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The American Surgeon Apr 2024Recent literature advocates for delayed or avoidance of catheter drainage of infected peri-pancreatic collections (IPCs) in acute pancreatitis (AP). This may not be...
Recent literature advocates for delayed or avoidance of catheter drainage of infected peri-pancreatic collections (IPCs) in acute pancreatitis (AP). This may not be realistic for patients at academic centers, many of whom are critically ill. We retrospectively reviewed 72 patients admitted to our institution from 2016-2021 with AP and IPCs. 34.7% had a Bedside Index of Severity in Acute Pancreatitis (BISAP) score ≥3, and 56.9% had a Balthazar score of E. 65.3% were admitted to the ICU, 51.4% experienced respiratory failure, and 47.2% had acute renal failure. In-hospital mortality was 9.7%. Catheter-based drainage alone was the most frequent intervention. Only 8 individuals did not undergo any drainage. Individuals with severe AP complicated by IPCs are critically ill. Avoidance or delay of source control could lead to significant morbidity. Until further research is done on this population, drainage should remain a central tenet of management of IPCs.
PubMed: 38655580
DOI: 10.1177/00031348241241721 -
Endoscopy International Open Apr 2024External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic...
External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic necrosis and is associated with significant morbidity. The present study aimed to report the initial outcome of a novel technique of two-scope guided tractogastrostomy for management of this condition. The present study was a retrospective analysis of data from patients with external pancreatic fistula and disconnected pancreatic duct syndrome, who underwent two-scope-guided tractogastrostomy. All the patients had a 24F or larger drain placed in the left retroperitoneum. Transgastric echo endoscopy and sinus tract endoscopy were performed simultaneously to place a stent between the gastric lumen and the sinus tract. Technical success was defined as placement of the stent between the tract and the stomach. Clinical success was defined as successful removal of the percutaneous drain without the occurrence of pancreatic fluid collection, ascites, external fistula, or another intervention 12 weeks after the procedure. Three patients underwent two scope-guided tractogastrostomy. Technical and clinical success were achieved in all the patients. No procedure-related side effects or recurrence occurred in any of the patients. Two-scope-guided tractogastrostomy for treatment of external pancreatic fistula due to disconnected pancreatic duct syndrome is a feasible technique and can be further evaluated.
PubMed: 38654964
DOI: 10.1055/a-2290-0768 -
Signal Transduction and Targeted Therapy Apr 2024The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2...
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
Topics: Animals; Humans; Male; Mice; Angiotensin-Converting Enzyme 2; COVID-19; Fibroblast Growth Factor 7; Human Embryonic Stem Cells; Insulin Secretion; Islets of Langerhans; Organoids; SARS-CoV-2
PubMed: 38654010
DOI: 10.1038/s41392-024-01790-8 -
Biochimica Et Biophysica Acta.... Jun 2024Glucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood...
OBJECTIVE
Glucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells.
METHODS
The effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1), and the murine pancreatic α cell line αTC1-6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay.
RESULTS
Under both normal- and high-fat diet conditions, Gcg-Piezo1 mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1-6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects.
CONCLUSION
Our study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.
Topics: Animals; Glucagon-Secreting Cells; Glucagon; Mice; Ion Channels; Mice, Knockout; Diet, High-Fat; Male; Signal Transduction; Insulin; Cell Line; Mechanistic Target of Rapamycin Complex 1; Mechanotransduction, Cellular; Mice, Inbred C57BL; Proglucagon; Pyrazines; Thiadiazoles
PubMed: 38653360
DOI: 10.1016/j.bbadis.2024.167185 -
Frontiers in Immunology 2024Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness... (Review)
Review
Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption. Alternatively, porcine islets have been considered as another source of insulin-secreting cells for transplantation in T1D patients, though xeno-transplants raise concerns over the risk of endogenous retrovirus transmission and immunological incompatibility. As a result, technological advancements have been made to protect transplanted islets from immune rejection and inflammation, ideally in the absence of chronic immunosuppression, to improve the outcomes and accessibility of allogeneic islet cell replacement therapies. These include the use of microencapsulation or macroencapsulation devices designed to provide an immunoprotective environment using a cell-impermeable layer, preventing immune cell attack of the transplanted cells. Other up and coming advancements are based on the use of stem cells as the starting source material for generating islet cells 'on-demand'. These starting stem cell sources include human induced pluripotent stem cells (hiPSCs) that have been genetically engineered to avoid the host immune response, curated HLA-selected donor hiPSCs that can be matched with recipients within a given population, and multipotent stem cells with natural immune privilege properties. These strategies are developed to provide an immune-evasive cell resource for allogeneic cell therapy. This review will summarize the immunological challenges facing islet transplantation and highlight recent bio-engineering and cell-based approaches aimed at avoiding immune rejection, to improve the accessibility of islet cell therapy and enhance treatment outcomes. Better understanding of the different approaches and their limitations can guide future research endeavors towards developing more comprehensive and targeted strategies for creating a more tolerogenic microenvironment, and improve the effectiveness and sustainability of islet transplantation to benefit more patients.
Topics: Islets of Langerhans Transplantation; Humans; Animals; Diabetes Mellitus, Type 1; Graft Rejection; Biomedical Engineering; Islets of Langerhans
PubMed: 38650946
DOI: 10.3389/fimmu.2024.1375177 -
Gan To Kagaku Ryoho. Cancer &... Apr 2024The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the...
BACKGROUND
The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the emergence of strain mutations, the number of infected people shows a wavy course. I have experienced a case of gastric cancer that underwent chemotherapy including an immune checkpoint inhibitors(ICI) early after COVID-19, so I will report it including a discussion.
CASE
A 71-year-old man. The patient visited our hospital with a chief complaint of stomach discomfort, and gastrointestinal endoscopy revealed advanced gastric cancer accompanied by narrowing of the gastric lumen. The histopathological examination showed a poorly differentiated adenocarcinoma. A CT scan of the chest and abdomen showed thickening of the entire gastric wall, indicating the presence of enlarged adjacent lymph nodes and infiltration into adjacent organs. No other obvious distant metastases were observed. Staging laparoscopy was performed, it revealed infiltration of the posterior wall of the stomach into the celiac artery and anterior surface of the pancreas. We determined that curative resection would be difficult. As a result of planning chemotherapy for locally advanced gastric cancer, the patient contracted COVID-19 due to a hospital- acquired infection. The patient's COVID-19 infection was managed with supportive care alone without severe complications, and they recovered within the course of treatment. Two weeks after the onset of the infection, chemotherapy(FOLFOX+ Nivo)was initiated. The patient completed up to 9 courses of chemotherapy, and the treatment response was determined to be stable disease(SD). Due to a tendency of stenosis in the gastric lumen, the possibility of future dilation procedures was considered. As a result, the patient underwent second-line chemotherapy with a combination of wPTX+RAM. After completing 1 course of treatment, the patient developed drug-induced interstitial pneumonia, which was managed with intensive care and steroid pulse therapy, resulting in improvement. There was progression of gastric lumen stenosis, and an endoscopic dilation procedure/stent placement was performed. Subsequently, there was a rapid increase in malignant ascites and a decline in activities of daily living(ADL), leading to palliative care. Unfortunately, the patient succumbed to cancer-related complications 10 months after the diagnosis.
DISCUSSION
In this case, the serial antibody titers of COVID-19 also indicated the sustained effectiveness of the multi-drug combination chemotherapy. The treatment course suggests a suspicion of drug-induced interstitial pneumonia due to PTX/RAM, but the long-term imaging follow-up implies that ICI may be the cause. When using ICI, COVID-19 infection alone may pose a potential risk factor.
Topics: Humans; Stomach Neoplasms; COVID-19; Aged; Male; Lung Diseases, Interstitial; Immune Checkpoint Inhibitors; Pandemics; Antineoplastic Combined Chemotherapy Protocols; Adenocarcinoma
PubMed: 38644324
DOI: No ID Found -
Metabolism: Clinical and Experimental Jul 2024Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from... (Review)
Review
Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic β-cells to meet the demand for insulin due to a relative β-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.
Topics: Humans; COVID-19; SARS-CoV-2; Diabetes Mellitus; Diabetes Mellitus, Type 1; Virus Diseases; Insulin-Secreting Cells; Diabetes Mellitus, Type 2
PubMed: 38642828
DOI: 10.1016/j.metabol.2024.155917 -
American Journal of Surgery Apr 2024Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after...
BACKGROUND
Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after pancreas-preserving duodenectomy (PPrD) with potentially less morbidity.
METHODS
Retrospective cohort of all adult (age >18) patients who underwent PPrD with curative intent of a neoplasm in or invading into the duodenum at our institution from 2011 to 2022 (n = 29), excluding tumors involving the Ampulla of Vater or the pancreas. Statistical analyses were performed using STATA.
RESULTS
R0 resection was achieved in 93 % patients. Ten (34.4 %) experienced postoperative complications (13.7 % within Clavien-Dindo III-V). PPrD patients had lower rates of pancreatic leak, delayed gastric emptying, and deep surgical site infection.
CONCLUSIONS
In this case series, we demonstrate PPrD is safe and effective, with a high rate of complete resection and lower complication rate than that seen in pancreaticoduodenectomy.
PubMed: 38641448
DOI: 10.1016/j.amjsurg.2024.04.017 -
Khirurgiia 2024To develop a method for direct transfistulous ultrasound in minimally invasive treatment of infected pancreatic necrosis.
OBJECTIVE
To develop a method for direct transfistulous ultrasound in minimally invasive treatment of infected pancreatic necrosis.
MATERIAL AND METHODS
There were 148 patients with infected pancreatic necrosis between 2015 and 2019 at the Krasnodar City Clinical Hospital No. 2. Drainage with 28-32 Fr tubes was carried out at the first stage, endoscopic transfistulous sequestrectomy - at the second stage (19 (12.8%) patients). In 84 (56.8%) patients, we applied original diagnostic method (transfistulous ultrasonic assessment of inflammatory focus).
RESULTS
There were 3 accesses to omental bursa in 93 (62.8%) patients and 2 in 43 (29.1%) patients. We also performed 2 access to retroperitoneal space in 63 (42.6%) patients and 1 access in 38 (25.8%) cases. Transfistulous ultrasound was used once in 19 (22.6%) patients, twice in 28 (33.3%) and 3 times in 37 (44.1%) patients. Examination was not performed in 18 (12.2%) patients due to the following reasons: migration of drainage catheters - 5, non-rectilinear fistulous tract - 13. No complications were observed.
CONCLUSION
Transfistulous ultrasound makes it possible to diagnose pathological changes in the pancreas and parapancreatic tissue at various stages of surgical treatment.
Topics: Humans; Pancreatitis, Acute Necrotizing; Treatment Outcome; Pancreas; Minimally Invasive Surgical Procedures; Endoscopy; Intraabdominal Infections; Drainage; Necrosis
PubMed: 38634582
DOI: 10.17116/hirurgia202404138 -
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