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Molecular Genetics and Metabolism... Sep 2024Hypertriglyceridemia (HTG) is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. It is well stablished that the severe...
Hypertriglyceridemia (HTG) is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. It is well stablished that the severe cases of disease often present with an underlying genetic cause. In this study, we determined the frequency and variation spectrum of genes involved in the triglyceride metabolism in a series of Brazilian patients with severe HTG. A total of 212 patients with very high HTG, defined with fasting triglycerides (TG) ≥ 880 mg/ dL, that underwent a multi-gene panel testing were included in this research. Germline deleterious variants (i.e. Pathogenic/Likely Pathogenic (P/LP) variants) were identified in 28 out of 212 patients, reflecting an overall diagnostic yield of 13% in our cohort. Variants of unknown significance (VUS) were identified in 87 patients, and represent 80% of detected variants in this dataset. We confirm the as the most frequently mutated gene in patients with severe HTG, and we had only one suspected case of familial chylomicronemia syndrome, caused by a homozygous variant in in our cohort. Notably, we report 16 distinct and novel variants (P/LP and VUS), each of them representing a single case, not previously reported in any public databases or other studies. Our data expand our knowledge of genetic variation spectrum in patients with severe HTG in the Brazilian population, often underrepresented in public genomic databases, being also a valuable clinical resource for genetic counseling and healthcare programs in the country.
PubMed: 38933898
DOI: 10.1016/j.ymgmr.2024.101100 -
Journal of Clinical Medicine Jun 2024: Acute pancreatitis (AP) is characterized by pancreatic gland inflammation, and its clinical course ranges from mild to severe. Predicting the severity of AP early and...
Comparison of Controlling Nutritional Status Score with Bedside Index for Severity in Acute Pancreatitis Score and Atlanta Classification for Mortality in Patients with Acute Pancreatitis.
: Acute pancreatitis (AP) is characterized by pancreatic gland inflammation, and its clinical course ranges from mild to severe. Predicting the severity of AP early and reliably is important. In this study, we investigate the potential use of the Controlling Nutritional Status (CONUT) score as a prognostic marker in acute pancreatitis. : We examined 336 patients who had been hospitalized with an AP diagnosis in the internal medicine clinic. The patients included in the study were followed up for 5 years. The study analyzed the specific variables of age, gender, and AP etiology as recorded biochemical parameters for all study participants and calculated the effects of age, sex, Bedside Index of Severity in AP (BISAP), the revised Atlanta classification, and the CONUT score on mortality. : When compared with surviving patients, non-surviving patients had higher scores for BISAP, CONUT, and the Atlanta Classification ( 0.001). In the non-surviving group, hemoglobin, lymphocyte, and albumin levels were significantly lower and creatinine, uric acid, and procalcitonin levels were significantly higher compared to the surviving group ( ˂ 0.001, 0.003, ˂0.001, ˂0.001, 0.005, ˂0.001, respectively). The multivariate analysis showed a significant association of mortality with age, CONUT, and BISAP scores ( ˂ 0.003, 0.001, 0.012 respectively). The CONUT score was separated into two groups based on the median value. The predicted survival time in the group with a CONUT score > 2 (53.8 months) was significantly lower than in the group with a CONUT score ≤ 2 (63.8 months). The cumulative incidence of all-cause mortality was significantly higher in the patients with higher CONUT scores. : This study has assigned the CONUT score as an independent risk factor for mortality in AP.
PubMed: 38929944
DOI: 10.3390/jcm13123416 -
Journal of Clinical Medicine Jun 2024: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients...
: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. : We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. : Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. : Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.
PubMed: 38929894
DOI: 10.3390/jcm13123366 -
Medicina (Kaunas, Lithuania) May 2024: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed...
: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed to assess the changes in serum glucose levels associated with the first episode of AP, as well as the impact of dysglycemia on outcomes such as the severity of inflammation, the length of hospitalization, mortality, and the persistence of hyperglycemia at follow-up. : All patients experiencing their first episode of AP, who presented to the Emergency Room (ER) between 1 January 2020 and 31 December 2023, were retrospectively included. On-admission serum glucose and peak serum glucose during hospitalization were the biological markers used to assess glucose metabolism impairment, and they were correlated with outcomes of AP. : Our study included 240 patients, 46.67% (112 patients) having a biliary etiology for an AP flare. Patients with COVID-19-associated AP exhibited the highest on-admission and peak serum glucose levels (244.25 mg/dL and 305.5 mg/dL, respectively). A longer hospital stay was noted in patients with peak serum glucose levels of ≥100 mg/dL (9.49 days) compared to normoglycemic patients (6.53 days). Both on-admission and peak glucose levels were associated with elevated CRP levels during hospitalization. A total of 83.78% of patients who received antibiotics exhibited on-admission hyperglycemia, and 72.07% had peak serum glucose levels of ≥100 mg/dL. The presence of hyperglycemia at follow-up was associated with both on-admission and peak serum glucose levels of ≥100 mg/dL, as well as with a longer stay, higher CRP levels, and antibiotic use during index admission. : On-admission hyperglycemia predicts a higher inflammatory response in patients at the first episode of AP, while the presence of hyperglycemia during hospitalization is associated with imaging and biological severity and longer hospitalizations, indicating a more severe disease course. Both on-admission and peak in-hospital hyperglycemia were identified as risk factors for sustained hyperglycemia at follow-up.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Pancreatitis; Blood Glucose; Adult; Length of Stay; Hyperglycemia; COVID-19; Aged; Hospitalization; Severity of Illness Index; Biomarkers
PubMed: 38929473
DOI: 10.3390/medicina60060856 -
Children (Basel, Switzerland) May 2024Pancreatic fluid collections (PFCs) are a well-known complication of pancreatitis. PFCs operative management includes percutaneous, endoscopic or surgical drainage. Even...
Pancreatic fluid collections (PFCs) are a well-known complication of pancreatitis. PFCs operative management includes percutaneous, endoscopic or surgical drainage. Even if in adult patients, endoscopic drainage is a well-established treatment, few data are available in pediatric setting. We report our single-center experience of EUS-guided cystogastrostomy and lumen-apposing metal stent (LAMS) positioning in children with PFCs; this, at the best of our knowledge, has never been reported before. All consecutive children with PFCs between April 2020 and November 2022 were enrolled in this retrospective study. PFCs were preoperatively evaluated with MRI or CT scan. All the procedures were performed under general anesthesia. A LAMS Hot-Axios 10 × 15 mm was placed in all patients. We evaluated technical feasibility and clinical outcomes, including complications and recurrence rates. Follow-up included clinical observation, blood tests and US. EUS-guided cystogastrostomy was performed in 3 children (2 males; median age 13.2 years). Median maximum cyst diameter was 14.7 cm (range 10-22 cm). Technical and clinical success rates were 100%. No intra or post-operative complications occurred. Our experience suggests that this can be considered a safe and feasible treatment of PCFs even in the pediatric population, as long as the procedure is performed by an expert Endoscopist in a pediatric tertiary-level Center.
PubMed: 38929223
DOI: 10.3390/children11060643 -
Diagnostics (Basel, Switzerland) Jun 2024This paper introduces a novel one-dimensional convolutional neural network that utilizes clinical data to accurately detect choledocholithiasis, where gallstones...
This paper introduces a novel one-dimensional convolutional neural network that utilizes clinical data to accurately detect choledocholithiasis, where gallstones obstruct the common bile duct. Swift and precise detection of this condition is critical to preventing severe complications, such as biliary colic, jaundice, and pancreatitis. This cutting-edge model was rigorously compared with other machine learning methods commonly used in similar problems, such as logistic regression, linear discriminant analysis, and a state-of-the-art random forest, using a dataset derived from endoscopic retrograde cholangiopancreatography scans performed at Olive View-University of California, Los Angeles Medical Center. The one-dimensional convolutional neural network model demonstrated exceptional performance, achieving 90.77% accuracy and 92.86% specificity, with an area under the curve of 0.9270. While the paper acknowledges potential areas for improvement, it emphasizes the effectiveness of the one-dimensional convolutional neural network architecture. The results suggest that this one-dimensional convolutional neural network approach could serve as a plausible alternative to endoscopic retrograde cholangiopancreatography, considering its disadvantages, such as the need for specialized equipment and skilled personnel and the risk of postoperative complications. The potential of the one-dimensional convolutional neural network model to significantly advance the clinical diagnosis of this gallstone-related condition is notable, offering a less invasive, potentially safer, and more accessible alternative.
PubMed: 38928692
DOI: 10.3390/diagnostics14121278 -
Diagnostics (Basel, Switzerland) Jun 2024Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis with a multifactorial pathogenesis. Historically, it has been classified as type 1 and type 2,... (Review)
Review
Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis with a multifactorial pathogenesis. Historically, it has been classified as type 1 and type 2, according to its clinical and histological features. The diagnosis of AIP is challenging and relies on a combination of clinical, histopathologic, serologic, and imaging characteristics. In the available guidelines, the imaging hallmarks of AIP are based on cross-sectional imaging and cholangiopancreatography retrograde endoscopic findings. Endoscopic ultrasound (EUS) is generally used for pancreatic tissue acquisition to rule out pancreatic cancer and diagnose AIP with limited accuracy. Several papers reported the reliability of EUS for providing informative morphologic features of AIP. Nowadays, the improvement in the resolution of EUS conventional images and the development of new ancillary technologies have further increased the diagnostic yield of EUS: contrast-enhanced EUS and EUS elastography are non-invasive and real-time techniques that strongly support the diagnosis and management of pancreatic diseases. In this review article, we will present the role of conventional EUS and ancillary diagnostic techniques in the diagnosis of AIP to support clinicians and endosonographers in managing this condition.
PubMed: 38928649
DOI: 10.3390/diagnostics14121233 -
International Journal of Molecular... Jun 2024Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in...
Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.
Topics: Animals; Carcinoma, Pancreatic Ductal; Pancreatitis; Mice; Pancreatic Neoplasms; Biomarkers, Tumor; Humans; Prognosis; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Cell Line, Tumor; Disease Progression
PubMed: 38928326
DOI: 10.3390/ijms25126619 -
International Journal of Molecular... Jun 2024We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced... (Review)
Review
Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.
We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.
Topics: Humans; Hyperparathyroidism, Primary; Insulin Resistance; Hypercalcemia; Pancreatitis; Female; Male; Proto-Oncogene Proteins; Pancreatic Neoplasms; Multiple Endocrine Neoplasia Type 1; Parathyroid Neoplasms; Adult; Parathyroidectomy; Neuroendocrine Tumors; Pancreas
PubMed: 38928056
DOI: 10.3390/ijms25126349 -
Cancers Jun 2024Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality... (Review)
Review
Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.
PubMed: 38927885
DOI: 10.3390/cancers16122179