Hidden Threat: Incidental Finding of Pancreatic Body Solid Pseudopapillary Tumor During Bariatric Evaluation With an Open Central Pancreatectomy Resolution.

Incidentalomas, or tumors found incidentally, are very common. However, pancreatic tumors are usually not found as incidentalomas. To date, these tumors represent a diagnostic and therapeutic challenge, since the risks and benefits associated with surgeries that can be performed to remove these tumors must be evaluated due to perioperative complications. It is vitally important to always carry out a correct approach that includes a histopathological study to allow timely identification of tumors that require surgical management or other preoperative treatment, such as chemotherapy or radiotherapy. The majority of these tumors are benign cystic tumors; however, there are cases, like the one presented here, where the tumor turns out to be a solid pseudopapillary tumor (SPT) that requires a different diagnostic and surgical approach. Also, in this case, the importance of evaluating the patient's general health status is highlighted to determine whether or not the required surgery can be performed at that moment or if any prior intervention is required. This case report talks about a patient in whom an incidental pancreatic tumor was found and how its management was carried out from diagnosis to the postoperative period.

BILE DUCT INJURY REPAIR IN A PATIENT WITH SITUS INVERSUS TOTALIS.

BACKGROUND: Bile duct injury (BDI) causes significant sequelae for the patient in terms of morbidity, mortality, and long-term quality of life, and should be managed in centers with expertise. Anatomical variants may contribute to a higher risk of BDI during cholecystectomy. AIMS: To report a case of bile duct injury in a patient with situs inversus totalis. METHODS: A 42-year-old female patient with a previous history of situs inversus totalis and a BDI was initially operated on simultaneously to the lesion ten years ago by a non-specialized surgeon. She was referred to a specialized center due to recurrent episodes of cholangitis and a cholestatic laboratory pattern. Cholangioresonance revealed a severe anastomotic stricture. Due to her young age and recurrent cholangitis, she was submitted to a redo hepaticojejunostomy with the Hepp-Couinaud technique. To the best of our knowledge, this is the first report of BDI repair in a patient with situs inversus totalis. RESULTS: The previous hepaticojejunostomy was undone and remade with the Hepp-Couinaud technique high in the hilar plate with a wide opening in the hepatic confluence of the bile ducts towards the left hepatic duct. The previous Roux limb was maintained. Postoperative recovery was uneventful, the drain was removed on the seventh post-operative day, and the patient is now asymptomatic, with normal bilirubin and canalicular enzymes, and no further episodes of cholestasis or cholangitis. CONCLUSIONS: Anatomical variants may increase the difficulty of both cholecystectomy and BDI repair. BDI repair should be performed in a specialized center by formal hepato-pancreato-biliary surgeons to assure a safe perioperative management and a good long-term outcome.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations.

Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles-all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.

The Hepatokine RBP4 Links Metabolic Diseases to Articular Inflammation.

OBJECTIVES: This study investigates the role of retinol binding protein 4 (RBP4) in an articular context. RBP4, a vitamin A transporter, is linked to various metabolic diseases. METHODS: Synovial fluid RBP4 levels were assessed in crystalline arthritis (CA) patients using ELISA. RBP4's impact on articular cell types was analysed in vitro through RT-PCR and flow cytometry. Proteomic analysis was conducted on primary human osteoarthritis chondrocytes (hOACs). RESULTS: Synovial fluid RBP4 concentrations in CA patients correlated positively with glucose levels and negatively with synovial leukocyte count and were elevated in hypertensive patients. In vitro, these RBP4 concentrations activated neutrophils, induced the expression of inflammatory factors in hOACs as well as synoviocytes, and triggered proteomic changes consistent with inflammation. Moreover, they increased catabolism and decreased anabolism, mitochondrial dysfunction, and glycolysis promotion. Both in silico and in vitro experiments suggested that RBP4 acts through TLR4. CONCLUSIONS: This study identifies relevant RBP4 concentrations in CA patients' synovial fluids, linking them to hypertensive patients with a metabolic disruption. Evidence is provided that RBP4 acts as a DAMP at these concentrations, inducing robust inflammatory, catabolic, chemotactic, and metabolic responses in chondrocytes, synoviocytes, and neutrophils. These effects may explain RBP4-related metabolic diseases' contribution to joint destruction in various rheumatic conditions like CA.

Bile duct injury repair in a patient with situs inversus totalis / Tratamento de lesão de via biliar em paciente com situs inversus totalis

ABSTRACT BACKGROUND: Bile duct injury (BDI) causes significant sequelae for the patient in terms of morbidity, mortality, and long-term quality of life, and should be managed in centers with expertise. Anatomical variants may contribute to a higher risk of BDI during cholecystectomy. AIMS: To report a case of bile duct injury in a patient with situs inversus totalis. METHODS: A 42-year-old female patient with a previous history of situs inversus totalis and a BDI was initially operated on simultaneously to the lesion ten years ago by a non-specialized surgeon. She was referred to a specialized center due to recurrent episodes of cholangitis and a cholestatic laboratory pattern. Cholangioresonance revealed a severe anastomotic stricture. Due to her young age and recurrent cholangitis, she was submitted to a redo hepaticojejunostomy with the Hepp-Couinaud technique. To the best of our knowledge, this is the first report of BDI repair in a patient with situs inversus totalis. RESULTS: The previous hepaticojejunostomy was undone and remade with the Hepp-Couinaud technique high in the hilar plate with a wide opening in the hepatic confluence of the bile ducts towards the left hepatic duct. The previous Roux limb was maintained. Postoperative recovery was uneventful, the drain was removed on the seventh post-operative day, and the patient is now asymptomatic, with normal bilirubin and canalicular enzymes, and no further episodes of cholestasis or cholangitis. CONCLUSIONS: Anatomical variants may increase the difficulty of both cholecystectomy and BDI repair. BDI repair should be performed in a specialized center by formal hepato-pancreato-biliary surgeons to assure a safe perioperative management and a good long-term outcome.

RESUMO RACIONAL: As lesões de via biliar (LVB) impõem sequelas significativas ao paciente em termos de morbidade, mortalidade e qualidade de vida a longo prazo, devendo ser manejadas em centros especializados. Variantes anatômicas podem contribuir para um maior risco de LVB durante colecistectomia. OBJETIVOS: Relatar paciente com lesão de via biliar associado a situs inversus totalis. MÉTODOS: Paciente do sexo feminino, 42 anos, com histórico prévio de situs inversus totalis e LVB inicialmente reparada simultaneamente à lesão, há 10 anos, por um cirurgião não especializado. Ela foi encaminhada a um centro especializado devido a episódios recorrentes de colangite e um padrão laboratorial colestático. Colangiressonância revelou uma grave estenose anastomótica. Devido à sua idade jovem e colangites recorrentes, foi submetida a uma revisão cirúrgica da hepaticojejunostomia com técnica de Hepp-Couinaud. Até onde sabemos, este é o primeiro relato de reparo de LVB em um paciente com situs inversus totalis. RESULTADOS: A hepaticojejunostomia realizado prèviamente foi desfeita e refeita empregando a técnica de Hepp-Couinaud, alta na placa hilar, com uma ampla abertura na confluência dos ductos biliares em direção ao ducto hepático esquerdo. A alça de roux anterior foi mantida. A recuperação pós-operatória transcorreu sem intercorrências, o dreno foi removido no sétimo dia pós-operatório, e a paciente está agora assintomática, com bilirrubina e enzimas canalículares normais, e sem mais episódios de colestase ou colangite. CONCLUSÕES: Variantes anatômicas podem aumentar a dificuldade tanto da colecistectomia quanto do reparo de LVB, o qual deve ser realizado em um centro especializado por cirurgiões hepatobiliares para garantir um manejo perioperatório seguro e um bom resultado a longo prazo.

Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.