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.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis:A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can cause hemorrhage of gastric varices(GV)related to portal hypertension(PH).However,such cases are rare.In addition,the association of PH with AIP is unclear.At the same time,the efficacy and duration of glucocorticoid therapy is also controversial.CASE SUMMARY In this case,we reported a case of GV in pancreatic PH associated with AIP.Enhanced abdominal computed tomography(CT)suggested splenic vein(SV)and superior mesenteric vein(SMV)thromboses.The patient received a long-term glucocorticoid therapy,that the initial dose of 40 mg is reduced weekly by 5 mg,and then reduced to 5 mg for long-term maintenance.CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized,pancreatic stiffness and swelling were ameliorated,and the GV almost completely disappeared.CONCLUSION Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Research Progress of Atomizers and Drugs Used in Atomization Therapy

At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Continuing episodes of pain in recurrent acute pancreatitis: Prospective follow up on a standardised protocol with drugs and pancreatic endotherapy

AIM To assess the outcomes of drug therapy(DT)followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.METHODS DT comprised of pancreatic enzymes and antioxidants failing which,endotherapy(ET;pancreatic sphincterotomy and stent placement)was done.The frequency of pain,its visual analogue score(VAS),quality of life(Qo L),serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET.Response was defined as at least 50%reduction in the severity of pain to below a score of 5.RESULTS Of the thirty nine patients analysed,21(53.9%)responded to DT and 18(46.1%)underwent ET.The VAS for pain(7.0±2.0 vs 1.3±2.5,P<0.001)and the number of days with pain per month decreased[1.0(1.0,2.0)vs 1.0(0.0,1.0),P<0.001],and the Qo L scores[55.0(44.0,66.0)vs 38.0(32.00,51.00),P<0.01]improved significantly during follow up.Similar significant improvements were seen in patients in the subgroups of DT and ET except for Qo L in ET.The serum C-peptide(P=0.001)and FE(P<0.001)levels improved significantly in the entire group and in the two subgroups of patients except for the C peptide levels in patients on DT.CONCLUSION A standardised protocol of DT,followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis,enhanced Qo L and improved pancreatic function.

Split-dose or hybrid nonsteroidal anti-inflammatory drugs and Nacetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis

BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.

Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy

Background:Patients with pancreatic ductal adenocarcinoma(PDAC)who undergo surgical resection and receive effective chemotherapy have the best chance for longterm survival.Unfortunately,because of the heterogeneity of pancreatic cancer,it is difficult to find a personalized treatment strategy for patients.Organoids are ideal preclinical models for personalized medicine.Therefore,we explore the cultivation conditions and construction methods of PDAC organoid models to screen the individualized therapy strategy.Methods:Fresh PDAC tissues from surgical resection were collected and digested with digestive enzymes;then the tumor cells were embedded in Matrigel with a suitable medium to establish the PDAC organoid models.The genetic stability of the organoids was analyzed using whole exon sequencing;hematoxylin and eosin staining and immunohistochemistry of organoids were performed to analyze their consistency with the pathological morphology of the patient's tumor tissue;After 2 days of organoid culture,we selected four commonly used clinical chemotherapy drugs for single or combined treatment to analyze drug sensitivity.Results:Two cases of PDAC organoid models were successfully established,and the results of their pathological characteristics and exome sequencing were consistent with those of the patient's tumor tissue.Both PDAC organoids showed more sensitivity to gemcitabine and cisplatin,and the combined treatment was more effective than monotherapy.Conclusion:Both organoids better retained the pathological characteristics,genomic stability,and heterogeneity with the original tumor.Individual PDAC organoids exhibited different sensitivities to the same drugs.Thus,this study provided ideal experimental models for screening individualized therapy strategy for patients with PDAC.

Immunomodulatory therapies for acute pancreatitis

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis:a meta-analysis

BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.

Retrospective study of steroid therapy for patients with autoimmune pancreatitis in a Chinese population

AIM:To explore the optimal steroid therapeutic strategy for autoimmune pancreatitis(AIP).METHODS:This study was conducted retrospectively in two large institutions in China.Patients with clinically,radiologically and biochemically diagnosed AIP were enrolled.The performed radiological investigations and biochemical tests,the regimen of the given steroid treatment,remission and relapse whether with and without steroid therapy were analyzed.RESULTS:Twenty-eight patients with AIP received steroid treatment,while 40 patients were treated surgically by pancreatoduodenectomy,distal pancreatectomy and choledochojejunostomy,radiofrequency ablation for the enlarged pancreatic head,percutaneous transhepatic biliary drainage and endoscopic biliary drainage.The starting oral prednisolone dose was 30 mg/d in 18(64.3%) patients and 40 mg/d in 10(35.7%) patients administered for 3 wk.The remission rate of AIP patients with steroid treatment(96.4%) was significantly higher than in those without steroid treatment(75%).Maintenance therapy(oral prednisolone dose 5 mg/d) was performed after remission for at least 6-12 mo to complete the treatment course.Similarly,the relapse rate was significantly lower in AIP patients with steroid treatment(28.6%) than in those without steroid treatment(42.5%).Steroid re-treatment was effective in all relapsed patients with or without steroid therapy.CONCLUSION:Steroid therapy should be considered in all patients with active inflammatory phase of AIP.However,the optimal regimen still should be trailed in larger numbers of patients with AIP.

Systematic review and meta-analysis on the prophylactic role of non-steroidal anti-inflammatory drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM: To critically appraise the published randomized, controlled trials on the prophylactic effectiveness of the non-steroidal anti-inflammatory drugs(NSAIDs), in reducing the risk of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis. METHODS: A systematic literature search(MEDLINE, Embase and the Cochrane Library, from inception of the databases until May 2015) was conducted to identify randomized, clinical trials investigating the role of NSAIDs in reducing the risk of post-ERCP pancreatitis. Random effects model of the meta-analysis was carried out, and results were presented as odds ratios(OR) with corresponding 95%CI.RESULTS: Thirteen randomized controlled trials on 3378 patients were included in the final meta-analysis. There were 1718 patients in the NSAIDs group and 1660 patients in non-NSAIDs group undergoing ERCP. The use of NSAIDs(through rectal route or intramuscular route) was associated with the reduced risk of post-ERCP pancreatitis [OR, 0.52(0.38-0.72), P = 0.0001]. The use of pre-procedure NSAIDs was effective in reducing approximately 48% incidence of post-ERCP pancreatitis, number needed to treat were 16 with absolute risk reduction of 0.05. But the risk of post-ERCP pancreattis was reduced by 55% if NSAIDs were administered after procedure. Similarly, diclofenac was more effective(55%) prophylactic agent compared to indomethacin(41%).CONCLUSION: NSAIDs seem to have clinically proven advantage of reducing the risk of post-ERCP pancreatitis.

Antioxidant therapy in the management of acute,chronic and post-ERCP pancreatitis:A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis （AP） or chronic pancreatitis （CP） and in the prevention of post-endoscopic retrograde cholangio-pancreatography （post-ERCP） pancreatitis （PEP） up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PER Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.

Resveratrol: A medical drug for acute pancreatitis

Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound extracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cytokines production in many experimental models. Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute pancreatitis (AP), the discovery of resveratrol as platelet and cytokines inhibitors has shed light on the treatment of AP, which still has significant mortality and morbidity. It is anticipated that this natural polyphenol could serve as a therapeutic compound in managing AP through different pathways.