495 research outputs found

    PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection

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    © 2023 by the American College of Cardiology Foundation. Published by Elsevier. This is the accepted manuscript version of an article which has been published in final form athttps://doi.org/10.1016/j.jacc.2022.10.030Background The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. Objectives The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. Methods In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. Results Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%). Conclusions PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)Peer reviewe

    Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study

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    Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p p p p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients

    COVID-19 occurrence and symptoms depending on vaccination status: a retrospective single-centre analysis of 27,209 patients

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    Introduction: Widespread immunization is critical to bringing the COVID-19 pandemic to an end. The objective of this cross-sectional data analysis was to investigate the impact of vaccination on the frequency of COVID-19 occurrence and the presence of its symptoms and clinical presentations. Material and methods: This was a retrospective, cross-sectional study, analysing medical records of patients hospitalized at the Dr Antoni Jurasz University Hospital No. 1 in Bydgoszcz in the years 2019–2021. The analysis considered age, sex, vaccination status, the result of the reverse transcription polymerase chain reaction (RT-PCR) test for the detection of SARS-CoV-2 RNA, and disease symptoms and clinical presentations in accordance with ICD-10 codes. Results: The study group consisted of 27,209 patients. There were 1,393 persons (5.12%) who tested positive for COVID-19. The vaccinated patients accounted for 17.3% (n = 4,704). Those vaccinated were significantly less likely to test positive for COVID-19 (3.93% vs. 5.38%; p &lt; 0.0001). Among unvaccinated patients with a positive test result for COVID-19, symptoms and/or clinical presentations occurred in 359 study participants (29.72%), while in vaccinated COVID-19-positive patients only in 49 persons (26.49%). The symptoms that occurred in both vaccinated and unvaccinated patients were mainly respiratory and circulatory. The most common clinical presentation, both in the group of vaccinated and unvaccinated patients, was viral pneumonia, not elsewhere classified (J12), which occurred in 17.30% and 9.19% of patients, respectively (p = 0.005). Other symptoms and clinical presentations showing a statistically significant difference in the frequency of occurrence between the groups were pneumonia in diseases classified elsewhere (J17; p = 0.019) and abnormalities of breathing (R06; p = 0.001). Conclusions: Vaccination against COVID-19 protects against symptomatic disease

    Determinants of Lipid Parameters in Patients without Diagnosed Cardiovascular Disease—Results of the Polish Arm of the EUROASPIRE V Survey

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    To assess the determinants of lipid parameters in primary care patients without diagnosed cardiovascular disease (CVD), a cross-sectional study was conducted during 2018–2019 with a total of 200 patients. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), small, dense LDL (sdLDL-C), and lipoprotein (a) (Lp(a)). Predictors of elevated and adequately controlled lipid parameters were assessed with logistic regression analysis. Older age was related to higher risk of TC ≥ 6.2 mmol/L [OR 1.03 (95% CI 1.0–1.05)], sdLDL-C ≥ 1.0 mmol/L [OR 1.05 (95% CI 1.0–1.1)], and decreased risk of Lp(a) ≥ 50 mg/dL [OR 0.97 (95% CI 0.94–0.99)]. Patients with diabetes mellitus (DM) had increased probability of TG ≥ 2.25 mmol/L [OR 3.77 (95% CI 1.34–10.6)] and Lp(a) ≥ 50 mg/dL [OR 2.97 (1.34–6.10)] as well as adequate control of TG and Lp(a). Higher material status was related to lower risk of TC ≥ 6.2 mmol/L [OR 0.19 (95% CI 0.04–0.82)] and LDL-C ≥ 3.6 mmol/L [OR 0.33 (95% CI 0.12–0.92)]. High BMI was related to increased [OR 1.14 (95% CI 1.02–1.29)], and female gender [OR 0.33 (95% CI 0.12–0.96)] and hypertension [OR 0.29 (95% CI 0.1–0.87)] to decreased risk of TG ≥ 2.25 mmol/L [OR 1.14 (95% CI 1.02–1.29)]. Taking lipid-lowering drugs (LLD) was associated with LDL-C < 2.6 mmol/L [OR 2.1 (95% CI 1.05–4.19)] and Lp(a) < 30 mg/dL [OR 0.48 (95% CI 0.25–0.93)]. Physical activity was related to LDL-C < 2.6 mmol/L [OR 2.02 (95% CI 1.02–3.98)]. Higher abdominal circumference was associated with decreased risk of TG < 1.7 mmol/L [OR 0.96 (95% CI 0.93–0.99)]. Elevated lipid parameters were related to age, gender, material status, BMI, history of DM, and hypertension. Adequate control was associated with age, education, physical activity, LLD, history of DM, and abdominal circumference

    Long-term cenobamate retention, efficacy, and safety: outcomes from Expanded Access Programme

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    Aim of the study. To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). Clinical rationale for the study. Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. Material and methods. We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. Results. 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18–57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0–8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50–350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. Conclusions and clinical implications. Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate

    Stanowisko ekspertów Polskiego Towarzystwa Kardiologicznego dotyczące stosowania andeksanetu alfa w warunkach polskich — interdyscyplinarny protokół

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    Andeksanet alfa (AA) jest rekombinowanym, nieaktywnym analogiem ludzkiego czynnika Xa (FXa), skutecznie odwracającym działanie jego inhibitorów — dostępnych w Polsce rywaroksabanu i apiksabanu. Lek otrzymał rejestrację po opublikowaniu wyników badania ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), w którym udowodniono jego skuteczność w przywracaniu hemostazy w zagrażających życiu krwawieniach w grupie pacjentów stosujących te leki przeciwkrzepliwe. Dlatego AA jest obecnie zalecany u pacjentów stosujących terapię apiksabanem lub rywaroksabanem z masywnymi i niemożliwymi do opanowania krwotokami, w tym udarami krwotocznymi i krwawieniami z przewodu pokarmowego. Najodpowiedniejsze do oszacowania stężenia rywaroksabanu i apiksabanu w osoczu, poza jego bezpośrednią oceną, są chromogenne testy anty-Xa specyficzne dla leku. Brak aktywności anty-Xa stwierdzony przy użyciu tych oznaczeń wyklucza istotne klinicznie stężenie inhibitora FXa w osoczu. Dawka AA nie powinna być natomiast modyfikowana na podstawie wyników badań hemostazy. Zależy ona wyłącznie od czasu, jaki upłynął od przyjęcia ostatniej dawki inhibitora FXa, oraz od dawki i rodzaju stosowanego przewlekle leku. Andeksanet alfa podawany jest w postaci bolusa dożylnego a następnie włączony zostaje wlew dożylny leku. Maksymalne odwrócenie aktywności anty-Xa następuje w ciągu 2 minut od zakończenia podawania bolusa, a kontynuowanie ciągłej infuzji dożylnej umożliwia utrzymanie efektu aż do 2 godzin po jego zakończeniu. Ponieważ aktywność leku przeciwkrzepliwego może się pojawić ponownie po zakończeniu wlewu, obecnie nie jest jasne, w jakim momencie po podaniu AA można (ponownie) podać inhibitory FXa lub heparynę

    Platelet-to-lymphocyte ratio as a prognostic biomarker for COVID-19 severity: a single center retrospective data analysis and systematic review with meta-analysis of 187 studies

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    INTRODUCTION: This study aims to evaluate the prognostic value of the platelet-to-lymphocyte ratio in determining the severity and mortality of adults hospitalized for COVID-19 using retrospective data and a meta-analysis of previous studies on the platelet-to-lymphocyte ratio worldwide. MATERIAL AND METHODS: A retrospective study was conducted at the Kırdar City Hospital (Istanbul, Turkey) and included 521 COVID-19 patients. A systematic literature search of EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases was performed for relevant trials relating to the PLR ratio in COVID-19 published before April 12, 2023. RESULTS: In the retrospective part of the study, PLR values were found to predict COVID-19 severity at admission with an AUC of 0.61 (SE = 0.03; 95% CI: 0.56 to 0.65; p = 0.0003) as well as survival status in a statistically significant fashion with an AUC of 0.59 (SE = 0.03; 95% CI: 0.55 to 0.64; p = 0.0004). Results of our meta-analysis showed a significant relationship between PLR and COVID-19 severity, with a pooled standardized mean difference (SMD) of 1.34 (95% CI: 1.13 to 1.55; p &lt; 0 .001), and that PLR was significantly lower among patients who survived compared to deceased patients (SMD = –1.32; 95% CI: 1.57 to –1.07; p &lt; 0.001). CONCLUSIONS: PLR is a valid, readily available marker that can distinguish COVID-19 individuals with distinct progression and survival outcomes

    Conley-Morse-Forman theory for generalized combinatorial multivector fields on finite topological spaces

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    We generalize and extend the Conley-Morse-Forman theory for combinatorial multivector fields introduced in Mrozek (Found Comput Math 17(6):1585–1633, 2017). The generalization is threefold. First, we drop the restraining assumption in Mrozek (Found Comput Math 17(6):1585–1633, 2017) that every multivector must have a unique maximal element. Second, we define the dynamical system induced by the multivector field in a less restrictive way. Finally, we also change the setting from Lefschetz complexes to finite topological spaces. Formally, the new setting is more general, because every Lefschetz complex is a finite topological space, but the main reason for switching to finite topologcial spaces is because the latter better explain some peculiarities of combinatorial topological dynamics. We define isolated invariant sets, isolating neighborhoods, Conley index and Morse decompositions. We also establish the additivity property of the Conley index and the Morse inequalities

    Therapeutic strategies targeting metabolic syndrome

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