Department: S., Saric, J., Hinic, S., Djokovic, A., Ðordevic, S., Bisenic, V., Markovic, O., Stamenkovic, S., Malenkovic, V., Tresnjak, J., Misic, G., Cotra, D., Tomovic, L., Vuckovic, V., Clinic of Emergency Internal Medicine, Obradovic, Military Medical Academy: S., Jovic, Z., Vukotic, S., Markovic, D., Djenic, N., Ristic Andjelkov, A., Bayes Genis, D. Ljubinka Spain: Hospital Universitario Germans Trias I. Pujol: A., Rodriguez Leor, O., Labata, C., Vallejo, N., Ferrer, E., Batlle, M., Fernandez Aviles, Hospital General Universitario Gregorio Mara~non: F., Sanz Ruiz, R., Casado, A., Loughlin, G., Zatarain, E., Anguita, J., Ferna ndez Santos, M. E., Pascual, C., Bermejo, J., Hernandez Garcia, Hospital Clinico Universitario Virgen de la Victoria: J. M., Jimenez Navarro, M., Dominguez, A., Carrasco, F., Mu~noz, A., Garcia Pinilla, J. M., Ruiz, J., Queipo de Llano, M. P., Hernandez, A., Fernandez, A., Jimenez Quevedo, Hospital Clinico San Carlos: P., Guerra, R., Biagioni, C., Gonzalez, R. A., Gomez deDiego, J. J., Mansson Broberg, L. Perez de Isla Sweden: Karolinska University Hospital: A., Sylve´n, C., Leblanc, K., Winter, R., Blomberg, P., Gunyeli, E., Ruck, A., Silva, C., Fo¨rstedt Switzerland: CardioCentro Ticino, J., Moccetti, Switzerland: T., Rossi, M., Pasotti, E., Petrova, I., Crljenica, C., Monti, C., Murzilli, R., Su¨rder, D., Moccetti, M., Turchetto, L., Locicero, V., Chiumiento, L., Maspoli, S., Mombelli, M., Anesini, A., Biggiogero, M., Ponti, G., Camporini, C., Polledri, S., Hill, G. Dolci United Kingdom: Kings College Hospital: J., Plymen, C., Amin Youssef, G., Mcdonagh, T., Drasar, E., Mijovic, A., Jouhra, F., Mcloman, D., Dworakowski, R., Webb, I., Byrne, J., and Potter, V.
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0301 basic medicine ,Male ,Cardiopoiesis ,Cardiovascular disease ,Disease severity ,Marker ,Precision medicine ,Regenerative medicine ,Stem cell ,Target population ,Adult ,Aged ,Double-Blind Method ,Female ,Heart Failure ,Humans ,Mesenchymal Stem Cell Transplantation ,Middle Aged ,Myocardial Ischemia ,Prospective Studies ,Treatment Outcome ,Young Adult ,Cardiology and Cardiovascular Medicine ,Cell- and Tissue-Based Therapy ,mesenchymal stem-cells ,030204 cardiovascular system & hematology ,Cardiorespiratory Medicine and Haematology ,outcomes ,Fast-Track Clinical Research ,Sudden cardiac death ,0302 clinical medicine ,Ischemia ,cardiovascular disease ,Clinical endpoint ,target population ,CHART Program ,Ejection fraction ,bone-marrow ,Heart Failure/Cardiomyopathy ,3. Good health ,Cohort ,Cardiology ,Fast Track ,disease severity ,delivery ,medicine.medical_specialty ,precision medicine ,Clinical Sciences ,regenerative medicine ,03 medical and health sciences ,cardiopoiesis ,Internal medicine ,medicine ,Adverse effect ,marker ,disease ,business.industry ,medicine.disease ,mortality ,Confidence interval ,Clinical trial ,stem cell ,Editor's Choice ,030104 developmental biology ,predictors ,Cardiovascular System & Hematology ,Heart failure ,business - Abstract
Altres ajuts: This work was supported by Celyad, SA (Mont-Saint-Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding). Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.
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- 2017
4. Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.
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Pratley RE, Tuttle KR, Rossing P, Rasmussen S, Perkovic V, Nielsen OW, Mann JFE, MacIsaac RJ, Kosiborod MN, Kamenov Z, Idorn T, Hansen MB, Hadjadj S, Bakris G, Baeres FMM, and Mahaffey KW
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Background: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m
2 , kidney replacement therapy, and kidney or CV death) by 24%., Objectives: This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population., Methods: Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee., Results: A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment., Conclusions: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)., Competing Interests: Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Pratley has received speaker fees paid to his employer, AdventHealth (through December 31, 2023) from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees directed to his institution from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd., Intas Pharmaceuticals, Eli Lilly, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; has received grants directed to his institution from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi; and has received personal fees (from January 1, 2024) from AdventHealth, a nonprofit entity. Dr Tuttle has received support from National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, and from Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, and the Doris Duke Foundation outside of the submitted work; has received consulting fees from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and has received speaker fees from Novo Nordisk. Dr Rossing has received grants from Bayer, AstraZeneca, and Novo Nordisk; has received honoraria paid to the Steno Diabetes Centre Copenhagen from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer; and has received consulting fees from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UptoDate; and is Board Director for George Clinical, St Vincent’s Health Australia and several independent medical research institutes. Dr Mann has received grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; has received consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; has received honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, as well as a leadership role in the Kidney Disease: Improving Global Outcomes group. Dr MacIsaac was a FLOW trial investigator and member of the FLOW global expert panel; has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent’s Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program, and The National Health and Medical Research Council of Australia; has received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, MSD, Novartis, and Boehringer Ingelheim; has been on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, AstraZeneca, and MSD; has received travel support from Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca; and has been a principal investigator for industry-sponsored clinical trials run by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag, and AbbVie. Dr Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Kamenov has received speaker fees from Actavis, AstraZeneca, Bayer-Schering, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, KRKA, Merck, MLD, MSD (Merck), Mundipharma, Mylan, Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, Servier, TEVA Pharmaceuticals, Valentis, Vedra, and Viatris. Dr Hadjadj has received grants from Asdia, Asten, AstraZeneca, Homeperf, LVL, Nestle Home Care, Pierre Fabre, and VitalAire; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier, and Valbiotis; has received speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Santé, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, and Valbiotis; and has received meeting invitations from AstraZeneca, Abbott, Dino Santé, Eli Lilly, and Novo Nordisk. Dr Bakris has received consulting fees from Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Novo Nordisk, and Dia Medica Therapeutics. Dr Mahaffey has received grants from the American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson and Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson and Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, and Theravance; and holds equity in Human, Medeloop, Precordior and Regencor. Drs Rasmussen, Nielsen, Idorn, Hansen, and Baeres are employees of and shareholders in Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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5. Impact of the Type of Anticoagulation Therapy on Long-Term Clinical Outcomes in Patients with Coronary Bifurcation Lesion and Atrial Fibrillation-Insights from the Bulgarian Bifurcation Registry.
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Mileva N, Vassilev D, Panayotov P, Nikolov P, Dimitrov G, Karamfiloff K, Rigatelli G, and Gil RJ
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- Humans, Male, Female, Aged, Prospective Studies, Middle Aged, Bulgaria epidemiology, Vitamin K antagonists & inhibitors, Treatment Outcome, Atrial Fibrillation drug therapy, Atrial Fibrillation complications, Anticoagulants therapeutic use, Registries statistics & numerical data, Coronary Artery Disease drug therapy, Coronary Artery Disease complications
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Background and Objectives : Patients with atrial fibrillation and coronary artery disease represent a group with a greater risk of mortality. To evaluate patients with atrial fibrillation (AF) and a significant coronary bifurcation lesion and compare the clinical outcomes between the patients on anticoagulant treatment with Vitamin K antagonist (VKA) and those on direct anticoagulant (DOAC). Materials and Methods : This is a prospective study of patients with AF and stable coronary artery disease, who had evidence of a significant coronary bifurcation lesion. A log-rank test was used to assess the difference in mortality between patients taking VKA and those on DOAC. The primary endpoint was the incidence of all-cause and cardiovascular death at mid-term. Results : A total of 226 patients with AF and a significant bifurcation lesion were included. The mean age was 70.9 ± 9.2, and 70% were males. Of the patients, 123 (54.7%) were on VKA treatment, and 103 (45.3%) were taking DOAC. For a median follow-up time of 55 (39-96) months, overall mortality was 40%, whereas CV mortality was 31%. Both all-cause (28.2% versus 50.4%, p = 0.020) and CV death (12.7% versus 24.9%, p = 0.032) were significantly lower in patients taking DOAC versus those on VKA. In patients treated with PCI, CV mortality was significantly lower in patients taking DOAC (21.4% versus 40.5%, p = 0.032). VKA therapy was an independent predictor of cardiovascular death (HR 1.88; 95% CI 1.11-3.18; p = 0.01), together with chronic kidney disease (HR 1.81; 95% CI 1.13-2.92; p = 0.01). Conclusions : Treatment with DOAC in patients with atrial fibrillation and coronary bifurcation lesion was associated with significantly lower mortality independently of the treatment approach. VKA was an independent predictor of CV mortality.
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- 2024
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6. Clinical and genetic variability among Bulgarian patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
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Chamova T, Ivanova N, Cherninkova S, Koleva M, Zlatareva D, Bojinova V, Mihova K, Georgiev M, Ferdinandov D, Bichev S, Kaneva R, Mitev V, Jordanova A, and Tournev I
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- Humans, Male, Bulgaria, Female, Phenotype, Child, Adult, Mutation, Adolescent, Magnetic Resonance Imaging, Spinocerebellar Ataxias genetics, Spinocerebellar Ataxias pathology, Spinocerebellar Ataxias congenital, Muscle Spasticity genetics, Muscle Spasticity pathology, Muscle Spasticity diagnosis, Muscle Spasticity diagnostic imaging, Heat-Shock Proteins genetics
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Background: Autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES)., Methods: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia., Results: Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2-hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT)., Conclusion: We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
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- 2024
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7. Characterisation of the novel MICA*112:02 allele by next generation sequencing.
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Ivanova M and Shivarov V
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- Humans, Exons, Base Sequence, Histocompatibility Testing, Sequence Analysis, DNA methods, High-Throughput Nucleotide Sequencing methods, Alleles, Histocompatibility Antigens Class I genetics
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The novel MICA*112:02 allele was detected by next generation sequencing., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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8. Characterisation of novel MICB alleles by next generation sequencing: MICB*055 and MICB*005:15.
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Shivarov V and Ivanova M
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- Humans, Base Sequence, Histocompatibility Testing methods, Sequence Analysis, DNA methods, Polymorphism, Genetic, High-Throughput Nucleotide Sequencing methods, Alleles, Exons, Histocompatibility Antigens Class I genetics
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Two novel MICB alleles with coding polymorphisms in exon 3 were detected by next generation sequencing., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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9. Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428.
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Musolf AM, Justice CM, Erdogan-Yildirim Z, Goovaerts S, Cuellar A, Shaffer JR, Marazita ML, Claes P, Weinberg SM, Li J, Senders C, Zwienenberg M, Simeonov E, Kaneva R, Roscioli T, Di Pietro L, Barba M, Lattanzi W, Cunningham ML, Romitti PA, and Boyadjiev SA
- Subjects
- Humans, Alleles, Bone Morphogenetic Protein 2 genetics, DNA, Intergenic genetics, Whole Genome Sequencing, RNA, Long Noncoding, Craniosynostoses genetics, Genome-Wide Association Study
- Abstract
Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios. Sequencing data for these trios were analyzed using the transmission disequilibrium test (TDT) and rare variant TDT (rvTDT) to identify high-risk rare gene variants. Sequencing data were also examined for copy number variants (CNVs) and de novo variants. TDT analysis identified a highly significant locus at 20p12.3, localized to the intergenic region between BMP2 and the noncoding RNA gene LINC01428. Three variants (rs6054763, rs6054764, rs932517) were identified as potential causal variants due to their probability of being transcription factor binding sites, deleterious combined annotation dependent depletion scores, and high minor allele enrichment in probands. Morphometric analysis of cranial vault shape in an unaffected cohort validated the effect of these three single nucleotide variants (SNVs) on dolichocephaly. No genome-wide significant rare variants, de novo loci, or CNVs were identified. Future efforts to identify risk variants for sNCS should include sequencing of larger and more diverse population samples and increased omics analyses, such as RNA-seq and ATAC-seq., (© 2024. The Author(s).)
- Published
- 2024
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10. Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.
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Núñez-Carpintero I, Rigau M, Bosio M, O'Connor E, Spendiff S, Azuma Y, Topf A, Thompson R, 't Hoen PAC, Chamova T, Tournev I, Guergueltcheva V, Laurie S, Beltran S, Capella-Gutiérrez S, Cirillo D, Lochmüller H, and Valencia A
- Subjects
- Humans, Neuromuscular Junction metabolism, Rare Diseases metabolism, Workflow, Receptors, Cholinergic genetics, Receptors, Cholinergic metabolism, Mutation, Myasthenic Syndromes, Congenital genetics, Myasthenic Syndromes, Congenital diagnosis
- Abstract
Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases., (© 2024. The Author(s).)
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- 2024
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11. Side branch predilatation during percutaneous coronary bifurcation intervention: Long-term mortality analysis.
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Vassilev D, Mileva N, Panayotov P, Nikolov P, Dosev L, Karamfiloff K, Rigatelli G, Gil RJ, Stankovic G, and Louvard Y
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Coronary Stenosis surgery, Coronary Stenosis therapy, Coronary Stenosis mortality, Coronary Stenosis diagnostic imaging, Registries, Treatment Outcome, Coronary Artery Disease mortality, Coronary Artery Disease surgery, Coronary Artery Disease therapy, Prospective Studies, Follow-Up Studies, Percutaneous Coronary Intervention
- Abstract
Background: Side branch predilatation (SBPD) during coronary bifurcation interventions is a technique that is not recommended by the latest guidelines. However, the data about the clinical outcomes after SBPD are surprisingly few., Aims: The current study aimed to explore the association between SBPD and mortality in long-term follow-up., Methods: All patients with coronary bifurcation stenoses revascularized with percutaneous coronary intervention were included in a prospective registry. Patients with stable angina and a bifurcation lesion with ≥50% diameter stenosis were included in the current analysis. Patients were assigned to two groups - those with SBPD(+) and those without SBPD(-). Propensity score matching was performed to equalize the risk factors and severity of coronary artery disease between the groups. A Kaplan-Meier analysis with a log-rank test for between-group differences was also performed., Results: From January 2013 to June 2021, 813 patients were included in the final study population. The mean age was 67 (10) years. After propensity score matching, 648 patients remained for analysis - 324 in each group. At a median follow-up of 57 months patients in the SBPD(+) group had a higher all-cause mortality (n = 107 (33%) vs. n = 98 [30.2%]; P = 0.045) and cardiovascular mortality (n = 82 [25.3%] vs. n = 70 [21.6%]; P = 0.03) when compared with SBPD(-) patients. SBPD was independently associated with all-cause and cardiovascular mortality., Conclusion: SBPD treatment of coronary bifurcation stenoses is associated with worse patient survival in the follow-up of up to 8 years. SBPD treatment gives better angiographic results, but this did not translate into better clinical outcomes.
- Published
- 2024
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12. Меtformin-associated maternal and neonatal outcomes in women with gestational diabetes - a retrospective cohort study.
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Yanachkova VE, Staynova R, Stoev S, and Kamenov Z
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- Humans, Female, Pregnancy, Retrospective Studies, Adult, Infant, Newborn, Glycated Hemoglobin analysis, Bulgaria epidemiology, Blood Glucose analysis, Blood Glucose metabolism, Blood Glucose drug effects, Diabetes, Gestational drug therapy, Diabetes, Gestational epidemiology, Metformin therapeutic use, Pregnancy Outcome epidemiology, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents adverse effects, Insulin
- Abstract
Objectives: To assess the maternal and neonatal outcomes in women with GDM treated with metformin, medical nutrition therapy (MNT) or insulin., Material and Methods: The current retrospective cohort study includes data from 233 women diagnosed with GDM who gave birth between January 2017 and January 2019 at an obstetrics and gynecology hospital in Sofia, Bulgaria. Patients were assigned to three groups, according to the treatment approach - metformin group (n = 70), insulin group (n = 40), and MNT group (n = 123). Values of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) have been evaluated at diagnosis of GDM and the third trimester of pregnancy. A comparative analysis of pregnancy outcomes and short-term neonatal characteristics in the investigated groups has been performed., Results: Women indicated for pharmacological treatment (metformin or insulin) had significantly higher BMI (p < 0.01), FPG (p < 0.001), and HbA1c levels (p < 0.001) at baseline. However, during pregnancy, patients treated with metformin showed a significantly lower BMI (p < 0.01), FPG (p < 0.01), and HbA1c (p < 0.01). Neonates born to metformin-treated mothers had lower birth weight compared to those born to women in the MNT and insulin groups (metformin vs MNT, p < 0.001; metformin vs insulin, p = 0.03). The lowest incidence of newborns with macrosomia and neonatal hypoglycemia has been observed in the metformin cohort. Not a single newborn with an Apgar score under 7 has been identified in the metformin group., Conclusions: According to the current analysis, women with GDM treated with metformin demonstrated better maternal and neonatal outcomes. No short-term complications in newborns have been associated with metformin use during pregnancy.
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- 2024
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13. High-resolution characterization of KIR genes polymorphism in healthy subjects from the Bulgarian population-A pilot study.
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Al Hadra B, Lukanov T, Mihaylova A, and Naumova E
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- Humans, Alleles, Pilot Projects, Healthy Volunteers, Bulgaria, Receptors, KIR genetics
- Abstract
Although killer-cell immunoglobulin-like receptor (KIR) gene content has been widely studied in health and disease, with the advancement of next-generation sequencing (NGS) technology the high-resolution characterization of this complex gene region has become achievable. KIR allele-level diversity has lately been described across human populations. The present study aimed to analyze for the first time the allele-level polymorphism of nine KIR genes in 155 healthy, unrelated individuals from the Bulgarian population by applying NGS. The highest degree of polymorphism was detected for the KIR3DL3 gene with 40 observed alleles at five-digit resolution in total, 22 of which were common. On the other hand, the KIR3DS1 gene was found to have the lowest degree of polymorphism among the studied KIR genes with one common allele: KIR3DS1*01301 (31.6%). To better understand KIR allelic associations and patterns in Bulgarians, we have estimated the pairwise linkage disequilibrium (LD) for the 10 KIR loci, where KIR2DL3*00501 allele was found in strong LD with KIR2DL1*00101 (D' = 1.00, R
2 = 0.742). This is the first study investigating KIR polymorphism at the allele level in a population from the South-East European region. Considering the effect of the populationally shaped KIR allelic polymorphism on NK cell function, this data could lead to a better understanding of the genetic heterogeneity of this region and can be carried into clinical practice by improvement of the strategies taken for NK-mediated diseases., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2024
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14. The role of periprocedural hemodynamic variables during carotid stenting for the mid-term general mortality in advanced age patients.
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Yaneva-Sirakova T, Zlatancheva G, Karamfiloff K, Traykov L, Petrov I, and Vassilev D
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- Humans, Aged, Risk Factors, Hemodynamics, Bradycardia complications, Stents adverse effects, Treatment Outcome, Retrospective Studies, Carotid Stenosis surgery, Carotid Stenosis complications, Hypotension etiology
- Abstract
Introduction: Carotid stenting may produce significant bradycardia and/or hypotension. This may have negative short- and long-term effects for the elderly high-risk patients. Their cerebral hemodynamics is with exhausted adaptive capacity because of the multiple cardiovascular risk factors, advanced age, and significant stenosis., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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15. Variation of tafamidis plasma levels during the treatment of TTR amyloidosis patients with Glu89Gln mutation.
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Smerikarova M, Bozhanov S, Tournev I, and Maslarska V
- Subjects
- Humans, Cohort Studies, Mutation, Prealbumin genetics, Prealbumin chemistry, Prealbumin metabolism, Amyloid Neuropathies, Familial drug therapy, Amyloid Neuropathies, Familial genetics, Amyloid Neuropathies, Familial diagnosis
- Abstract
Purpose: The transthyretin kinetic stabilizer tafamidis, used as a first-line therapy of amyloidosis patients, binds selectively to the transthyretin protein structure and thus prevents its dissociation. The limited information regarding tafamidis application in Glu89Gln amyloidosis patients imposed our research team to determine and evaluate its individual mean plasma levels and their biological variation., Methods: The present cohort study investigated Bulgarian amyloidosis patients, grouped by gender, age, and therapy duration. A total of sixty patients aged 40-75 years and therapy duration up to 9 years were included. A precise and accurate high-performance liquid chromatography method with ultraviolet detection was used for plasma concentration measurement., Results: Mean plasma concentrations were 5.13 ± 2.64 µmol/L and showed low intra-individual (18.50%) and high inter-individual variability (51.43%). No significant difference was observed between tafamidis plasma levels and therapy duration with p = 0.5941 (p < 0.05 considered significant), but a significant positive correlation was found between plasma concentration, gender, and age with obtained results about p-value 0.0001 and 0.0235, respectively., Conclusion: The summary results of the study showed differences that may be based on some specific clinical features of the Glu89Gln mutation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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16. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
- Author
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Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, Darst BF, Sheng X, Xu Y, Chou AJ, Benlloch S, Dadaev T, Brook MN, Plym A, Sahimi A, Hoffman TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Laisk T, Figuerêdo J, Muir K, Ito S, Liu X, Uchio Y, Kubo M, Kamatani Y, Lophatananon A, Wan P, Andrews C, Lori A, Choudhury PP, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Rentsch CT, Cho K, Mcmahon BH, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder A, Stroomberg HV, Batra J, Chambers S, Horvath L, Clements JA, Tilly W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordstrom T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein S, Cook MB, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM Jr, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Koutros S, Beane Freeman LE, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Butler EN, Mohler JL, Taylor JA, Kogevinas M, Dierssen-Sotos T, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Pilie P, Yu Y, Bohlender RJ, Gu J, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Brenner H, Chen X, Holleczek B, Schöttker B, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas CM, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Abraham A, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen J, Petrovics G, Casey G, Wang Y, Tettey Y, Lachance J, Tang W, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Yamoah K, Govindasami K, Chokkalingam AP, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Shittu O, Amodu O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Diop H, Gundell SM, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Kachuri L, Varma R, McKean-Cowdin R, Torres M, Preuss MH, Loos RJF, Zawistowski M, Zöllner S, Lu Z, Van Den Eeden SK, Easton DF, Ambs S, Edwards TL, Mägi R, Rebbeck TR, Fritsche L, Chanock SJ, Berndt SI, Wiklund F, Nakagawa H, Witte JS, Gaziano JM, Justice AC, Mancuso N, Terao C, Eeles RA, Kote-Jarai Z, Madduri RK, Conti DV, and Haiman CA
- Subjects
- Humans, Male, Black People genetics, Genome-Wide Association Study, Hispanic or Latino genetics, Polymorphism, Single Nucleotide, Risk Factors, White People genetics, Asian People genetics, Genetic Predisposition to Disease, Prostatic Neoplasms genetics
- Abstract
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2023
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17. Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.
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De Colle C, Paolisso P, Gallinoro E, Bertolone DT, Mileva N, Fabbricatore D, Valeriano C, Herman R, Beles M, De Oliveira EK, Mancusi C, Heggermont W, Collet C, Vanderheyden M, De Luca N, Van Camp G, Barbato E, Bartunek J, and Penicka M
- Subjects
- Humans, Stroke Volume, Prospective Studies, Echocardiography, Ventricular Function, Left, Heart Failure complications, Heart Failure epidemiology, Heart Failure drug therapy, Aortic Valve Insufficiency complications, Aortic Valve Insufficiency epidemiology
- Abstract
Objective: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF)., Methods: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected., Results: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography., Conclusion: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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18. Efficacy and safety of Aviron Rapid® in adolescents and children with viral acute upper respiratory tract infection: a multi-center, randomized, double blind, placebo-controlled clinical trial.
- Author
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Markova RM, Tzotcheva IS, Perenovska P, Mangarov A, Nikolaeva-Glomb L, and Hadjiev V
- Subjects
- Adolescent, Child, Humans, Double-Blind Method, Respiratory Tract Infections drug therapy
- Abstract
Introduction: Acute upper respiratory tract infections (AURTIs) are associated with a significant burden on society attributed to medical care and loss of productivity. Novel therapies that are able to shorten disease duration, while providing symptom relief and being well tolerated, are an unmet medical need., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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19. Mixed Eccrine Cutaneous Tumor with Folliculo-Sebaceous Differentiation: Case Report and Literature Review.
- Author
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Kisova D, Dikov T, Ivanova V, Stoyanov H, and Yordanova G
- Subjects
- Female, Humans, Middle Aged, Biopsy, Cell Differentiation, Confusion, Skin Neoplasms diagnosis, Adenoma, Pleomorphic
- Abstract
Background/Introduction: Cutaneous mixed tumor is a rare benign neoplasm that exhibits a wide range of metaplastic changes and differentiation in the epithelial, myoepithelial, and stromal components, which is often confused with various other skin lesions. Case report: We present an unusual case of a 58-year-old woman with a mixed tumor of the upper lip, previously misdiagnosed as adnexal carcinoma on a preoperative biopsy. The excision biopsy shows a well-circumscribed lesion composed of various cells and structures featuring folliculo-sebaceous differentiation embedded in a prominent chondromyxoid stroma. The immunohistochemical study proves the various lineages of differentiation and classifies the neoplasm as the less common eccrine subtype of cutaneous mixed tumor. Discussion: The common embryologic origin of the folliculo-sebaceous apocrine complex leads to a great histological variety of cellular components of mixed tumors and the formation of structures that resemble established types of adnexal neoplasms, which could be a diagnostic pitfall, especially on a small incision biopsy.
- Published
- 2023
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20. Relationship between coronary volume, myocardial mass, and post-PCI fractional flow reserve.
- Author
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Mileva N, Ohashi H, Paolisso P, Leipsic J, Mizukami T, Sonck J, Norgaard BL, Otake H, Ko B, Maeng M, Munhoz D, Nagumo S, Belmonte M, Vassilev D, Andreini D, Barbato E, Koo BK, De Bruyne B, and Collet C
- Subjects
- Humans, Prospective Studies, Treatment Outcome, Coronary Angiography methods, Predictive Value of Tests, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease therapy, Coronary Artery Disease complications, Fractional Flow Reserve, Myocardial, Percutaneous Coronary Intervention adverse effects, Coronary Stenosis diagnostic imaging, Coronary Stenosis therapy, Coronary Stenosis complications
- Abstract
Background: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) carries prognostic information. Yet, myocardial mass subtended by a stenosis influences FFR. We hypothesized that a smaller coronary lumen volume and a large myocardial mass might be associated with lower post-PCI FFR., Aim: We sought to assess the relationship between vessel volume, myocardial mass, and post-PCI FFR., Methods: This was a subanalysis with an international prospective study of patients with significant lesions (FFR ≤ 0.80) undergoing PCI. Territory-specific myocardial mass was calculated from coronary computed tomography angiography (CCTA) using the Voronoi's algorithm. Vessel volume was extracted from quantitative CCTA analysis. Resting full-cycle ratio (RFR) and FFR were measured before and after PCI. We assessed the association between coronary lumen volume (V) and its related myocardial mass (M), and the percent of total myocardial mass (%M) with post-PCI FFR., Results: We studied 120 patients (123 vessels: 94 left anterior descending arteries, 13 left Circumflex arteries, 16 right coronary arteries). Mean vessel-specific mass was 61 ± 23.1 g (%M 39.6 ± 11.7%). The mean post-PCI FFR was 0.88 ± 0.06 FFR units. Post-PCI FFR values were lower in vessels subtending higher mass (0.87 ± 0.05 vs. 0.89 ± 0.07, p = 0.047), and with lower V/M ratio (0.87 ± 0.06 vs. 0.89 ± 0.07, p = 0.02). V/M ratio correlated significantly with post-PCI RFR and FFR (RFR r = 0.37, 95% CI: 0.21-0.52, p < 0.001 and FFR r = 0.41, 95% CI: 0.26-0.55, p < 0.001)., Conclusion: Post-PCI RFR and FFR are associated with the subtended myocardial mass and the coronary volume to mass ratio. Vessels with higher mass and lower V/M ratio have lower post-PCI RFR and FFR., (© 2023 Wiley Periodicals LLC.)
- Published
- 2023
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21. Anandamide is associated with waist-to-hip ratio but not with Body Mass Index in women with polycystic ovary syndrome.
- Author
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Kabakchieva P, Gateva A, Velikova T, Georgiev T, and Kamenov Z
- Subjects
- Female, Humans, Body Mass Index, Endocannabinoids, Waist-Hip Ratio, Polycystic Ovary Syndrome complications, Polycystic Ovary Syndrome metabolism
- Abstract
Background: The endocannabinoid system is involved in the regulation of energy balance and ovarian function and may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The purpose of the present study is to determine anandamide (AEA) levels in PCOS patients and controls and to analyze its association with metabolic and hormonal disturbances in women with PCOS., Methods: The study included 88 women - 58 patients with PCOS (25.9±5.2 years) and 30 healthy controls (27.6±5.2 years). Further, patients were divided into two subgroups according to their waist-to-hip ratio (WHR): android type PCOS (WHR≥0.85; N.=26) and gynoid type PCOS (WHR<0.85; N.=32). Detailed anthropometric measurements, hormonal and biochemical tests and pelvic ultrasound were obtained between the 3rd and 5th day of a menstrual cycle. AEA was examined by ELISA kits., Results: Patients with PCOS and healthy controls did not differ in anthropometric, metabolic parameters, AEA, and sex hormone-binding globulin (SHBG) levels. The PCOS group had increased total testosterone, FAI, DHEAS, androstenedione, and 17-OH-progesterone levels (P<0.001) and elevated LH/FSH ratio (P=0.023). A negative correlation between AEA levels was found with glycaemia at 120 minutes (r=-0.304, P=0.020) and WHR (r=-0.266, P=0.044). In the subanalysis of patients, the gynoid type group had significantly higher levels of AEA than the android type PCOS (5.4 [2.3;8.8] vs. 2.5 [1.8;5.1]; P=0.020)., Conclusions: AEA did not differ between healthy women and patients, but a significant difference in its levels was found in PCOS patients divided according to their body constitution type.
- Published
- 2023
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22. Reply to SGLT-2 inhibitors: Post-infarction interventional effects.
- Author
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Paolisso P, Bergamaschi L, Gragnano F, Gallinoro E, Cesaro A, Sardu C, Mileva N, Foà A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Esposito G, Morici N, Andrea OJ, Casella G, Mauro C, Vassilev D, Galie N, Santulli G, Marfella R, Calabrò P, Barbato E, and Pizzi C
- Subjects
- Humans, Hypoglycemic Agents, Infarction, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2
- Abstract
Competing Interests: Competing interests The authors declare that they have no competing interests.
- Published
- 2023
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23. Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries.
- Author
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Logroscino G, Piccininni M, Graff C, Hardiman O, Ludolph AC, Moreno F, Otto M, Remes AM, Rowe JB, Seelaar H, Solje E, Stefanova E, Traykov L, Jelic V, Rydell MT, Pender N, Anderl-Straub S, Barandiaran M, Gabilondo A, Krüger J, Murley AG, Rittman T, van der Ende EL, van Swieten JC, Hartikainen P, Stojmenovic GM, Mehrabian S, Benussi L, Alberici A, Dell'Abate MT, Zecca C, and Borroni B
- Subjects
- Male, Humans, Female, Aged, Incidence, Retrospective Studies, Syndrome, Europe epidemiology, Frontotemporal Dementia epidemiology, Amyotrophic Lateral Sclerosis, Frontotemporal Lobar Degeneration epidemiology
- Abstract
Importance: Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches., Objective: To assess the incidence of FTLD across Europe., Design, Setting, and Participants: The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021., Main Outcomes and Measures: Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity., Results: Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057., Conclusions and Relevance: The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.
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- 2023
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24. Impact of nonalcoholic fatty liver disease-related metabolic state on depression.
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Ntona S, Papaefthymiou A, Kountouras J, Gialamprinou D, Kotronis G, Boziki M, Polyzos SA, Tzitiridou M, Chatzopoulos D, Thavayogarajah T, Gkolia I, Ntonas G, Vardaka E, and Doulberis M
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- Humans, Dysbiosis, Depression, Liver metabolism, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Insulin Resistance
- Abstract
Nonalcoholic fatty liver disease (NAFLD), also recently referred as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by hepatocyte steatosis in the setting of metabolic risk conditions and in the absence of an underlying precursor, for instance alcohol consumption, hepatotropic viruses and hepatotoxic drugs. A possible association between NAFLD and depression has been proposed, owing to intersecting pathophysiological pathways. This narrative review aimed to summarize the current evidence that illustrate the potential pathophysiological and clinical linkage between NAFLD-related metabolic state and depression. Prefrontal cortex lesions are suggested to be a consequence of liver steatosis-associated systematic hyperinflammatory state, a phenomenon also occurring in depression. In addition, depressive symptoms are present in neurotransmitter imbalances. These abnormalities seem to be correlated with NAFLD/MAFLD, in terms of insulin resistance (IR), ammonia and gut dysbiosis' impact on serotonin, dopamine, noradrenaline levels and gamma aminobutyric acid receptors. Furthermore, reduced levels of nesfatin-1 and copine-6-associated BDNF (brain-derived neurotrophic factor) levels have been considered as a probable link between NAFLD and depression. Regarding NAFLD-related gut dysbiosis, it stimulates mediators including lipopolysaccharides, short-chain fatty acids and bile acids, which play significant role in depression. Finally, western diet and IR, which are mainstay components of NAFLD/MAFLD, are, also, substantiated to affect neurotransmitters in hippocampus and produce neurotoxic lipids that contribute to neurologic dysfunction, and thus trigger emotional disturbances, mainly depressive symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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25. Intravascular ultrasound imaging in evaluation of aortic stiffness: A proof-of-concept study.
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Mileva NB and Vassilev DI
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- Humans, Ultrasonography, Aorta diagnostic imaging, Echocardiography methods, Ultrasonography, Interventional, Vascular Stiffness
- Abstract
Background: Aortic stiffness is a well-known cardio-vascular risk factor. For years, different methods have been studied in the assessment of aortic elastic properties and large arterial stiffness for risk stratification. Herein is an assessment of the role of intravascular ultrasound (IVUS) imaging for the evaluation of aortic elastic properties., Methods: Intravascular ultrasound imaging of the aorta was performed in 12 patients with transthoracic echocardiography (TTE) and computed tomography (CT) evidence for enlargement of the ascending aorta - diameter ≥ 40.0 mm. Mechanical properties of the aorta were derived from the measured diameters and intra-aortic pressure. Paired samples T-test analyses were performed to determine differences between measurements derived by TTE, CT and IVUS., Results: Mean values of the calculated elastic properties via IVUS of the ascending aorta were as follows: compliance 0.021 ± 0.02; strain 205 ± 4.3; aortic stiffness index 4.3 ± 0.75; elastic modulus 0.31 ± 0.05. On paired T-test analysis maximum ascending aortic diameter measured by CT aortography and IVUS did not differ significantly (t = -0.19, p = 0.985), but a significant difference between IVUS measurements and TTE derived diameters was found (t = 13.118, p = 0.034). On average, IVUS diameters were 2.3 mm larger than the results acquired by TTE (95% confidence interval: 14.21-17.13)., Conclusions: Intravascular ultrasound examination of the ascending aorta provided larger diameters than the ones collected by means of TTE. However, IVUS measurements did not differ significantly from diameters derived by CT aortography.
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- 2023
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26. Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry.
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Paolisso P, Bergamaschi L, Gragnano F, Gallinoro E, Cesaro A, Sardu C, Mileva N, Foà A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Esposito G, Morici N, Andrea OJ, Casella G, Mauro C, Vassilev D, Galie N, Santulli G, Marfella R, Calabrò P, Pizzi C, and Barbato E
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- Humans, Risk Factors, Registries, Treatment Outcome, Percutaneous Coronary Intervention adverse effects, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Myocardial Infarction drug therapy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Acute Kidney Injury etiology
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Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users)., Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization., Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33-0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21-0.98; p = 0.041)., Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI., Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT., Clinicaltrials: gov Identifier: NCT05261867., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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27. Procedural Outcomes After Percutaneous Coronary Interventions in Focal and Diffuse Coronary Artery Disease.
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Mizukami T, Sonck J, Sakai K, Ko B, Maeng M, Otake H, Koo BK, Nagumo S, Nørgaard BL, Leipsic J, Shinke T, Munhoz D, Mileva N, Belmonte M, Ohashi H, Barbato E, Johnson NP, De Bruyne B, and Collet C
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- Humans, Prospective Studies, Percutaneous Coronary Intervention, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery, Fractional Flow Reserve, Myocardial
- Abstract
Background Coronary artery disease (CAD) patterns play an essential role in the decision-making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes. Methods and Results This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post-PCI FFR >0.90 was considered an optimal result. Focal disease was defined as PPG >0.73 (highest PPG tertile). Overall, 113 patients (116 vessels) were included. Patients with focal disease were younger than those with diffuse CAD (61.4±9.9 versus 65.1±8.7 years, P =0.042). PCI in vessels with high PPG (focal CAD) resulted in higher post-PCI FFR (0.91±0.07 in the focal group versus 0.86±0.05 in the diffuse group, P <0.001) and larger minimal stent area (6.3±2.3 mm
2 in focal versus 5.3±1.8 mm2 in diffuse CAD, P =0.015) compared withvessels with low PPG (diffuse CAD). The PPG was associated with the change in FFR after PCI ( R2 =0.51, P <0.001). The PPG significantly improved the capacity to predict optimal PCI results compared with an angiographic assessment of CAD patterns (area under the curvePPG 0.81 [95% CI, 0.73-0.88] versus area under the curveangio 0.51 [95% CI, 0.42-0.60]; P <0.001). Conclusions PCI in vessels with focal disease defined by the PPG resulted in greater improvement in epicardial conductance and larger minimal stent area compared with diffuse disease. PPG, but not angiographically defined CAD patterns, distinguished patients attaining superior procedural outcomes. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03782688.- Published
- 2022
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28. Developmental venous anomaly causing obstructive hydrocephalus due to aqueductal stenosis: а case report.
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Bogovski S, Sirakova K, Sirakov A, Vladev G, and Sirakov S
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- Humans, Brain, Gliosis, Cerebral Aqueduct, Hydrocephalus
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Cerebral developmental venous anomalies are asymptomatic benign cerebrovascular malformations that are commonly found accidentally on brain magnetic resonance imaging. It is not uncommon for cerebrospinal fluid flow to be obstructed at the level of the aqueduct of Sylvius, causing an obstructive non-communicating hydrocephalus. Most notable reasons for such an obstruction at that level are tumors, congenital etiology, or post-inflammatory gliotic atresia., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2022
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29. In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study.
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Cesaro A, Gragnano F, Paolisso P, Bergamaschi L, Gallinoro E, Sardu C, Mileva N, Foà A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Esposito G, Morici N, Oreglia JA, Casella G, Mauro C, Vassilev D, Galie N, Santulli G, Pizzi C, Barbato E, Calabrò P, and Marfella R
- Abstract
Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients., Objectives: To investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users)., Methods: Patients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization., Results: The study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%, p = 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually ( p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14-0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04-0.97; p = 0.046) but not of AF occurrence., Conclusions: In T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control., Trial Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cesaro, Gragnano, Paolisso, Bergamaschi, Gallinoro, Sardu, Mileva, Foà, Armillotta, Sansonetti, Amicone, Impellizzeri, Esposito, Morici, Oreglia, Casella, Mauro, Vassilev, Galie, Santulli, Pizzi, Barbato, Calabrò and Marfella.)
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- 2022
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30. Prospective evaluation of the learning curve and diagnostic accuracy for Pre-TAVI cardiac computed tomography analysis by cardiologists in training: The LEARN-CT study.
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Paolisso P, Gallinoro E, Andreini D, Mileva N, Esposito G, Bermpeis K, Bertolone DT, Munhoz D, Belmonte M, Fabbricatore D, Sonck J, Collet C, Penicka M, De Bruyne B, Vanderheyden M, and Barbato E
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- Aortic Valve, Humans, Learning Curve, Predictive Value of Tests, Reproducibility of Results, Tomography, X-Ray Computed methods, Aortic Valve Stenosis, Cardiologists, Heart Valve Prosthesis
- Abstract
Background: To investigate the learning curve and the minimum number of cases required for a cardiologist in training to acquire the skills to an accurate pre-TAVI cardiac CT (CCT) analysis using a semi-automatic software., Methods: In this prospective, observational study, 40 CCTs of patients scheduled for TAVI were independently evaluated twice by 5 readers (80 readings each, 400 in total): a certified TAVI-CT specialist served as the reference reader (RR) and 4 cardiology fellows (2 interventional and 2 non-invasive cardiac imaging) as readers. The primary outcome was the minimum number of cases required to achieve an accuracy in imaging interpretation ≥80%, defined as the agreement between each reader and the RR in both balloon and self-expandable valve size choice. The secondary outcomes were the intra- and inter-observer variability., Results: After 50 readings (25 cases repeated twice) cardiology fellows were able to select the appropriate valve size with ≥ 80% of accuracy compared to the RR, independently of valve calcification, image quality and slice thickness. Learning curves of both interventional and non-invasive cardiac imaging fellows showed a similar trend. Cardiology fellows achieved a very high intra- and inter-observer reliability for both perimeter and area assessment, with an intraclass correlation coefficient (ICC) ranging from 0.96 to 0.99., Conclusions: Despite the individual differences, cardiology fellows required 50 readings (25 cases repeated twice) to get adequately skilled in the pre-TAVI CCT interpretation. These results provide valuable information for developing adequate training sessions and education protocols for both companies and cardiologists involved., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)
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- 2022
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31. Burn-Induced Acute Kidney Injury-Two-Lane Road: From Molecular to Clinical Aspects.
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Niculae A, Peride I, Tiglis M, Sharkov E, Neagu TP, Lascar I, and Checherita IA
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- Biomarkers, Humans, Kidney metabolism, Lipocalin-2, Tissue Inhibitor of Metalloproteinase-2 metabolism, Acute Kidney Injury metabolism, Burns complications
- Abstract
Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28-100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.
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- 2022
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32. HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population.
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Al Hadra B, Lukanov TI, and Ivanova MI
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- Alleles, Bulgaria, Gene Frequency, HLA-B Antigens genetics, Haplotypes, Humans, Linkage Disequilibrium, Polymorphism, Genetic, Histocompatibility Antigens Class I genetics
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Although human leukocyte antigen (HLA) gene polymorphism has been investigated in many populations around the world, the data on MHC class I chain-related (MIC) genes are still limited. The present study is aimed to analyze the allelic polymorphism of MICA and MICB genes and haplotype associations with HLA-B locus in 132 healthy, unrelated individuals from the Bulgarian population by next generation sequencing (NGS). A total of 36 MICA and 16 MICB alleles were observed with the highest frequency detected for MICA*008:01 (17.1%) and MICB*005:02 (32.4%). Further, two and three-loci haplotype frequencies and pairwise linkage disequilibrium were estimated. Highly significant global linkage disequilibrium was found between either HLA-B and MICA and MICB genes. This is the first study on MICA and MICB allelic polymorphism, linkage disequilibrium, and haplotype polymorphism in the Bulgarian population. These results will allow for better characterization of the genetic heterogeneity of the Bulgarian population and could contribute to further analyses on MICA and MICB clinical significance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
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- 2022
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33. Presbyopia correction with a new Extended Depth of Focus Intraocular Lens.
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Hristova R, Tsvetkova G, Cholakova D, Ivanova G, and Haykin V
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- Aged, Aged, 80 and over, Female, Humans, Male, Patient Satisfaction, Phacoemulsification, Prospective Studies, Prosthesis Design, Refraction, Ocular, Cataract Extraction, Cataract complications, Cataract therapy, Lens Implantation, Intraocular, Lenses, Intraocular, Presbyopia complications, Presbyopia surgery
- Abstract
Extended depth of focus intraocular lenses (EDoF IOLs) offer an expanded number of modalities for simultaneous cataract and presbyopia treatment. The objective of the current study was to assess clinical outcomes with a new mono-EDoF intraocular lens and to analyze the effect of different parameters on postoperative results. The inclusion criteria were defined as uneventful cataract surgery, no history of concomitant ocular disease, implantation of ZOE Primus-HD lens. Parameters from IOL Master 500 were analyzed. The main outcome measures were postoperative uncorrected distance (UDVA) and intermediate (UIVA) visual acuity. The study included 39 eyes of 37 patients (15 males and 22 females) with a mean age of 73.59±7.71. Postoperatively, the UDVA improved to 0.84±0.16 ( p <0.001) and UIVA was 0.86±0.14. There was no correlation between K1, K2 and IOL power with both postoperative UDVA and IDVA. Moreover, there was no statistically significant difference between UDVA and UIVA between patients with mean K value over or under 44.0D ( p =0.204 and p =0.817, respectively). The results of a multinomial logistic regression analysis for the predictive value of the factors K1, K2 and IOL power demonstrated no statistical significance, except for UIVA with a significant influence of IOL power ( p =0.024) in patients with less than 0.9 Snellen visual acuity. The implantation of the new mono-EDoF ZOE Primus-HD lens led to improvement in both UDVA and UIVA. Patients with keratometry values less than 44.0D could still benefit from the mono-EDoF lenses. Further studies including wavefront aberrometry are needed to study the interaction between corneal aberrations and EDoF IOLs. Abbreviations: IOL = Intraocular lens, UDVA = Uncorrected distance visual acuity, UIVA = Uncorrected intermediate visual acuity, D = Diopters, EDoF = Enhanced Depth of Focus, MF IOL = Multifocal intraocular lens, AUC = area under the curve., (© The Authors.Romanian Society of Ophthalmology.)
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- 2022
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34. Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry.
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Paolisso P, Bergamaschi L, Santulli G, Gallinoro E, Cesaro A, Gragnano F, Sardu C, Mileva N, Foà A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Casella G, Mauro C, Vassilev D, Marfella R, Calabrò P, Barbato E, and Pizzi C
- Subjects
- Blood Glucose metabolism, Humans, Registries, Sodium-Glucose Transporter 2, Troponin metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 drug therapy, Hyperglycemia epidemiology, Myocardial Infarction diagnosis, Myocardial Infarction drug therapy, Myocardial Infarction epidemiology, Percutaneous Coronary Intervention adverse effects, Sodium-Glucose Transporter 2 Inhibitors adverse effects
- Abstract
Background: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents., Methods: In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels., Results: The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status., Conclusions: Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease., Trial Registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT., Clinicaltrials: gov Identifier: NCT05261867., (© 2022. The Author(s).)
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- 2022
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35. Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.
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Justice CM, Musolf AM, Cuellar A, Lattanzi W, Simeonov E, Kaneva R, Paschall J, Cunningham M, Wilkie AOM, Wilson AF, Romitti PA, and Boyadjiev SA
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- Alleles, Carrier Proteins genetics, Humans, Craniosynostoses genetics, Genome-Wide Association Study
- Abstract
Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes ( BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.
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- 2022
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36. Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis.
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Mileva N, Nagumo S, Mizukami T, Sonck J, Berry C, Gallinoro E, Monizzi G, Candreva A, Munhoz D, Vassilev D, Penicka M, Barbato E, De Bruyne B, and Collet C
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- Coronary Angiography, Coronary Vessels diagnostic imaging, Female, Humans, Male, Microcirculation, Prevalence, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology, Coronary Vasospasm diagnostic imaging, Coronary Vasospasm epidemiology, Microvascular Angina
- Abstract
Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.
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- 2022
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37. Physiological and angiographic outcomes of PCI in calcified lesions after rotational atherectomy or intravascular lithotripsy.
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Gallinoro E, Monizzi G, Sonck J, Candreva A, Mileva N, Nagumo S, Munhoz D, Buytaert D, Mastrangelo A, Andreini D, Galli S, Bartorelli AL, Barbato E, De Bruyne B, and Collet C
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- Coronary Angiography, Humans, Treatment Outcome, Atherectomy, Coronary methods, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery, Fractional Flow Reserve, Myocardial, Lithotripsy, Percutaneous Coronary Intervention, Vascular Calcification diagnostic imaging, Vascular Calcification surgery
- Abstract
Background: Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL., Methods: Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90., Results: From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669)., Conclusions: Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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38. Development, validation, and reproducibility of the pullback pressure gradient (PPG) derived from manual fractional flow reserve pullbacks.
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Sonck J, Mizukami T, Johnson NP, Nagumo S, Gallinoro E, Candreva A, Mileva N, Munhoz D, Shinke T, Svanerud J, Barbato E, De Bruyne B, and Collet C
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- Coronary Angiography, Coronary Vessels diagnostic imaging, Humans, Predictive Value of Tests, Reproducibility of Results, Treatment Outcome, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease therapy, Coronary Stenosis, Fractional Flow Reserve, Myocardial, Percutaneous Coronary Intervention
- Abstract
Fractional flow reserve (FFR) pullbacks assess the location and magnitude of pressure drops along the coronary artery. The pullback pressure gradient (PPG) quantifies the FFR pullback curve and provides a numeric expression of focal versus diffuse coronary artery disease. This study aims (1) to validate the PPG using manual FFR pullbacks compared with motorized FFR pullbacks as a reference; and (2) to determine the intra- and interoperator reproducibility of the PPG derived from manual FFR pullbacks. Patients with stable coronary artery disease and an FFR ≤ 0.80 were included. All patients underwent FFR pullback evaluation either with a motorized device or manually, depending on the study cohort. The agreement of the PPG between repeated pullbacks was assessed using the Bland-Altman method. Overall, 116 FFR pullback maneuvers (96 manual and 20 motorized) were analyzed. There was excellent agreement between the PPG derived from manual and motorized pullbacks (mean difference -0.01 ± 0.07, 95% limits of agreement [LOA] -0.14 to 0.12). The intra- and interoperator reproducibility of PPG derived from manual pullbacks were excellent (mean difference <0.01, 95% LOA -0.11 to 0.12, and mean difference <0.01, 95% LOA -0.12 to 0.11, respectively). The duration of the pullback maneuver did not impact the reproducibility of the PPG (r = 0.12, 95% CI: -0.29 to 0.49, p = 0.567). Manual pullbacks allow for an accurate PPG calculation. The inter- and intraoperator reproducibility of PPG derived from manual pullbacks were excellent., (© 2022 Wiley Periodicals LLC.)
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- 2022
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39. Mapping genomic loci implicates genes and synaptic biology in schizophrenia.
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Trubetskoy V, Pardiñas AF, Qi T, Panagiotaropoulou G, Awasthi S, Bigdeli TB, Bryois J, Chen CY, Dennison CA, Hall LS, Lam M, Watanabe K, Frei O, Ge T, Harwood JC, Koopmans F, Magnusson S, Richards AL, Sidorenko J, Wu Y, Zeng J, Grove J, Kim M, Li Z, Voloudakis G, Zhang W, Adams M, Agartz I, Atkinson EG, Agerbo E, Al Eissa M, Albus M, Alexander M, Alizadeh BZ, Alptekin K, Als TD, Amin F, Arolt V, Arrojo M, Athanasiu L, Azevedo MH, Bacanu SA, Bass NJ, Begemann M, Belliveau RA, Bene J, Benyamin B, Bergen SE, Blasi G, Bobes J, Bonassi S, Braun A, Bressan RA, Bromet EJ, Bruggeman R, Buckley PF, Buckner RL, Bybjerg-Grauholm J, Cahn W, Cairns MJ, Calkins ME, Carr VJ, Castle D, Catts SV, Chambert KD, Chan RCK, Chaumette B, Cheng W, Cheung EFC, Chong SA, Cohen D, Consoli A, Cordeiro Q, Costas J, Curtis C, Davidson M, Davis KL, de Haan L, Degenhardt F, DeLisi LE, Demontis D, Dickerson F, Dikeos D, Dinan T, Djurovic S, Duan J, Ducci G, Dudbridge F, Eriksson JG, Fañanás L, Faraone SV, Fiorentino A, Forstner A, Frank J, Freimer NB, Fromer M, Frustaci A, Gadelha A, Genovese G, Gershon ES, Giannitelli M, Giegling I, Giusti-Rodríguez P, Godard S, Goldstein JI, González Peñas J, González-Pinto A, Gopal S, Gratten J, Green MF, Greenwood TA, Guillin O, Gülöksüz S, Gur RE, Gur RC, Gutiérrez B, Hahn E, Hakonarson H, Haroutunian V, Hartmann AM, Harvey C, Hayward C, Henskens FA, Herms S, Hoffmann P, Howrigan DP, Ikeda M, Iyegbe C, Joa I, Julià A, Kähler AK, Kam-Thong T, Kamatani Y, Karachanak-Yankova S, Kebir O, Keller MC, Kelly BJ, Khrunin A, Kim SW, Klovins J, Kondratiev N, Konte B, Kraft J, Kubo M, Kučinskas V, Kučinskiene ZA, Kusumawardhani A, Kuzelova-Ptackova H, Landi S, Lazzeroni LC, Lee PH, Legge SE, Lehrer DS, Lencer R, Lerer B, Li M, Lieberman J, Light GA, Limborska S, Liu CM, Lönnqvist J, Loughland CM, Lubinski J, Luykx JJ, Lynham A, Macek M Jr, Mackinnon A, Magnusson PKE, Maher BS, Maier W, Malaspina D, Mallet J, Marder SR, Marsal S, Martin AR, Martorell L, Mattheisen M, McCarley RW, McDonald C, McGrath JJ, Medeiros H, Meier S, Melegh B, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mitjans M, Molden E, Molina E, Molto MD, Mondelli V, Moreno C, Morley CP, Muntané G, Murphy KC, Myin-Germeys I, Nenadić I, Nestadt G, Nikitina-Zake L, Noto C, Nuechterlein KH, O'Brien NL, O'Neill FA, Oh SY, Olincy A, Ota VK, Pantelis C, Papadimitriou GN, Parellada M, Paunio T, Pellegrino R, Periyasamy S, Perkins DO, Pfuhlmann B, Pietiläinen O, Pimm J, Porteous D, Powell J, Quattrone D, Quested D, Radant AD, Rampino A, Rapaport MH, Rautanen A, Reichenberg A, Roe C, Roffman JL, Roth J, Rothermundt M, Rutten BPF, Saker-Delye S, Salomaa V, Sanjuan J, Santoro ML, Savitz A, Schall U, Scott RJ, Seidman LJ, Sharp SI, Shi J, Siever LJ, Sigurdsson E, Sim K, Skarabis N, Slominsky P, So HC, Sobell JL, Söderman E, Stain HJ, Steen NE, Steixner-Kumar AA, Stögmann E, Stone WS, Straub RE, Streit F, Strengman E, Stroup TS, Subramaniam M, Sugar CA, Suvisaari J, Svrakic DM, Swerdlow NR, Szatkiewicz JP, Ta TMT, Takahashi A, Terao C, Thibaut F, Toncheva D, Tooney PA, Torretta S, Tosato S, Tura GB, Turetsky BI, Üçok A, Vaaler A, van Amelsvoort T, van Winkel R, Veijola J, Waddington J, Walter H, Waterreus A, Webb BT, Weiser M, Williams NM, Witt SH, Wormley BK, Wu JQ, Xu Z, Yolken R, Zai CC, Zhou W, Zhu F, Zimprich F, Atbaşoğlu EC, Ayub M, Benner C, Bertolino A, Black DW, Bray NJ, Breen G, Buccola NG, Byerley WF, Chen WJ, Cloninger CR, Crespo-Facorro B, Donohoe G, Freedman R, Galletly C, Gandal MJ, Gennarelli M, Hougaard DM, Hwu HG, Jablensky AV, McCarroll SA, Moran JL, Mors O, Mortensen PB, Müller-Myhsok B, Neil AL, Nordentoft M, Pato MT, Petryshen TL, Pirinen M, Pulver AE, Schulze TG, Silverman JM, Smoller JW, Stahl EA, Tsuang DW, Vilella E, Wang SH, Xu S, Adolfsson R, Arango C, Baune BT, Belangero SI, Børglum AD, Braff D, Bramon E, Buxbaum JD, Campion D, Cervilla JA, Cichon S, Collier DA, Corvin A, Curtis D, Forti MD, Domenici E, Ehrenreich H, Escott-Price V, Esko T, Fanous AH, Gareeva A, Gawlik M, Gejman PV, Gill M, Glatt SJ, Golimbet V, Hong KS, Hultman CM, Hyman SE, Iwata N, Jönsson EG, Kahn RS, Kennedy JL, Khusnutdinova E, Kirov G, Knowles JA, Krebs MO, Laurent-Levinson C, Lee J, Lencz T, Levinson DF, Li QS, Liu J, Malhotra AK, Malhotra D, McIntosh A, McQuillin A, Menezes PR, Morgan VA, Morris DW, Mowry BJ, Murray RM, Nimgaonkar V, Nöthen MM, Ophoff RA, Paciga SA, Palotie A, Pato CN, Qin S, Rietschel M, Riley BP, Rivera M, Rujescu D, Saka MC, Sanders AR, Schwab SG, Serretti A, Sham PC, Shi Y, St Clair D, Stefánsson H, Stefansson K, Tsuang MT, van Os J, Vawter MP, Weinberger DR, Werge T, Wildenauer DB, Yu X, Yue W, Holmans PA, Pocklington AJ, Roussos P, Vassos E, Verhage M, Visscher PM, Yang J, Posthuma D, Andreassen OA, Kendler KS, Owen MJ, Wray NR, Daly MJ, Huang H, Neale BM, Sullivan PF, Ripke S, Walters JTR, and O'Donovan MC
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- Alleles, Genetic Predisposition to Disease genetics, Genomics, Humans, Polymorphism, Single Nucleotide genetics, Genome-Wide Association Study, Schizophrenia genetics
- Abstract
Schizophrenia has a heritability of 60-80%
1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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40. A Complex Combination Therapy for a Complex Disease-Neuroimaging Evidence for the Effect of Music Therapy in Schizophrenia.
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Ivanova E, Panayotova T, Grechenliev I, Peshev B, Kolchakova P, and Milanova V
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Schizophrenia is a disease characterized by clinical polymorphism: a combination of diverse syndromes defined by differences in structure, course and outcome. The etiology and pathogenesis of this mental disorder is still not completely understood, in spite of the achievements in the fields of neuroscience, genetics, neuroimaging and others. Different treatment strategies have been developed for patients with schizophrenia, but the search for new pharmacological agents continues with the mission of achieving a more effective control over the disease manifestations (positive and negative symptoms), improvement of the patients' social functioning and quality of life. The accumulated clinical experience has revealed that drug treatment and the inclusion in various rehabilitation programs and social skills training shows promising results in these patients. In recent years a plethora of evidence has been compiled regarding the role of music therapy as a possible alternative in the combination treatment of patients with mental disorders, schizophrenia included. Thus, the purpose of this review is to present the reader with a more detailed and science-based account of the beneficial effect of music therapy on the general wellbeing of patients diagnosed with schizophrenia. To fulfill our goal, we will focus mainly on the evidence provided by modern neuroimaging research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ivanova, Panayotova, Grechenliev, Peshev, Kolchakova and Milanova.)
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- 2022
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41. Impact of Helicobacter pylori-related metabolic syndrome with hyperhomocysteinemia on extragastric pathologies.
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Kountouras J, Doulberis M, Polyzos SA, Kazakos E, Vardaka E, Touloumtzi M, Manolakis A, Tzitiridou-Chatzopoulou M, Liatsos C, Sotiriades ES, Ntona S, and Papaefthymiou A
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- Humans, Helicobacter Infections complications, Helicobacter Infections pathology, Helicobacter pylori pathogenicity, Hyperhomocysteinemia complications, Metabolic Syndrome microbiology
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- 2022
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42. Performance of non-invasive myocardial work to predict the first hospitalization for de novo heart failure with preserved ejection fraction.
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Paolisso P, Gallinoro E, Mileva N, Moya A, Fabbricatore D, Esposito G, De Colle C, Beles M, Spapen J, Heggermont W, Collet C, Van Camp G, Vanderheyden M, Barbato E, Bartunek J, and Penicka M
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- Hospitalization, Humans, Stroke Volume physiology, Systole, Ventricular Function, Left physiology, Heart Failure diagnosis, Heart Failure therapy
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Aims: Non-invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. We aim to investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LV ejection fraction., Methods and Results: Twenty-nine patients with transthoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure-strain loop using speckle-tracking and brachial artery blood pressure. Global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death [major adverse cardiovascular events (MACE)] and all-cause of death [major adverse events (MAE)] were assessed. At baseline, future HFpEF patients showed lower global work index, global constructive work, GWE, and higher GWW than controls (all P < 0.05). At admission vs. baseline, GWE significantly decreased, and GWW increased in the HFpEF group (P < 0.05), whereas no significant difference was observed in the controls over time. GWW, with a cut-off of 170 mmHg%, showed the largest area under the curve (AUC) to predict first HFpEF hospitalization [AUC = 0.80, 95% confidence interval (CI) 0.69-0.91, P < 0.001], MACE (AUC = 0.80, 95% CI 0.66-0.90, P < 0.001), and MAE (AUC = 0.79, 95% CI 0.62-0.88, P = 0.001). GWW > 170 mmHg% was associated with a 4-fold increase of MACE (HR = 4.5, 95% CI 1.59-13.12, P = 0.005) and a 3-fold higher risk of MAE (HR = 2.9, 95% CI 1.24-6.6, P = 0.014)., Conclusions: In ambulatory patients with preserved LV ejection fraction and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnoea., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2022
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43. A novel technique of proximal optimization with kissing balloon inflation in bifurcation lesions.
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Vassilev D, Mileva N, Panayotov P, Georgieva D, Koleva G, Collet C, Rigatelli G, and Gil RJ
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- Humans, Coronary Angiography methods, Treatment Outcome, Stents, Angioplasty, Balloon, Coronary methods, Percutaneous Coronary Intervention methods, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery
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Background: Percutaneous coronary interventions (PCI) of bifurcation lesions poses a technical challenge with a high complication rate. Kissing balloon inflation (KBI) and proximal optimization technique (POT) are used to correct bifurcation carina after stenting. However, both may still lead to uncomplete strut apposition to the side branch (SB) lateral wall. Proposed herein, is a new stent-optimization technique following bifurcation stenting consisting of a combination of POT and KBI called proximal optimization with kissing balloon inflation (POKI)., Methods: Bench and in-vivo evaluations were performed. For the bench visualization bifurcated silicone mock vessel was used. The POKI technique was simulated using a 3.5 mm POT balloon. For the in-vivo evaluation patients with angiographic bifurcation lesions in a native coronary artery with diameter ≥ 2.5 mm and ≤ 4.5 mm, SB diameter ≥ 2.0 mm, and percentage diameter stenosis (%DS) more than 50% in the main vessel (MV) were included. Provisional stenting was the default strategy., Results: In total 41 vessels were evaluated. The target vessel was left main in 9 (22.0%) patients, left anterior descending artery - in 26 (63.4%), left circumflex artery - in 4 (9.8%) and right coronary artery - in 2 (4.9%). The predominant type of bifurcation was Medina 1-1-1 (61.8%). Baseline proximal MV DS% was 60.0 ± 23.7%, distal MV DS% - 58.8 ± 28.9% and SB DS% 53.0 ± 32.0%. The application of POKI was feasible in 41 (100%) of the vessels. Post-PCI residual DS at proximal MV was 11.5 ± 15.4%, distal MV - 6.6 ± 9.3%, and SB - 22.9 ± 28.5%. Both procedural and angiographic success was 100%., Conclusions: POKI is a novel stent-optimization technique for bifurcation lesions. It showed excellent feasibility and success rate both in bench and in-vivo evaluation.
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- 2022
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44. A mediastinal malignant thyroid paraganglioma: A case report and literature review.
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Yankov G, Ivanovа S, Genadieva M, Alexieva M, Yanev N, and Ivanova D
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Introduction and Importance: Thyroid cancer is the most common endocrine malignancy, while primary paraganglioma of the thyroid gland (TP) is an unusual tumour and in rare cases, this disease tends to mimic thyroid cancer. They are rare extra-adrenal neuroendocrine tumours originating from the neural crest, and are found almost exclusively in the head and neck area., Case Presentation: We present a case of a 53-year-old man, in whom a mediastinal lesion originating from the left lobe of the thyroid gland was found on routine ultrasound and subsequent computed tomography (CT)., Clinical Discussion: Total thyroidectomy and lymph dissection were performed. A review of the literature was made and a discussion was held regarding the diagnosis, the importance of surgical treatment and further behaviour., Conclusion: Surgical removal of the thyroid gland is the main treatment, followed by radiation therapy. The diagnosis and differential diagnosis with other thyroid tumours is extremely important in terms of subsequent behaviour and prognosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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45. Implementation of TREC/KREC detection protocol for newborn SCID screening in Bulgaria: a pilot study.
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Marinova M, Georgyeva A, Yordanova V, Ivanov N, Atanasova V, Naumova E, and Kandilarova SM
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Neonatal screening for inborn errors of immunity (IEI), based on quantification of T-cell-receptor- excision circles (TRECs) and kappa-deleting recombination-excision circles (KRECs) from dried blood spots (DBS), allows early diagnosis and improved outcomes for the affected children. Determination of TREC/KREC levels from prospectively collected newborns' Guthrie cards and from DBS samples of patients with confirmed IEI was done using a commercial kit. Retrospective assessment of flow cytometry evaluation of TREC/KREC correspondence with lymphocyte subpopulations and evaluation of the correlations between TREC and KREC with immune cells, based on the data from patients with suspected or confirmed immune disorders, were conducted. 2,228 Guthrie cards were tested, 1276 for TREC only and 952 for both TREC and KREC. Eight newborns (0.36%) were TREC positive and 10 (1.05%) had KREC below the cut-off. The re-testing rate was 1.88%. Retrospective analysis demonstrated that the TREC/KREC assay identifies 100% of severe combined immune deficiencies (SCID) cases when DBS were collected at birth. Correlation analysis showed moderate significant correlations between TREC and the absolute numbers of CD4 cells (r = 0.634, p < 0.01) and total T cells (r = 0.536, p < 0.01). The ability of KREC levels to predict abnormal absolute (AUC of 0.772) and relative (AUC 0.731) levels of B cells was demonstrated., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)
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- 2022
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46. Determinants of functional significance of coronary bifurcation lesions and clinical outcomes after physiology-guided treatment.
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Vassilev D, Mileva N, Collet C, Nikolov P, Karamfiloff K, Naunov V, Sonck J, Hristova I, Georgieva D, Rigatelli G, Kassab GS, and Gil RJ
- Abstract
Objectives: To determine the rate of functionally significant (fractional flow reserve, FFR ≤ 0.80) coronary bifurcation stenoses that are considered anatomically significant based on angiographic estimation and to define predictors of functional significance of stenoses in main vessel and side branch., Background: To date, the rate of functionally significant stenoses in angiographic significant coronary bifurcation stenoses has not been specifically determined., Methods: Patients with significant angiographic bifurcation lesions defined as diameter stenosis >50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). The protocol was approved by the local ethics committee., Results: Overall, 171 patients with bifurcation lesions were included. Mean FFR in MV was 0.80 ± 0.01 and 0.84 ± 0.09 in SB. 46% (n = 78) of bifurcation lesions were functionally significant when assessed with FFR. Diameter stenosis in main vessel, lesion length, side branch territory and SYNTAX score (SS) were found as predictors for lesion functional severity (main vessel FFR ≤ 0.80). At the time of follow-up, there were no differences between the treated and deferred group regarding rates of all-cause death, cardio-vascular death, MACEs and POCE., Conclusion: Less than half of all angiographic significant bifurcation lesions were functionally significant when assessed with FFR. There was no difference in clinical outcomes at mean time of three years follow-up in treated and deferred lesion., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carlos Collet reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular and Philips Volcano. The other co-authors have no conflict of interest related to this manuscript., (© 2021 The Authors.)
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- 2021
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47. Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.
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Jung A, Orenti A, Dunlevy F, Aleksejeva E, Bakkeheim E, Bobrovnichy V, Carr SB, Colombo C, Corvol H, Cosgriff R, Daneau G, Dogru D, Drevinek P, Vukic AD, Fajac I, Fox A, Fustik S, Gulmans V, Harutyunyan S, Hatziagorou E, Kasmi I, Kayserová H, Kondratyeva E, Krivec U, Makukh H, Malakauskas K, McKone EF, Mei-Zahav M, de Monestrol I, Olesen HV, Padoan R, Parulava T, Pastor-Vivero MD, Pereira L, Petrova G, Pfleger A, Pop L, van Rens JG, Rodic M, Schlesser M, Storms V, Turcu O, Woz Niacki L, Yiallouros P, Zolin A, Downey DG, and Naehrlich L
- Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes., Methods: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis., Results: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function)., Conclusion: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes., Competing Interests: Conflict of interest: A. Jung has nothing to disclose. Conflict of interest: A. Orenti has nothing to disclose. Conflict of interest: F. Dunlevy reports support for the present manuscript from Chiesi Farmaceutici SpA. Conflict of interest: E. Aleksejeva has nothing to disclose. Conflict of interest: E. Bakkeheim has nothing to disclose. Conflict of interest: V. Bobrovnichy has nothing to disclose. Conflict of interest: S.B. Carr reports receiving speaker honoraria from Vertex and Chiesi, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Vertex, Profile Pharma and Chiesi, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from UK CF Trust; PI for Pharmacovigilance study, payment to institution from Pharmaxis, outside the submitted work. Conflict of interest: C. Colombo has nothing to disclose. Conflict of interest: H. Corvol has nothing to disclose. Conflict of interest: R. Cosgrif declares outside the submitted work to be the director of the Cystic Fibrosis Trust. Conflict of interest: G. Daneau has nothing to disclose. Conflict of interest: D. Dogru has nothing to disclose. Conflict of interest: P. Drevinek reports grants or contracts from Ministry of Health, Czech Republic, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Actelion Pharmaceuticals, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Vertex Pharmaceuticals, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Society for Medical Microbiology, outside the submitted work. Conflict of interest: A.D. Vukic has nothing to disclose. Conflict of interest: I. Fajac reports grants or contracts from Boehringer Ingelheim, Celtaxsys, Corbus Pharmaceuticals, and Vertex Pharmaceuticals, outside the submitted work; consulting fees from Boehringer Ingelheim and Vertex Pharmaceuticals, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Boehringer Ingelheim, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for European Cystic Fibrosis Society. Conflict of interest: A. Fox support for the present manuscript from Chiesi Farmaceutici SpA. Conflict of interest: S. Fustik has nothing to disclose. Conflict of interest: V. Gulmans has nothing to disclose. Conflict of interest: S. Harutyunyan has nothing to disclose. Conflict of interest: E. Hatziagorou has nothing to disclose. Conflict of interest: I. Kasmi has nothing to disclose. Conflict of interest: H. Kayserová has nothing to disclose. Conflict of interest: E. Kondratyeva reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from All-Russian online school with international participation, outside the submitted work. Conflict of interest: U. Krivec has nothing to disclose. Conflict of interest: H. Makukh has nothing to disclose. Conflict of interest: K. Malakauskas has nothing to disclose. Conflict of interest: E.F. McKone reports grants or contracts from vertex, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Roche Pharmaceuticals, outside the submitted work; support for attending meetings and/or travel from A Menarini, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Insmed and Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: M. Mei-Zahav has nothing to disclose. Conflict of interest: I. de Monestrol reports grant from Vertex for an academic research study regarding gastrointestinal outcome in CF patients taking Orkambi medication, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Swedish CF Registry and the Swedish Society of Medicine's CF working group. Conflict of interest: H.V. Olesen has nothing to disclose. Conflict of interest: R. Padoan has nothing to disclose. Conflict of interest: T. Parulava has nothing to disclose. Conflict of interest: M.D. Pastor-Vivero has nothing to disclose. Conflict of interest: L. Pereira has nothing to disclose. Conflict of interest: G. Petrova reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from TEVA Pharmaceuticals, Mylan and Alvogen, outside the submitted work. Conflict of interest: A. Pfleger has nothing to disclose. Conflict of interest: L. Pop has nothing to disclose. Conflict of interest: J.G. van Rens has nothing to disclose. Conflict of interest: M. Rodić has nothing to disclose. Conflict of interest: M. Schlesser has nothing to disclose. Conflict of interest: V. Storms has nothing to disclose. Conflict of interest: O. Turcu has nothing to disclose. Conflict of interest: L. Woźniacki has nothing to disclose. Conflict of interest: P. Yiallouros has nothing to disclose. Conflict of interest: A. Zolin has nothing to disclose. Conflict of interest: D.G. Downey has nothing to disclose. Conflict of interest: L. Naehrlich reports support for the present manuscript from Chiesi Farmaceutici SpA; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ArticulateScience LLC, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Trial Steering committee of CF Storm, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Society for German CF Registry European CF Patient Registry, outside the submitted work; other financial or nonfinancial interests from Vertex Pharmaceuticals and Boehringer Ingelheim; Institutional fees for site participation (PI) in clinical trials from Vertex Pharmaceuticals and Boehringer Ingelheim., (Copyright ©The authors 2021.)
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48. Bifurcation functional significance score as predictor of mortality: a validating study.
- Author
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Vassilev D, Mileva N, Collet C, Nikolov P, Sokolova K, Karamfiloff K, Naunov V, Sonck J, Rigatelli G, Kassab GS, and Gil RJ
- Subjects
- Aged, Coronary Artery Disease pathology, Coronary Artery Disease therapy, Female, Humans, Male, Prospective Studies, Survival Rate, Treatment Outcome, Coronary Angiography methods, Coronary Artery Disease mortality, Percutaneous Coronary Intervention methods, Registries statistics & numerical data
- Abstract
Considerable progress has been made in the treatment of coronary bifurcation stenosis. Anatomical characteristics of the vessel and lesion, however, fail to give information about the functional significance of the bifurcation stenosis. To the best of our knowledge, there is no study that systematically establishes the baseline functional significance of coronary stenosis and its effect on procedural and clinical outcomes. Patients with significant angiographic bifurcation lesions defined as diameter stenosis > 50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). 169 patients from Fiesta study (derivation cohort) and 555 patients from prospective bifurcation registry (clinical effect cohort) were analyzed to validate angiographic prediction score (BFSS) used to determine the potentially functional significance of coronary bifurcation stenosis. Bifurcation functional significance score (including the following parameters-SYNTAX ≥ 11, SB/MB BARI score, MV %DS ≥ 55%, main branch (MB) %DS ≥ 65%, lesion length ≥ 25 mm) with a maximum value of 11 was developed. A cut-off value of 6.0 was shown to give the best discriminatory ability-with accuracy 87% (sensitivity 77%, specificity 96%, p < 0.001). There was also a significant difference in all-cause mortality between patients with BFSS ≥ 6.0 vs. BFSS < 6.0-25.5% vs. 18.4%, log-rank p = 0.001 as well as cardiac mortality: BFSS ≥ 6.0 vs. BFSS < 6.0-17.7% vs. 14.5%, log-rank (p = 0.016). The cardiac mortality was significantly lower in patients with smaller absolute SB territory, p = 0.023. An angiographic score (BFSS) with good discriminatory ability to determine the functional significance of coronary bifurcation stenosis was developed. The value for BFSS ≥ 6.0 can be used as a discriminator to define groups with higher risk for all-cause and cardiac mortality. Also, we found that the smaller side branches pose greater mortality risk., (© 2021. The Author(s).)
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49. Phenotypic Differences of Glu89Gln Genotype in ATTR Amyloidosis From Endemic Loci: Update From THAOS.
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Gentile L, Tournev I, Amass L, Chapman D, and Mazzeo A
- Abstract
Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, clinically heterogeneous disease with spontaneous (wild-type) and hereditary (ATTRv) forms. The Glu89Gln variant is primarily associated with cardiomyopathy and prevalent in Italy and Bulgaria. The objective of this analysis was to better understand the profile of patients with ATTRv Glu89Gln amyloidosis in the Transthyretin Amyloidosis Outcomes Survey (THAOS)., Methods: THAOS is an ongoing, global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers with mutations in the transthyretin gene. Demographic and clinical characteristics of all symptomatic patients with the ATTRv Glu89Gln variant enrolled in THAOS are described (data cutoff, January 6, 2020)., Results: There were 91 patients with ATTRv Glu89Gln amyloidosis with the majority from Bulgaria (n = 53) or Italy (n = 29). All patients were Caucasian and 50.5% were male. Patients from Bulgaria had a mean (standard deviation) age at enrollment of 57.1 (8.2) years, and duration of symptoms of 8.6 (9.6) years, compared with 54.8 (8.6) and 5.0 (4.1) years in Italy. In Bulgaria, 39.6% of patients were of a predominantly cardiac phenotype, 18.9% predominantly neurologic, and 41.5% mixed. In Italy, 3.4% of patients were predominantly cardiac, 62.1% predominantly neurologic, and 34.5% mixed., Conclusions: The majority of patients with ATTRv Glu89Gln amyloidosis in THAOS are from Bulgaria or Italy. There were notable phenotypic differences, with the cardiac phenotype more common in Bulgaria and the neurologic phenotype more common in Italy. Over one-third of patients had a mixed phenotype, suggesting a potential role of multiple genetic and/or environmental factors and the need for comprehensive assessment of all patients., Trial Registration: ClinicalTrials.gov: NCT00628745., (© 2021. The Author(s).)
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50. Molecular characterization and natural history of linear porokeratosis: A case series.
- Author
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Saleva-Stateva M, Hess M, Technau-Hafsi K, Weibel L, Badea MA, Boente MDC, Theiler M, Fiandrino MJ, Hoeger P, Zimmer A, Rafei-Shamsabadi D, Balabanova M, Fischer J, Boerries M, and Has C
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- Adolescent, Adult, Child, Connexin 26, Female, Humans, Male, Mevalonic Acid, Middle Aged, Porokeratosis diagnosis, Skin, Skin Neoplasms diagnosis, Exome Sequencing, Porokeratosis genetics, Skin Neoplasms genetics
- Abstract
Competing Interests: Conflicts of interest None disclosed.
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- 2021
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