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Frontiers in Immunology 2023Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that... (Review)
Review
Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that a complex and multifactorial interplay between genetic and environmental factors, such as viruses, play a crucial role in the development of the disease. Research over the past few decades has shown that there is not one single viral culprit, nor one single genetic pathway, causing the disease. Rather, viral infections, most notably enteroviruses (EV), appear to accelerate the autoimmune process leading to T1D and are often seen as a precipitator of clinical diagnosis. In support of this hypothesis, the use of anti-viral drugs has recently shown efficacy in preserving beta cell function after onset of diabetes. In this review, we will discuss the various pathways that viral infections utilize to accelerate the development of T1D. There are three key mechanisms linking viral infections to beta-cell death: One is modulated by the direct infection of islets by viruses, resulting in their impaired function, another occurs in a more indirect fashion, by modulating the immune system, and the third is caused by heightened stress on the beta-cell by interferon-mediated increase of insulin resistance. The first two aspects are surprisingly difficult to study, in the case of the former, because there are still many questions about how viruses might persist for longer time periods. In the latter, indirect/immune case, viruses might impact immunity as a hit-and-run scenario, meaning that many or all direct viral footprints quickly vanish, while changes imprinted upon the immune system and the anti-islet autoimmune response persist. Given the fact that viruses are often associated with the precipitation of clinical autoimmunity, there are concerns regarding the impact of the recent global coronavirus-2019 (COVID-19) pandemic on the development of autoimmune disease. The long-term effects of COVID-19 infection on T1D will therefore be discussed, including the increased development of new cases of T1D. Understanding the interplay between viral infections and autoimmunity is crucial for advancing our knowledge in this field and developing targeted therapeutic interventions. In this review we will examine the intricate relationship between viral infections and autoimmunity and discuss potential considerations for prevention and treatment strategies.
Topics: Humans; Diabetes Mellitus, Type 1; Pancreas; Enterovirus Infections; Virus Diseases; Coronavirus Infections; COVID-19
PubMed: 38239343
DOI: 10.3389/fimmu.2023.1326711 -
Preventive Veterinary Medicine Mar 2024Pancreas Disease (PD) is a viral disease that affects Atlantic salmon (Salmo salar) in Norwegian, Scottish and Irish aquaculture. It is caused by salmonid alphavirus...
Pancreas Disease (PD) is a viral disease that affects Atlantic salmon (Salmo salar) in Norwegian, Scottish and Irish aquaculture. It is caused by salmonid alphavirus (SAV) and represents a significant problem in salmonid farming. Infection with SAV leads to reduced growth, mortality, product downgrading, and has a significant financial impact for the farms. The overall aim of this study is to evaluate the effect of various factors on the transmission of SAV and to create a predictive model capable of providing an early warning system for salmon farms within the Norwegian waters. Using a combination of publicly available databases, specifically BarentsWatch, and privately held PCR analyses a feature set consisting of 11 unique features was created based on the input parameters of the databases. An ensemble model was developed based on this feature set using XG-Boost, Ada-Boost, Random Forest and a Multilayer Perceptron. It was possible to successfully predict SAV transmission with 94.4% accuracy. Moreover, it was possible to predict SAV transmission 8 weeks in advance of a 'PD registration' at individual aquaculture salmon farming sites. Important predictors included well boat movement, environmental factors, proximity to sites with a 'PD registration' and seasonality.
Topics: Animals; Alphavirus; Alphavirus Infections; Salmonidae; Aquaculture; Pancreatic Diseases; Fish Diseases; Salmo salar
PubMed: 38232517
DOI: 10.1016/j.prevetmed.2023.106095 -
Diabetologia Apr 2024The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with...
Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes.
AIMS/HYPOTHESIS
The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity.
METHODS
Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk.
RESULTS
The COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively).
CONCLUSIONS/INTERPRETATION
Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.
Topics: Humans; Child, Preschool; Diabetes Mellitus, Type 1; Autoimmunity; Body Mass Index; Pandemics; Islets of Langerhans; Overweight; COVID-19; Autoantibodies
PubMed: 38214711
DOI: 10.1007/s00125-023-06079-z -
IScience Jan 2024An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously...
An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously demonstrated that enhancing serum acetate and butyrate using a dietary supplement (HAMSAB) improved glycemia in non-obese diabetic (NOD) mice and patients with established T1D. The effects of SCFA on immune-infiltrated islet cells remain to be clarified. Here, we performed single-cell RNA sequencing on islet cells from NOD mice fed an HAMSAB or control diet. HAMSAB induced a regulatory gene expression profile in pancreas-infiltrated immune cells. Moreover, HAMSAB maintained the expression of β-cell functional genes and decreased cellular stress. HAMSAB-fed mice showed preserved pancreatic endocrine cell identity, evaluated by decreased numbers of poly-hormonal cells. Finally, SCFA increased insulin levels in human β-like cells and improved transplantation outcome in NOD/SCID mice. Our findings support the use of metabolite-based diet as attractive approach to improve glucose control in T1D.
PubMed: 38213620
DOI: 10.1016/j.isci.2023.108694 -
Trials Jan 2024The spleen plays a significant role in the clearance of circulating microorganisms. Sequelae of splenectomy, especially immunodeficiency, can have a deleterious effect...
Autogenic splenic implantation versus splenectomy in patients undergoing distal pancreatectomy for benign or low-grade malignant lesions of the distal pancreas: study protocol for a multicentre, open-label, randomized controlled trial (RESTORE).
BACKGROUND
The spleen plays a significant role in the clearance of circulating microorganisms. Sequelae of splenectomy, especially immunodeficiency, can have a deleterious effect on a patient's health and even lead to death. Hence, splenectomy should be avoided and spleen preservation during elective surgery has become a treatment goal. However, this cannot be achieved in every patient due to intraoperative technical difficulties or oncological reasons. Autogenic splenic implantation (ASI) is currently the only possible way to preserve splenic function when a splenectomy is necessary. Experience largely stems from trauma patients with a splenic rupture. Splenic immune function can be measured by the body's clearing capacity of encapsulated bacteria. The aim of this study is to assess the splenic immune function after ASI was performed during minimally invasive (laparoscopic or robotic) distal pancreatectomy with splenectomy.
METHODS
This is the protocol for a multicentre, randomized, open-labelled trial. Thirty participants with benign or low-grade malignant lesions of the distal pancreas requiring minimally invasive distal pancreatectomy and splenectomy will be allocated to either additional intraoperative ASI (intervention) or no further intervention (control). An additional 15 patients who will undergo spleen-preserving distal pancreatectomy serve as the control group with normal splenic function. Six months postoperatively, after assumed restoration of splenic function, patients will be given a Salmonella typhi (Typhim Vi™) vaccine. The Salmonella typhi vaccine is a polysaccharide vaccine. The specific antibody titres immediately before and 4 to 6 weeks after vaccination will be measured. The ratio between pre- and post-vaccination antibody count is the primary outcome measure and secondary outcome measures include intraoperative details, length of hospital stay, 30-day mortality and morbidity.
DISCUSSION
This study will investigate the splenic immune function of patients who undergo ASI during minimally invasive distal pancreatectomy with splenectomy. The splenic immune function will be measured using the surrogate outcome of specific antibody titre after vaccination with a Salmonella typhi vaccine. The results will reveal details about splenic function after ASI and guide further treatment options for patients when a splenectomy cannot be avoided. It might eventually lead to a new standard of care making sometimes more demanding and time-consuming spleen-preserving procedures redundant.
TRIAL REGISTRATION
International Standard Randomized Controlled Trials Number (ISRCTN) ISRCTN10171587. Prospectively registered on 18 February 2019.
Topics: Humans; Multicenter Studies as Topic; Pancreas; Pancreatectomy; Randomized Controlled Trials as Topic; Spleen; Splenectomy; Vaccines
PubMed: 38195501
DOI: 10.1186/s13063-023-07714-1 -
Cureus Dec 2023Positron emission tomography (PET) is an integral part of the imaging of solid tumors in today's oncology practice. The most commonly used PET radiotracer is...
Gallium68-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET/CT as an Alternative to Fluoro18-Fluorodeoxyglucose (18F-FDG) PET/CT: Discussion in a Case of Metastatic Adenocarcinoma of Pancreas.
Positron emission tomography (PET) is an integral part of the imaging of solid tumors in today's oncology practice. The most commonly used PET radiotracer is 18F-Fluorodeoxyglucose (18F-FDG). FDG PET has imaging characteristics of a high tumor-to-background uptake ratio and is used in the detection of primary as well as metastatic sites. However, a significant pitfall is its inability to differentiate between neoplastic and infective lesions. To address this concern, many PET radiotracers have been developed and tried over time, a promising one being radiolabelled fibroblast activation protein inhibitor (FAPI). Fibroblast-activated protein (FAP) is a type II transmembrane glycoprotein expressed by cancer-associated fibroblasts (CAFs); it forms a significant component of the tumor stroma. Since there is over-expression of CAF in the majority of malignancies, it is a potential target for molecular imaging using PET. Several radiolabeled FAP inhibitors have been developed for PET imaging of malignancies and have also been used in theranostic applications.
PubMed: 38186547
DOI: 10.7759/cureus.50183 -
Clinical Gastroenterology and... May 2024Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in...
BACKGROUND & AIMS
Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens.
METHODS
We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP.
RESULTS
We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose.
CONCLUSIONS
Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
Topics: Humans; Male; Middle Aged; Female; Retrospective Studies; Autoimmune Pancreatitis; Europe; Aged; Treatment Outcome; Adult; Steroids; Aged, 80 and over
PubMed: 38184096
DOI: 10.1016/j.cgh.2023.12.010 -
Japanese Journal of Infectious Diseases May 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. Previous studies have primarily focused on the epidemiological and clinical...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. Previous studies have primarily focused on the epidemiological and clinical characteristics of patients with SFTS, whereas pancreatic injury has received little attention. This study investigated the effects of pancreatic injury on the prognosis of patients with SFTS. A total of 156 patients diagnosed with SFTS between April 2016 and April 2022 were included in the analysis. Multivariate logistic regression analysis showed that pancreatic injury (odds ratio [OR] = 3.754, 95% confidence interval [CI]: 1.361-79.036, P = 0.024) and neurological symptoms (OR = 18.648, 95% CI: 4.921-70.668, P < 0.001) were independent risk factors for mortality. The receiver operating characteristic curve indicated that serum pancreatic enzymes were predictive of progression to death in patients with SFTS. The area under the curve (AUC) for amylase was 0.711, with an optimal cutoff value of 95.5 U/L, sensitivity of 96.4%, and specificity of 35.9%. Lipase had an AUC of 0.754, an optimal cutoff value of 354.75 U/L, sensitivity of 75%, and specificity of 67.2%. Thus, pancreatic injury was associated with a poor prognosis of SFTS and can be used as an important reference for SFTS determination and prognostic assessment.
Topics: Humans; Male; Female; Prognosis; Middle Aged; Aged; Severe Fever with Thrombocytopenia Syndrome; ROC Curve; Risk Factors; Adult; Aged, 80 and over; Pancreas; Amylases; Retrospective Studies; Lipase
PubMed: 38171850
DOI: 10.7883/yoken.JJID.2022.571 -
Frontiers in Surgery 2023Pancreatic necrosis is one of the most severe acute abdominal conditions, accounting for 15%-20% of all patients with acute pancreatitis and characterized by significant...
INTRODUCTION
Pancreatic necrosis is one of the most severe acute abdominal conditions, accounting for 15%-20% of all patients with acute pancreatitis and characterized by significant rates of postoperative complications and mortality. Patients with pancreatic necrosis, in which pathological changes are localized in the proximal pancreas and retroperitoneal space, deserve special attention. This form of the disease includes patients with disconnected main pancreatic duct (MPD) syndrome who have a difficult prognosis.
AIM
The aim of the study was an improvement of treatment results in patients with necrotizing pancreatitis and signs of the dissociation of the pancreas duct system using the endoscopic transpapillary stent placement method.
MATERIAL AND METHODS
This study was a retrospective cohort study. There were 32 patients with acute necrotizing pancreatitis who were managed using the endoscopic transpapillary stent placement method between 2019 and 2021. Disconnected MPD syndrome was diagnosed in all 32 patients. In total, 26 patients were admitted to hospital in the first 72 h, while 6 patients were admitted after 72 h. We diagnosed the necrotizing process located in the proximal and central areas of the pancreas and peripancreatic space in all these patients ("model III").
RESULTS
Positive results related to transpapillary stent placement were noted in 24 (75%) patients (first cohort). A total of 20 patients from this group were admitted to hospital in the first 48 h, and 4 patients were admitted later than 72 h from the onset of disease. Moreover, 8 patients (25%; second cohort) failed to succeed in transpapillary stent placement. Complications in the first cohort occurred in 3 (12.5%) patients: dislocation of the stent into the duodenum occurred in 1 patient, and bleeding after papillosphincterotomy took place in 2 patients. Meanwhile, infected necrotized pancreatitis developed in 5 patients, and 1 patient (5%) died. Complications among the second cohort occurred in 2 (25%) patients: erosive bleeding (after debridement). Infected necrotized pancreatitis developed in 4 patients, and 2 patients (25%) died.
CONCLUSIONS
Endoscopic transpapillary stent placement is an effective minimally invasive approach in the management of patients with necrotizing pancreatitis.
PubMed: 38148749
DOI: 10.3389/fsurg.2023.1328304 -
Viruses Dec 2023Salmonid 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...
In Situ Detection of Salmonid Alphavirus 3 (SAV3) in Tissues of Atlantic Salmon in a Cohabitation Challenge Model with a Special Focus on the Immune Response to the Virus in the Pseudobranch.
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.
Topics: Animals; Alphavirus; Salmo salar; Fish Diseases; Alphavirus Infections; Heart
PubMed: 38140691
DOI: 10.3390/v15122450