Elevated Amylase Research Articles

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Differences in glucose homeostasis and islet injury among diverse mice strains post acute pancreatitis

Diverse animal models have been used to study postpancreatitis diabetes mellitus (PPDM) development; however, no study has yet conducted a comparative analysis of the specific differences in glucose homeostasis and islet injury between these models. Therefore, we investigated the differences in pancreatic islet injury and glucose homeostasis among diverse strains in a cerulein-induced acute pancreatitis (AP) model to determine the appropriate animal model for PPDM. BALB/cJ, C57BL/6J, C57BL/6 N, and FVB/NJ mice were administered cerulein to induce AP. Serum amylase levels, pancreatic acinar injury, blood glucose homeostasis, islet function, and islet injury were measured and analyzed. All strains exhibited elevated amylase secretion post pancreatitis, and BALB/cJ, C57BL/6J, and C57BL/6 N mice exhibited sex-related differences. All strains exhibited pancreatic acinar injury post pancreatitis but mostly recovered within 15 days. Overall, glucose homeostasis remained balanced post pancreatitis in all strains compared to that in the control groups, except in FVB/NJ male and female mice, which exhibited an imbalance in glucose homeostasis on day 7 post pancreatitis. All the strains, except BALB/cJ mice, exhibited a decline in Homeostasis model assessment-β(HOMA-β) values post pancreatitis, with significant decrease in C57BL/6J females and FVB/NJ males. Islet size decreased post pancreatitis in all strains, except BALB/cJ mice. Pancreatic islet insulin secretion levels significantly decreased in male FVB/NJ mice post pancreatitis onset and did not recover within 15 days. Therefore, FVB/NJ male mice are a useful model for studying PPDM.

Clinical characteristics and influencing factors of severe fever with thrombocytopenia syndrome complicated by viral myocarditis: a retrospective study

ObjectiveThis study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors.MethodsRetrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM.ResultsSFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001–1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM.ConclusionElevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Molecular Characterization Analysis and Adaptive Responses of Spodoptera frugiperda (Lepidoptera: Noctuidae) to Nutritional and Enzymatic Variabilities in Various Maize Cultivars.

The fall armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), a common agricultural pest known for its extensive migration and wide host ranges, causes considerable harm to maize (Zea mays L.). In this study, we utilized two molecular marker genes, COI and Tpi, to compare the genetic characteristics of the collected original samples. Additionally, through an interactive study between S. frugiperda larvae and six maize varieties aiming to understand the insect's adaptability and resistance mechanisms, our analysis revealed that both the COI and Tpi genes identified S. frugiperda as the corn strain. Further examination of the larvae showed significant differences in nutritional indices, digestive, and detoxification enzyme activities. Special maize varieties were found to offer higher efficiency in nutrient conversion and assimilation compared with common varieties. This study revealed adaptations in S. frugiperda's digestive and detoxification processes in response to the different maize varieties. For instance, larvae reared on common maize exhibited elevated amylase and lipase activities. Interestingly, detoxification enzyme activities exhibited different patterns of variation in different maize varieties. The Pearson correlation analysis between nutritional indices, enzyme activities, and the nutritional content and secondary metabolites of maize leaves provided deeper insights into the pest's adaptability. The results highlighted significant relationships between specific nutritional components in maize and the physiological responses of S. frugiperda. Overall, our findings contribute substantially to the understanding of S. frugiperda's host plant adaptability, offering critical insights for the development of sustainable pest management strategies.

Selection of endovascular treatment strategies and analysis of the efficacy of different locations and types of splenic artery aneurysms

PurposeTo analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs).MethodsSixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed.ResultsAmong the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic.ConclusionEndovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)—Primary safety and short-term efficacy results for cohort E.

326 Background: The standard neoadjuvant treatment in Japan for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is DTX + CDDP + 5-FU (DCF). In addition, immune checkpoint inhibitors (ICIs) have shown a survival benefit for ESCC and are promising as neoadjuvant treatment for several cancers. We previously reported that neoadjuvant CDDP + 5-FU + nivolumab (Nivo) or DCF + Nivo therapy was tolerable and showed promising efficacy for ESCC. However, the efficacy of neoadjuvant treatment and safety of subsequent surgery remain unclear for 5-FU + l-LV + L-OHP + DTX (FLOT), the global standard of care for perioperative esophagogastric adenocarcinoma, plus ICI for ESCC. Methods: JCOG1804E (FRONTiER) is a multi-cohort phase I study designed to evaluate the safety and efficacy of Nivo combined with neoadjuvant chemotherapy in ESCC. The eligibility criteria were histologically proven ESCC staged as cT1N1-3M0 or cT2-3N0-3M0 (8th UICC TNM classification), age 20-75 years, performance status (PS) ≤1, and no prior cancer therapy. The primary endpoint was the incidence of dose-limiting toxicity (DLT) from the initial dose to postoperative day 30. The secondary endpoints included adverse events during the perioperative period and at 30 days and the objective response rate, R0 resection rate, histopathological complete response rate, and completion rate of the protocol treatment including planned chemotherapy as below followed by R0 resection. Among five study cohorts, patients in cohort E were planned to receive four courses of FLOT+Nivo–5-FU (2600 mg/m2), l-LV (200 mg/m2), L-OHP (85 mg/m2), DTX (50 mg/m2), and Nivo (240 mg)–on day 1 every 2 weeks. Results: Of the 12 patients enrolled in cohort E (median age [range]: 64.5 [53-71] years, PS 0/1: 12/0, clinical stage I/II/III/IVA: 4/5/3/0), 4 developed DLT (grade 3 mucositis, erythema multiforme, and pneumonitis, n=1 each; grade 5 pneumonitis, n=1), which was within the prespecified range of safety (n ≤ 4). Other grades≥3 adverse events were neutropenia (n=7), leukopenia (n=6), fever, fatigue, febrile neutropenia, rash, elevated amylase, elevated hepatic enzyme, hypotension, and thrombocytopenia (n=1 each) during FLOT + Nivo, and anastomotic leakage (n=1) during the postoperative period. One patient discontinued FLOT + Nivo due to DLT of erythema multiforme, eleven patients (91.7%) completed the protocol treatment and R0 resection rate achieved 91.7% (11/12). In cohort E, the objective response rate in patients with measurable lesion was 0% (0/4). However, 5 patients (41.7%) achieved a pathological complete response, and 6 (50.0%) achieved a pathological complete response in primary tumors among 12 patients. Conclusions: Neoadjuvant FLOT + Nivo followed by surgery for locally advanced ESCC was tolerated and showed promising efficacy. Clinical trial information: NCT03914443 .

Effects of Dietary Yeast, Saccharomyces cerevisiae, and Costmary, Tanacetum balsamita, Essential Oil on Growth Performance, Digestive Enzymes, Biochemical Parameters, and Disease Resistance in Nile Tilapia, Oreochromis niloticus

The present study assessed the effects of dietary yeast, Saccharomyces cerevisiae, and costmary, Tanacetum balsamita, essential oil on growth performance, biochemical parameters, and disease resistance of Nile tilapia, Oreochromis niloticus. Four diets containing 1 g/kg yeast (Sc), 0.1 g/kg costmary essential oil (Tb), 1 g/kg yeast + 0.1 g/kg costmary essential oil (Sc + Tb), and without Sc and Tb (control) were formulated and fed (2.5% per day) to triplicate groups of fish (average: 9.8 g; SD : 0.12) for 8 weeks. Each replicate was a 70‐L tank, stocked with 25 fish. Then, the fish were intraperitoneally challenged by Aeromonas hydrophila, and blood samples were taken from the fish before and 12 hr postinfection. All experimental groups showed significantly higher growth performance and feed efficiency, compared to the control, and the highest values were related to Sc + Tb treatment (P &lt; 0.001). Sc group showed significant elevations in the intestinal amylase, lipase, and protease activities, but Tb group showed only elevation in lipase activity. The highest amylase (P = 0.026), lipase (P = 0.036), and protease (P = 0.009) activities were observed in Sc + Tb treatment. The postchallenge survival of Sc (70.0%), Tb (73.3%), and Sc + Tb (76.6%) treatments were significantly (P = 0.038) higher than the control (56.6%). Bacterial challenge significantly increased plasma cortisol, glucose, malondialdehyde, glutathione peroxidase, and superoxide dismutase, but decreased lysozyme, alternative complement, albumin, globulin, and catalase (P &lt; 0.001). The Tb treatment showed improvements in plasma antioxidant, immunological, and biochemical parameters, compared to the Sc treatment. The Sc + Tb treatment showed the highest albumin, globulin, lysozyme, total immunoglobulin, alternative complement, glutathione peroxidase, and superoxide dismutase, but the lowest cortisol, glucose, malondialdehyde, and catalase, before/after the challenge (P &lt; 0.001). In conclusion, dietary Sc + Tb supplementation positively affects growth performance, antioxidant, and immunological responses, thereby augments resistance of Nile tilapia to A. hydrophila infection.

Pneumatosis Intestinalis and Pneumoperitoneum After Lung Transplantation: Single-Center Experience and Systematic Review.

Background: Pneumatosis intestinalis (PI) and pneumoperitoneum are some of the complications after lung transplantation (LT). But only limited reports are published. The purpose of this study is to review our experience and perform a systematic review to discuss the possible causes, risk factors, and management. Methods: We reviewed the characteristics, management, and outcome of the patients who developed PI or pneumoperitoneum after LT in our institution from 2013 to 2022. We also performed a systematic review to discuss the management and outcome. Results: PI and pneumoperitoneum were found in 15 out of 729 patients (2.06%) in our institution. We also found 50 patients in the systematic review. Tracheostomy was performed in 40% and gastrointestinal procedures were performed in 55.6%. Laparotomy was performed in 23.4%. A total of 44.6% of patients had benign physical exams or no symptoms. Rejection was seen in 42.9%. A total of 28.6% of patients died during follow-up periods. Conclusions: This report has the largest number of patients so far with PI and pneumoperitoneum after LT. These conditions have a high rejection and high mortality rate. Mechanical ventilation, tracheostomy, gastrointestinal procedure, CMV infection, Clostridium difficile (C. difficile) infection, and immunosuppression can be the risk factors, and the management includes laparotomy or conservative management. It is generally recommended to proceed with laparotomy if patients have portal venous gas, elevated white blood cell count, elevated lactic acid level, decreased bicarbonate level, elevated amylase level, metabolic acidosis, abdominal tenderness, or abdominal distension. Otherwise, most of the patients recover with conservative management with nil per os (NPO), metronidazole, ganciclovir, antibiotics, high-flow oxygen, and holding mycophenolate mofetil (MMF).

Dual-crosslinking immunostimulatory hydrogel synchronously suppresses pancreatic fistula and pancreatic cancer relapse post-resection

In pancreatic cancer (PC), surgical resection remains the sole curative option, albeit patients undergoing resection are susceptible to postoperative pancreatic fistula (PF) formation and tumor recurrence. An unmet need exists for a unified strategy capable of concomitantly averting PF and tumor relapse to mitigate morbidity in PC patients after surgery. Herein, an original dual crosslinked biological sealant hydrogel (methacrylate-hyaluronic acid-dopamine (MA-HA-DA) and sulfhydryl-hyaluronic acid-dopamine (SH-HA-DA)) was engineered as a drug depot and loaded with polydopamine-cloaked cytokine interleukin-15 and platelets conjugated with anti-TIGIT. In vitro analyses validated favorable tissue adhesion, cytocompatibility, and stability of the hydrogels. In a PF rodent model, the hydrogel effectively adhered to the pancreatic stump, sealing the severed pancreatic end and impeding post-operative elevations in amylase and lipase. In PC murine models, hydrogels potently stimulated CD8+ T and NK cells to deter residual tumor re-growth and distant metastasis. This innovative hydrogel strategy establishes a new framework for concomitant prevention of PF and PC recurrence.

Not all hematological malignancies in the gastrointestinal tract are lymphoma

Abstract Introduction/Objective Myeloid sarcoma (MS) is a rare entity that may develop in patients with acute myeloid leukemia (AML). Presentation of MS in the gastrointestinal (GI) tract is uncommon. We describe two cases of MS involving unusual sites: the stomach and appendix. Methods/Case Report A 64-year-old female consulted for fatigue and abdominal pain. A CT scan of abdomen/pelvis revealed appendicitis and CBC showed 76% blasts. An appendectomy was performed. Histologic examination demonstrated the appendiceal wall infiltrated by malignant cells, ultimately demonstrated to be positive for MPO and weak/variable CD117. In the second case, a 50-year-old male presented to the emergency department for nausea, vomiting, and elevated amylase. Esophagogastroduodenoscopy with endoscopic ultrasound demonstrated pancreatic inflammatory changes and a subepithelial nodule in the gastric fundus. Biopsy of the nodule revealed gastric epithelium infiltrated by sheets of malignant cells, ultimately demonstrated to be positive for CD34, myeloperoxidase and CD43. Results (if a Case Study enter NA) NA Conclusion MS is defined as a tumor of myeloid blasts forming outside the bone marrow. Overall, it is an uncommon entity that can occur in patients with known AML, and rarely, as the first sign of AML. Presentation of MS in the GI tract is infrequent (10%), involving primarily the small intestine (63%). The differential diagnosis includes lymphoma, poorly differentiated carcinomas, and melanomas. A review of the clinical history for AML or other myeloproliferative neoplasms should raise suspicion of MS. Expression of lymphoid markers and scant tissue for IHC studies can be diagnostic challenges, rendering B cell lymphoma as the most common misdiagnosis of MS in up to 40-47% of cases. Our two MS cases presented exclusively with GI symptoms without previously known AML and involved unusual GI sites. IHC for myeloid lineage, monocytic or myelomonocytic differentiation should be considered in specific cases. In patients without prior AML diagnosis, especially without hematologic findings, MS is a diagnostic challenge.

A case of lung adenocarcinoma with markedly elevated amylase in airway secretions

A 45-year-old male patient was admitted to the hospital because of intermittent cough and expectoration for more than 1 year, worsened by dyspnea for 2 months, and was finally diagnosed with lung adenocarcinoma. The CT scan of the chest revealed lesions of diversity with fibrosis, mass and effusion, but his severe cough limited biopsy of the lesions. The difficult process of diagnosis was aided by the further analysis of the sputum, which showed significantly elevated amylase without any evidence of pancreatic disease. The cough was relieved by intravenous pumping octreotide acetate, and both CT-guided lung biopsy and transbronchial biopsy revealed the lung adenocarcinoma. The diagnostic process of this case provided a helpful diagnostic thinking and demonstrated the rare clinical features of lung adenocarcinoma.

A Phase I Study of Asciminib (ABL001) in Combination with Dasatinib and Prednisone for BCR-ABL1-Positive ALL and Blast Phase CML in Adults

Introduction:Oral ABL1 kinase inhibitors rapidly produce deep remissions in BCR::ABL1+ acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphoid blast crisis (CML-LBC). Second generation TKIs such as dasatinib (DAS) are more effective than imatinib (Foa et al. Blood 2011) but patients may develop resistance. Asciminib (ASC), previously ABL001, is a STAMP (Specifically Targeting the ABL Myristoyl Pocket) allosteric ABL1 inhibitor that binds to a site spatially distinct from ATP-competitive TKIs. Combination treatment with an allosteric and an ATP-competitive TKI may deepen clinical responses and limit mutational resistance as supported by a cell line xenograft model of CML (Wylie et al. Nature 2017) and patient-derived xenograft models of BCR::ABL1+ ALL. We hypothesized that dual ABL blockade with catalytic domain and allosteric inhibitors would be tolerable and active in BCR::ABL1+ ALL and CML-LBC. Methods: This investigator initiated, phase I study (NCT03595917) of asciminib (ASC) in combination with DAS plus prednisone (pred) for BCR::ABL1+ ALL studied ASC in escalating doses in a 3+3 design with the primary objective to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); a 10 patient (pt) expansion cohort was then accrued. Secondary objectives define the depth and durability of responses. Pts with BCR::ABL1+ ALL or CML-LBC newly diagnosed ≥ 50 years (yrs), or unfit; or relapsed/refractory (no prior DAS or ASC) were eligible in dose escalation; all pts ≥18 yrs were eligible in dose expansion. Pts received DAS 140 mg/day(d) and pred 60 mg/m 2/d 1-24 (max 120 mg/d, tapered d 25-32) with escalating daily doses of ASC (DL1: 40 mg; DL2: 80 mg; DL3: 160 mg). DAS and ASC were given in 28-d cycles indefinitely in setting of clinical benefit, with allogeneic stem cell transplant (SCT) consolidation after d85 per treating physician. Dose-limiting toxicity (DLT) was initially defined as CTCAEv4 non-heme toxicity grade (gr) 3+; the study was amended to assess DLT via CTCAEv5. Correlative science efforts seek to define biomarkers of response and resistance to dual ABL1 blockade. Results:The study enrolled 25 pts (48% female), with 14 in dose escalation (13 evaluable), and 11 in expansion (10 evaluable). Most (92%) had new ALL (p190: 15/23, p210: 8/23; 8% had CML-LBC. Median age was 65 yrs (range 33 - 85; 8 pts 70+). Median WBC was 15.1 K/μL (range 0.9 - 251.9 K/μL). No pt had CNS disease. DL1 and DL2 enrolled 3 pts each without DLT. Two of 3 pts at DL3 developed asymptomatic CTCAEv4 gr 3 amylase elevation during C1 meeting original DLT criteria. A 4 th pt enrolled on re-opened DL3 under an amendment defining asymptomatic CTCAEv4 gr 3 amylase/lipase elevations persisting ≤5d to not be a DLT. This pt experienced an asymptomatic CTCAEv4 gr 3 lipase elevation meeting DLT criteria. Thus, the study de-escalated to DL2, re-opening under an amendment assessing DLTs via CTCAEv5. Of note, all DLTs at DL3 would be gr &amp;lt;3 per CTCAEv5. Four more pts (3 evaluable) enrolled at DL2 without a DLT. Thus, ASC 80 mg/d was declared the RP2D, and 11 pts age ≥18 yrs enrolled in an expansion cohort, 10 of whom initiated study treatment. No pt had symptomatic pancreatitis. Rates of molecular response after 3 cycles among all evaluable patients were 58.3% (14/24) for MRD 3.0 and 25.0% (6/24) for MRD 4.0. Evaluable pts with new ALL treated at the RP2D achieved molecular response rates after 3 cycles of 78.6% (11/14) for MRD 3.0 and 42.9% (6/14) for MRD 4.0. Both patients with imatinib-refractory CML-LBC progressed (C9, C3). Of those with ALL, 8 bridged to SCT after 2-8 cycles; 2 elected local care (C5, C7); 1 transitioned to ponatinib for inadequate response plus recurrent DAS pulmonary toxicity (C4); 6 remained on study treatment until disease progression (C4 - MRD+, C45, C11, C11); 3 remain on study. Correlative science evaluation of serial pt biospecimens in pursuit of predictive biomarkers will be shared at the meeting. Conclusion: Dual ABL1 kinase inhibition with ASC and DAS plus pred in BCR::ABL1+ ALL and CML-LBC is feasible and tolerable in adults with BCR::ABL1+ ALL and CML-LBC. DLTs at ASC 160 mg/d were asymptomatic amylase and lipase elevation, without clinical sequelae. ASC 80 mg/day was declared the RP2D, and an expansion cohort of 10 pts was completed. High rates of molecular response and bridging to transplant highlight encouraging preliminary activity. A phase II expansion cohort incorporating blinatumomab is now open.

A Comparative Study on UHPLC-HRMS Profiles and Biological Activities of Inula sarana Different Extracts and Its Beta-Cyclodextrin Complex: Effective Insights for Novel Applications.

Within this particular framework, the extracts obtained from Inula sarana using a variety of solvents, included n-hexane, ethyl acetate, dichloromethane (DCM), 70% ethanol, ethanol, and water. The extracts obtained from n-hexane, ethyl acetate, and DCM were then subjected to a specific method for their incorporation into β-cyclodextrin (β-CD). The establishment of complex formation was validated through the utilization of scanning electron microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The identification of phytochemical components was executed using UHPLC-HRMS. Furthermore, the total phenolic and flavonoid content was evaluated using the Folin-Ciocalteu assay and the AlCl3 method. Subsequently, the determination of antioxidant capacity was conducted utilizing DPPH, ABTS, CUPRAC, Frap, PBD, and MCA assays. The enzyme inhibitory activities of the samples (extracts and β-CD complexes) were also examined by AChE, BChE, tyrosinase, α-glucosidase, and α-amylase. The findings indicated that water and 70% ethanol extracts contained the highest phenolic content. One hundred and fourteen bioactive compounds were identified by UHPLC-HRMS analysis. This study unveiled a substantial array of flavonoids, phenolic acid-hexosides and caffeoylhexaric acids within I. sarana, marking their initial identification in this context. Among the various extracts tested, the 70% ethanol extract stood out due to its high flavonoid content (jaceosidin, cirsiliol, and eupatilin) and hydroxybenzoic and hydroxycinnamic acid hexosides. This extract also displayed notably enhanced antioxidant activity, with ABTS, CUPRAC, and FRAP test values of 106.50 mg TE/g dry extract, 224.31 mg TE/g dry extract, and 110.40 mg TE/g, respectively. However, the antioxidant values of the complex extracts with β-CD were generally lower than those of the pure extracts, an observation warranting significant consideration. In terms of enzyme inhibition activity, the ethanol and 70% ethanol extracts exhibited higher inhibitory effects on AChE, tyrosinase, and α-glucosidase. Conversely, n-hexane displayed stronger inhibitory activity against BChE. The ethyl acetate extract demonstrated elevated amylase inhibitory activity. However, the antioxidant values of the complex extracts with β-CD were generally lower than those of the pure extracts, a noteworthy observation, while water and extracts from the I. sarana complex with β-CD exhibited minimal or negatable inhibitory activity against specific enzymes.

S2180 A Case of Immunotherapy Causing Elevated Amylase and Lipase in the Absence of Pancreatitis

S2180 A Case of Immunotherapy Causing Elevated Amylase and Lipase in the Absence of Pancreatitis

Abnormal elevation of serum amylase in a patient with acute depression in a state of sub-stupor: A case report

Serum amylase predominantly comprises pancreatic and salivary amylases and its elevation is commonly associated with pancreatitis and other physical diseases. This case report presents a 63-year-old male with first-episode depression who exhibited abnormally elevated serum amylase. Shortly after admission, the patient entered a sub-stupor state. The patient developed symptoms such as high fever and excessive sweating on the second night. In addition, myocardial damage was observed. The serum amylase was found to be elevated in the morning on the 3rd day. Following symptomatic and supportive treatments, the patient&amp;rsquo;s serum amylase level gradually dropped to drop to normal over approximately 2 weeks. On careful analysis of the patient&amp;rsquo;s medical condition, we suspect the increased serum amylase level may be linked to his psychiatric symptoms. Based on this case, we speculate that besides physical illness, the stupor symptoms observed in patients with depression may also lead to elevated serum amylase. Therefore, clinicians must prioritize addressing psychiatric symptoms when encountering such situations.

Acute pancreatitis after cesarean section

The prevalence of acute pancreatitis in pregnancy is low; similarly to the non-pregnant population, the outcome varies from mild to fatal forms. Occurrence of the disease in pregnancy is mostly in the third trimester or the postpartum period. The most common cause of acute pancreatitis is cholelithiasis but hypertriglyceridemia, fatty diet, obesity and alcohol consumption are further predisposing factors. A 27-year-old twin-pregnant woman developed acute severe pain 2 days after a cesarean section. Labor tests showed elevated amylase (1080 U/L) and lipase (2670 U/L) serum levels. For the purpose of pain relief, we inserted an epidural catheter and indicated an abdominal computer tomography examination. The abdominal imaging did not show morphological disorder of the pancreas or cholangial obstruction. We performed conservative therapy, early per os feeding, pain relief and fluid resuscitation. On the postpartum 7. day, the serum pancreas enzyme levels decreased to normal and the patient - with her babies - was discharged home. Though acute pancreatitis is a rare event in pregnancy, we should consider it in cases with acute, typical or non-typical pain. It is challenging to differentiate the disease from the acute syndromes of pregnancy. Orv Hetil. 2023; 164(31): 1231-1234.

Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients

BackgroundGastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years.MethodsPatients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40–60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival.ResultsThe median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death.ConclusionsNAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis.

This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis. 59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the post-hoc analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy. Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice. https://www.crd.york.ac.uk/PROSPERO, identifier 345350.

The consequences of switching from Gilenya® to generics for fingolimod.

On May 2017, two generic drugs for fingolimod were introduced into the market in Israel, and most MS patients treated with Gilenya® (Novartis) were switched to fingolimod (Teva), or to Finolim (Rafa). In this study we analyzed the consequences of switching to generic fingolimod in a single MS center. Study population included relapsing MS patients who were treated with Gilenya® for at least two year before May 2017, switched to generic fingolimod and remained on treatment for at least 2 years thereafter. Data before and after the switch were compared. Twenty-seven patients fulfilled the inclusion criteria (F=20, RRMS=20, SPMS=7, average age 49±11.4 years, average disease duration=16.6±7.6 years). Seventeen patients had to be switched back to the original Gilenya® due to intolerable new or worsening clinical adverse events (n=9), clinical relapse (n=1), clinical relapse with adverse events (n=3), elevation of liver enzymes > X3 ULN (n=3) and elevation of amylase (n=1). Expanded Disability Status Scale (EDSS) score increased in 4 patients during the year before the switch, and in 12 patients during the year of treatment with generic fingolimod (p=0.036). The tolerability, retention rate and probably efficacy of generic fingolimod seems to be lower than the original Gilenya®.

A phase I/II study of durvalumab and stereotactic ablative body radiotherapy (SABR) in locally advanced (LA) and borderline resectable (BR) pancreatic cancer.

4164 Background: Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB) in genomically unselected patients (pts). Synergistic effects of combined ICB and radiotherapy have been suggested in varied solid tumors. Few studies have evaluated this approach in pts with PC. We sought to evaluate the safety and efficacy of PD-L1 inhibitor durvalumab (D) and SABR after induction chemotherapy, in LA and BR PC. Herein, we present phase II data from two cohorts. Methods: A multi-institutional, non-randomized phase 1/2 trial of SABR and D was conducted at Cedars-Sinai Medical Center (CS) and Memorial Sloan Kettering (MSK). Key eligibility: ECOG 0-1; unresectable PC, with stable/responding disease following 2-3 cycles gemcitabine and nab-paclitaxel (GnP) or 4-6 months (m) FOLFIRINOX (FFX). CS enrolled pts with BR and LA PC; MSK enrolled pts with LA PC only. All pts received SABR between dose 1 and 2 of D, with slight variation in ablative radiation techniques (CS: 33Gy/5#; MSK: MRI adaptive ablative radiation, 50Gy/5#). D dosed on day 1: 750mg x 4 doses Q14 days, and subsequently Q2 or Q4 weeks x 1 year total, or until resection, progression of disease (POD), or limiting toxicity. Primary endpoint: 6-month progression free survival (6 m PFS). Secondary endpoints: rate of downstaging to resectability, objective response by RECIST v1.1, duration of response, PFS, Overall Survival (OS). PFS and OS estimated from consent date using Kaplan-Meier method. Association between surgery and outcomes was analyzed as a time dependent covariate in univariate Cox regression models for OS and PFS. To assess immunogenomic biomarkers of response, pre- and on-treatment tissue, blood and microbiome samples were gathered. Results: Between 08/2017 and 05/2022, N= 36 enrolled. Median age 67.5 years (range 48-79), 39% (14/36) female. Performance Status: N=12 (33%) ECOG 0; N= 24 (67%) ECOG 1. Median duration chemotherapy: 3.5 m (range 1.4, 5.8). Staging: N=31 (86%) LA; N=5 (14%) BR. N = 9 (25%) underwent resection; all R0. Conversion to resection was not associated with PFS (HR 0.45; 95% CI 0.17, 1.17, p=0.1) or OS (HR 0.69; 95% CI 0.26, 1.84, p=0.5). Survival and response data summarized in table. Toxicities of special interest: Grade 3 treatment-related: in N= 7; diarrhea N= 2; elevated AST/ALT N= 2; lipase/amylase elevation, N=1; nausea N=1. Grade 4: amylase elevation N=1. Conclusions: D and SABR after induction chemotherapy in LA and BR PC is safe, had an encouraging 6-m PFS of 69% and favorable R0 resection rate, warranting further evaluation. Immuno-genomic biospecimen analyses underway. Clinical trial information: NCT03245541 . [Table: see text]