Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge.

Diagnosing early-stage pancreatic cancer (PC) remains a clinical challenge. Hence, studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative. This article aims to underscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC, thereby improving its management and prognosis.

The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases.

In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE's role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands.

Improving the radiological diagnosis of hepatic artery thrombosis after liver transplantation: Current approaches and future challenges.

Hepatic artery thrombosis (HAT) is a devastating vascular complication following liver transplantation, requiring prompt diagnosis and rapid revascularization treatment to prevent graft loss. At present, imaging modalities such as ultrasound, computed tomography, and magnetic resonance play crucial roles in diagnosing HAT. Although imaging techniques have improved sensitivity and specificity for HAT diagnosis, they have limitations that hinder the timely diagnosis of this complication. In this sense, the emergence of artificial intelligence (AI) presents a transformative opportunity to address these diagnostic limitations. The develo pment of machine learning algorithms and deep neural networks has demon strated the potential to enhance the precision diagnosis of liver transplant com plications, enabling quicker and more accurate detection of HAT. This article examines the current landscape of imaging diagnostic techniques for HAT and explores the emerging role of AI in addressing future challenges in the diagnosis of HAT after liver transplant.

Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage T2DM is widely documented. These dietary compounds exert their beneficial effects through several actions, including the protection of pancreatic islet ß-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorate diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer.

Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products (RAGE) axis activation in the development of neoplasms, including gastric cancer (GC). This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu, not only by supporting phenotypic changes favoring growth and dissemination of tumor cells, but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection. In the present review, we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis. Finally, the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.

THERAPEUTIC APPROACH OF COMPLICATED HYDATID DISEASE: ROLE OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN CHOLANGIOHYDATIDOSIS.

BACKGROUND: Hydatid disease, a parasitic infestation caused by Echinococcus granulosus larvae, is an infectious disease endemic in different areas, such as India, Australia, and South America. The liver is well known as the organ most commonly affected by hydatid disease and may present a wide variety of complications such as hepatothoracic hydatid transit, cyst superinfection, intra-abdominal dissemination, and communication of the biliary cyst with extravasation of parasitic material into the bile duct, also called cholangiohydatidosis. Humans are considered an intermediate host, exposed to these larvae by hand-to-mouth contamination of the feces of infected dogs. AIM: This study aimed to highlight the role of endoscopic retrograde cholangiopancreatography in patients with acute cholangitis secondary to cholangiohydatidosis. METHODS: Considering the imaging findings in a 36-year-old female patient with computed tomography and magnetic resonance imaging showing a complex cystic lesion in liver segment VI, with multiple internal vesicles and a wall defect cyst that communicates with the intrahepatic biliary tree, endoscopic biliary drainage was performed by endoscopic retrograde cholangiopancreatography with papillotomy, leading to the discharge of multiple obstructive cysts and hydatid sand from the main bile duct. RESULTS: Clinical and laboratory findings improved after drainage, with hospital discharge under oral antiparasitic treatment before complete surgical resection of the hepatic hydatid cyst. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography is a safe and useful method for the treatment of biliary complications of hepatic hydatid disease and should be considered the first-line procedure for biliary drainage in cases of cholangiohydatid disease involving secondary acute cholangitis.

Association between diabetes and cancer. Current mechanistic insights into the association and future challenges.

Compelling pieces of epidemiological, clinical, and experimental research have demonstrated that Diabetes mellitus (DM) is a major risk factor associated with increased cancer incidence and mortality in many human neoplasms. In the pathophysiology context of DM, many of the main classical actors are relevant elements that can fuel the different steps of the carcinogenesis process. Hyperglycemia, hyperinsulinemia, metabolic inflammation, and dyslipidemia are among the classic contributors to this association. Furthermore, new emerging actors have received particular attention in the last few years, and compelling data support that the microbiome, the epigenetic changes, the reticulum endoplasmic stress, and the increased glycolytic influx also play important roles in promoting the development of many cancer types. The arsenal of glucose-lowering therapeutic agents used for treating diabetes is wide and diverse, and a growing body of data raised during the last two decades has tried to clarify the contribution of therapeutic agents to this association. However, this research area remains controversial, because some anti-diabetic drugs are now considered as either promotors or protecting elements. In the present review, we intend to highlight the compelling epidemiological shreds of evidence that support this association, as well as the mechanistic contributions of many of these potential pathological mechanisms, some controversial points as well as future challenges.

Receptor of advanced glycation end-products axis and gallbladder cancer: A forgotten connection that we should reconsider.

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms, including gallbladder cancer. In this regard, data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products (RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu, thus supporting tumor growth and development. AGEs are formed in biological systems or foods, and food-derived AGEs, also known as dietary AGEs are known to contribute to the systemic pool of AGEs. Once they bind to RAGE, the activation of multiple and crucial signaling pathways are triggered, thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration. In the present review, we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer, and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

The RAGE/multiligand axis: a new actor in tumor biology.

The receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein which actively participates in several chronic inflammation-related diseases. RAGE, in addition to AGEs, has a wide repertoire of ligands, including several damage-associated molecular pattern molecules or alarmins such as HMGB1 and members of the S100 family proteins. Over the last years, a large and compelling body of evidence has revealed the active participation of the RAGE axis in tumor biology based on its active involvement in several crucial mechanisms involved in tumor growth, immune evasion, dissemination, as well as by sculpturing of the tumor microenvironment as a tumor-supportive niche. In the present review, we will detail the consequences of the RAGE axis activation to fuel essential mechanisms to guarantee tumor growth and spreading.

Therapeutic approach of complicated hydatid disease: role of endoscopic retrograde cholangiopancreatography in cholangiohydatidosis / Abordagem terapêutica da doença hidática complicada: papel da colangiopancreatografia retrógrada endoscópica na colangiohidatidose

ABSTRACT BACKGROUND: Hydatid disease, a parasitic infestation caused by Echinococcus granulosus larvae, is an infectious disease endemic in different areas, such as India, Australia, and South America. The liver is well known as the organ most commonly affected by hydatid disease and may present a wide variety of complications such as hepatothoracic hydatid transit, cyst superinfection, intra-abdominal dissemination, and communication of the biliary cyst with extravasation of parasitic material into the bile duct, also called cholangiohydatidosis. Humans are considered an intermediate host, exposed to these larvae by hand-to-mouth contamination of the feces of infected dogs. AIM: This study aimed to highlight the role of endoscopic retrograde cholangiopancreatography in patients with acute cholangitis secondary to cholangiohydatidosis. METHODS: Considering the imaging findings in a 36-year-old female patient with computed tomography and magnetic resonance imaging showing a complex cystic lesion in liver segment VI, with multiple internal vesicles and a wall defect cyst that communicates with the intrahepatic biliary tree, endoscopic biliary drainage was performed by endoscopic retrograde cholangiopancreatography with papillotomy, leading to the discharge of multiple obstructive cysts and hydatid sand from the main bile duct. RESULTS: Clinical and laboratory findings improved after drainage, with hospital discharge under oral antiparasitic treatment before complete surgical resection of the hepatic hydatid cyst. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography is a safe and useful method for the treatment of biliary complications of hepatic hydatid disease and should be considered the first-line procedure for biliary drainage in cases of cholangiohydatid disease involving secondary acute cholangitis.

RESUMO RACIONAL: A doença hidática, uma infestação parasitária causada pelas larvas de Echinococcus granulosus, é uma doença infecciosa endêmica em diferentes áreas como Índia, Austrália e América do Sul. O fígado é conhecido como o órgão mais comumente afetado pela hidatidose, podendo apresentar uma grande variedade de complicações como trânsito hidático hepato-torácico, superinfecção do cisto, disseminação intra-abdominal e comunicação do cisto biliar com extravasamento de material parasitário para o ducto biliar ou também chamada de colangio-hidatidose O ser humano é considerado um hospedeiro intermediário, exposto a essas larvas pela contaminação mão-boca das fezes de cães infectados. OBJETIVO: Destacar o papel da endoscópica por colangiopancreatografia retrógrada em pacientes com colangite aguda secundária à colangio-hidatidose. MÉTODOS: Considerando os achados de imagem, em paciente feminina de 36 anos de idade, com imagens de tomografia computadorizada e ressonância magnética mostrando uma lesão cística complexa no segmento hepático VI, com múltiplas vesículas internas e um defeito de parede cística que se comunica com a árvore biliar intra-hepática foi realizada drenagem biliar endoscópica por colangiopancreatografia retrógrada com papilotomia, levando à descarga de múltiplos cistos obstrutivos e areia hidática da via biliar principal. RESULTADOS: Os achados clínicos e laboratoriais melhoraram após a drenagem, com alta hospitalar sob tratamento antiparasitário oral antes da ressecção cirúrgica completa do cisto hidático hepático. CONCLUSÕES: A endoscópica por colangiopancreatografia retrógrada é um método seguro e útil para o tratamento das complicações biliares da hidatidose hepática, devendo ser considerado o procedimento de primeira linha para drenagem biliar nos casos de colangio-hidatidose que envolve colangite aguda secundária.

Pattern recognition receptors and their roles in the host response to Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is highly prevalent, affecting 4.4 billion people globally. This pathogen is a risk factor in the pathogenesis of more than 75% of worldwide cases of gastric cancer. Pattern recognition receptors are essential in the innate immune response to H. pylori infection. They recognize conserved pathogen structures and myriad alarmins released by host cells in response to microbial components, cytokines or cellular stress, thus triggering a robust proinflammatory response, which is crucial in H. pylori-induced gastric carcinogenesis. In this review, we intend to highlight the main pattern recognition receptors involved in the recognition and host response to H. pylori, as well as the main structures recognized and the subsequent inflammatory response.

Estudio anatómico de la hiperostosis porótica en órbitas oculares: cribra orbitalia en la población arqueológica de Tutuquén, región del Maule, Chile / Anatomical study of porotic hyperostosis in the eye orbits: cribra orbitalia in the archaeological population of Tutuquén, Maule region, Chile

RESUMEN: La cribra orbitalia o hiperostosis porótica del techo orbitario es considerada una manifestación ósea microperforativa de condiciones patológicas hematológicas, especialmente la anemia ferropénica. Este hallazgo, se enmarca de manera casi exclusiva a estudios en poblaciones arqueológicas. El propósito de este estudio fue describir la expresión de cribra orbitalia en una población arqueológica de Chile central. Restos óseos de 32 individuos fueron analizados, los cuales fueron obtenidos de la población del Monumento Arqueológico Cementerio Tutuquén, los que están depositados en el Museo Regional de Rancagua. En cada una de la muestras incluidas, se evaluaron períodos de datación, sexo, rango etáreo, presencia v/s ausencia de cribra orbitalia y en los casos en que ésta estuvo presente, se determinó su intensidad mediante visión directa con lente de aumento. Un 59,38 % de los individuos presentó cribra orbitalia. De éstos, 26,32 % fueron de sexo femenino, 31,58 % de sexo masculino y 42,10 % indeterminado. De los individuos del período 10.000 AP, 33,33 % presentó cribra orbitalia; de los individuos del período 7.000 AP un 50 % y de los individuos pertenecientes al período 1.000 AP, un 68,4 %. Al clasificar la severidad de la cribra orbitalia se observó que 31,57 % de los individuos presentaron Cribra orbitalia tipo I; 36,84 % tipo II; 10,52 % tipo III; 10,52 % tipo IV y 10,52 % tipo V. Los datos aportados complementarán el conocimiento morfopatológico de la órbita ocular humana desde el estudio de poblaciones arqueológicas.

SUMMARY: The cribra orbitalia or porotic hyperostosis of the orbital roof is considered a microperforative bone manifestation of hematological pathological conditions, especially iron deficiency anemia. This finding is almost exclusively part of studies in archaeological populations. The purpose of this study was to describe the expression of cribra orbitalia in an archaeological population of central Chile. Bone remains of 32 individuals were analyzed, which were obtained from the population of the Tutuquén Cemetery Archaeological Monument, which are deposited in the Regional Museum of Rancagua. In each of the included samples, dating periods, sex, age range, presence v / s absence of cribra orbitalia were evaluated and in the cases in which it was present, its intensity was determined by direct vision with a magnifying lens. The 59.38 % of the individuals presented cribra orbitalia. Of these, 26.32 % were female, 31.58 % male, and 42.10 % undetermined. Of the individuals in the period 10,000 BP, 33.33 % presented cribra orbitalia; of the individuals of the period 7,000 AP, 50% and of the individuals belonging to the period 1,000 AP, 68.4 %. When classifying the severity of the cribra orbitalia, it was observed that 31.57 % of the individuals had type I; 36.84 % type II; 10.52 % type III; 10.52 % type IV and 10.52 % type V. The data provided will complement the morpho-pathological knowledge of the human eye orbit from the study of archaeological populations.

Advanced-glycation end-products axis: A contributor to the risk of severe illness from COVID-19 in diabetes patients.

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products (RAGE) in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus (DM). During the coronavirus disease 2019 (COVID-19) pandemic, many clinical reports have pointed out that DM increases the risk of COVID-19 complications, hospitalization requirements, as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate. In the present review, we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype, as well as the contribution of RAGE signaling in lung inflammation, may then lead to the increased mortality risk of COVID-19 in these patients. Additionally, the cross-talk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection, as well as the role of this multi-ligand receptor on the obesity-associated low-grade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19, are also discussed.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases: A dangerous liaison?

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products (RAGE) axis activation in many clinical entities. Since the beginning of the coronavirus disease 2019 pandemic, there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in inflammatory gastrointestinal disorders, such as inflammatory bowel diseases (IBD). However, clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection. In the present review, we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients, the RAGE axis activation as well as the cross-talk with the renin-angiotensin system, are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme (ACE) 2. The soluble form of RAGE functions as a decoy for its ligands, and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation, particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

Dehiscencia timpánica (foramen de Huschke): a más de 300 años de su primera descripción / Tympanic dehiscence (Huschke's foramen): more than 300 years after its first description

RESUMEN: La dehiscencia timpánica o Foramen de Huschke se considera un rasgo craneal morfológico menor, hipostósico, no estocástico, transitorio, ubicado en la placa timpánica del hueso temporal, cuya expresión se considera fisiológica hasta los 5 años de edad. La mención de este rasgo en la literatura es escasa, generando controversias entre de los anatomistas que la han descrito. El epónimo Huschke, anatomista alemán, quien ha sido mencionado como el primero en observarla en 1844. Sin embargo, existen antecedentes de que dicha característica ósea fue previamente descrita por otros autores casi 200 años antes. La actual denominación, dehiscencia timpánica, fue dada en 1878 por Bürkner, siendo aceptada hasta el día de hoy. El objetivo de este artículo es realizar un análisis histórico de la descripción morfológica de la dehiscencia timpánica en la literatura anatómica especializada.

SUMMARY: Tympanic dehiscence or Huschke's Foramen is considered a minor, hypostosic, non-stochastic, transitory morphological cranial feature, located in the tympanic plate of the temporal bone, whose expression is considered physiological up to 5 years of age. The mention of this feature in the literature is scarce, generating controversy among the anatomists who have described it. The eponymous Huschke, a German anatomist, who has been mentioned as the first to observe it in 1844. However, there is a history that this bone characteristic was previously described by other authors almost 200 years earlier. The current name, tympanic dehiscence, was given in 1878 by Bürkner, being accepted until today. The objective of this article is to carry out a historical analysis of the morphological description of tympanic dehiscence in specialized anatomical literature.

Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer.

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.