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Antioxidants (Basel, Switzerland) May 2024The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative... (Review)
Review
The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included ( = 41 MP; = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.
PubMed: 38929081
DOI: 10.3390/antiox13060642 -
Iranian Journal of Medical Sciences Feb 2024Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic... (Review)
Review
BACKGROUND
Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic review, we evaluated and studies on the effect of inhibition or activation of the Shh pathway on the production, differentiation, maintenance, and endocrine activity of IPCs.
METHODS
A systematic review was conducted using all available experimental studies published between January 2000 and November 2022. The review aimed at determining the effect of Shh manipulation on the differentiation of stem cells (SCs) into IPCs. Keywords and phrases using medical subject headings were extracted, and a complete search was performed in Web of Science, Embase, ProQuest, PubMed, Scopus, and Cochrane Library databases. The inclusion criteria were manipulation of Shh in SCs, SCs differentiation into IPCs, and endocrine activity of mature IPCs. Articles with incomplete data and duplications were excluded.
RESULTS
A total of 208 articles were initially identified, out of which 11 articles were included in the study. The effect of Shh inhibition in the definitive endoderm stage to produce functional IPCs were confirmed. Some studies showed the importance of Shh re-activation at late-stage differentiation for the generation of efficient IPCs. It is proposed that baseline concentrations of Shh in mature pancreatic β-cells affect insulin secretion and endocrine activities of the cells. However, Shh overexpression in pancreatic β-cells ultimately leads to improper endocrine function and inadequate glucose-sensing insulin secretion.
CONCLUSION
Accurate manipulation of the Shh signaling pathway can be an effective approach in the production and maintenance of functional IPCs.
Topics: Hedgehog Proteins; Insulin; Cell Differentiation; Signal Transduction; Insulin-Secreting Cells
PubMed: 38356490
DOI: 10.30476/ijms.2023.95425.2678 -
Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
Translational Oncology Jun 2024Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the...
INTRODUCTION
Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context.
AIM
This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps.
METHODS
This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information.
RESULT
Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin.
CONCLUSION
Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.
PubMed: 38878612
DOI: 10.1016/j.tranon.2024.102036 -
Cureus Apr 2024Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to... (Review)
Review
Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to hyperglycemia and associated long-term systemic complications and even death. Immunotherapy demonstrates beta cell function-preserving potential; however, its impact on C-peptide levels, a definitive biomarker of beta cell function, and endogenous insulin secretion remain unclear. A systematic review of various immunotherapeutic interventions is hence needed for a comprehensive assessment of their effectiveness as well as identifying research gaps and influencing future research and clinical decisions. An extensive literature search was done in PubMed, Scopus, and Cochrane Library databases using precise keywords and filters to identify relevant studies. Three independent reviewers assessed eligibility according to predetermined eligibility criteria, and data was extracted. The Cochrane risk of bias assessment tool (RoB 2.0) was used to evaluate the quality and validity of the included studies. A senior reviewer resolved discrepancies and differences of opinion between independent reviewers. A total of 11 studies were included, with 1464 study participants. Both Phase II and III trials were included. Within the included studies, four studies assessed the anti-CD3 monoclonal antibody otelixizumab as an intervention. Another anti-CD3 monoclonal antibody, teplizumab, was assessed as an intervention in four studies, whereas two studies assessed the anti-CD20 antibody rituximab and one study assessed abatacept as its interventional drug. Otelixizumab demonstrated benefits at higher doses but was associated with adverse effects like Ebstein-Barr virus reactivation and cytomegalovirus infection, while at lower doses it failed to show a significant difference in C-peptide levels or glycosylated hemoglobin (HbA1c). Teplizumab, on the other hand, showed promise in reducing C-peptide loss and exogenous insulin requirements and was associated with adverse events such as rash, lymphopenia, urinary tract infection, and cytokine release syndrome. However, these reactions were only associated with therapy initiation, and they subsided on their own. Rituximab improved C-peptide responses, and abatacept therapy demonstrated reduced loss of C-peptide, improved C-peptide levels, and lowered HbA1c. Teplizumab, rituximab, otelixizumab, and abatacept show potential for preserving beta cell function by reducing C-peptide loss in patients with type I diabetes mellitus. However, careful monitoring of adverse reactions, particularly viral infections and cytokine release syndrome, is necessary for the safe implementation of these therapies.
PubMed: 38800168
DOI: 10.7759/cureus.58981 -
Drug Discoveries & Therapeutics Jul 2023Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the...
Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.
Topics: Mice; Animals; Cornus; Diabetes Mellitus, Type 2; Polyphenols; NF-kappa B; Diabetes Mellitus, Experimental; C-Peptide; Liver; Pancreas; Insulin
PubMed: 37245985
DOI: 10.5582/ddt.2022.01097 -
Journal of Clinical Medicine Jan 2024Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies... (Review)
Review
Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.
PubMed: 38337524
DOI: 10.3390/jcm13030830 -
Scandinavian Journal of Surgery : SJS :... Jun 2024Clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) occurs in 20%-40% of patients and remains a leading cause of morbidity... (Review)
Review
BACKGROUND/AIMS
Clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) occurs in 20%-40% of patients and remains a leading cause of morbidity and increased healthcare cost in this patient group. Recently, several studies suggested decreased risk of CR-POPF with the use of peri-firing compression (PFC) technique. The aim of this report was to conduct a systematic review to get an overview of the current knowledge on the use of PFC in DP. In addition, our experience with PFC was presented.
METHODS
The systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Also, 19 patients undergoing DP with the use of PFC at Oslo University Hospital were studied. The primary endpoint was incidence of CR-POPF.
RESULTS
Seven articles reporting a total of 771 patients were ultimately included in the systematic review. Only two of these were case-control studies examining outcomes in patients with and without PFC, while the rest were case series. These were heterogeneous in terms of staplers used, cartridge selection policy, and PFC technique. Both case-control studies reported significantly reduced CR- POPF incidence with PFC. Eight (21%) of our patients developed CR-POPF after DP with PFC. Only one patient developed CR-POPF among those with pancreatic transection site thickness ⩽1.5 cm.
CONCLUSION
Evidence on potential benefits of PFC in DP is limited in quantity and quality. Our findings suggest that the use of PFC does not lead to reduction in the incidence of CR-POPF. Yet, there might be a benefit from PFC when dealing with a thin pancreas.
Topics: Humans; Pancreatic Fistula; Pancreatectomy; Postoperative Complications; Male; Female; Middle Aged; Surgical Stapling; Aged
PubMed: 37982224
DOI: 10.1177/14574969231211084 -
Cirugia Y Cirujanos 2024The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial.
MATERIALS AND METHOD
We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid's databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included.
RESULTS
The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001).
CONCLUSIONS
PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD.
Topics: Humans; Drainage; Pancreaticoduodenectomy; Preoperative Care; Postoperative Complications; Stents; Surgical Wound Infection; Randomized Controlled Trials as Topic; Gastric Emptying; Ampulla of Vater; Pancreatic Neoplasms; Common Bile Duct Neoplasms
PubMed: 38862121
DOI: 10.24875/CIRU.23000318 -
Cureus Feb 2024Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This systematic review delves into the potential of salivary biomarkers as a non-invasive means for identifying PDAC at its incipient stages. Saliva's proximity to the circulatory system enables the detection of tumor-derived biomolecules, making it an ideal candidate for mass screening. The analysis of three selected studies reveals promising candidates such as Neisseria mucosa, Fusobacterium periodonticum, polyamines, and specific long non-coding RNAs (lncRNAs). Notably, polyamines like spermine show potential in distinguishing PDAC, while lncRNAs HOX transcript antisense RNA (HOTAIR) and plasmacytoma variant translocation 1 (PVT1) exhibit superior sensitivity and specificity compared to traditional serum markers. However, challenges, including small sample sizes and a lack of validation, underscore the need for standardized diagnostic panels and large-scale collaborative studies. Advancements in nanotechnology, machine learning, and ethical considerations are crucial for harnessing the diagnostic potential of saliva. The review emphasizes the imperative for extensive clinical trials to validate salivary biomarkers, ensuring not only diagnostic accuracy but also cost-effectiveness, patient compliance, and long-term benefits in the realm of PDAC screening. Longitudinal studies are recommended to unravel temporal changes in salivary biomarkers, shedding light on disease progression and treatment response.
PubMed: 38550499
DOI: 10.7759/cureus.55003