Search Results (9)

This review aims to summarize the role of endoscopic therapy in the management and outcomes of recurrent acute pancreatitis (RAP). RAP is a clinical entity characterized by repeated episodes of acute pancreatitis in the setting of a normal gland or chronic pancreatitis (CP). The aetiology of RAP can be identified in about 70% of cases; for the remaining cases, the term “idiopathic” (IRAP) is used. However, advanced diagnostic techniques may reduce the percentage of IRAP to 10%. Recognized causes of RAP are gallstone disease, including microlithiasis and biliary sludge, sphincter of Oddi dysfunction (SOD), pancreatic ductal abnormalities (either congenital or acquired) interfering with pancreatic juice or bile outflow, genetic mutations, and alcohol consumption. SOD, as a clinical entity, was recently revised in the Rome IV consensus, which only recognized type 1 dysfunction as a true pathological condition, while type 2 SOD was defined as a suspected functional biliary sphincter disorder requiring the documentation of elevated basal sphincter pressure to be considered a true clinical entity and type 3 was abandoned as a diagnosis and considered functional pain. Endoscopic therapy by retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) has been proven effective when a mechanical obstruction is found and can be removed. If an obstruction is not documented, few treatment options are available to prevent the recurrence of pancreatitis and progression toward chronic disease. In gallstone disease, endoscopic biliary sphincterotomy (EBS) is effective when a dilated common bile duct or biliary sludge/microlithiasis is documented. In type 1 SOD, biliary or dual sphincterotomy is generally successful, while in type 2 SOD, endotherapy should be reserved for patients with documented sphincter dysfunction. However, in recent years, doubts have been expressed about the real efficacy of sphincterotomy in this setting. When sphincter dysfunction is not confirmed, endotherapy should be discouraged. In pancreas divisum (PD), minor papilla sphincterotomy is effective when there is a dilated dorsal duct, and the success rate is the highest in RAP patients. In the presence of obstructive conditions of the main pancreatic duct, pancreatic endotherapy is generally successful if RAP depends on intraductal hypertension. However, despite the efficacy of endotherapy, progression toward CP has been shown in some of these patients, mainly in the presence of PD, very likely depending on underlying genetic mutations. In patients with IRAP, the real utility of endotherapy still remains unclear; this is because several unknown factors may play a role in the disease, and data on outcomes are few, frequently contradictory or uncontrolled, and, in general, limited to a short period of time. Full article

Background: Pancreas disease (PD) is a serious disease in European salmonid aquaculture caused by salmonid alphavirus (SAV), of which six genotypes (SAV1–6) have been described. The use of inactivated virus and DNA PD vaccines is common in marine salmonid aquaculture and has contributed to a reduction of the occurrence of disease; however, outbreaks are still frequent. Methods: In this study, we compared the long-term protection after immunization of Atlantic salmon (Salmo salar) with three different clones of attenuated infectious SAV3. The clones were made by site-directed mutagenesis targeting the glycoprotein E2 to disrupt the viral attachment and/or nuclear localization signal (NLS) of the capsid protein to disrupt the viral suppression of cellular nuclear-cytosol trafficking. The resulting clones (Clones 1–3) were evaluated after injection of Atlantic salmon for infection dynamics, genetic stability, transmission, and protection against a subsequent SAV3 challenge. Results: Attenuated clones demonstrated reduced virulence, as indicated by lower viral RNA loads, diminished transmission to cohabitant fish, and minimal clinical symptoms compared to the virulent wild-type virus. The clones mutated in both capsid and E2 exhibited the most attenuation, observed as rapid clearing of the infection and showing little transmission, while the clone with glycoprotein E2 mutations displayed greater residual virulence but provided stronger protection, seen as reduced viral loads upon subsequent challenge with SAV3. Despite their attenuation, all viral clones caused significant reductions in weight gain. Conclusions: Despite promising attenuation and protection, this study highlights the trade-offs between virulence and immunogenicity in live vaccine design. Concerns over environmental risks, such as the shedding of genetically modified virus, necessitate further evaluation. Future efforts should optimize vaccine candidates to balance attenuation, immunogenicity, and minimal side effects. Full article

Type 1 diabetes (T1D) is a complex disease driven by the immune system attacking the insulin-producing beta cells in the pancreas. Understanding the role of different T cell subpopulations in the development and progression of T1D is crucial. By employing flow cytometry to compare the characteristics of T cells, we can pinpoint potential indicators of treatment response or therapeutic inefficacy. Our study reveals elevated prolactin (PRL) levels in T1D patients, along with a decreased production of key cytokines. Additionally, PD1 appears to play a significant role in T1D. Notably, PRL levels correlate with an earlier disease onset and a specific T cell phenotype, hinting at the potential influence of PRL. These findings highlight the need for further research to identify promising cellular targets for more effective and tailored therapies. Full article

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope^®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that the pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in this study. In situ hybridization detected SAV3 in different tissues of Atlantic salmon during the acute phase of the infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus in different adipose tissues associated with the internal organs of the salmon suggests a specific affinity of SAV3 to adipocyte components. The inconsistent immune response to SAV3 in the pseudobranch after infection did not mitigate the infection in that tissue and is probably responsible for the persistent low infection at 4 weeks post-challenge. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental infection course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon. Full article

Viral disease poses a major barrier to sustainable aquaculture, with outbreaks causing large economic losses and growing concerns for fish welfare. Genomic epidemiology can support disease control by providing rapid inferences on viral evolution and disease transmission. In this study, genomic epidemiology was used to investigate salmonid alphavirus (SAV), the causative agent of pancreas disease (PD) in Atlantic salmon. Our aim was to reconstruct SAV subtype-2 (SAV2) diversity and transmission dynamics in recent Norwegian aquaculture, including the origin of SAV2 in regions where this subtype is not tolerated under current legislation. Using nanopore sequencing, we captured ~90% of the SAV2 genome for n = 68 field isolates from 10 aquaculture production regions sampled between 2018 and 2020. Using time-calibrated phylogenetics, we infer that, following its introduction to Norway around 2010, SAV2 split into two clades (SAV2a and 2b) around 2013. While co-present at the same sites near the boundary of Møre og Romsdal and Trøndelag, SAV2a and 2b were generally detected in non-overlapping locations at more Southern and Northern latitudes, respectively. We provide evidence for recent SAV2 transmission over large distances, revealing a strong connection between Møre og Romsdal and SAV2 detected in 2019/20 in Rogaland. We also demonstrate separate introductions of SAV2a and 2b outside the SAV2 zone in Sognefjorden (Vestland), connected to samples from Møre og Romsdal and Trøndelag, respectively, and a likely 100 km Northward transmission of SAV2b within Trøndelag. Finally, we recovered genomes of SAV2a and SAV3 co-infecting single fish in Rogaland, involving novel SAV3 lineages that diverged from previously characterized strains >25 years ago. Overall, this study demonstrates useful applications of genomic epidemiology for tracking viral disease spread in aquaculture. Full article

Pancreas disease (PD) and sleeping disease (SD), caused by an alphavirus, are endemic in European salmonid aquaculture, causing significant mortality, reduced growth and poor flesh quality. In 2010, a new variant of salmonid alphavirus emerged in Norway, marine salmonid alphavirus genotype 2 (SAV2). As this genotype is highly prevalent in Scotland, transmission through well boat traffic was hypothesized as one possible source of infection. In this study, we performed full-length genome sequencing of SAV2 sampled between 2006 and 2012 in Norway and Scotland, and present the first comprehensive full-length characterization of Norwegian marine SAV2 strains. We analyze their relationship with selected Scottish SAV2 strains and explore the genetic diversity of SAV. Our results show that all Norwegian marine SAV2 share a recent last common ancestor with marine SAV2 circulating in Scotland and a higher level of genomic diversity among the Scottish marine SAV2 strains compared to strains from Norway. These findings support the hypothesis of a single introduction of SAV2 to Norway sometime from 2006–2010, followed by horizontal spread along the coast. Full article

Marek’s disease (MD) is an infectious malignant T-cell lymphoma proliferative disease caused by Marek’s disease virus (MDV). In recent years, the emergence of very virulent (vv) and/or very virulent plus (vv +) strains of MDV in the field has been suggested as one of the causes of vaccination failure. The pathogenicity of the MDV strain GX18NNM4, isolated from a clinical outbreak in a broiler breeder flock that was vaccinated with CVI988/Rispens, was investigated. In the vaccination-challenge test, GX18NNM4 was able to break through the protections provided by the vaccines CVI988 and 814. It also significantly reduced body weight gain and caused marked gross lesions and a large area of infiltration of neoplastic lymphocyte cells in the heart, liver, pancreas, etc. of the infected birds. In addition, the expressions of programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), in the spleens and cecal tonsils (CTs) of the unvaccinated challenged birds were significantly increased compared to those in the vaccinated challenged birds, indicating that the PD-1/PD-L1 pathway is related to immune evasion mechanisms. The results showed that the GX18NNM4 strain could cause severe immunosuppression and significantly decrease the protections provided by the current commercial vaccines, thus showing GX18NNM4 to be a vv + MDV strain. Full article

(1) Aim: To evaluate clinicopathological features and postoperative outcomes including survival in patients who underwent pancreaticoduodenectomy (PD) for periampullary diseases. (2) Methods: We retrospectively reviewed 3078 cases of PD performed in our center for 25 years. Periampullary diseases were divided into benign and malignancy groups. All cases were also classified by location. The time of 25 years was divided to different periods (5 years per period) to compare outcomes. Overall survival was compared between subdivided periods. (3) Results: Hospitalization became significantly shorter from 28.0 days in the 1st period to 13.8 days in the 5th period. Overall complication rate was significantly increased since the 3rd period. The rate without postoperative pancreatic fistula (POPF) was high at 98.7% in the 1st period. This might be because drain amylase on the 3rd day after PD was not routinely checked in the past. Thus, POPF was not detected. In survival analysis of adenocarcinoma of pancreas, bile duct, and ampulla, overall survival was found to be improved significantly in recent years. (4) Conclusions: Our study revealed that outcomes were improved with increasing number of PDs performed. Although POPF and overall complications showed increases more recently, those were detected and managed, resulting in shorter hospitalization and improved outcomes. Full article

Exosomes are membrane vesicles which offer potential as blood derived biomarkers for malign tumors in clinical practice. Pancreatic cancer is counted among cancer diseases with the highest mortality. The present work seeks to assess whether pancreatic carcinomas release exosomes which express c-Met (proto-oncogene mesenchymal-epithelial transition factor) and PD-L1 (programmed cell death 1 ligand 1), and whether the detection of such expression in serum has diagnostic or prognostic meaning for the affected patients. Exosome isolation was performed on culture media of one benign pancreatic cell line and ten pancreatic carcinoma cell lines as well as on serum samples from 55 patients with pancreatic ductal adenocarcinoma (PDAC), 26 patients with chronic pancreatitis and 10 patients with benign serous cyst adenoma of the pancreas. Exosomes were bound to latex beads and stained with antibodies against c-Met or PD-L1. Analysis of fluorescence intensity was performed by flow cytometry. In terms of c-Met, the mean fluorescence intensity of PDAC-patients was significantly higher than the fluorescence intensity of the comparative patients with benign disease (p < 0.001). A diagnostic test based on c-Met resulted in a sensitivity of 70%, a specificity of 85% and a diagnostic odds ratio of 13:2. The specificity of the test can be further improved by combining it with the established tumor marker carbohydrate antigen 19-9 (CA 19-9). In addition, c-Met-positive patients showed a significantly shorter postoperative survival time (9.5 vs. 21.7 months, p < 0.001). In terms of PD-L1, no significant difference between fluorescence intensity of PDAC-patients and comparative patients was detectable. However, PD-L1-positive PDAC-patients also showed a significantly shorter postoperative survival time (7.8 vs. 17.2 months, p = 0.043). Thus, both markers can be considered as negative prognostic factors. Full article