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Journal of Veterinary Diagnostic... Jul 2024Liver lobe torsion has been reported in many species, with frequent reports in rabbits. Here we describe caudate liver lobe torsion and concurrent necrohemorrhagic...
Liver lobe torsion has been reported in many species, with frequent reports in rabbits. Here we describe caudate liver lobe torsion and concurrent necrohemorrhagic typhlocolitis in a Patagonian mara (syn: Patagonian cavy, Patagonian hare, ). Following acute death, postmortem examination findings included torsion of the hepatic caudate process, which had fibrous adhesions to the pancreas indicating chronicity. The cecal apex and proximal 30 cm of colon had regionally reddened serosa and diffusely roughened and reddened mucosa with brown-red and granular luminal contents. Key histologic findings included massive necrosis of the torsed hepatic caudate lobe, consistent with infarction, necrotizing hepatitis in remaining areas of liver, necrohemorrhagic typhlocolitis, adrenocortical necrosis and hemorrhage, and renal tubular degeneration and necrosis with tubular casts. Bacterial culture of cecal contents yielded pure growth of spp. Death was attributed to toxemia or bacteremia resulting from spp. infection, as the hepatic lobe torsion appeared chronic. It was undetermined if the liver lobe torsion predisposed to gastrointestinal compromise and infection. Patagonian maras have some anatomical similarities to rabbits and are highly cursorial, not dissimilar to hares, spp. We speculate that these characteristics may increase the likelihood of hepatic caudate lobe torsion in this species.
Topics: Animals; Animals, Zoo; Torsion Abnormality; Liver Diseases; Liver; Salmonella Infections, Animal; Typhlitis; Female; Fatal Outcome
PubMed: 38702955
DOI: 10.1177/10406387241248594 -
Cureus Apr 2024Cancer (including pancreatic cancer) can develop following a infection within one year of tuberculosis infection. However, it is unclear whether tuberculosis infection...
Cancer (including pancreatic cancer) can develop following a infection within one year of tuberculosis infection. However, it is unclear whether tuberculosis infection increases the risk of developing adenosquamous carcinoma of the pancreas (ASCP), an extremely rare cancer with a poorer prognosis than pancreatic ductal adenocarcinoma (PDAC). Herein, we report a case of rapid growing ASCP discovered upon a resection for neck tuberculous lymphadenitis. The patient was a 57-year-old woman. An excisional biopsy of the swollen right neck lymph nodes revealed tuberculous lymphadenitis. One month after the biopsy, an abdominal computed tomography scan showed a 2.0 cm (diameter) ischemic tumor in the pancreatic tail. The tissue obtained using endoscopic ultrasonography-guided fine-needle aspiration led to the pathological diagnosis of ASCP. Two months after the biopsy, the tumor had grown to 3.5 cm (diameter), and invasion of the stomach and colon was suspected. Distal pancreatectomy, splenectomy, partial gastrectomy, and transverse colectomy were performed. The final diagnosis was ASCP (4.7 cm, pT3, pN0, cM0, and pStage IIA). Postoperative adjuvant combination chemotherapy combined with antituberculosis drugs was administered orally. We report the first case of rapidly growing adenosquamous carcinoma resected from the pancreas in association with tuberculous lymphadenitis. Additional evidence is needed to confirm that tuberculosis infection increases the risk of developing pancreatic adenosquamous cell carcinoma because its potential role in promoting squamous metaplasia is unclear.
PubMed: 38694677
DOI: 10.7759/cureus.57382 -
Cancer Science Apr 2024Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival of less than 10%. More knowledge of the immune response developed in patients with...
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival of less than 10%. More knowledge of the immune response developed in patients with PDAC is pivotal to develop better combination immune therapies to improve clinical outcome. In this study, we used mass cytometry time-of-flight to undertake an in-depth characterization of PBMCs from patients with PDAC and examine the differences with healthy controls and patients with benign diseases of the biliary system or pancreas. Peripheral blood mononuclear cells from patients with PDAC or benign disease are characterized by the increase of pro-inflammatory cells, as CD86 classical monocytes and memory T cells expressing CCR6 and CXCR3, associated with T helper 1 (Th1) and Th17 immune responses, respectively. However, PBMCs from patients with PDAC present also an increase of CD39 regulatory T cells and CCR4CCR6CXCR3 memory T cells, suggesting Th2 and regulatory responses. Concluding, our results show PDAC develops a multifaceted immunity, where a proinflammatory component is accompanied by regulatory responses, which could inhibit potential antitumor mechanisms.
PubMed: 38686549
DOI: 10.1111/cas.16147 -
Biology Apr 2024Numerous studies have demonstrated that bacteriophages (phages) can effectively treat intestinal bacterial infections. However, research on the impact of phages on...
Numerous studies have demonstrated that bacteriophages (phages) can effectively treat intestinal bacterial infections. However, research on the impact of phages on overall body health once they enter the intestine is limited. This study utilized weaned piglets as subjects to evaluate the systemic effects of an orally administered phage cocktail on their health. Twelve 21-day-old weaned piglets were divided into control (CON) and phage gavage (Phages) groups. The phage cocktail consisted of five lytic phages, targeting serovar Choleraesuis (), Enteropathogenic (EPEC), and Shiga tox-in-producing (STEC). The phages group received 10 mL of phage cocktail orally for 20 consecutive days. The results show that the phage gavage did not affect the piglets' growth performance, serum biochemical indices, or most organ indices, except for the pancreas. However, the impact on the intestine was complex. Firstly, although the pancreatic index decreased, it did not affect the secretion of digestive enzymes in the intestine. Secondly, phages increased the pH of jejunum chyme and relative weight of the ileum, and enhanced intestinal barrier function without affecting the morphology of the intestine. Thirdly, phages did not proliferate in the intestine, but altered the intestinal microbiota structure and increased concentrations of microbial metabolites isobutyric acid and isovaleric acid in the colonic chyme. In addition, phages impacted the immune status, significantly increasing serum IgA, IgG, and IgM, as well as serum and intestinal mucosal IFN-γ, IL-1β, IL-17, and TGF-β, and decreasing IL-4 and IL-10. They also activated toll-like receptors TLR-4 and TLR-9. Apart from an increase in basophil numbers, the counts of other immune cells in the blood did not change. This study indicates that the impact of phages on body health is complex, especially regarding immune status, warranting further attention. Short-term phage gavage did not have significant negative effects on health but could enhance intestinal barrier function.
PubMed: 38666883
DOI: 10.3390/biology13040271 -
Endoscopy International Open Apr 2024External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic...
External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic necrosis and is associated with significant morbidity. The present study aimed to report the initial outcome of a novel technique of two-scope guided tractogastrostomy for management of this condition. The present study was a retrospective analysis of data from patients with external pancreatic fistula and disconnected pancreatic duct syndrome, who underwent two-scope-guided tractogastrostomy. All the patients had a 24F or larger drain placed in the left retroperitoneum. Transgastric echo endoscopy and sinus tract endoscopy were performed simultaneously to place a stent between the gastric lumen and the sinus tract. Technical success was defined as placement of the stent between the tract and the stomach. Clinical success was defined as successful removal of the percutaneous drain without the occurrence of pancreatic fluid collection, ascites, external fistula, or another intervention 12 weeks after the procedure. Three patients underwent two scope-guided tractogastrostomy. Technical and clinical success were achieved in all the patients. No procedure-related side effects or recurrence occurred in any of the patients. Two-scope-guided tractogastrostomy for treatment of external pancreatic fistula due to disconnected pancreatic duct syndrome is a feasible technique and can be further evaluated.
PubMed: 38654964
DOI: 10.1055/a-2290-0768 -
Signal Transduction and Targeted Therapy Apr 2024The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2...
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
Topics: Animals; Humans; Male; Mice; Angiotensin-Converting Enzyme 2; COVID-19; Fibroblast Growth Factor 7; Human Embryonic Stem Cells; Insulin Secretion; Islets of Langerhans; Organoids; SARS-CoV-2
PubMed: 38654010
DOI: 10.1038/s41392-024-01790-8 -
Frontiers in Immunology 2024Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness... (Review)
Review
Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption. Alternatively, porcine islets have been considered as another source of insulin-secreting cells for transplantation in T1D patients, though xeno-transplants raise concerns over the risk of endogenous retrovirus transmission and immunological incompatibility. As a result, technological advancements have been made to protect transplanted islets from immune rejection and inflammation, ideally in the absence of chronic immunosuppression, to improve the outcomes and accessibility of allogeneic islet cell replacement therapies. These include the use of microencapsulation or macroencapsulation devices designed to provide an immunoprotective environment using a cell-impermeable layer, preventing immune cell attack of the transplanted cells. Other up and coming advancements are based on the use of stem cells as the starting source material for generating islet cells 'on-demand'. These starting stem cell sources include human induced pluripotent stem cells (hiPSCs) that have been genetically engineered to avoid the host immune response, curated HLA-selected donor hiPSCs that can be matched with recipients within a given population, and multipotent stem cells with natural immune privilege properties. These strategies are developed to provide an immune-evasive cell resource for allogeneic cell therapy. This review will summarize the immunological challenges facing islet transplantation and highlight recent bio-engineering and cell-based approaches aimed at avoiding immune rejection, to improve the accessibility of islet cell therapy and enhance treatment outcomes. Better understanding of the different approaches and their limitations can guide future research endeavors towards developing more comprehensive and targeted strategies for creating a more tolerogenic microenvironment, and improve the effectiveness and sustainability of islet transplantation to benefit more patients.
Topics: Islets of Langerhans Transplantation; Humans; Animals; Diabetes Mellitus, Type 1; Graft Rejection; Biomedical Engineering; Islets of Langerhans
PubMed: 38650946
DOI: 10.3389/fimmu.2024.1375177 -
Infectious Diseases & Clinical... Sep 2023This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. (Review)
Review
OBJECTIVE
This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes.
MATERIALS AND METHODS
It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias.
RESULTS
Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%).
CONCLUSION
Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.
PubMed: 38633556
DOI: 10.36519/idcm.2023.239 -
Signal Transduction and Targeted Therapy Apr 2024
Topics: Humans; SARS-CoV-2; Pandemics; COVID-19; Pancreas
PubMed: 38627360
DOI: 10.1038/s41392-024-01807-2 -
Transplant International : Official... 2024A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the... (Clinical Trial)
Clinical Trial Observational Study
A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (β-cell Tx; = 51) to control T1D patients ( = 272). Fear of coronavirus infection was higher in those with β-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, < 0.001). A previous β-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with β-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), = 0.038). Fewer patients with β-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with β-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).
Topics: Female; Humans; Male; Anxiety; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Glycemic Control; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Pandemics; Public Health
PubMed: 38601276
DOI: 10.3389/ti.2024.12278