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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 -
Journal of Infection in Developing... Jun 2023Stenotrophomonas maltophilia is a Gram-negative, opportunistic pathogen associated with a high morbidity and mortality rate. We report our clinical experience in...
INTRODUCTION
Stenotrophomonas maltophilia is a Gram-negative, opportunistic pathogen associated with a high morbidity and mortality rate. We report our clinical experience in treating a patient with infected pancreatic necrosis caused by multidrug-resistant (MDR) S. maltophilia with a novel drug combination.
CASE REPORT
A 65-year-old male with history of type II diabetes was admitted with acute pancreatitis, voluminous ascites, and signs of sepsis after undergoing an echo-endoscopy procedure with pancreas biopsy to investigate a Wirsung duct dilatation. Retroperitoneal fluid culture revealed S. maltophilia resistant to colistin and with intermediate susceptibility to trimethoprim-sulfamethoxazole and levofloxacin. The synergy between aztreonam (ATM) and ceftazidime/avibactam (CZA) was demonstrated using the combined disk pre-diffusion test.
CONCLUSIONS
There are sparse data providing guidance on the optimal regimen against MDR S. maltophilia infections. Although in this case a surgical excision was essential, combination of ATM and CZA provided effective synergistic antimicrobial treatment with clinical cure of severe acute pancreatitis infected with S. maltophilia. The combined disk pre-diffusion test with ATM and CZA requires no special equipment and can be routinely performed in clinical microbiology labs. Combination of ATM with CZA should be considered for cases of MDR S. maltophilia infections with limited treatment options.
Topics: Male; Humans; Aged; Aztreonam; Ceftazidime; Anti-Bacterial Agents; Stenotrophomonas maltophilia; Diabetes Mellitus, Type 2; Acute Disease; Pancreatitis; Drug Combinations; Microbial Sensitivity Tests; Gram-Negative Bacterial Infections
PubMed: 37406060
DOI: 10.3855/jidc.17290 -
Journal of Veterinary Diagnostic... Jul 2023Hepatic trematodosis by opisthorchiid flukes has been reported sporadically in North American fish-eating raptors. Bald eagles () infected by these flukes often have...
Hepatic trematodosis by opisthorchiid flukes has been reported sporadically in North American fish-eating raptors. Bald eagles () infected by these flukes often have various degrees of granulomatous cholangitis, pericholangitis, necrosis of adjacent hepatocytes, and subsequent hepatic fibrosis. Species identification has been complicated by the inability to dissect intact specimens from liver tissue. Between 2007 and 2018, 5 juvenile bald eagles with massive hepatic trematodosis were identified at autopsy. Histologically, flukes were non-spinous. Parasitologic identification revealed ventral suckers (80-93 µm diameter), and uteri containing golden, operculated eggs (~25.0 × 12.0 µm). An unfixed frozen liver sample of one eagle was analyzed by PCR and DNA sequencing targeting the large subunit rRNA, ITS region, and genes of the parasite. The fluke DNA sequences shared 99.6%, 98.4%, and 87.0% similarity, respectively, with , a newly described opisthorchiid species infecting the liver and pancreas of fish-eating birds in Europe and Asia. Infection by is highly pathogenic in several piscivorous bird species. The clinical significance of trematodosis in our 5 cases is uncertain because all birds had comorbidities.
Topics: Animals; Eagles; Liver; Necrosis; Bird Diseases; Europe
PubMed: 37204007
DOI: 10.1177/10406387231176227 -
Infection and Drug Resistance 2023Infection is a common complication of acute pancreatitis (AP). (KP) is one of the most common pathogens associated with nosocomial infections. Our study focuses on...
OBJECTIVE
Infection is a common complication of acute pancreatitis (AP). (KP) is one of the most common pathogens associated with nosocomial infections. Our study focuses on investigating the clinical characteristics and risk factors for death of infections in AP patients, further to quantify the prognosis of the patients, and provide evidence for guiding antibiotic use and improving prognosis.
METHODS
The data of epidemiology, clinical manifestations and drug resistance rate with infections in AP patients from January 1, 2012 to August 30, 2022 were retrospectively collected. Logistic regression model and Cox regression model were, respectively, used to determine the risk factors for carbapenem-resistant (CRKP) acquisition and death. The nomogram prediction model was built by RMS software package to predict the 90-day survival rate.
RESULTS
One hundred and twenty-six AP patients combined with infections, with a mortality rate of 34.9%. The most common infection sites were pancreas and peri-pancreas (54.8%), followed by lung (20.6%) and blood stream (18.3%). The resistance rate of to commonly used antibiotics in clinical practice was high, especially CRKP, which was only sensitive to sulfamethoxazole-trimethoprim (SMZ-TMP) and tigecycline (TGC) (resistance rates were 37.57% and 17.57%, respectively). Independent risk factors for CPKP acquisition were male (OR = 1.655, 95% CI 0.642-4.265, P = 0.017) and PICC/CVC implantation (OR = 3.157, 95% CI 1.223-8.147, P = 0.021). Independent risk factors for mortality included carbapenem resistance (HR = 2.556, 95% CI 1.011-6.462, P = 0.047), hemorrhage (HR = 2.392, 95% CI 1.104-5.182, P = 0.027), septic shock (HR = 3.022, 95% CI 1.312-6.959, P = 0.009), age >60 years (HR = 2.977, 95% CI 1.303-6.799, P = 0.01), creatinine >177μmol/L (HR = 2.815, 95% CI 1.075-7.369, P = 0.035).
CONCLUSION
infection has become a serious threat for AP patients, which recommends us more attention and active new strategies seeking.
PubMed: 37576517
DOI: 10.2147/IDR.S410397 -
Trials Sep 2023Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate...
The effect of perioperative of dexamethasone on postoperative complications after pancreaticoduodenectomy (PANDEX): a study protocol for a pragmatic multicenter randomized controlled trial.
BACKGROUND
Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate of patients undergoing PD has decreased significantly, postoperative complication rates remain high. Dexamethasone, a synthetic glucocorticoid with potent anti-inflammatory and metabolic effects, has been proven to have a favorable effect on certain complications. However, the role it plays in post-pancreatectomy patients has not been systematically evaluated. The aim of this study is to assess the effect of dexamethasone on postoperative complications after PD.
METHODS
The PANDEX trial is an investigator-initiated, multicentric, prospective, randomized, double-blinded, placebo-control, pragmatic study. The trial is designed to enroll 300 patients who are going to receive elective PD. Patients will be randomized to receive 0.2 mg/kg dexamethasone or saline placebo, administered as an intravenous bolus within 5 min after induction of anesthesia. The primary outcome is the Comprehensive Complication Index (CCI) score within 30 days after the operation. The secondary outcomes include postoperative major complications (Clavien-Dindo≥3), postoperative pancreatic fistula (POPF), post-pancreatectomy acute pancreatitis (PPAP), infection, and unexpected relaparotomy, as well as postoperative length of stay, 30-day mortality, and 90-day mortality.
DISCUSSION
The PANDEX trial is the first randomized controlled trial concerning the effect of dexamethasone on postoperative complications of patients undergoing PD, with the hypothesis that the intraoperative use of dexamethasone can reduce the incidence of postoperative complications and improve short-term outcomes after PD. The results of the present study will guide the perioperative use of dexamethasone and help improve the clinical management of post-pancreatectomy patients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05567094. Registered on 30 September 30 2022.
Topics: Humans; Pancreatectomy; Pancreaticoduodenectomy; Acute Disease; Prospective Studies; Pancreatitis; Postoperative Complications; Intestines; Dexamethasone; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37660052
DOI: 10.1186/s13063-023-07571-y -
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 -
Transplant International : Official... 2024The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney...
The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.
Topics: Humans; Kidney Transplantation; Kidney; Bacteremia; Hospitalization; Pancreas
PubMed: 38444997
DOI: 10.3389/ti.2024.12235 -
World Journal of Gastroenterology Jul 2023The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975... (Review)
Review
The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. The adipose tissue is the initial site of obesity impairments. During excessive energy intake, it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs. The pancreas is one of the organs most affected by obesity. Once lipotoxicity becomes chronic, there is an increase in insulin secretion by pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten the survival of the pancreatic islets, which tend to become dysfunctional, reaching exhaustion in the long term. As for the liver, lipotoxicity favors lipogenesis and impairs beta-oxidation, resulting in hepatic steatosis. This silent disease affects around 30% of the worldwide population and can evolve into end-stage liver disease. Although therapy for hepatic steatosis remains to be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways, leading to insulin resistance relief, improved thermogenesis, and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation. This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases, focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
Topics: Humans; Peroxisome Proliferator-Activated Receptors; Insulin Resistance; Diabetes Mellitus, Type 2; COVID-19; Adipose Tissue; Obesity; Metabolic Diseases; Pancreas; Fatty Liver
PubMed: 37475842
DOI: 10.3748/wjg.v29.i26.4136 -
Frontiers in Cellular and Infection... 2023Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system....
INTRODUCTION
Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system. IgG4-related diseases (IgG4-RD) are intractable diseases in which IgG4 levels in the blood are elevated, causing inflammation in organs such as the liver, pancreas, and salivary glands. IgG4-RD are known to be more prevalent in males than in females, but the etiology remains to be elucidated. This study was conducted to investigate the relationship between gut microbiota (GM) and serum IgG4 levels in the general population.
METHODS
In this study, the relationship between IgG4 levels and GM evaluated in male and female groups of the general population using causal inference. The study included 191 men and 207 women aged 40 years or older from Shika-machi, Ishikawa. GM DNA was analyzed for the 16S rRNA gene sequence using next-generation sequencing. Participants were bifurcated into high and low IgG4 groups, depending on median serum IgG4 levels.
RESULTS
ANCOVA, Tukey's HSD, linear discriminant analysis effect size, least absolute shrinkage and selection operator logistic regression model, and correlation analysis revealed that , , , and group were associated with IgG4 levels in women, while , group, , 1, and were associated with IgG4 levels in men. Linear non-Gaussian acyclic model indicated three genera, , group, and , and showed a presumed causal association with IgG4 levels in women.
DISCUSSION
This differential impact of the GM on IgG4 levels based on sex is a novel and intriguing finding.
Topics: Humans; Male; Female; Gastrointestinal Microbiome; Immunoglobulin G4-Related Disease; RNA, Ribosomal, 16S; Salivary Glands; Immunoglobulin G
PubMed: 37908763
DOI: 10.3389/fcimb.2023.1272398 -
Biology Open Nov 2023Trypanosoma brucei colonise and multiply in the blood vasculature, as well as in various organs of the host's body. Lymph nodes have been previously shown to harbour...
Trypanosoma brucei colonise and multiply in the blood vasculature, as well as in various organs of the host's body. Lymph nodes have been previously shown to harbour large numbers of parasites, and the lymphatic system has been proposed as a key site that allows T. brucei distribution through, and colonization of the mammalian body. However, visualization of host-pathogen interactions in the lymphatic system has never captured dynamic events with high spatial and temporal resolution throughout infection. In our work, we used a mixture of tools including intravital microscopy and ex vivo imaging to study T. brucei distribution in 20 sets of lymph nodes. We demonstrate that lymph node colonization by T. brucei is different across lymph node sets, with the most heavily colonised being the draining lymph nodes of main tissue reservoirs: the gonadal white adipose tissue and pancreas. Moreover, we show that the lymphatic vasculature is a pivotal site for parasite dispersal, and altering this colonization by blocking LYVE-1 is detrimental for parasite survival. Additionally, parasites within the lymphatic vasculature have unique morphological and behavioural characteristics, different to those found in the blood, demonstrating that across both types of vasculature, these environments are physically separated. Finally, we demonstrate that the lymph nodes and the lymphatic vasculature undergo significant alterations during T. brucei infection, resulting in oedema throughout the host's body.
Topics: Animals; Trypanosomiasis, African; Trypanosoma brucei brucei; Lymphatic System; Mammals
PubMed: 37870927
DOI: 10.1242/bio.059992