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Nature Metabolism Feb 2021Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2...
Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.
Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme 2; COVID-19; Cells, Cultured; Diabetes Mellitus; Female; Humans; Islets of Langerhans; Male; Pancreas, Exocrine; Pancreatic Diseases; SARS-CoV-2; Serine Endopeptidases; Virus Internalization; Virus Replication
PubMed: 33536639
DOI: 10.1038/s42255-021-00347-1 -
Gastroenterology May 2020
Topics: Channelopathies; Humans; Liver Cirrhosis; Macrophages; Pancreas; Pancreatitis, Chronic; Peritonitis; Phenotype
PubMed: 32205170
DOI: 10.1053/j.gastro.2020.03.027 -
Transplantation Sep 2022Since November 2021, a new variant of concern (VOC), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.529 (Omicron) has emerged as the...
BACKGROUND
Since November 2021, a new variant of concern (VOC), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.529 (Omicron) has emerged as the dominant coronavirus disease 2019 (COVID-19) infection worldwide. We describe the clinical presentation, risk factors, and outcomes in a cohort of kidney and kidney pancreas transplant recipients with COVID-19 caused by Omicron infection.
METHODS
We included all kidney and kidney pancreas transplant recipients diagnosed with SARS-CoV-2 Omicron infections between December 26, 2021, and January 14, 2022, in a single transplant center in Australia. Identification of the VOC Omicron was confirmed using phylogenetic analysis of SARS-CoV-2 sequences.
RESULTS
Forty-one patients with kidney (6 living and 33 deceased) and kidney pancreas transplants were diagnosed with the VOC Omicron (lineage B.1.1.529/BA.1) infection during the study period. The mean age (SD) at the time of diagnosis was 52 (11.1) y; 40 (out of 41) (98%) had received at least 2 doses of COVID-19 vaccine. Cough was the most frequent symptom (80.5%), followed by myalgia (70.7%), sore throat (63.4%), and fever (58.5%). After a follow-up time of 30 d, 1 (2.4%) patient died, 2 (4.9%) experienced multiorgan failure, and 5 (12.2%) had respiratory failure; 11 (26.8%) patients developed other superimposed infections. Compared with recipients who did not receive sotrovimab antibody therapy, the odds ratio (95% confidence interval) for hospitalization among patients who received sotrovimab was 0.05 (0.005-0.4).
CONCLUSIONS
Despite double or triple dose vaccination, VOC Omicron infections in kidney and kidney pancreas transplant recipients are not necessarily mild. Hospitalization rates remained high (around 56%), and sotrovimab use may prevent hospitalization.
Topics: Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Humans; Kidney; Pancreas; Phylogeny; Risk Factors; SARS-CoV-2; Transplant Recipients
PubMed: 35675438
DOI: 10.1097/TP.0000000000004203 -
European Journal of Gastroenterology &... Apr 2021
Topics: Acute Disease; Humans; Necrosis; Pancreas; Pancreatitis
PubMed: 33657607
DOI: 10.1097/MEG.0000000000002125 -
United European Gastroenterology Journal Sep 2021The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context,... (Review)
Review
BACKGROUND
The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients.
OBJECTIVE
At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context.
METHODS/RESULTS/CONCLUSION
We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.
Topics: Biomarkers; COVID-19; Delivery of Health Care; Disease Management; Endoscopy, Digestive System; Gastroenterology; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Liver Diseases; Liver Transplantation; Pancreas; Risk Factors; SARS-CoV-2; Telemedicine
PubMed: 34190413
DOI: 10.1002/ueg2.12115 -
Advances in Medical Sciences Sep 2019The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large... (Review)
Review
The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large proportion of the total protein in the cell. Protein folding, glycosylation, sorting and transport are essential tasks of the ER and a compromised ER folding network has been recognized to be a key component in the disease pathogenicity of common neurodegenerative, metabolic and malignant diseases. On the other hand, the ER protein folding machinery also holds significant potential for therapeutic interventions. Many causes can lead to ER stress. A disturbed calcium homeostasis, the generation of reactive oxygen species (ROS) and a persistent overload of misfolded proteins within the ER can drive the course of adisease. In this review the role of ER-stress in diseases of the liver and pancreas will be examined using pancreatitis and Wilson´s disease as examples. Potential therapeutic targets in ER-stress pathways will also be discussed.
Topics: Animals; Endoplasmic Reticulum Stress; Humans; Liver; Pancreas; Protein Folding; Unfolded Protein Response
PubMed: 30978662
DOI: 10.1016/j.advms.2019.03.004 -
Radiographics : a Review Publication of... Aug 2023
Topics: Humans; Ascariasis; Pancreas; Pancreatitis; Biliary Tract Diseases
PubMed: 37471244
DOI: 10.1148/rg.230049 -
AJR. American Journal of Roentgenology Aug 2021The purpose of this study was to evaluate the safety and efficacy of percutaneous drainage of peripancreatic fluid collections after pancreas transplant and to...
The purpose of this study was to evaluate the safety and efficacy of percutaneous drainage of peripancreatic fluid collections after pancreas transplant and to determine factors predicting a successful clinical outcome. This single-center retrospective study included 28 patients who underwent percutaneous drainage for peripancreatic collections after transplant between January 2008 and December 2018. Clinical success was defined as drainage resulting in resolution of symptoms. Primary clinical success was defined as symptom resolution after the initial drainage procedure, and secondary success was defined as symptom resolution after additional drainage procedures. Operative intervention or death was considered clinical failure. Patient, collection, and procedural factors were assessed for their potential impact on the clinical outcome. Clinical success was achieved in 23 of 28 drainage procedures (82.1%), with primary success in 15 procedures. Of the five patients with failed drainage procedures, three required pancreatectomies, one required surgical washout, and one died from a disseminated infection. The median duration of drainage in the clinical success group was 25 days (range, 3-136 days), and patients with longer drainage periods had more successful outcomes ( = .04). Graft pancreatitis was diagnosed in five patients (17.9%) and was not associated with drainage outcome ( = .21). Collections were positive for bacterial growth in 13 patients (46.4%) and were high in amylase in 12 (42.9%). We observed drainage failure in collections with polymicrobial growth and in the presence of fistulas ( = .05 and = .07, respectively). Patients with successful outcomes had smaller collection volumes ( = .045). No complications attributed to drainage were encountered. Percutaneous drainage is safe and effective for management of peripancreatic fluid collections after pancreas transplant.
Topics: Adult; Body Fluids; Drainage; Female; Humans; Male; Pancreas; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 34036810
DOI: 10.2214/AJR.20.23059 -
Zeitschrift Fur Gastroenterologie Jul 2022Chronic pancreatitis (CP) is a frequent cause for hospitalization and is associated with impaired quality of life and reduced overall survival. The German Society for...
INTRODUCTION
Chronic pancreatitis (CP) is a frequent cause for hospitalization and is associated with impaired quality of life and reduced overall survival. The German Society for Gastroenterology (DGVS) has recently completed the S3-Guideline "Pancreatitis" that summarizes key findings on epidemiology, diagnostic and therapeutic concepts for acute and chronic pancreatitis. Here, we recapitulate the most relevant findings for clinicians regarding CP.
RESULTS
The most common cause of CP is chronic alcohol abuse, other causes are hereditary pancreatitis, autoimmune pancreatitis, hyperparathyroidism and idiopathic forms. Apart from the classical hereditary pancreatitis (PRSS1 mutation), a number of genetic associations have been discovered over the last years that are associated with an increased risk to develop idiopathic CP. The conservative management of CP is focused on the appropriate management of exocrine and endocrine insufficiency, and the prevention and treatment of secondary complications such as osteoporosis, vitamin deficiencies and malnutrition. Local complications (bile duct stenosis, duodenal stenosis, pseudocysts and chronic pain) should be managed in multidisciplinary teams in specialized pancreas centres with expert surgeons, radiologists and gastroenterologists. Infected or symptomatic pseudocysts should be primarily addressed by endoscopic drainage. In contrast, patients with chronic pain, dilated pancreas duct and opioid use should be considered for early surgical intervention.
CONCLUSION
Chronic pancreatitis is associated with increased morbidity and mortality and often leads to hospital admissions. The clinical management of complex patients with local complications requires an interdisciplinary approach to tailor available therapeutic modalities depending on the stage of the disease and pre-existing comorbidities.
Topics: Chronic Disease; Chronic Pain; Humans; Pancreas; Pancreatitis, Chronic; Quality of Life
PubMed: 34798674
DOI: 10.1055/a-1659-4636 -
Clinical Transplantation Nov 2023BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited...
BACKGROUND
BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients.
METHODS
We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized.
RESULTS
Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m .
CONCLUSIONS
BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.
Topics: Adult; Humans; BK Virus; Pancreas Transplantation; Retrospective Studies; Polyomavirus Infections; Kidney; Kidney Diseases; Pancreas; Kidney Failure, Chronic; Transplant Recipients; Tumor Virus Infections
PubMed: 37705389
DOI: 10.1111/ctr.15135