Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with dyslipidemia playing a key role in its progression. Despite advances in lipid-lowering therapy (LLT), LDL-C (Low-Density Lipoprotein Cholesterol) goal achievement remains suboptimal. This study evaluated LDL-C goal attainment in Colombian patients with very high cardiovascular risk (CVR) due to coronary artery disease (CAD) following ESC/EAS guidelines updates. EDHIPO MARCA (Evaluación De adherencia a la terapia HIPOlipemiante en pacientes de Muy Alto Riesgo CArdiovascular) is a retrospective, multicenter study assessing LDL-C goal achievement in patients with CAD. Data were collected from previous coronary angiogram reports and medical records across 11 Colombian healthcare institutions with certified interventional cardiology services. Patients with CAD who had at least one follow-up LDL-C measurement and an LLT prescription within 12 months post-angiogram were included. LDL-C goal attainment was assessed across three periods—2011–2012, 2016–2017, and 2021–2022—corresponding to the updates of ESC/EAS guidelines (2011, 2016, and 2019, respectively). The LDL-C goals were <70 mg/dL for the first two periods and <55 mg/dL for the most recent one. LDL-C was measured or estimated using the Friedewald equation. Descriptive analyses were performed. A total of 1,788 patients were included, with a median age of 66 years (IQR: 59–74), and 70.7
Background: The rising burden of orally transmitted Chagas disease in South America underscores the need for a deeper understanding of this food-borne transmission route. Despite its relevance, key aspects such as transmission dynamics, epidemiology, and clinical outcomes remain insufficiently explored, limiting prevention and treatment strategies. Methods: A systematic review (PROSPERO 2024-CRD42024542461) of reported outbreaks from 1965 to 2023 was conducted. Three reviewers independently screened and selected studies using predefined criteria. Data on epidemiology, contamination sources, clinical findings, diagnostics (cardiac, serological, molecular), vector species, and parasite lineages were extracted. Findings: We compiled data from 111 outbreaks involving 1187 cases (55% males), 77 deaths, in 6 countries. Contaminated food sources were identified in 63 outbreaks (56.7%), with reliable confirmation in 8 (7.2%), acai fruit being the most common source (28%). Outbreaks occurred mainly in sylvatic and tropical regions, coinciding with warm seasons and crop harvest periods. Selvatic parasite lineages predominated (98%), with Rhodnius spp. triatomines being implicated in 28%. The median incubation period was 22 days. Case fatality ratio was 6.5%. Acute infection presented with fever (80%), facial edema (20%), altered ECG (39.2%) and Echo (28.9%). Despite antiparasitic treatment, cardiac alterations persisted after 1 and 4 years. A ten-year follow-up showed no chronic Chagasic cardiomyopathy, though risk markers and persistent T. cruzi-specific IgG were reported. Data reinforces gaps mainly in long-term clinical, serological and molecular follow-up. More integrated strategies are needed to enhance outbreak detection and management. Funding: Fiocruz, CNPq and Faperj (Brazil) and FOCEM/Mercosur. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human data was extracted from manuscripts published in PubMed, Web of Science, Embase, LILACS and Scielo databases. Grey literature sources were also searched to identify possible relevant data about outbreak descriptions not previously included in peer-reviewed scientific publications. These sources included PhD thesis, dissertation databases, conference abstracts, and online local newspaper reports. We also included reported cases of acute ChD from Colombian and Brazilian online government health surveillance databases. The cited references are available at Dataverse UNR (https://dataverse.unr.edu.ar/), in the following link: https://doi.org/10.57715/UNR/ZFRC4G I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data supporting the findings of this review are available at RDA-UNR: https://doi.org/10.57715/UNR/ZFRC4G
Background: In recent years, compounds known as Proteolysis Targeted Chimeras (PROTACs) have revitalized the field of bioactive molecule design. These compounds promote proteolysis of therapeutic targets by recruiting them to ubiquitin ligases. One of the most commonly used classes of compounds in the synthesis of PROTACs are immunomodulatory imides (IMiDs), such as thalidomide (TLD), which interact with the E3 ligase CRL4CRBN via the CULT domain of the cereblon protein (CRBN). This domain has been identified in proteins across various phylogenetic groups, including trypanosomatids, leading to the hypothesis that IMiD-derived PROTACs should be active in these organisms. Methods: The trypanocidal activity of the PROTAC dBET1 and its separated components (JQ1 and TLD) were assayed using a T. cruzi strain expressing β-glalactosidase. Potential CRL4-E3L complexes from humans and trypanosomatids were assembled in silico with MultimerMapper. The IMiD-binding site of HsCRBN and its trypanosomatid homologs were analyzed using molecular dynamics and docking simulations. Results: We demonstrate that the compound dBET1 does not function as a PROTAC in Trypanosoma cruzi. In silico structural analysis of CRL4-E3L complex orthologs revealed that the trypanosomal CULT-containing protein is not part of such a complex. Molecular dynamics simulations showed that the pocket of this CULT domain is smaller than that of mammalian CRBN and cannot accommodate IMiDs within. Conclusions: We underscore the importance of functional and structural validation in drug discovery, particularly when extrapolating mechanisms between evolutionarily distant species. While PROTACs hold promise in human therapeutics, our work advocates for re-evaluating the rationale behind thalidomide-based PROTACs in trypanosomatid research.
