Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Endoscopic ultrasound features of autoimmune pancreatitis: The typical findings and chronic pancreatitis changes

BACKGROUND Few studies have fully described endoscopic ultrasound(EUS)features of newly diagnosed autoimmune pancreatitis(AIP)involving both typical findings and chronic pancreatitis(CP)features.The typical EUS findings are prevalent in the diffuse type AIP but may not be as common for the focal type,and the differences between the diffuse and focal AIP need to be specified.AIM To demonstrate the EUS features of newly diagnosed AIP and the difference between diffuse and focal AIP.METHODS This retrospective single center study included 285 patients of newly diagnosed type 1 AIP following the international consensus diagnostic criteria,with the EUS procedures accomplished before corticosteroid initiation.We explored the EUS features and compared the typical AIP and CP features between the diffuse and focal AIP cases.The Rosemont criteria were employed for CP features definition and CP change level comparison.RESULTS For the typical AIP features,there were significantly more patients in the diffuse group with bile duct wall thickening(158 of 214 cases,73.4%vs 37 of 71 cases,52.1%,P=0.001)and peripancreatic hypoechoic margin(76 of 214 cases,35.5%vs 5 of 71 cases,7.0%,P<0.001).For the CP features,there were significantly more patients in the focal group with main pancreatic duct dilation(30 of 214 cases,14.0%vs 18 of 71 cases,25.3%,P=0.03).The cholangitis-like changes were more prevalent in the focal cases with pancreatic head involvement.The CP change level was relatively limited for newly diagnosed AIP cases in both groups.CONCLUSION This study demonstrated the difference in the typical AIP and CP features between diffuse and focal AIP and indicated the limited CP change level in newly diagnosed AIP.

Jejunal cavernous lymphangioma manifested as gastrointestinal bleeding with hypogammaglobulinemia in adult: A case report and literature review

BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult diagnosed with jejunal lymphangioma presenting with melena,anemia and hypogammaglobulinemia.We also summarize and analyze all 23 reported cases from 1961 to 2019,and propose an algorithm for identification and management of small bowel lymphangioma.CASE SUMMARY A case of a 29-year-old woman presented with persistent melena and irondeficiency anemia,accompanied by hypogammaglobulinemia.No lesions were found in the initial workup with esophagogastroduodenoscopy,colonoscopy and computed tomography(CT)enterography.Ultimately,capsule endoscopy and double-balloon enteroscopy revealed a 3 cm×2 cm primary lesion with intensive white lymphatic dilatatory changes and visible fresh blood stains,accompanied by a small satellite lesion.The patient underwent complete surgical resection of these lesions,and histopathological examination confirmed a diagnosis of cavernous lymphangioma of the jejunum.The patient showed no evidence of disease at the time of this report.CONCLUSION We recommend CT,capsule endoscopy and enteroscopy to identify the lesions of lymphangioma.Laparoscopic surgery with histological diagnosis is an ideal curative method.

Spontaneous gallbladder perforation and colon fistula in hypertriglyceridemia-related severe acute pancreatitis:A case report

BACKGROUND Gallbladder perforation and gastrointestinal fistula are rare but serious complications of severe acute pancreatitis(SAP).However,neither spontaneous gallbladder perforation nor cholecysto-colonic fistula has been reported in acalculous acute pancreatitis patients.CASE SUMMARY A 31-year-old male presenting with epigastric pain was diagnosed with hypertriglyceridemia-related SAP.He suffered from multiorgan failure and was able to leave the intensive care unit on day 20.Three percutaneous drainage tubes were placed for profound exudation in the peripancreatic region and left paracolic sulcus.He developed spontaneous gallbladder perforation with symptoms of fever and right upper quadrant pain 1 mo after SAP onset and was stabilized by percutaneous drainage.Peripancreatic infection appeared 1 mo later and was treated with antibiotics but without satisfactory results.Then multiple colon fistulas,including a cholecysto-colonic fistula and a descending colon fistula,emerged 3 mo after the onset of SAP.Nephroscopy-assisted peripancreatic debridement and ileostomy were carried out immediately.The fistulas achieved spontaneous closure 7 mo later,and the patient recovered after cholecystectomy and ileostomy reduction.We presume that the causes of gallbladder perforation are poor bile drainage due to external pressure,pancreatic enzyme erosion,and ischemia.The possible causes of colon fistulas are pancreatic enzymes or infected necrosis erosion,ischemia,and iatrogenic injury.According to our experience,localized gallbladder perforation can be stabilized by percutaneous drainage.Pancreatic debridement and proximal colostomy followed by cholecystectomy are feasible and valid treatment options for cholecysto-colonic fistulas.CONCLUSION Gallbladder perforation and cholecysto-colonic fistula should be considered in acalculous SAP patients.

Percutaneous aspiration and sclerotherapy of a giant simple hepatic cyst causing obstructive jaundice:A case report and review of literature

BACKGROUND Giant simple hepatic cysts causing intrahepatic duct dilatation and obstructive jaundice are uncommon.A variety of measures with different clinical efficacies and invasiveness have been developed.Nonsurgical management,such as percutaneous aspiration and sclerotherapy,is often applied.CASE SUMMARY The case is a 39-year-old female with a 5-mo history of cutaneous and scleral icterus,loss of appetite,and dark urine.Lab tests showed jaundice and liver function abnormalities.Imaging revealed a giant simple hepatic cyst obstructing the intrahepatic bile ducts.A combination of percutaneous catheter aspiration and lauromacrogol sclerotherapy was successfully performed and the effects were satisfactory with the size of cyst decreasing from 13.7 cm×13.1 cm to 3.0 cm×3.0 cm.Further literature review presented the challenges of managing giant simple hepatic cysts that cause obstructive jaundice and compared the safety and efficacy of a combination of percutaneous aspiration and lauromacrogol sclerotherapy with other management strategies.CONCLUSION Giant simple hepatic cysts can cause obstructive jaundice,and a combination of percutaneous catheter aspiration and sclerotherapy with lauromacrogol are suggested to treat such cases.

Steroid hormone 20-hydroxyecdysone disturbs fat body lipid metabolism and negatively regulates gluconeogenesis in Hyphantria cunea larvae

The steroid hormone 20-hydroxyecdysone(20E)has been described to regulate fat body lipid metabolism in insects,but its accurate regulatory mechanism,especially the crosstalk between 20E-induced lipid metabolism and gluconeogenesis remains largely unclear.Here,we specially investigated the effect of 20E on lipid metabolism and gluconeogenesis in the fat body of Hyphantria cunea larvae,a notorious pest in forestry.Lipidomics analysis showed that a total of 1907 lipid species were identified in the fat body of H.cunea larvae assigned to 6 groups and 48 lipid classes.The differentially abundant lipids analysis showed a significant difference between 20E-treated and control samples,indicating that 20E caused a remarkable alteration of lipidomics profiles in the fat body of H.cunea larvae.Further studies demonstrated that 20E accelerated fatty acidβ-oxidation,inhibited lipid synthesis,and promoted lipolysis.Meanwhile,the activities of pyruvate carboxylase,phosphoenolpyruvate carboxykinase,fructose-1,6-bisphosphatase,and glucose-6-phosphatase were dramatically suppressed by 20E in the fat body of H.cunea larvae.As well,the transcriptions of genes encoding these 4 rate-limiting gluconeogenic enzymes were significantly downregulated in the fat body of H.cunea larvae after treatment with 20E.Taken together,our results revealed that 20E disturbed fat body lipid homeostasis,accelerated fatty acidβ-oxidation and promoted lipolysis,but negatively regulated gluconeogenesis in H.cunea larvae.The findings might provide a new insight into hormonal regulation of glucose and lipid metabolism in insect fat body.

Temporality-enhanced knowledge memory network for factoid question answering

Question answering is an important problem that aims to deliver specific answers to questions posed by humans in natural language.How to efficiently identify the exact answer with respect to a given question has become an active line of research.Previous approaches in factoid question answering tasks typically focus on modeling the semantic relevance or syntactic relationship between a given question and its corresponding answer.Most of these models suffer when a question contains very little content that is indicative of the answer.In this paper,we devise an architecture named the temporality-enhanced knowledge memory network(TE-KMN) and apply the model to a factoid question answering dataset from a trivia competition called quiz bowl.Unlike most of the existing approaches,our model encodes not only the content of questions and answers,but also the temporal cues in a sequence of ordered sentences which gradually remark the answer.Moreover,our model collaboratively uses external knowledge for a better understanding of a given question.The experimental results demonstrate that our method achieves better performance than several state-of-the-art methods.