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Reviews in Medical Virology Mar 2023Among the environmental factors associated with type 1 diabetes (T1D), viral infections of the gut and pancreas has been investigated most intensely, identifying... (Review)
Review
Among the environmental factors associated with type 1 diabetes (T1D), viral infections of the gut and pancreas has been investigated most intensely, identifying enterovirus infections as the prime candidate trigger of islet autoimmunity (IA) and T1D development. However, the association between respiratory tract infections (RTI) and IA/T1D is comparatively less known. While there are significant amounts of epidemiological evidence supporting the role of respiratory infections in T1D, there remains a paucity of data characterising infectious agents at the molecular level. This gap in the literature precludes the identification of the specific infectious agents driving the association between RTI and T1D. Furthermore, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on the development of IA/T1D remains undeciphered. Here, we provide a comprehensive overview of the evidence to date, implicating RTIs (viral and non-viral) as potential risk factors for IA/T1D.
Topics: Humans; Diabetes Mellitus, Type 1; Islets of Langerhans; COVID-19; SARS-CoV-2; Respiratory Tract Infections
PubMed: 36790804
DOI: 10.1002/rmv.2429 -
Journal of Visceral Surgery Aug 2016The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately... (Review)
Review
The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non-operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early.
Topics: Abdominal Injuries; Angiography; Embolization, Therapeutic; Hemoperitoneum; Humans; Infections; Laparotomy; Pancreas; Pancreaticoduodenectomy; Postoperative Complications; Spleen; Splenectomy
PubMed: 27402320
DOI: 10.1016/j.jviscsurg.2016.04.005 -
EBioMedicine Aug 2017Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different... (Review)
Review
Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different approaches to explain the biology of T1D, beyond the presence and activity of autoreactive lymphocytes. In this review, we propose inflammatory pathways as triggers for T1D. Within the scope of those inflammatory pathways and in understanding the pathogenesis of disease, we suggest that viruses, in particular Coxsackieviruses, act by causing a type 1 interferonopathy within the pancreas and the microenvironment of the islet. As such, this connection and common thread represents an exciting platform for the development of new diagnostic, treatment and/or prevention options.
Topics: Animals; Cellular Microenvironment; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Immunity, Innate; Interferons; Islets of Langerhans; Pancreatic Diseases; Signal Transduction
PubMed: 28663145
DOI: 10.1016/j.ebiom.2017.06.014 -
Cell Metabolism Aug 2021Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen...
Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Animals; COVID-19; Cell Transdifferentiation; Chlorocebus aethiops; Cyclohexylamines; Cytokines; Eukaryotic Initiation Factor-2; Female; Glucagon; Host-Pathogen Interactions; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Phenotype; SARS-CoV-2; Signal Transduction; Tissue Culture Techniques; Trypsin; Vero Cells; Young Adult
PubMed: 34081913
DOI: 10.1016/j.cmet.2021.05.015 -
Journal of Endocrinological... Mar 2022Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. However, the cause of severe acute respiratory syndrome coronavirus...
PURPOSE
Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. However, the cause of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on the incidence of diabetes is unclear. In the SARS-CoV-2-infected cells, host microRNAs (miRNAs) may target the native gene transcripts as well as the viral genomic and subgenomic RNAs. Here, we investigated the role of miRNAs in linking Diabetes to SARS-CoV-2 infection in the human pancreas.
METHODS
Differential gene expression and disease enrichment analyses were performed on an RNA-Seq dataset of human embryonic stem cell-derived (hESC) mock-infected and SARS-CoV-2-infected pancreatic organoids to obtain the dysregulated Diabetes-associated genes. The miRNA target prediction for the Diabetes-associated gene transcripts and the SARS-CoV-2 RNAs has been made to determine the common miRNAs targeting them. Minimum Free Energy (MFE) analysis was done to identify the miRNAs, preferably targeting SARS-CoV-2 RNAs over the Diabetes-associated gene transcripts.
RESULTS
The gene expression and disease enrichment analyses of the RNA-Seq data have revealed five biomarker genes, i.e., CP, SOCS3, AGT, PSMB8 and CFB that are associated with Diabetes and get significantly upregulated in the pancreas following SARS-CoV-2-infection. Four miRNAs, i.e., hsa-miR-298, hsa-miR-3925-5p, hsa-miR-4691-3p and hsa-miR-5196-5p, showed preferential targeting of the SARS-CoV-2 genome over the cell's Diabetes-associated messenger RNAs (mRNAs) in the human pancreas.
CONCLUSION
Our study proposes that the differential targeting of the Diabetes-associated host genes by the miRNAs may lead to diabetic complications or new-onset Diabetes that can worsen the condition of COVID-19 patients.
Topics: 3' Untranslated Regions; 5' Untranslated Regions; COVID-19; Comorbidity; Diabetes Mellitus; Gene Expression Regulation; Humans; MicroRNAs; Pancreas; RNA, Messenger; RNA, Viral; SARS-CoV-2
PubMed: 34669152
DOI: 10.1007/s40618-021-01693-3 -
Science Advances Mar 2024Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and...
Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8 T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8 T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8 T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.
Topics: Humans; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Insulin-Secreting Cells; Antibodies; Coxsackievirus Infections; Epitopes; Peptides; Antiviral Agents
PubMed: 38446892
DOI: 10.1126/sciadv.adl1122 -
Gastroenterology Clinics of North... Mar 2023Coronavirus disease 2019 (COVID-19) pulmonary involvement has been extensively reported in the literature. Current data highlight how COVID-19 is a systemic disease,... (Review)
Review
Coronavirus disease 2019 (COVID-19) pulmonary involvement has been extensively reported in the literature. Current data highlight how COVID-19 is a systemic disease, affecting many other organs, including the gastrointestinal, hepatobiliary, and pancreatic organs. Recently, these organs have been investigated using imaging modalities of ultrasound and particularly computed tomography. Radiological findings of the gastrointestinal, hepatic, and pancreatic involvement in patients with COVID-19 are generally nonspecific but are nonetheless helpful to evaluate and manage COVID-19 patients with involvement of these organs.
Topics: Humans; COVID-19; SARS-CoV-2; Radiation Oncology; Gastrointestinal Tract; Liver; Pancreas; COVID-19 Testing
PubMed: 36813425
DOI: 10.1016/j.gtc.2022.10.006 -
World Journal of Gastroenterology May 2022The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However,... (Review)
Review
The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However, clinical characteristics of COVID-19-attributed AP remain unclear. We performed a narrative review to elucidate relation between COVID-19 and AP using the PubMed database. Some basic and pathological reports revealed expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, key proteins that aid in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the pancreas. The experimental and pathological evaluation suggested that SARS-CoV-2 infects human endocrine and exocrine pancreas cells, and thus, SARS-CoV-2 may have a direct involvement in pancreatic disorders. Additionally, systemic inflammation, especially in children, may cause AP. Levels of immune mediators associated with AP, including interleukin (IL)-1β, IL-10, interferon-γ, monocyte chemotactic protein 1, and tumor necrosis factor-α are higher in the plasma of patients with COVID-19, that suggests an indirect involvement of the pancreas. In real-world settings, some clinical features of AP complicate COVID-19, such as a high complication rate of pancreatic necrosis, severe AP, and high mortality. However, clinical features of COVID-19-attributed AP remain uncertain due to insufficient research on etiologies of AP. Therefore, high-quality clinical studies and case reports that specify methods for differential diagnoses of other etiologies of AP are needed.
Topics: Acute Disease; COVID-19; Child; Humans; Pancreas; Pancreatitis; SARS-CoV-2
PubMed: 35664035
DOI: 10.3748/wjg.v28.i19.2034 -
World Journal of Gastroenterology Dec 2014It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of... (Review)
Review
It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3(rd) d to the 14(th) d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis.
Topics: Acute Disease; Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Cytokines; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunologic Factors; Immunosuppressive Agents; Inflammation Mediators; Pancreas; Pancreatitis; Signal Transduction; Treatment Outcome
PubMed: 25493006
DOI: 10.3748/wjg.v20.i45.16935 -
The Journal of Hospital Infection Oct 2022Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant...
BACKGROUND
Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients.
AIM
To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients.
METHODS
Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function.
FINDINGS
Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79).
CONCLUSION
SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.
Topics: Adult; Cohort Studies; Humans; Kidney; Kidney Transplantation; Pancreas; Pancreas Transplantation; Risk Factors; Surgical Wound Infection; Switzerland
PubMed: 35840001
DOI: 10.1016/j.jhin.2022.07.009