Faculty of Medicine

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Association between antithrombotic treatment and outcomes at 1-year follow-up in patients with atrial fibrillation: the EORP-AF General Long-Term Registry
(Oxford University Press (OUP), 2019)
Boriani, Giuseppe
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Proietti, Marco
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Laroche, Cécile
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Fauchier, Laurent
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Marin, Francisco
In recent years, stroke prevention in patients with atrial fibrillation (AF) has radically changed, with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs). Contemporary European data on AF thromboprophylaxis are needed.
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Contemporary stroke prevention strategies in 11 096 European patients with atrial fibrillation: a report from the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) Long-Term General Registry
(Oxford University Press (OUP), 2018)
Boriani, Giuseppe
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Proietti, Marco
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Laroche, Cécile
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Fauchier, Laurent
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Marin, Francisco
Contemporary data regarding atrial fibrillation (AF) management and current use of oral anticoagulants (OACs) for stroke prevention are needed.
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Impact of malignancy on outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EURObservational research programme in atrial fibrillation general long-term registry
(Wiley, 2022-07)
Malavasi, Vincenzo L
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Vitolo, Marco
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Proietti, Marco
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Diemberger, Igor
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Fauchier, Laurent
The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management.
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Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry
(Wiley, 2022-06)
Ding, Wern Yew
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Potpara, Tatjana S
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Blomström-Lundqvist, Carina
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Boriani, Giuseppe
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Marin, Francisco
Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF.
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Adjuvant chemotherapy plus concurrent chemoradiotherapy (CCRT) in advanced gastric adenocarcinoma treatment as standard of care
(2020)
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Lazarova, Emilija
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Berat, Meri
Introduction. Despite a worldwide decline in incidence based on GLOBOCAN 2018 data, stomach cancer is the 5th most common neoplasm and the 3rd most deadly cancer. In 90% of cases, its histology is adenocarcinoma, either of the intestinal type or of diffuse. Helicobacter pylori infection, smoking, salt and nitrate-rich foods are the most important factors of risk. The interactions between dietary factors, environmental factors and the development of gastric cancer are well described with clearly identified dietary exposures strongly associated with gastric cancer induction and prevention. Postoperative fluoropyrimidine-based CCRT and chemotherapy is standard adjuvant treatment of resected gastric adenocarcinoma. Materials and methods. Patients with subtotal gastrectomy and D1 lymph node dissection were treated with 2 cycles of Capecitabine (DD 2500 mg/m2 po bid/21day cycle) followed by chemoradiotherapy and another of 2 cycles chemotherapy with Capecitabine (DD 2500 mg/m2 po bid/21d cycle). CT simulation with oral contrast application was performed followed by delineation of target volumes and organs at risk according to CRITICS protocol. 3D conformal postoperative chemoirradiation was delivered with standard fractionation (TTD 50.4 Gy/1.8 Gy) with concurrent application of Capecitabine 1650mg/m2/bid/d1-5. Adjuvant treatment was delivered in postoperative period of 6 months. Results. Adjuvant chemotherapy and chemoradiotherapy prolongs disease free survival (DFS) and improves quality of life. CT-based 3D conformal treatment planning and delivery of postoperative chemoirradiation is minimum standard of care of gastric cancer treatment. Conclusion. Multidisciplinary decision making team approach is preferred. Primary treatment option for patients with potentially resectable locoregional gastric tumors is surgery. The guidelines have included postoperative chemo/chemoradiotherapy treatment depending of tumor stage, nodal status, extent of lymph node dissection and other risk factors (differentiation, lymphovascular invasion, neural invasion, surgical margins). Adjuvant chemotherapy and chemoradiotherapy prolongs disease free survival (DFS) and improves quality of life. Keywords: Gastric cancer, chemoirradiation, CCRT, DFS, 3D conformal, postoperative
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POSTOPERATIVE ADJUVANT INTENSITY-MODULATED RADIOTHERAPY FOR RADICALLY RESECTED RECTAL ADENOCARCINOMA: DATA FROM EVERYDAY PRACTICE
(Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, 2022-05-04)
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Grozdanovska, Biljana
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Introduction: Adjuvant radiochemotherapy is a standard treatment in patients with surgically treated stage II or III rectal adenocarcinoma who did not undergo neoadjuvant radiotherapy. Intensity-modulated radiation therapy (IMRT) was only marginally investigated in postoperative setting. Material and methods: A longitudinal observational analysis was conducted in patients with radically resected stage II or III rectal adenocarcinoma treated with IMRT at the University Clinic for Radiotherapy and Oncology as part of the adjuvant postoperative treatment. The dose-volume parameters of the radiotherapy plans, as well as acute side effects of 40 patients were analyzed. Results: The average dose received by the target volume was 49.95 Gy (range 27-54 Gy). The mean volume of peritoneal cavity receiving 45 Gy (V45) was 102.73 cm3 (±52.10), V30 for pelvic bones was 38.3% (±5.48), V40 for bladder 52.48% (±10.9). The most frequent acute side effects were diarrhea in 17 (42.5%), lymphopenia in 34 (85%) and thrombocytopenia in 26 patients (65%). Most of the side effects were self-limiting and caused disruption of the radiation treatment only in 3 patients (7.5%). Conclusion: Integrating IMRT in the adjuvant treatment of locally advanced rectal cancer provides a good dose distribution and organs at risk sparing. The treatment is well tolerated, the side effects are mainly of lesser degrees and easily managed. A prospective trial comparing IMRT with 3-dimensional conformal radiotherapy is needed to assess whether IMRT offers a better perspective for adjuvant treatment. Keywords: rectal adenocarcinoma, adjuvant treatment, remove adjuvant treatment, intensity-modulated radiotherapy, acute side effects
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Successful treatment of massive pulmonary embolism with rescue fibrinolysis in young patient with homocystinemia – case report
(Faculty of Medical Sciences, University of Kragujevac, 2020-10-01)
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Lazarova, Emilija
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Pulmonary embolism (PE) is the most frequently missed diag- nosis in the urgent clinical department with serious consequences. Patients with unprovoked PE have increased risk of recurrent PE. Approximately 5 to 8% of PE patients have inherited thrombo- philias. A solated homocystinemia is a rare cause of unprovoked acute pulmonary embolism. Timely diagnosis and proper treat- ment can prevent complications, costs and mortality and provide patient better quality of life. We are presenting a 42-year-old woman was admitted to our emergency department with the first episode of severe dyspnea and chest pain. She had no history of previous cardiovascular or respiratory disease and no history of previous pulmonary embolism (PE) or deep vein thrombosis (DVT). Urgent echocardiography showed indirect signs of pul- monary embolism which was confirmed by the pulmonary artery CT angiography performed one day after the patient’s admission. After two days of heparin infusion, she developed a hemodynamic instability with cardiogenic shock and was treated successfully with fibrinolysis. After the clinical stabilization, she was put on the rivaroxaban therapy, which was recommended for additional six months. The thrombophilia profile was done two weeks after stop- ping the therapy with rivaroxaban. The thrombophilia panel came back positive for high levels of homocysteine (67 μmol/L), with other thrombophilia results within normal limits. The patient was stable during the follow-up period. Pulmonary embolism should be always suspected in younger patients with acute severe dysp- nea even without provocable risk factors. High suspicion level and fast diagnosis are lifesaving. In younger patients presented with unprovoked pulmonary embolism, clinicians should consider inherited prothrombotic factors and homocystinemia as a poten- tial cause. Rescue fibrinolysis is a lifesaving therapy in hemody- namic worsening in intermediate high-risk PE patients. A longer anticoagulation therapy should be considered in these cases with novel oral anticoagulants that are recommended as safer and su- perior therapy.
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Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
(Springer Science and Business Media LLC, 2020)
Zhang, Haoyu
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Ahearn, Thomas U
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Lecarpentier, Julie
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Barnes, Daniel
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Beesley, Jonathan
Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
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Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
(Cold Spring Harbor Laboratory, 2019-09-24)
Zhang, Haoyu
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Ahearn, Thomas U.
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Lecarpentier, Julie
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Barnes, Daniel
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Beesley, Jonathan
<jats:title>Abstract</jats:title><jats:p>Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study (GWAS) including 133,384 breast cancer cases and 113,789 controls, plus 18,908 <jats:italic>BRCA1</jats:italic> mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status and tumor grade. We identified 32 novel susceptibility loci (<jats:italic>P</jats:italic><5.0×10<jats:sup>-8</jats:sup>), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate <0.05). Five loci showed associations (<jats:italic>P</jats:italic><0.05) in opposite directions between luminal- and non-luminal subtypes. <jats:italic>In-silico</jats:italic> analyses showed these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 37.6% for triple-negative and 54.2% for luminal A-like disease. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.</jats:p>
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Dosimetric comparison of two-dimensional versus three-dimensional intracavitary brachytherapy in locally advanced cervical cancer
(National Library of Serbia, 2018)
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Chakalaroski, Petar
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Dimitrovska, Nadica

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