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2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

2026-05-12T17:37:39Z

Título: 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19 Autor: Farge, Dominique; Frere, Corinne; Connors, Jean M.; Khorana, Alok A.; Kakkar, Ajay; Ay, Cihan; Muñoz, Andrés; Brenner, Benjamin; Prata, Pedro H.; Brilhante, Dialina; Antic, Darko; Casais, Patricia; Guillermo Espósito, María Cecilia; Ikezoe, Takayuki; Abutalib, Syed A.; Meillon García, Luis A.; Bounameaux, Henri; Pabinger, Ingrid; Douketis, James; International Initiative on Thrombosis and Cancer (ITAC) advisory panel Resumen: The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding. Descripción: Collaborators International Initiative on Thrombosis and Cancer (ITAC) advisory panel: Walter Ageno, Fernando Ajauro, Thierry Alcindor, Pantep Angchaisuksiri, Juan I Arcelus, Raquel Barba, Ali Bazarbachii, Audrey Bellesoeur, Okba Bensaoula, Ilham Benzidia, Darius Bita, Viktoria Bitsadze, Dorit Blickstein, Mark Blostein, Isabel Bogalho, Antonio Brandao, Rodrigo Calado, Antoine Carpentier, Jose Manuel Ceresetto, Rufaro Chitsike, Jérôme Connault, Catarina Jacinto Correia, Benjamin Crichi, Erich V De Paula, Ahmet M Demir, Laure Deville, Ludovic Doucet, Vera Dounaevskaia, Cécile Durant, Martin Ellis, Joseph Emmerich, Anna Falanga, Carme Font, Enrique Gallardo, Thomas Gary, Filipe Gonçalves, Jean-Christophe Gris, Hiromi Hayashi, Adrian Hij, Luis Jara-Palomares, David Jiménez, Jamilya Khizroeva, Michel N'Guessan, Florian Langer, Claire Le Hello, Christine Le Maignan, Ramón Lecumberri, Lai Heng Lee, Zachary Liederman, Luisa Lopes Dos Santos, Duarte Henrique Machado, Alexander Makatsariya, Alberto Maneyro, Zora Marjanovic, Serban Milhaileanu, Manuel Monreal, Sara Morais, Antonio Moreira, Mikio Mukai, Arlette Ndour, Luciana Correa Oliveira, Remedios Otero-Candelara, Maria Carolina Tostes Pintao, Florian Posch, Pascal Prilollet, Hanadi Rafii, Daniel Dias Ribeiro, Hanno Riess, Marc Righini, Helia Robert-Ebadi, Cynthia Rothschild, Andre Roussin, José Antonio Rueda Camino, Pedro Ruiz-Artacho, Gleb Saharov, Joana Santos, Maxime Sebuhyan, Ali Shamseddine, Galia Spectre Spectre, Ali Taher, Javier Trujillo-Santos, Inna Tzoran, Stéphane Villiers, Raymond Wong, Yugo Yamashita, Alexandra Yannoutsos, Chikao Yasuda.

Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system

2026-05-12T17:36:52Z

Título: Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system Autor: García Roche, Mercedes; Talmón, Daniel; Cañibe, Guillermo; Astessiano, Ana Laura; Mendoza, Alejandro; Quijano, Celia; Cassina, Adriana; Carriquiry, Mariana Resumen: The objective of this study was to assess hepatic ATP synthesis in Holstein cows of North American and New Zealand origins and the gluconeogenic pathway, one of the pathways with the highest ATP demands in the ruminant liver. Autumn-calving Holstein cows of New Zealand and North American origins were managed in a pasture-based system with supplementation of concentrate that represented approximately 33% of the predicted dry matter intake during 2017, 2018, and 2019, and hepatic biopsies were taken during mid-lactation at 174 ± 23 days in milk. Cows of both strains produced similar levels of solids-corrected milk, and no differences in body condition score were found. Plasma glucose concentrations were higher for cows of New Zealand versus North American origin. Hepatic mitochondrial function evaluated measuring oxygen consumption rates showed that mitochondrial parameters related to ATP synthesis and maximum respiratory rate were increased for cows of New Zealand compared with North American origin. However, hepatic gene expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase kinase was increased in North American compared with New Zealand cows. These results altogether suggest an increased activity of the tricarboxylic cycle in New Zealand cows, leading to increased ATP synthesis, whereas North American cows pull tricarboxylic cycle intermediates toward gluconeogenesis. The fact that this occurs during mid-lactation could account for the increased persistency of North American cows, especially in a pasture-based system. In addition, we observed an augmented mitochondrial density in New Zealand cows, which could be related to feed efficiency mechanisms. In sum, our results contribute to the elucidation of hepatic molecular mechanisms in dairy cows in production systems with higher inclusion of pastures.

Epidemiology and Risk Factors for the Development of Infectious Complications in Newly Diagnosed Multiple Myeloma: A Multicenter Prospective Cohort Study in Latin America

2026-05-12T16:53:21Z

Título: Epidemiology and Risk Factors for the Development of Infectious Complications in Newly Diagnosed Multiple Myeloma: A Multicenter Prospective Cohort Study in Latin America Autor: Bove, Virginia; Riva, Eloísa; Vásquez, Jule; Peña, Camila; Seehaus, Cristian; Samanez, César; Bustos, Justina; Hernández, Marcos; Fernández, Julio; Ríos, Oliday; Rodríguez, Yusaima; Figueredo, Irving; Fantl, Dorotea; Malpica, Luis Resumen: Infections are a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in this patient population are lacking. METHODS We conducted a prospective cohort study of patients with newly diagnosed MM (NDMM) in seven Latin American countries between June 2019 and May 2020. Patients with active disease, on active therapy, and with a follow-up of 6 months from the time of diagnosis were included. Our primary end point was the number of infectious events that required hospitalization for ≥ 24 hours. RESULTS Of 248 patients with NDMM, 89 (35.9%) had infectious complications (113 infectious events), the majority (67.3%) within the first 3 months from diagnosis. The most common sites of infection were respiratory (38%) and urinary tract (31%). The microbial agent was identified in 57.5% of patients with gram-negative bacteria (73.5%) as the most common pathogen. Viral infections were infrequent, and no patients with fungal infection were reported. In the multivariable analysis, diabetes mellitus (odds ratio [OR], 2.71; 95% CI, 1.23 to 6.00; P = .014), creatinine ≥ 2 mg/dL (OR, 4.87; 95% CI, 2.29 to 10.35; P < .001), no use of trimethoprim-sulfamethoxazole prophylaxis (OR, 6.66; 95% CI, 3.43 to 12.92; P < .001), and treatment with immunomodulatory drugs (OR, 3.02; 95% CI, 1.24 to 6.29; P = .003) were independent factors associated with bacterial infections. At 6 months, 21 patients (8.5%) had died, 47.6% related to infectious complications. CONCLUSION Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.

Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions

2026-05-12T16:04:50Z

Título: Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions Autor: Tossounian, Maria-Armineh; Baczynska, María; Dalton, William; Newell, Charlie; Yilin, Ma; Das, Sayoni; Semelak, Jonathan Alexis; Estrin, Darío; Filonenko, Valeriy; Trujillo, Madia; Sew Yeu, Peak-Chew; Skehel, Mark; Fraternali, Franca; Orengo, Christine; Gout, Iván Resumen: Coenzyme A (CoA) is a key cellular metabolite known for its diverse functions in metabolism and regulation of gene expression. CoA was recently shown to play an important antioxidant role under various cellular stress conditions by forming a disulfide bond with proteins, termed CoAlation. Using anti-CoA antibodies and liquid chromatography tandem mass spectrometry (LC-MS/MS) methodologies, CoAlated proteins were identified from various organisms/tissues/cell-lines under stress conditions. In this study, we integrated currently known CoAlated proteins into mammalian and bacterial datasets (CoAlomes), resulting in a total of 2093 CoAlated proteins (2862 CoAlation sites). Functional classification of these proteins showed that CoAlation is widespread among proteins involved in cellular metabolism, stress response and protein synthesis. Using 35 published CoAlated protein structures, we studied the stabilization interactions of each CoA segment (adenosine diphosphate (ADP) moiety and pantetheine tail) within the microenvironment of the modified cysteines. Alternating polar-non-polar residues, positively charged residues and hydrophobic interactions mainly stabilize the pantetheine tail, phosphate groups and the ADP moiety, respectively. A flexible nature of CoA is observed in examined structures, allowing it to adapt its conformation through interactions with residues surrounding the CoAlation site. Based on these findings, we propose three modes of CoA binding to proteins. Overall, this study summarizes currently available knowledge on CoAlated proteins, their functional distribution and CoA–protein stabilization interactions.