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Cellular and Molecular Gastroenterology... 2021Differences in pancreatic anatomy, size, and function exist in men and women. The anatomical differences could contribute to the increase in complications associated... (Review)
Review
Differences in pancreatic anatomy, size, and function exist in men and women. The anatomical differences could contribute to the increase in complications associated with pancreatic surgery in women. Although diagnostic criteria for pancreatitis are the same in men and women, major sex differences in etiology are reported. Alcohol and tobacco predominate in men, whereas idiopathic and obstructive etiologies predominate in women. Circulating levels of estrogens, progesterone, and androgens contribute significantly to overall health outcomes; premenopausal women have lower prevalence of cardiovascular and pancreatic diseases suggesting protective effects of estrogens, whereas androgens promote growth of normal and cancerous cells. Sex chromosomes and gonadal and nongonadal hormones together determine an individual's sex, which is distinct from gender or gender identity. Human pancreatic disease etiology, outcomes, and sex-specific mechanisms are largely unknown. In rodents of both sexes, glucocorticoids and estrogens from the adrenal glands influence pancreatic secretion and acinar cell zymogen granule numbers. Lack of corticotropin-releasing factor receptor 2 function, a G protein-coupled receptor whose expression is regulated by both estrogens and glucocorticoids, causes sex-specific changes in pancreatic histopathology, zymogen granule numbers, and endoplasmic reticulum ultrastructure changes in acute pancreatitis model. Here, we review existing literature on sex differences in the normal exocrine pancreas and mechanisms that operate at homeostasis and diseased states in both sexes. Finally, we review pregnancy-related pancreatic diseases and discuss the effects of sex differences on proposed treatments in pancreatic disease.
Topics: COVID-19; Female; Hormones; Humans; Male; Pancreas, Exocrine; Pancreatic Diseases; Pregnancy; Sex Characteristics
PubMed: 33895424
DOI: 10.1016/j.jcmgh.2021.04.005 -
American Journal of Transplantation :... Feb 2023The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the...
The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the COVID-19 pandemic was not as pronounced in pancreas transplantation as in other organs. The number of simultaneous pancreas-kidney transplants (SPKs) decreased from 827 to 820, whereas the number of pancreas-after-kidney transplants and pancreas transplants alone increased marginally to compensate. The proportion of patients with type 2 diabetes on the waiting list increased to 22.9% in 2021, compared with 20.1% in 2020. Consequently, the proportion of transplants in patients with type 2 diabetes increased from 21.3% in 2020 to 25.9% in 2021. The proportion of transplants in older recipients (aged 55 years or older) also increased to 13.5% in 2021 from 11.7% in 2020. Outcomes after SPK continue to be the best of the three categories of pancreas transplants: 1-year graft failure for kidney at 5.7% and pancreas at 10.5% for transplants performed in 2020. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants in large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020.
Topics: Humans; United States; Aged; Tissue and Organ Procurement; Diabetes Mellitus, Type 2; Graft Survival; COVID-19; Pancreas Transplantation; Pancreas
PubMed: 37132349
DOI: 10.1016/j.ajt.2023.02.005 -
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 -
Annual Review of Medicine Jan 2022Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental... (Review)
Review
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome.
Topics: Autoimmunity; Diabetes Mellitus, Type 1; Enterovirus; Enterovirus Infections; Humans; Insulin-Secreting Cells
PubMed: 34794324
DOI: 10.1146/annurev-med-042320-015952 -
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 -
Transplantation Proceedings May 2022The SARS-CoV-2 pandemic was a real test of doctors' abilities to adapt and respond to patients' needs. The course of infection varied from influenza-like symptoms to...
The SARS-CoV-2 pandemic was a real test of doctors' abilities to adapt and respond to patients' needs. The course of infection varied from influenza-like symptoms to severe infections with multi-organ failure and death. Therefore, the possibility of vaccination against the COVID-19 virus brought great hope. Since 2004, 240 pancreas and pancreas with kidney (simultaneous pancreas and kidney transplantation, pancreas after kidney, pancreas transplants alone) transplants were performed in our center. Currently, 130 transplant patients are under the care of the transplant clinic. All patients were informed about the possibility of vaccination against SARS-CoV-2 with the mRNA vaccine. The aim of the study was to evaluate the development of antibodies to SARS-CoV-2 in patients who had previously undergone transplantation. Fifty-three patients were vaccinated with the full double dose and 37 patients received an additional third dose. The level of antibodies in the IgM and IgG classes was assessed in patients' serum. The level of antibodies was assessed before administration of the vaccine and then after administration of the first and second doses. Most patients had no response to vaccination after 1 dose of the vaccine and 21 patients achieved therapeutic antibody levels after the full dose of vaccination. However, the highest titer of immunoglobulins was found in recipients who received the third dose. The use of vaccinations is safe and can protect the group of patients after pancreas transplantation from serious complications of SARS-CoV-2 infection despite the use of immunosuppressive drugs.
Topics: Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Pancreas; SARS-CoV-2; Transplant Recipients; Vaccination; Vaccines; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35437149
DOI: 10.1016/j.transproceed.2022.03.002 -
BMC Surgery May 2023Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently,...
BACKGROUND
Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy.
METHODS
To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated.
RESULTS
All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection.
CONCLUSION
PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.
Topics: Humans; Pancreaticojejunostomy; Pancreaticoduodenectomy; Anastomosis, Surgical; Pancreas; Pancreatic Fistula; Postoperative Complications; Suture Techniques
PubMed: 37248522
DOI: 10.1186/s12893-023-02054-y -
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 -
Nature Reviews. Endocrinology May 2016Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental... (Review)
Review
Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection--particularly by enteroviruses (for example, coxsackievirus)--as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.
Topics: Animals; Diabetes Mellitus, Type 1; Humans; Insulin-Secreting Cells; Virus Diseases
PubMed: 27020257
DOI: 10.1038/nrendo.2016.30 -
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