Pub Date : 2024-10-01Epub Date: 2024-05-04DOI: 10.1097/MPA.0000000000002370
Galande Sheethal, Archana Verma, Raghvendra Mall, Kishore Vl Parsa, Ranjeet K Tokala, Ratnakar Bynigeri, Pavan Kumar Pondugala, Krishna Vemula, S Sai Latha, Divya Tej Sowpati, Surya S Singh, G V Rao, Rupjyoti Talukdar, Thirumala-Devi Kanneganti, D Nageshwar Reddy, Mitnala Sasikala
Objectives: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to lack of understanding on factor(s) triggering insulin secretory defects. Therefore, we aimed to delineate the molecular mechanism of β-cell dysfunction in CP.
Materials and methods: Transcriptomic analysis was conducted to identify endocrine-specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis of NR4A1-overexpressed (OE) MIN6 cells on NovaSeq6000 identified aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure, whereas downstream effect was examined by Fura2 AM-based fluorimetric and imaging studies. Mice with CP were treated with IFN-γ-neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion.
Results: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 μg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 μg/mg protein per minute, P = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ-neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold ( P = 0.03), showed improved insulin secretion (4.4 ± 0.2-fold, P = 0.01), and associated with increased Ca 2+ levels (2.39 ± 0.06-fold, P = 0.009).
Conclusions: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.
{"title":"Modulation of Nuclear Receptor 4A1 Expression Improves Insulin Secretion in a Mouse Model of Chronic Pancreatitis.","authors":"Galande Sheethal, Archana Verma, Raghvendra Mall, Kishore Vl Parsa, Ranjeet K Tokala, Ratnakar Bynigeri, Pavan Kumar Pondugala, Krishna Vemula, S Sai Latha, Divya Tej Sowpati, Surya S Singh, G V Rao, Rupjyoti Talukdar, Thirumala-Devi Kanneganti, D Nageshwar Reddy, Mitnala Sasikala","doi":"10.1097/MPA.0000000000002370","DOIUrl":"10.1097/MPA.0000000000002370","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to lack of understanding on factor(s) triggering insulin secretory defects. Therefore, we aimed to delineate the molecular mechanism of β-cell dysfunction in CP.</p><p><strong>Materials and methods: </strong>Transcriptomic analysis was conducted to identify endocrine-specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis of NR4A1-overexpressed (OE) MIN6 cells on NovaSeq6000 identified aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure, whereas downstream effect was examined by Fura2 AM-based fluorimetric and imaging studies. Mice with CP were treated with IFN-γ-neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion.</p><p><strong>Results: </strong>Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 μg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 μg/mg protein per minute, P = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ-neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold ( P = 0.03), showed improved insulin secretion (4.4 ± 0.2-fold, P = 0.01), and associated with increased Ca 2+ levels (2.39 ± 0.06-fold, P = 0.009).</p><p><strong>Conclusions: </strong>Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.</p>","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":" ","pages":"e760-e773"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/mpa.0000000000002389
Savannah R Smith,Juan M Sarmiento
BACKGROUNDSmall mucinous cystic neoplasms (MCN) of the pancreas are managed with operative resection in otherwise healthy patients; however, postoperative diabetes development is not considered in recommendations for resection.METHODSVia probabilistic microsimulation Markov modeling, we assessed clinical and economic implications of laparoscopic distal pancreatectomy (LDP) versus surveillance for non-DM patients with suspected MCN of 2 cm without high-risk or worrisome features. Primary outcomes included quality-adjusted life years (QALYs), medical costs (2021 USD), and incremental cost-effectiveness ratios (ICERs). We conducted sensitivity analyses to evaluate the robustness of our model to changes in input parameters. All analyses were repeated for a population with pre-DM.RESULTSSurveillance resulted in 6.52 QALYs and $61,200, while LDP accumulated 6.12 QALYs and $63,700. Almost 20% of the LDP cohort developed DM over the first 10 years, compared to 11% of the surveillance cohort. In a pre-DM cohort, LDP remained Dominated in the base case, with over 40% developing DM postoperatively. In sensitivity analyses, surveillance remained the preferred strategy in most iterations for both cohorts.CONCLUSIONSSurveillance for small suspected MCNs without high-risk features is the preferred strategy from a clinical and economic standpoint. Consensus guidelines should consider the long-term implications of postoperative diabetes development following LDP.
{"title":"Cost-effectiveness of operative intervention for mucinous cystic neoplasm: the role of post-operative diabetes.","authors":"Savannah R Smith,Juan M Sarmiento","doi":"10.1097/mpa.0000000000002389","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002389","url":null,"abstract":"BACKGROUNDSmall mucinous cystic neoplasms (MCN) of the pancreas are managed with operative resection in otherwise healthy patients; however, postoperative diabetes development is not considered in recommendations for resection.METHODSVia probabilistic microsimulation Markov modeling, we assessed clinical and economic implications of laparoscopic distal pancreatectomy (LDP) versus surveillance for non-DM patients with suspected MCN of 2 cm without high-risk or worrisome features. Primary outcomes included quality-adjusted life years (QALYs), medical costs (2021 USD), and incremental cost-effectiveness ratios (ICERs). We conducted sensitivity analyses to evaluate the robustness of our model to changes in input parameters. All analyses were repeated for a population with pre-DM.RESULTSSurveillance resulted in 6.52 QALYs and $61,200, while LDP accumulated 6.12 QALYs and $63,700. Almost 20% of the LDP cohort developed DM over the first 10 years, compared to 11% of the surveillance cohort. In a pre-DM cohort, LDP remained Dominated in the base case, with over 40% developing DM postoperatively. In sensitivity analyses, surveillance remained the preferred strategy in most iterations for both cohorts.CONCLUSIONSSurveillance for small suspected MCNs without high-risk features is the preferred strategy from a clinical and economic standpoint. Consensus guidelines should consider the long-term implications of postoperative diabetes development following LDP.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"2016 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/mpa.0000000000002390
Gretchen A Cress,Karen T Scudiero,Fuchenchu Wang,Vanessa B Patrick,Phoebe M Wood,Ying Yuan,Mark E Lowe,Aliye Uc,
OBJECTIVESThe aim of this study was to determine patient reported burdensome experiences and research interests in children with acute recurrent pancreatitis or chronic pancreatitis and their families.METHODSChildren with pancreatitis and their families completed a web-based survey. Subject prioritized rankings of symptoms or quality of life issues and topics for future research were assessed. Data are presented as family and children scores.RESULTSAmong 80 participants, 18 were children with pancreatitis and 62 were family members. Top 5 ranked symptoms or quality of life issues were:1) pain, 2) fatigue, 3) missing school, 4) upset stomach, and 5) not knowing when an attack will occur. Top 5 ranked future research topics were:1) how to prevent a pancreatitis attack, 2) how pancreatitis affects other parts of the body, 3) ways to treat or handle pain, 4) what is the cause of pancreatitis, and 5) teach doctors about pancreatitis.CONCLUSIONSThis study highlights the importance of patient and family input in caring for children with pancreatitis. The most bothersome symptoms were pain, fatigue and upset stomach. Children with pancreatitis and families would like future research to primarily focus on prevention of pancreatitis attacks, pain therapy, and complications of pancreatitis.
{"title":"PATIENT AND FAMILY INPUT TO DETERMINE EXPERIENCES AND RESEARCH INTERESTS IN PEDIATRIC PANCREATITIS: AN INSPPIRE-2 STUDY.","authors":"Gretchen A Cress,Karen T Scudiero,Fuchenchu Wang,Vanessa B Patrick,Phoebe M Wood,Ying Yuan,Mark E Lowe,Aliye Uc,","doi":"10.1097/mpa.0000000000002390","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002390","url":null,"abstract":"OBJECTIVESThe aim of this study was to determine patient reported burdensome experiences and research interests in children with acute recurrent pancreatitis or chronic pancreatitis and their families.METHODSChildren with pancreatitis and their families completed a web-based survey. Subject prioritized rankings of symptoms or quality of life issues and topics for future research were assessed. Data are presented as family and children scores.RESULTSAmong 80 participants, 18 were children with pancreatitis and 62 were family members. Top 5 ranked symptoms or quality of life issues were:1) pain, 2) fatigue, 3) missing school, 4) upset stomach, and 5) not knowing when an attack will occur. Top 5 ranked future research topics were:1) how to prevent a pancreatitis attack, 2) how pancreatitis affects other parts of the body, 3) ways to treat or handle pain, 4) what is the cause of pancreatitis, and 5) teach doctors about pancreatitis.CONCLUSIONSThis study highlights the importance of patient and family input in caring for children with pancreatitis. The most bothersome symptoms were pain, fatigue and upset stomach. Children with pancreatitis and families would like future research to primarily focus on prevention of pancreatitis attacks, pain therapy, and complications of pancreatitis.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"108 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVESEndoscopic pancreatic stenting (EPS) is an effective treatment modality for painful chronic pancreatitis. However, little is known about the factors that cause pain recurrence after stent removal, and there are no clear criteria for stent removal. We aimed to develop a prediction model for pain recurrence by identifying its risk factors.METHODSWe retrospectively reviewed 95 patients who underwent EPS due to pain for the first time using a single plastic stent between January 2007 and July 2022 at our institute. Univariate and multivariate stepwise Cox proportional hazards models were used to identify the risk factors for pain recurrence, and a prediction model was developed based on the identified factors.RESULTSOf the 95 enrolled patients, 89 (93.7%) achieved pain relief and 73 (76.8%) did stent removal. Of the 69 patients with a follow-up period ≥6 months after stent removal, 29 (42.0%) had pain recurrence during the median follow-up period of 59 months. Serum lipase level (p = 0.034) and pancreatic parenchymal thickness (p = 0.022) on computed tomography or magnetic resonance imaging were identified as independent risk factors for pain recurrence. The prediction model based on the identified factors had good discrimination ability, with a concordance index of 0.74, and could stratify pain recurrence rates.CONCLUSIONSWe identified the risk factors and developed a new prediction model for pain recurrence following stent removal. This model might be useful for decision-making in pancreatic stent management, such as deciding whether to remove a pancreatic stent, continue EPS, or convert to surgery.
{"title":"Risk factors and a prediction model for pain recurrence after pancreatic stent removal in painful chronic pancreatitis.","authors":"Tetsuya Takikawa,Kiyoshi Kume,Yu Tanaka,Kazuhiro Kikuta,Yohei Ogata,Waku Hatta,Shin Hamada,Shin Miura,Ryotaro Matsumoto,Takanori Sano,Akira Sasaki,Hidehiro Hayashi,Misako Sakano,Tomoo Manaka,Atsushi Masamune","doi":"10.1097/mpa.0000000000002392","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002392","url":null,"abstract":"OBJECTIVESEndoscopic pancreatic stenting (EPS) is an effective treatment modality for painful chronic pancreatitis. However, little is known about the factors that cause pain recurrence after stent removal, and there are no clear criteria for stent removal. We aimed to develop a prediction model for pain recurrence by identifying its risk factors.METHODSWe retrospectively reviewed 95 patients who underwent EPS due to pain for the first time using a single plastic stent between January 2007 and July 2022 at our institute. Univariate and multivariate stepwise Cox proportional hazards models were used to identify the risk factors for pain recurrence, and a prediction model was developed based on the identified factors.RESULTSOf the 95 enrolled patients, 89 (93.7%) achieved pain relief and 73 (76.8%) did stent removal. Of the 69 patients with a follow-up period ≥6 months after stent removal, 29 (42.0%) had pain recurrence during the median follow-up period of 59 months. Serum lipase level (p = 0.034) and pancreatic parenchymal thickness (p = 0.022) on computed tomography or magnetic resonance imaging were identified as independent risk factors for pain recurrence. The prediction model based on the identified factors had good discrimination ability, with a concordance index of 0.74, and could stratify pain recurrence rates.CONCLUSIONSWe identified the risk factors and developed a new prediction model for pain recurrence following stent removal. This model might be useful for decision-making in pancreatic stent management, such as deciding whether to remove a pancreatic stent, continue EPS, or convert to surgery.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"58 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/mpa.0000000000002381
Camilla Mattiuzzi,Giuseppe Lippi
{"title":"Mortality trends for acute pancreatitis during the COVID-19 pandemic in the US.","authors":"Camilla Mattiuzzi,Giuseppe Lippi","doi":"10.1097/mpa.0000000000002381","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002381","url":null,"abstract":"","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"38 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/mpa.0000000000002387
Jingyang Yin,Shixiang Guo,Jiali Yang,Renpei Xia,Huaizhi Wang
OBJECTIVESTo explore the association between PRIM2 expression and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) from multi clinic centers.METHODSSamples from PDAC patients were collected and processed to tissue microarray (TMA). PRIM2 expression was detected by immunohistochemistry (IHC) of in 127 enrolled PDAC patients, which underwent surgical resection from January 2012 to December 2018, with complete follow-up, were enrolled and grouped by PRIM2 stain level into two groups. The expression differences, the association to clinicopathologic features and the survival were evaluated by the groups. Data of RNA/protein expression and clinical features from public databases were used for validation.RESULTSPRIM2 was highly expressed in PDAC patients and associated with poor-prognosis in patients with PDAC. Association was found between increased PRIM2 levels and pathology grade (p = 0.050). Moreover, in multivariate analysis of survival, the highly expression of PRIM2 was identified as an independent risk factor for poor survival (HR1.78, p = 0.031). Analysis on public databases validated above results.CONCLUSIONSHigh expression of PRIM2 associated with poor prognosis in PDAC patients, PRIM2 could be used as an independent risk indicator.
{"title":"Increased PRIM2 expression associated with poor-prognosis in patients with pancreatic ductal adenocarcinoma.","authors":"Jingyang Yin,Shixiang Guo,Jiali Yang,Renpei Xia,Huaizhi Wang","doi":"10.1097/mpa.0000000000002387","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002387","url":null,"abstract":"OBJECTIVESTo explore the association between PRIM2 expression and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) from multi clinic centers.METHODSSamples from PDAC patients were collected and processed to tissue microarray (TMA). PRIM2 expression was detected by immunohistochemistry (IHC) of in 127 enrolled PDAC patients, which underwent surgical resection from January 2012 to December 2018, with complete follow-up, were enrolled and grouped by PRIM2 stain level into two groups. The expression differences, the association to clinicopathologic features and the survival were evaluated by the groups. Data of RNA/protein expression and clinical features from public databases were used for validation.RESULTSPRIM2 was highly expressed in PDAC patients and associated with poor-prognosis in patients with PDAC. Association was found between increased PRIM2 levels and pathology grade (p = 0.050). Moreover, in multivariate analysis of survival, the highly expression of PRIM2 was identified as an independent risk factor for poor survival (HR1.78, p = 0.031). Analysis on public databases validated above results.CONCLUSIONSHigh expression of PRIM2 associated with poor prognosis in PDAC patients, PRIM2 could be used as an independent risk indicator.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"10 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/mpa.0000000000002385
Gal Lenz,Lynn Miao,Ayelet Lenz,Jacob Mares,Janine Quijano,Heather N Zook,Hirotake Komatsu,Pablo Garcia,Kevin Ferreri,Hsun Teresa Ku,Fouad Kandeel
OBJECTIVEIslet transplantation is an effective treatment for type 1 diabetes. However, transplant success depends on quick islet assessment because islets deteriorate 2-3 days after isolation. A new tool, single-cell Western blot (scWestern), offers results within one day. In this study, we aimed to test the suitability of scWestern to detect protein markers for beta (insulin), alpha (glucagon), and delta (somatostatin) cells, the three major endocrine cell types in islets.METHODSWe characterized the antibody specificity, signal intensity, and cell identification on the scWestern platform, and then compared the islet cell composition analysis between scWestern and immunohistochemistry performed by the Integrated Islet Distribution Program (IIDP).RESULTSIslet cell composition is comparable for alpha and beta cells, but not delta cells. Protein expression levels of insulin, glucagon, and somatostatin in individual islet cells varied greatly, highlighting cell type heterogeneity. Surprisingly, scWestern revealed double-hormonal cells (~1%), co-expressing insulin and somatostatin or insulin and glucagon, in non-diabetic and non-obese adult human islets, which was confirmed by confocal immunofluorescence microscopy.CONCLUSIONSThese results demonstrate that each alpha, beta, and delta cells express varying levels of peptide hormones, and a small subpopulation co-expresses double hormones in normal human islets. The scWestern platform will enable timely assessment of beta cell mass in isolated islets before clinical transplantation.
目的胰岛移植是治疗 1 型糖尿病的有效方法。然而，移植成功与否取决于能否快速评估胰岛，因为胰岛在分离后 2-3 天就会恶化。一种新工具--单细胞 Western 印迹（scWestern）可在一天内得到结果。在本研究中，我们旨在测试单细胞 Western 印迹法是否适合检测胰岛中三种主要内分泌细胞类型--β（胰岛素）、α（胰高血糖素）和δ（体生长抑素）细胞的蛋白质标记物。方法我们对 scWestern 平台上的抗体特异性、信号强度和细胞识别进行了鉴定，然后比较了 scWestern 和综合胰岛分布计划 (IIDP) 免疫组化进行的胰岛细胞组成分析。单个胰岛细胞中胰岛素、胰高血糖素和体生长抑素的蛋白表达水平差异很大，突出表明了细胞类型的异质性。令人惊讶的是，scWestern 发现了双激素细胞（约 1%），在非糖尿病和非肥胖成人胰岛中共同表达胰岛素和体节素或胰岛素和胰高血糖素，共聚焦免疫荧光显微镜证实了这一点。scWestern平台可在临床移植前及时评估离体胰岛中β细胞的数量。
{"title":"Characterization of Human Pancreatic Islet Cells using a Single-Cell Western Blot Platform.","authors":"Gal Lenz,Lynn Miao,Ayelet Lenz,Jacob Mares,Janine Quijano,Heather N Zook,Hirotake Komatsu,Pablo Garcia,Kevin Ferreri,Hsun Teresa Ku,Fouad Kandeel","doi":"10.1097/mpa.0000000000002385","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002385","url":null,"abstract":"OBJECTIVEIslet transplantation is an effective treatment for type 1 diabetes. However, transplant success depends on quick islet assessment because islets deteriorate 2-3 days after isolation. A new tool, single-cell Western blot (scWestern), offers results within one day. In this study, we aimed to test the suitability of scWestern to detect protein markers for beta (insulin), alpha (glucagon), and delta (somatostatin) cells, the three major endocrine cell types in islets.METHODSWe characterized the antibody specificity, signal intensity, and cell identification on the scWestern platform, and then compared the islet cell composition analysis between scWestern and immunohistochemistry performed by the Integrated Islet Distribution Program (IIDP).RESULTSIslet cell composition is comparable for alpha and beta cells, but not delta cells. Protein expression levels of insulin, glucagon, and somatostatin in individual islet cells varied greatly, highlighting cell type heterogeneity. Surprisingly, scWestern revealed double-hormonal cells (~1%), co-expressing insulin and somatostatin or insulin and glucagon, in non-diabetic and non-obese adult human islets, which was confirmed by confocal immunofluorescence microscopy.CONCLUSIONSThese results demonstrate that each alpha, beta, and delta cells express varying levels of peptide hormones, and a small subpopulation co-expresses double hormones in normal human islets. The scWestern platform will enable timely assessment of beta cell mass in isolated islets before clinical transplantation.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"11 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTIONPain is the foremost complication of chronic pancreatitis (CP), affecting about 70% of patients. However, the pathophysiological understanding and management of CP-related pain is complex, likely as patients have diverse "pain phenotypes" responding differently to treatment. This study aims to develop a bedside test panel to identify distinct pain phenotypes, investigate the temporal evolution, and determine whether they can be used to predict treatment response.METHODThe INPAIN study is an international, multi-center, observational, longitudinal cohort study comprised of 4 sub-studies. The studies will prospectively enroll 400 CP patients (50 without pain and 350 with pain) and 50 control subjects, conducting biannual observations for four years. The test panel is comprised of comprehensive subjective and objective assessment parameters. Statistical analysis strategies differ across the sub-studies. A model to predict treatment efficacy will be developed using various machine learning techniques, including an artificial intelligence approach, with internal cross-validation. Trajectories in pain parameters will be characterized by graphical analysis and mixed effect models.DISCUSSIONThe INPAIN study aims to comprehensively understand pain in CP through a test panel developed for routine clinical use. This tool has the potential to personalize treatments, improve clinical practice, enhance patient care, improve quality of life, and minimize treatment side effects.
{"title":"Individualized Pain Treatment in Chronic Pancreatitis (INPAIN): An International, Multicenter, Investigator-initiated, Prospective, Cohort Study.","authors":"Rasmus Hagn-Meincke,Ana Dugic,Ankit Agarwal,Anna Evans Phillips,Anna Waage,Dhiraj Yadav,Divya Pillai,Elaina Vivian,Enrique de-Madaria,Imran Khan Niazi,Jeffrey Easler,Jens Brøndum Frøkjær,Julia McNabb-Baltar,Louise Kuhlmann Asferg,Mahya Faghih,Maria Belen Garay Montiel,Mathias Cook,Misbah Unnisa,Paul Tarnasky,Peter Hegyi,Pramod Garg,Rasmus Bach Nedergaard,Robert Edwards,Rupjyoti Talukdar,Shagufta Farheen,Søren Schou Olesen,Soumya Jagannath,Suzette Schmidt,Vikesh Singh,Zoltán Hajnády,Asbjørn Mohr Drewes,","doi":"10.1097/mpa.0000000000002388","DOIUrl":"https://doi.org/10.1097/mpa.0000000000002388","url":null,"abstract":"INTRODUCTIONPain is the foremost complication of chronic pancreatitis (CP), affecting about 70% of patients. However, the pathophysiological understanding and management of CP-related pain is complex, likely as patients have diverse \"pain phenotypes\" responding differently to treatment. This study aims to develop a bedside test panel to identify distinct pain phenotypes, investigate the temporal evolution, and determine whether they can be used to predict treatment response.METHODThe INPAIN study is an international, multi-center, observational, longitudinal cohort study comprised of 4 sub-studies. The studies will prospectively enroll 400 CP patients (50 without pain and 350 with pain) and 50 control subjects, conducting biannual observations for four years. The test panel is comprised of comprehensive subjective and objective assessment parameters. Statistical analysis strategies differ across the sub-studies. A model to predict treatment efficacy will be developed using various machine learning techniques, including an artificial intelligence approach, with internal cross-validation. Trajectories in pain parameters will be characterized by graphical analysis and mixed effect models.DISCUSSIONThe INPAIN study aims to comprehensively understand pain in CP through a test panel developed for routine clinical use. This tool has the potential to personalize treatments, improve clinical practice, enhance patient care, improve quality of life, and minimize treatment side effects.","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":"81 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-03-27DOI: 10.1097/MPA.0000000000002355
Marwin A Farrugia, Anaïs Darnaude, Elena Santos-Pérez, Eve Gelsi
{"title":"A Case of Thrombotic Microangiopathy Within Acute Pancreatitis.","authors":"Marwin A Farrugia, Anaïs Darnaude, Elena Santos-Pérez, Eve Gelsi","doi":"10.1097/MPA.0000000000002355","DOIUrl":"10.1097/MPA.0000000000002355","url":null,"abstract":"","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":" ","pages":"e710-e711"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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