-
Gastroenterology Sep 2023Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the...
BACKGROUND & AIMS
Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death.
METHODS
This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries.
RESULTS
Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.
Topics: Humans; Latin America; Liver Cirrhosis; Prospective Studies; COVID-19; Acute-On-Chronic Liver Failure; Inflammation; Prognosis
PubMed: 37263305
DOI: 10.1053/j.gastro.2023.05.033 -
Frontiers in Endocrinology 2023For more than a century, enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D). Uncontrolled viral response pathways repeatedly...
INTRODUCTION
For more than a century, enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D). Uncontrolled viral response pathways repeatedly presented during childhood highly correlate with autoimmunity and T1D. Virus responses evoke chemokines and cytokines, the "cytokine storm" circulating through the body and attack cells especially vulnerable to inflammatory destruction. Intra-islet inflammation is a major trigger of β-cell failure in both T1D and T2D. The genetic contribution of islet inflammation pathways is apparent in T1D, with several mutations in the interferon system. In contrast, in T2D, gene mutations are related to glucose homeostasis in β cells and insulin-target tissue and rarely within viral response pathways. Therefore, the current study evaluated whether enteroviral RNA can be found in the pancreas from organ donors with T2D and its association with disease progression.
METHODS
Pancreases from well-characterized 29 organ donors with T2D and 15 age- and BMI-matched controls were obtained from the network for pancreatic organ donors with diabetes and were analyzed in duplicates. Single-molecule fluorescence hybridization analyses were performed using three probe sets to detect positive-strand enteroviral RNA; pancreas sections were co-stained by classical immunostaining for insulin and CD45.
RESULTS
There was no difference in the presence or localization of enteroviral RNA in control nondiabetic and T2D pancreases; viral infiltration showed large heterogeneity in both groups ranging from 0 to 94 virus cells scattered throughout the pancreas, most of them in the exocrine pancreas. Very rarely, a single virus cell was found within islets or co-stained with CD45 immune cells. Only one single T2D donor presented an exceptionally high number of viruses, similarly as seen previously in T1D, which correlated with a highly reduced number of β cells.
DISCUSSION
No association of enteroviral infection in the pancreas and T2D diabetes could be found. Despite great similarities in inflammatory markers in islets in T1D and T2D, long-term enteroviral infiltration is a distinct pathological feature of T1D-associated autoimmunity and in T1D pancreases.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enterovirus Infections; Insulin; Inflammation; RNA
PubMed: 38027145
DOI: 10.3389/fendo.2023.1236574 -
Diabetologia Dec 2023Clinically symptomatic type 1 diabetes (stage 3 type 1 diabetes) is preceded by a pre-symptomatic phase, characterised by progressive loss of functional beta cell mass... (Review)
Review
Clinically symptomatic type 1 diabetes (stage 3 type 1 diabetes) is preceded by a pre-symptomatic phase, characterised by progressive loss of functional beta cell mass after the onset of islet autoimmunity, with (stage 2) or without (stage 1) measurable changes in glucose profile during an OGTT. Identifying metabolic tests that can longitudinally track changes in beta cell function is of pivotal importance to track disease progression and measure the effect of disease-modifying interventions. In this review we describe the metabolic changes that occur in the early pre-symptomatic stages of type 1 diabetes with respect to both insulin secretion and insulin sensitivity, as well as the measurable outcomes that can be derived from the available tests. We also discuss the use of metabolic modelling to identify insulin secretion and sensitivity, and the measurable changes during dynamic tests such as the OGTT. Finally, we review the role of risk indices and minimally invasive measures such as those derived from the use of continuous glucose monitoring.
Topics: Humans; Diabetes Mellitus, Type 1; Blood Glucose; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Blood Glucose Self-Monitoring; Insulin Resistance; Insulin-Secreting Cells; Insulin
PubMed: 37712956
DOI: 10.1007/s00125-023-06011-5 -
Cell & Bioscience Aug 2023Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained β cell-reactive immune... (Review)
Review
Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained β cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory β cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.
PubMed: 37641145
DOI: 10.1186/s13578-023-01110-7 -
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 -
Journal of Investigative Surgery : the... Dec 2023Our objective is to compare the early outcomes associated with passive (gravity) drainage (PG) and active drainage (AD) after surgery. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Our objective is to compare the early outcomes associated with passive (gravity) drainage (PG) and active drainage (AD) after surgery.
METHODS
Studies published until April 28, 2022 were retrieved from the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science databases.
RESULTS
Nine studies with 14,169 patients were identified. Two groups had the same intra-abdominal infection rate (RR: 0.55; = 0.13); In subgroup analysis of pancreaticoduodenectomy, active drainage had no significant effect on postoperative pancreatic fistula (POPF) rate (RR: 1.21; = 0.26) and clinically relevant POPF (CR-POPF) (RR: 1.05; = 0.72); Active drainage was not associated with lower percutaneous drainage rate (RR: 1.00; = 0.96), incidence of sepsis (RR: 1.00; = 0.99) and overall morbidity (RR: 1.02; = 0.73). Both groups had the same POPF rate (RR: 1.20; = 0.18) and CR-POPF rate (RR: 1.20; = 0.18) after distal pancreatectomy. There was no difference between two groups on the day of drain removal after pancreaticoduodenectomy (Mean difference: -0.16; = 0.81) and liver surgery (Mean difference: 0.03; = 0.99).
CONCLUSIONS
Active drainage is not superior to passive drainage and both drainage methods can be considered.
Topics: Humans; Abdomen; Pancreas; Drainage; Pancreatectomy; Postoperative Complications; Pancreaticoduodenectomy
PubMed: 37733388
DOI: 10.1080/08941939.2023.2180115 -
Cureus Sep 2023This research presents a systematic review focusing on rituximab's therapeutic applications in immunoglobulin G4 (IgG4)-related disease (IgG4-RD), a rare condition... (Review)
Review
This research presents a systematic review focusing on rituximab's therapeutic applications in immunoglobulin G4 (IgG4)-related disease (IgG4-RD), a rare condition characterized by immune-mediated systemic inflammation and tissue fibrosis, as well as the clinical features of IgG4-RD. While the disease commonly affects organs such as the bile ducts, lymph nodes, retroperitoneum, pancreas, and salivary glands, it can potentially involve other organs. This intricacy often leads to diagnostic challenges due to clinical overlaps with cancer, infections, and other autoimmune disorders. The diagnosis of IgG4-RD necessitates a comprehensive approach involving laboratory tests, imaging studies, and clinical assessments. Symptoms can vary, ranging from lymphadenopathy to jaundice, affecting multiple organs. Although elevated blood IgG4 levels and findings of tissue involvement and fibrosis on imaging can be suggestive, they lack the specificity for a definitive diagnosis. Early diagnosis is crucial for initiating corticosteroids and immunosuppressive to prevent further damage from IgG4-RD. This study highlights the therapeutic role of rituximab in managing this condition. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, the research identifies and evaluates relevant literature across various electronic databases, including PubMed, ScienceDirect, and Google Scholar. This review includes 14 selected publications, comprising three systematic reviews, three observational studies, four narrative reviews, and four case reports. The study design ensures a comprehensive evaluation of rituximab's potential efficacy in treating IgG4-RD and its associated clinical characteristics. Based on this study, it can be concluded that IgG4-RD can potentially be treated with rituximab, particularly in cases of relapse and maintaining remission.
PubMed: 37701160
DOI: 10.7759/cureus.45044 -
Journal of Molecular Medicine (Berlin,... Aug 2023Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying...
Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
Topics: Female; Humans; COVID-19; SARS-CoV-2; Interferons; Pancreas
PubMed: 37246981
DOI: 10.1007/s00109-023-02334-3 -
Heliyon May 2024Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick...
BACKGROUND
Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide.
METHODS
Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue.
RESULTS
Autopsy tissue evaluation demonstrated in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by -induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia.
CONCLUSIONS
Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.
PubMed: 38779029
DOI: 10.1016/j.heliyon.2024.e31159