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1.
Mod Pathol ; : 100585, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39094734

ABSTRACT

Inactivating alterations in the SWItch/Sucrose Non-Fermentable (SWI/SNF) Chromatin Remodeling Complex subunits have been described in multiple tumor types. Recent studies focused on SMARC subunits of this complex to understand their relationship with tumor characteristics and therapeutic opportunities. To date, pancreatic cancer with these alterations has not been well-studied, although isolated cases of undifferentiated carcinomas have been reported. Herein, we screened 59 pancreatic undifferentiated carcinomas for alterations in SWI/SNF complex-related [SMARCB1 (BAF47/INI1), SMARCA4 (BRG1), SMARCA2 (BRM)] proteins and/or genes using immunohistochemistry (IHC) and/or next-generation sequencing (NGS). Cases with alterations in SWI/SNF complex-related proteins/genes were compared to cases without alterations, as well as to 96 conventional pancreatic ductal adenocarcinomas (PDAC). In all tumor groups, MMR and PD-L1 protein expression were also evaluated. Thirty of 59 (51%) undifferentiated carcinomas had a loss of SWI/SNF complex-related protein expression or gene alteration. Twenty-seven of 30 (90%) SWI/SNF-deficient undifferentiated carcinomas had rhabdoid morphology [vs. 9/29 (31%) SWI/SNF-retained undifferentiated carcinomas; p < 0.001] and all expressed cytokeratin, at least focally. Immunohistochemically, SMARCB1 protein expression was absent in 16/30 (53%) cases, SMARCA2 in 4/30 (13%), and SMARCA4 in 4/30 (13%); both SMARCB1 and SMARCA2 protein expressions were absent in 1/30 (3%). Five of 8 (62.5%) SWI/SNF-deficient undifferentiated carcinomas that displayed loss of SMARCB1 protein expression by IHC were found to have corresponding SMARCB1 deletions by NGS. Analysis of canonical driver mutations for PDAC in these cases showed KRAS (2/5) and TP53 (2/5) abnormalities. Median CPS for PD-L1 (E1L3N) was significantly higher in the undifferentiated carcinomas with/without SWI/SNF deficiency compared to the conventional PDACs (p < 0.001). SWI/SNF-deficient undifferentiated carcinomas were larger (p < 0.001) and occurred in younger patients (p < 0.001). Patients with SWI/SNF-deficient undifferentiated carcinoma had worse overall survival compared to patients with SWI/SNF-retained undifferentiated carcinoma (p = 0.004) and PDAC (p < 0.001). Our findings demonstrate that SWI/SNF-deficient pancreatic undifferentiated carcinomas are frequently characterized by rhabdoid morphology, exhibit highly aggressive behavior, and have a negative prognostic impact. The ones with SMARCB1 deletions appear to be frequently KRAS wild-type. Innovative developmental therapeutic strategies targeting this genomic basis of the SWI/SNF complex and the therapeutic implications of EZH2 inhibition (NCT03213665), SMARCA2 degrader (NCT05639751), or immunotherapy are currently under investigation.

2.
Abdom Radiol (NY) ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115682

ABSTRACT

PURPOSE: Tumoral heterogeneity poses a challenge for personalized cancer treatments. Especially in metastasized cancer, it remains a major limitation for successful targeted therapy, often leading to drug resistance due to tumoral escape mechanisms. This work explores a non-invasive radiomics-based approach to capture textural heterogeneity in liver lesions and compare it between colorectal cancer (CRC) and pancreatic cancer (PDAC). MATERIALS AND METHODS: In this retrospective single-center study 73 subjects (42 CRC, 31 PDAC) with 1291 liver metastases (430 CRC, 861 PDAC) were segmented fully automated on contrast-enhanced CT images by a UNet for medical images. Radiomics features were extracted using the Python package Pyradiomics. The mean coefficient of variation (CV) was calculated patient-wise for each feature to quantify the heterogeneity. An unpaired t-test identified features with significant differences in feature variability between CRC and PDAC metastases. RESULTS: In both colorectal and pancreatic liver metastases, interlesional heterogeneity in imaging can be observed using quantitative imaging features. 75 second-order features were extracted to compare the varying textural characteristics. In total, 18 radiomics features showed a significant difference (p < 0.05) in their expression between the two malignancies. Out of these, 16 features showed higher levels of variability within the cohort of pancreatic metastases, which, as illustrated in a radar plot, suggests greater textural heterogeneity for this entity. CONCLUSIONS: Radiomics has the potential to identify the interlesional heterogeneity of CT texture among individual liver metastases. In this proof-of-concept study for the quantification and comparison of imaging-related heterogeneity in liver metastases a variation in the extent of heterogeneity levels in CRC and PDAC liver metastases was shown.

3.
Clin Transplant ; 38(8): e15386, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39087488

ABSTRACT

BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.


Subject(s)
Graft Survival , Lymphoproliferative Disorders , Pancreas Transplantation , Postoperative Complications , Humans , Pancreas Transplantation/adverse effects , Male , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/epidemiology , Female , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Follow-Up Studies , Risk Factors , Prognosis , Middle Aged , Incidence , Survival Rate , Retrospective Studies , Graft Rejection/etiology , Graft Rejection/mortality , Kidney Transplantation/adverse effects , Young Adult
4.
Article in English | MEDLINE | ID: mdl-39087927

ABSTRACT

OBJECTIVE: To assess the capacity of fetal pancreatic size, before standard blood testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. RESULTS: Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). CONCLUSIONS: Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

5.
J Pediatr Genet ; 13(3): 237-244, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39086451

ABSTRACT

Although 40 years have passed since the first case of DiGeorge's syndrome was described, and the knowledge about this disorder has steadily increased since that time, 22q11.2 deletion syndrome (DS) remains a challenging diagnosis because its clinical presentation varies widely. We describe an infant with 22q11.2 DS who presented with annular pancreas, anorectal malformation, Morgagni-type congenital diaphragmatic hernia, and ventricular septal defect. This constellation of anomalies has never been described in DiGeorge's syndrome. Here, we provide a case presentation and a thorough review of the literature.

6.
World J Gastrointest Surg ; 16(7): 2031-2039, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39087122

ABSTRACT

BACKGROUND: The consistency of pancreatic apparent diffusion coefficient (ADC) values and intravoxel incoherent motion (IVIM) parameter values across different magnetic resonance imaging (MRI) devices significantly impacts the patient's diagnosis and treatment. AIM: To explore consistency in image quality, ADC values, and IVIM parameter values among different MRI devices in pancreatic examinations. METHODS: This retrospective study was approved by the local ethics committee, and informed consent was obtained from all participants. In total, 22 healthy volunteers (10 males and 12 females) aged 24-61 years (mean, 28.9 ± 2.3 years) underwent pancreatic diffusion-weighted imaging using 3.0T MRI equipment from three vendors. Two independent observers subjectively scored image quality and measured the pancreas's overall ADC values and signal-to-noise ratios (SNRs). Subsequently, regions of interest (ROIs) were delineated for the IVIM parameters (true diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction) using post-processing software. These ROIs were on the head, body, and tail of the pancrease. The subjective image ratings were assessed using the kappa consistency test. Intraclass correlation coefficients (ICCs) and mixed linear models were used to evaluate each device's quantitative parameter values. Finally, a pairwise analysis of IVIM parameter values across each device was performed using Bland-Altman plots. RESULTS: The Kappa value for the subjective ratings of the different observers was 0.776 (P < 0.05). The ICC values for inter-observer and intra-observer agreements for the quantitative parameters were 0.803 [95% confidence interval (CI): 0.684-0.880] and 0.883 (95%CI: 0.760-0.945), respectively (P < 0.05). The ICCs for the SNR between different devices was comparable (P > 0.05), and the ICCs for the ADC values from different devices were 0.870, 0.707, and 0.808, respectively (P < 0.05). Notably, only a few statistically significant inter-device agreements were observed for different IVIM parameters, and among those, the ICC values were generally low. The mixed linear model results indicated differences (P < 0.05) in the f-value for the pancreas head, D-value for the pancreas body, and D-value for the pancreas tail obtained using different MRI machines. The Bland-Altman plots showed significant variability at some data points. CONCLUSION: ADC values are consistent among different devices, but the IVIM parameters' repeatability is moderate. Therefore, the variability in the IVIM parameter values may be associated with using different MRI machines. Thus, caution should be exercised when using IVIM parameter values to assess the pancreas.

7.
Cureus ; 16(7): e63603, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39087146

ABSTRACT

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors that predominantly affect young females and are typically located in the body and tail of the pancreas. Here, we present the case of a 59-year-old male with a large, heavily calcified SPN in the pancreatic head. His surgical history includes an aborted pancreaticoduodenectomy due to vascular involvement, followed by a gastrojejunostomy. Twenty years after the initial discovery, a pancreaticoduodenectomy was performed - the first of its kind - where the pancreas was completely atrophied, and no pancreaticojejunostomy was performed. Histological examination revealed typical features of SPN. This case demonstrates that even with relatively large lesions in a male patient over an extended duration, SPNs can still exhibit favorable features, highlighting the absence of specific preoperative markers for aggressive tumors. Therefore, unless there is an absolute contraindication, complete resection of all SPNs remains advisable.

8.
Acta Radiol Open ; 13(8): 20584601241259847, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39091589

ABSTRACT

Lipomatous pseudohypertrophy of the pancreas (LPH) is a rare disease in which the pancreatic parenchyma is replaced with mature adipose tissue. It is an idiopathic condition whose diagnosis is made based on histopathological analyses. Herein, we report the case of a 50-year-old male patient with a lipomatous mass in the head of the pancreas on computed tomography for close examination of a renal tumor. We suspected liposarcoma, and laparotomy was performed. However, histological analyses revealed LPH. Several imaging findings of LPH can enable a noninvasive diagnosis and help its clinical approach.

9.
Acta Radiol Open ; 13(8): 20584601241269617, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39091590

ABSTRACT

Ectopic pancreas within the mesentery is rare. In this case report, a 61-year-old man with an ectopic pancreas within the jejunal mesentery for over 20 years developed chronic pancreatitis that progressed to acute exacerbation. Our computed tomography (CT) performed for acute abdomen assessment suggested acute appendicitis or Meckel's diverticulitis. However, a CT scan taken 20 years ago revealed a structure indicative of an ectopic pancreas in the mesentery, and further imaging findings taken 10 and 4 years ago confirmed progression to chronic pancreatitis. Furthermore, we found a pancreatic stone confined in the luminal structure that corresponded to the main pancreatic duct; this stone eventually caused acute exacerbation. In summary, we report a case of mesenteric ectopic pancreas that showed typical findings of progression and acute exacerbation of chronic pancreatitis on CT.

10.
Sci Rep ; 14(1): 17450, 2024 08 12.
Article in English | MEDLINE | ID: mdl-39134590

ABSTRACT

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed ß-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with ß-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.


Subject(s)
Diabetes Mellitus, Type 2 , Disease Models, Animal , Insulin Receptor Substrate Proteins , Insulin-Secreting Cells , Mesocricetus , Animals , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Insulin Receptor Substrate Proteins/metabolism , Insulin Receptor Substrate Proteins/genetics , Cricetinae , Insulin/metabolism , Gene Knockout Techniques , Male , Humans , Blood Glucose/metabolism
11.
Article in English | MEDLINE | ID: mdl-39128875

ABSTRACT

We introduce a novel notation system for pancreatectomy designed to provide a clear and concise representation of surgical procedures. As surgical techniques and the scope of pancreatic surgeries continue to diversify, existing communication methods among medical professionals regarding the specifics of the surgeries have proven inadequate. Our proposed notation system clearly indicates the approach (open, laparoscopic, or robot-assisted), type of surgery (e.g., pancreatoduodenectomy, distal pancreatectomy), and extent of resection and accompanying resected organs or vasculature. These elements are all recorded in this order by using abbreviations. For example, a pancreatoduodenectomy with pancreatic transection just above the SMA and combined resection of the SMV would be noted as "OPD(hb')-SMV". This new notation system allows for concise expression of the essential information on performed procedures of pancreatic resection, leading to smooth information sharing. This initiative is an essential step towards standardizing pancreatic surgery documentation on a global scale. Here, we present the development and application of this system, highlighting its potential to transform surgical communication and documentation.

12.
Stem Cell Res Ther ; 15(1): 243, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39113141

ABSTRACT

Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cell Transplantation/methods , Animals , Biological Products/pharmacology , Biological Products/therapeutic use , Wound Healing/drug effects
13.
Neurosci Lett ; 837: 137919, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39089611

ABSTRACT

The sympathetic nervous system is crucial for the regulation of visceral organ function. For instance, the activation of the sympathetic nervous system promotes glycogenolysis in the liver and modulates glucagon and insulin release from the pancreas, thereby raising blood glucose levels. A decrease in sympathetic nerve activity has the opposite effect. Although such acute effects of sympathetic activity changes have been studied, their long-term outcomes have not been previously examined. In this study, we removed the celiac/superior mesenteric ganglia, where sympathetic postganglionic neurons innervating pancreas and liver locate, and examined its effects on glucose homeostasis and islet size several weeks after surgery. Consistent with the reduction in gluconeogenesis, glucose tolerance improved in gangliectomized mice. However, contrary to our expectation that the inhibition of pancreatic function by sympathetic nerves would be relieved with gangliectomy, insulin or C-peptide release did not increase. Examining the size distribution of pancreatic islets, we identified that the gangliectomy led to a size reduction in large islets and a decrease in the proportion of α and ß cells within each islet, as analyzed by immunostaining for insulin and glucagon, respectively. These results indicate that the absence of sympathetic nerve activity reduces the size of the pancreatic islets within a few weeks to reinstate the homeostatic mechanism of blood glucose levels.


Subject(s)
Ganglia, Sympathetic , Glucagon , Islets of Langerhans , Animals , Islets of Langerhans/metabolism , Ganglia, Sympathetic/metabolism , Glucagon/metabolism , Male , Blood Glucose/metabolism , Insulin/metabolism , Mice, Inbred C57BL , Mice , Organ Size , Glucose Tolerance Test , Ganglionectomy/methods
14.
Turk J Gastroenterol ; 35(3): 239-254, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39128120

ABSTRACT

BACKGROUND/AIMS:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it. MATERIALS AND METHODS:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured. RESULTS:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates. CONCLUSION:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.


Subject(s)
Elasticity Imaging Techniques , Fatty Liver , Metabolic Syndrome , Pancreatic Diseases , Humans , Turkey/epidemiology , Female , Middle Aged , Male , Prevalence , Adult , Risk Factors , Metabolic Syndrome/epidemiology , Pancreatic Diseases/epidemiology , Fatty Liver/epidemiology , Body Mass Index , Aged , Pancreas/diagnostic imaging , Pancreatic Elastase/analysis , Waist Circumference , Insulin Resistance , Blood Glucose/analysis , Blood Glucose/metabolism
15.
Int J Mol Sci ; 25(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125590

ABSTRACT

Ras-related Rap1A GTPase is implicated in pancreas ß-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein ß (Ero1lß), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lß and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.


Subject(s)
Insulin , Mice, Inbred C57BL , Pancreas , Proteomics , Signal Transduction , rap1 GTP-Binding Proteins , Animals , rap1 GTP-Binding Proteins/metabolism , rap1 GTP-Binding Proteins/genetics , Mice , Proteomics/methods , Insulin/metabolism , Pancreas/metabolism , Insulin-Secreting Cells/metabolism , Mice, Knockout , Guanine Nucleotide Exchange Factors/metabolism , Guanine Nucleotide Exchange Factors/genetics , Insulin Secretion , Male , Glucose/metabolism
16.
Acta Diabetol ; 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126517

ABSTRACT

AIM: The purpose of this study was to develop a questionnaire to examine the future acceptance of Automatic insulin delivery systems (AIDs), their perceived usefulness, ease of use, and trust in the device in subjects with type 1 diabetes (T1D). METHODS: A questionnaire in Italian, based on the Technology Acceptance Model, was developed to examine intention to use AIDs, considered as a measure of future acceptance, and its determinants to use the system. A total of 43 questions for children and 46 for parents were included, and a 5-point Likert scale was used. RESULTS: 239 subjects with T1D using multiple daily injections (MDI) or sensor-augmented pump (SAP) and their parents completed the questionnaire. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient for children and adolescents was 0.92 and 0.93 for parents, indicating excellent internal consistency in both groups. Parent-youth agreement was 0.699 (95% confidence interval: 0.689-0.709), indicating a good agreement between the two evaluations. Factor analysis identified measurement factors for the "artificial pancreas (AP)-acceptance labeled benefits and hassles of AIDs, and the internal consistency of the total scale was alpha = 0.94 for subjects with T1D and 0.95 for parents. The level of AP acceptance was more than neutral: 3.91 ± 0.47 and 3.99 ± 0.43 (p = 0.07) for youths and parents, respectively (possible score range 1 to 5, neutral score is 3.0). Parents reported higher scores in the benefit items than children-adolescents (p = 0.04). CONCLUSIONS: We developed a new questionnaire based on the items available in the literature, and we demonstrated that the "AP-acceptance" reveals a meaningful factor structure, good internal reliability, and agreement between parent-young people evaluations. This measure could be a valuable resource for clinicians and researchers to assess AP acceptance in pediatric patients with T1D and their parents. This patient profiling approach could help to enroll candidates for AIDs with proper expectations and who most likely will benefit from the system.

17.
Biomater Adv ; 164: 213980, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39126900

ABSTRACT

New therapeutic approaches to treat type 1 diabetes mellitus relies on pancreatic islet transplantation. Here, developing immuno-isolation strategies is essential to eliminate the need for systemic immunosuppression after pancreatic islet grafts. A solution is the macro-encapsulation of grafts in semipermeable matrixes with a double function: separating islets from host immune cells and facilitating the diffusion of insulin, glucose, and other metabolites. This study aims to synthesize and characterize different types of gelatin-collagen matrixes to prepare a macro-encapsulation device for pancreatic islets that fulfill these functions. While natural polymers exhibit superior biocompatibility compared to synthetic ones, their mechanical properties are challenging to reproduce. To address this issue, we conducted a comparative analysis between photo-crosslinked gelatin matrixes and chemically crosslinked collagen matrixes. We show that the different crosslinkers and polymerization methods influence the survival and glucose-stimulated insulin production of pancreatic ß cells (INS1) in vitro, as well as the in vitro and in vivo stability of the matrix and the immuno-isolation in vivo. Among the matrixes, the stiff multilayer GelMA matrixes (8.5 kPa), fabricated by digital light processing, were the best suited for pancreatic ß cells macro-encapsulation regarding these parameters. Within the alveoli of this matrix, pancreatic ß cells spontaneously formed aggregates.

18.
World J Clin Cases ; 12(22): 5140-5144, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39109006

ABSTRACT

BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.

19.
Magn Reson Med Sci ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39111877

ABSTRACT

PURPOSE: This study aimed to evaluate the feasibility of single-shot echo planar diffusion-weighted imaging with compressed SENSE (EPICS-DWI) for pancreas assessment by comparing with single-shot echo planar DWI with parallel imaging (PI-DWI). METHODS: This multicenter prospective study included 27 consecutive participants with untreated pancreatic ductal adenocarcinoma (PDAC) (15 men; mean age, 67 ± 10 years) who underwent pancreatic protocol MRI including both PI-DWI and EPICS-DWI. Two radiologists independently and randomly reviewed the high b-value DWI images and qualitatively assigned confidence scores for overall image quality, image noise, pancreas conspicuity, and PDAC conspicuity using a 5-point scale. One radiologist measured the PDAC-to-pancreas contrast-to-noise-ratio (CNR) on high b-value DWI images and the apparent diffusion coefficient (ADC) value of PDAC. Qualitative and quantitative parameters were compared between PI-DWI and EPICS-DWI using the Wilcoxon signed-rank test. RESULTS: The confidence scores for overall image quality (P < 0.001 in both radiologists) and image noise (P < 0.001 in both radiologists) were higher in EPICS-DWI than in PI-DWI. The pancreas conspicuity was better in EPICS-DWI than in PI-DWI in one of the radiologists (P = 0.02 and 0.06). The PDAC conspicuity was comparable between PI-DWI and EPICS-DWI (P > 0.99 in both radiologists). The PDAC-to-pancreas CNR was higher in EPICS-DWI than in PI-DWI (P = 0.02), while the ADC value of PDAC in PI-DWI was not significantly different compared to that in EPICS-DWI (P = 0.48). CONCLUSION: The image quality and PDAC-to-pancreas CNR was improved in EPICS-DWI compared to PI-DWI. However, the conspicuity and ADC value of PDAC were comparable between PI-DWI and EPICS-DWI.

20.
Eur Radiol ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112752

ABSTRACT

OBJECTIVES: To develop and validate imaging-based models for predicting the malignancy risk of intraductal papillary mucinous neoplasm (IPMN). MATERIALS AND METHODS: We retrospectively analyzed data from 241 IPMN patients who underwent preoperative CT and MRI for model development. Cyst size, presence and size of the enhancing mural nodule (EMN), main pancreatic duct (MPD) diameter, thickened/enhancing cyst wall, abrupt MPD caliber change with distal atrophy, and lymphadenopathy were assessed. Multiple logistic regression models predicting malignancy risk were created using either continuous (Model C) or dichotomized variables (Model D) using these imaging features. Validation included internal (n = 55) and external (n = 43) datasets. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and compared with that of the international guideline-based model (Model F). RESULTS: Model C identified age, EMN size, MPD diameter, and lymphadenopathy as independent predictors on CT, and age and presence and size of EMN on MRI. Model D identified age ≥ 68, cyst size ≥ 31 mm, EMN ≥ 6 mm, MPD ≥ 7 mm, and lymphadenopathy as independent predictors on CT, and age ≥ 68, EMN ≥ 4.5 mm, and lymphadenopathy on MRI. Model C (AUC, 0.763-0.899) performed slightly better than Model D (AUC, 0.753-0.912) without statistical significance. No significant difference was observed between Models C and F (AUC, 0.729-0.952). Combining Model C with obstructive jaundice improved performance (AUC, 0.802-0.941) without statistical significance. CONCLUSION: Our imaging-based models effectively predicted the malignancy risk of IPMNs, comparable to international consensus guidelines. CLINICAL RELEVANCE STATEMENT: Imaging features are important for predicting the malignant potential of IPMNs. Our imaging-based model may help determine surgical candidacy for patients with IPMNs. KEY POINTS: Non-invasively determining the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) allows for appropriate treatment decision-making We identified multiple imaging features that are associated with malignant transformation and developed models for this prediction. Our model performs comparably with international consensus guidelines in predicting the malignant potential of IPMNs.

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