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Journal of Neuroendocrinology Aug 2023This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine...
This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Insulinoma; Gastrinoma; Glucagonoma
PubMed: 37578384
DOI: 10.1111/jne.13318 -
Kidney International Mar 2024Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney... (Review)
Review
Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.
Topics: Adult; Humans; Child; Glomerulosclerosis, Focal Segmental; Sclerosis; Kidney Transplantation; Transplantation, Homologous; Nephrotic Syndrome; Recurrence; Plasmapheresis
PubMed: 38142038
DOI: 10.1016/j.kint.2023.10.017 -
Gastroenterology Oct 2023Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with...
BACKGROUND & AIMS
Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance.
METHODS
International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer.
RESULTS
Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5).
CONCLUSIONS
The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.
Topics: Humans; Pancreatic Intraductal Neoplasms; Carcinoma, Pancreatic Ductal; Retrospective Studies; Pancreatic Neoplasms; Pancreas; Cysts; Pancreatic Ducts
PubMed: 37406887
DOI: 10.1053/j.gastro.2023.06.022 -
Journal of Materials Chemistry. B Nov 2023Bioprinting, as a groundbreaking technology, enables the fabrication of biomimetic tissues and organs with highly complex structures, multiple cell types, mechanical... (Review)
Review
Bioprinting, as a groundbreaking technology, enables the fabrication of biomimetic tissues and organs with highly complex structures, multiple cell types, mechanical heterogeneity, and diverse functional gradients. With the growing demand for organ transplantation and the limited number of organ donors, bioprinting holds great promise for addressing the organ shortage by manufacturing completely functional organs. While the bioprinting of complete organs remains a distant goal, there has been considerable progress in the development of bioprinted transplantable tissues and organs for regenerative medicine. This review article recapitulates the current achievements of organ 3D bioprinting, primarily encompassing five important organs in the human body (, the heart, kidneys, liver, pancreas, and lungs). Challenges from cellular techniques, biomanufacturing technologies, and organ maturation techniques are also deliberated for the broad application of organ bioprinting. In addition, the integration of bioprinting with other cutting-edge technologies including machine learning, organoids, and microfluidics is envisioned, which strives to offer the reader the prospect of bioprinting in constructing functional organs.
Topics: Humans; Tissue Engineering; Bioprinting; Printing, Three-Dimensional; Regenerative Medicine; Heart
PubMed: 37850299
DOI: 10.1039/d3tb01630g -
Hepatology (Baltimore, Md.) Oct 2023The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism...
BACKGROUND AND AIMS
The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive.
APPROACH AND RESULTS
A mouse model of a high-fat diet-induced NASH was used in the myeloid-specific stimulator of interferon genes (STING) knockout or STING/yes-associated protein (YAP) double knockout mice. Liver injury, lipid accumulation, lipid droplet proteins, autophagic genes, chromatin immunoprecipitation coupled with massively parallel sequencing, and RNA-Seq were assessed in vivo and in vitro . We found that high-fat diet-induced oxidative stress activates STING and YAP pathways in hepatic macrophages. The acrophage STING deficiency (myeloid-specific STING knockout) enhances nuclear YAP activity, reduces lipid accumulation, and increases autophagy-related proteins ATG5, ATG7, and light chain 3B but diminishes LD protein perilipin 2 expression. However, disruption of STING and YAP (myeloid STING and YAP double knockout) increases serum alanine aminotransferase and triglyceride levels and reduces β-fatty acid oxidation gene expression but augments perilipin 2 levels, exacerbating high-fat diet-induced lipid deposition. Chromatin immunoprecipitation coupled with massively parallel sequencing reveals that macrophage YAP targets transmembrane protein 205 and activates AMP-activated protein kinase α, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase activation. Protein disulfide isomerase activates hypoxia-inducible factor-1α signaling, increases autophagosome colocalization with LDs, and promotes the degradation of perilipin 2 by interacting with chaperone-mediated autophagy chaperone HSC70.
CONCLUSIONS
The macrophage STING-YAP axis controls hepatic steatosis by reprogramming lipid metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathway. These findings highlight the regulatory mechanism of the macrophage STING-driven YAP activity on lipid control.
PubMed: 37870294
DOI: 10.1097/HEP.0000000000000638