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Jose P Lopez-Lopez,1,2,* Ana Maria Gonzalez,1,* Paola Lanza,1 Patricio Lopez-Jaramillo1 1MASIRA Research Institute, Universidad de Santander (UDES), Bucaramanga, Santander, Colombia; 2Department of Internal Medicine. Cardiology Unit, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia*These authors contributed equally to this workCorrespondence: Patricio Lopez-Jaramillo, MASIRA Research Institute, Facultad de Ciencias de la Salud, Universidad de Santander (UDES), Bloque G, piso 6, Bucaramanga, Santander, Colombia, Tel +57 315 306 8939, Email jplopezj@gmail.comBackground: Higher medication adherence reduces the risk of new cardiovascular events. However, there are individual and health system barriers that lead to lower adherence. The polypill has demonstrated benefits in cardiovascular morbidity and mortality mainly driven by an increase in adherence. We aim to evaluate the impact of the polypill on adherence to cardiovascular medication, its efficacy and safety in cardiovascular disease (CVD) prevention.Methods: A systematic review following PRISMA guidelines was conducted. Databases were searched from January 2003 to December 2022. We included randomized, pragmatic, or real-world clinical trials and observational studies. The primary outcome was medication adherence, secondary outcomes were efficacy in cardiovascular disease in primary and secondary prevention and safety.Results: From the 490 publications screened, 13 met the inclusion criteria and were incorporated into a comparative table Of those included, 70% were randomized controlled trials (RCTs) and 53.8% focused on secondary prevention. Most of the studies received a high and moderate quality rating. Self-report, pill counting and, the Morisky scale were the most frequent methods to evaluate adherence (84.6%). Compared with standard medication, the polypill improved overall medication adherence by 13%, with percentages ranging from 7.6% to 34.9%.

The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in cytology and cell block samples is rarely performed, and its diagnostic value in cytology has not been well established. In this study, we sought to determine if VE1 is suitable for FNA and cell block method.

We read with interest the reply by Manley et al to our letter supporting telocytes (TCs) as possible precursors of gastrointestinal mesenchymal tumors [1], [2]. We would like to clarify that the tumors we think derive from TCs along with inflammatory fibroid polyps (IFPs) are actually PDGFRA-mutant gastrointestinal stromal tumors (GISTs), that is, “genuine” GISTs (concurring to form this tumor group together with the other GIST subtypes, distinguished by diverse pathogenetic mechanisms, which likewise feature distinctive morphology and clinical features). Therefore, in this regard, the definition “PDGFRA-mutant polyps arising sporadically and syndromically within the stomach and diagnosed as GISTs,” ascribed to us by Manley and colleagues, is inaccurate. Actually, PDGFRA-mutant GISTs are in most cases not polypoid, rather constituting intramural masses, with clear-cut histologic and immunophenotypical features [3]. We have recently produced morphogenetic evidence of the origin of these tumors, along with typical IFPs, from TCs, exploiting the opportunity offered by the concurrent presence of a prominent TC hyperplasia [4]. In the same article, we proposed to define IFP as “telocytoma” because this term conveys both the neoplastic and histotypic natures of these tumors. Conversely, tumors typical of PDGFRA-mutant syndrome whose nosology is less straightforward are the fibrous tumors defined as GISTs by De Raedt and colleagues [5] and described also by Carney and Stratakis [6] and by ourselves [7]. These tumors not only do not exhibit morphologic features typical of GISTs but also do not express CD117 and DOG1; in addition, they have been found mostly in the small intestine, unlike PDGFRA-mutant GISTs, which show a strong predilection for the stomach. We have previously discussed in depth this issue, supporting these “fibrous tumors” as a possible variant of IFP [7]. In conclusion, in our opinion, PDGFRA mutations can determine 3 types of lesions in the gastrointestin

PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT-mutant settings but not in PDGFRA-mutant ones, challenging the precursor role of ICC for PDGFRA-driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall “fibrosis” has been reported in germline PDGFRA-mutants. Taking the opportunity offered by its presence in a germline PDGFRA-mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA-mutant counterpart of germline KIT mutation-associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA-mutant GISTs. We propose the term “telocytoma” for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic (“telocytary”) essence of this tumour, unlike IFP, which rather evokes an inflammatory-hyperplastic lesion.

Based on the morphologic/immunophenotypic evidence produced so far, a precursor role of TCs not only for IFPs, but also for PDGFRA-driven GISTs appears more than a pure hypothesis. However, further studies (especially ultrastructural) are warranted to definitively settle this issue.

BACKGROUND/AIM: In genetically engineered murine models of pancreatic ductal adenocarcinomas (PDAC), high levels of Runx3 increase the metastatic potential of cancer cells. In this study we evaluated the role of Runx3 in human pancreatic cancer. MATERIALS AND METHODS: Runx3 was retrospectively assessed by immunohistochemistry in seventy-eight tumor samples of patients who underwent surgical resection for PDCA and were followed at least for 24 months. RESULTS: Thirty-two cases resulted completely negative for Runx3; forty-six showed highly variable expression. We established an optimal cut-off value of Runx3 in predicting distant metastasis equal to 0.04. The odds ratio (ORs) for development of distant metastases at multivariate analysis for patients having Runx3 ≥0.04 was 4.26 (p=0.043) and 4.68 (p=0.032) after adjusting for residual tumor and treatment, respectively; OR for development of metastases in multiple sites was 4.28 (p=0.025) for Runx3 ≥0.04. CONCLUSION: Our results support the ability of Runx3 to contribute to the dissemination of human PDAC thus confirming the observations from murine models.

Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-ÎoB pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-ÎoB molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level.

It has been generally demonstrated that the valine-to-glutamic acid substitution at position 600 (V600E) in the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA-based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC.