Elevated Amylase Research Articles

Acute pancreatitis occurring after COVID-19 vaccine: a case report and literature review

BackgroundVaccines are uncommon causes of pancreatitis, and only a few case reports have described COVID-19 vaccine-related pancreatitis.Case presentationA 45-year-old male patient applied to the emergency department due to having serious abdominal pain. Pfizer-BioNTech COVID-19 vaccine, the last dose was administered 1 week ago. One week after vaccination, he experienced abdominal pain. Laboratory tests demonstrated elevated C-reactive protein, amylase, and lipase levels, and Ig G4 levels were normal. Abdominal computer tomography (CT) displayed acute edematous pancreatitis and peripancreatic inflammatory changes. The patient was diagnosed with acute pancreatitis due to the vaccine.ConclusionWe should be aware that acute pancreatitis induced by the vaccine may occur a few days or weeks after the vaccine, especially in patients who have risk factors for acute pancreatitis.

The Link between Salivary Amylase Activity, Overweight, and Glucose Homeostasis.

Butyrate, a short-chain fatty acid (SCFA) produced by the fermentation of dietary fibers in the colon, plays a pivotal role in regulating metabolic health, particularly by enhancing insulin sensitivity. Given the rising incidence of metabolic disorders, understanding the factors that influence butyrate production is of significant interest. This study explores the link between salivary amylase activity and butyrate levels in overweight women of reproductive age. Participants were categorized into low (LSA) and high (HSA) salivary amylase activity groups and further divided into two subgroups: one followed a low-starch diet (LS), and the other underwent caloric restriction (CR). We assessed salivary amylase activity and measured serum butyrate concentrations to examine their associations. Our findings showed a significant, though weak, positive correlation (ρ = 0.0486, p < 0.05), suggesting a link between salivary amylase activity and butyrate levels. The statistical significance, despite the weak correlation, implies that this relationship is not random. Moreover, higher baseline butyrate levels were observed in women with elevated salivary amylase activity. Also, women with low salivary amylase activity on a low-starch diet experienced a more pronounced increase in butyrate levels compared to those on caloric restriction. These results suggest that salivary amylase activity and dietary intake interact to influence butyrate production, with potential implications for improving insulin sensitivity and metabolic health. The study underscores the potential of butyrate in enhancing insulin sensitivity and promoting overall metabolic well-being. Further research is necessary to clarify the mechanisms involved and to understand the long-term effects of butyrate on metabolic health across different populations.

Bufalin alleviates inflammatory response and oxidative stress in experimental severe acute pancreatitis through activating Keap1-Nrf2/HO-1 and inhibiting NF-κB pathways

Severe acute pancreatitis (SAP) is a prevalent acute inflammatory disease that is clinically manifested by systemic inflammation dysregulation, resulting in a significantly elevated mortality rate. Bufalin has been verified to have potent pharmacological properties, including analgesic, anti-tumor and anti-inflammatory effects. However, it remains unclear whether bufalin inhibits SAP. Thus, we aim to explore the impact of bufalin in SAP rats and to evaluate the potential mechanisms of action. In addition to analyzing serum biochemistry and pancreatic tissue pathology, we elucidated its mechanisms of action through enzyme-linked immunosorbent assay (ELISA), immunohistochemical analysis, Western blot, and quantitative real-time PCR. The results demonstrated that bufalin dose-dependently reversed the elevation of serum Amylase (Amy) and Lipase (LPS) levels in SAP rats, alleviating pancreatic tissue pathological damage. Bufalin exhibited potent antioxidant effects by reducing malondialdehyde (MDA) levels, decreasing Superoxide dismutase (SOD) and glutathione(GSH) consumption, inhibiting the interaction of Keap1-Nrf2, and increasing HO-1 expression. Furthermore, bufalin inhibited TNF-α, IL-6, IL-1β, p-NF-κB-p65, p-IκBα, and NF-κB-p65 expression, while enhancing IκBα expression, ultimately confirming its anti-inflammatory effects on SAP. In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis

BackgroundSkin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently.Case presentationA 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient’s dialysis effluent initially appeared red. Upon examination of the patient’s peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient’s method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged.ConclusionsIn the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Effects of dietary supplementation of spray dried hog plum (Spondias pinnata (L.f.) Kurz) fruit powder on growth, digestive enzyme activity, and skin mucus immune parameters of climbing perch (Anabas testudineus (Bloch, 1972)

The effects of dietary supplementation of spray-dried hog plum (Spondias pinnata (L.f.) Kurz) fruit powder (SPP) on growth, digestive enzyme activity, and skin mucus immune parameters of climbing perch (Anabas testudineus (Bloch, 1972)) were examined. The fish (N = 330; 2.00±0.1 g) were assigned to five groups in triplicates. They were fed different SPP levels at 0, 5, 10, 15, and 20 g/kg diet for eight weeks. Flavonoids, terpenoids, phenolic compounds, tannins, steroids, glycosides, and glycosides were detected in SPP. The SPP containing diet significantly improved growth parameters (P &lt; 0.05) without a negative effect on the survival rate (P &gt; 0.05). Intestinosomatic and hepatosomatic indices significantly declined in the fish fed SPP added diets (P &lt; 0.05). There were significant elevations in digestive enzyme activities, amylase, protease, lipase, trypsin, pepsin, and esterase, in the tested fish compared to the control fish (P &lt; 0.05). Additionally, fish fed SPP containing diets showed a significant enhancement of total protein, immunoglobulin M, lysozyme, antiprotease, alkaline phosphatase, and esterase in the skin mucus compared to the control group (P &lt; 0.05). Significantly higher levels of superoxide dismutase, catalase, and total antioxidant capacity were detected in fish fed SPP containing diets compared to the control (P &lt; 0.05). These findings suggest that dietary SPP supplementation can effectively enhance fish growth, digestive enzyme activities, and mucosal immune parameters in the climbing perch. The suitable level of SPP observed in this present study was 13.00 – 15.88 g/kg diet.

Characteristics of sialolithiasis in Israel, a big-data retrospective study of 5100 cases.

The aim of this study was to identify risk factors for sialolithiasis patients using a large community and hospital-based cohort. A retrospective case-control study was conducted on 20,396 individuals, including 5100 sialolithiasis patients and 15,296 matched controls. Demographics and laboratory data were obtained from electronic medical records. Statistical analyses were performed to identify significant differences between the two groups. A p-value of <0.05 was considered significant. Sialolithiasis was more prevalent in women, with a mean age at diagnosis of 55.75 years. Several geographic location variables emerged as risk factors for sialolithiasis including Israeli birth, higher socioeconomic communities, and specific areas of residency. Tobacco smoking (odds ratio = 1.46) was a significant risk factor. Low high-density lipoprotein levels, elevated triglycerides, and elevated amylase levels were associated with sialolithiasis. This study provides valuable insights into the demographic and laboratory characteristics of sialolithiasis patients, indicating that area of residency and lifestyle factors contribute to the risk of developing sialolithiasis. The findings may contribute to a better understanding of the disease and the development of preventative measures or early diagnostics tools.

UPLC-QTOF-MS characterized, herbal medicine, pancogrit modulates NF-κB and JAK2/STAT3 signaling pathways in cell-based model of TNF-α dependent acute pancreatitis

Acute pancreatitis develops as a local inflammatory condition of the pancreas due to a wide range of factors including overdose of alcohol or drugs, gall stones, etc. At present, medications based on herbal formulations have gained importance due to their better safety profile. Current study assessed the pharmacological effects of Pancogrit, an herbal medicine, in caerulein and TNF-α-induced in vitro pancreatitis models. A comprehensive evaluation of phytometabolites present in Pancogrit was conducted and 85 phytometabolites were identified through UPLC-QTOF-MS and UPLC-UV. The bioactivity and mode of action of Pancogrit were assessed in caerulein-induced AR42J (rat pancreatic acinar) cells, TNF-α-induced PANC-1 (human pancreatic duct) cells, and NF-κB reporter cells. Pancogrit was found to decrease the elevated amylase and lipase activity in caerulein-induced AR42J cells. It ameliorated the increased ROS levels, IL-6, IL-8 release and NF-κB activity in TNF-α-induced PANC-1 and NF-κB reporter cells. Pancogrit also downregulated IL-6, IL-1β, ICAM-1, and STAT3 gene expression in PANC-1 cells. Moreover, Pancogrit inhibited the protein expression levels of phosphorylated STAT3, phosphorylated and total JAK2 in TNF-α-induced PANC-1 cells. Taken together, Pancogrit is a clinically relevant therapeutic agent for mitigation of pancreatitis.

Psychological Stress and Intraocular Pressure in Glaucoma: A Randomized Controlled Trial

To evaluate the intraocular pressure (IOP) behavior after applying a standardized protocol to induce psychological stress in primary open-angle glaucoma (POAG) patients. Randomized controlled trial. A total of 39 POAG patients were included: 18 in the stress group and 21 in the control group. Patients were randomized to undergo the Trier Social Stress Test (TSST) or to be included in the control group. All participants were submitted to a modified diurnal tension curve (DTC) 1 to 4 weeks before randomization, with 3 IOP measurements performed between 8:00 AM and 2:00 PM. We evaluated the response to the TSST by measuring the levels of salivary cortisol, salivary amylase, IOP, mean arterial pressure and heart rate before, immediately after, and 40 minutes after the TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals. Changes in IOP (mmHg), salivary cortisol and amylase, heart rate, mean arterial pressure and STAI scores. At baseline, there were no significant differences between the groups regarding age (P=0.661), gender (P=0.669), salivary cortisol (P=0.104) and mean DTC IOP for the right (P=0.439) and left (P=0.576) eyes. We observed a significant mean IOP increase of 3.8 mmHg (right eye, P<0.001) and 4.1mmHg (left eye, P<0.001) when we compared IOP measurements obtained during the DTC and immediately after TSST. Salivary cortisol (5.9 nmol/L, P=0.004), salivary amylase (323,388 UL, P=0.004), mean arterial pressure (10.1mmHg, P<0.001) and heart rate (12.9bpm, P<0.001) also increased significantly after the TSST. In addition, 61.1% (11 out of 18) of the patients in the TSST group showed an IOP increase greater than 4 mmHg following the test. The STAI-state score significantly increased after the TSST compared to baseline (P<0.001) and decreased from post-stress to the recovery period (P<0.001). POAG patients present significant elevations of IOP, salivary cortisol and amylase, mean arterial pressure, heart rate and STAI scores after psychological stress induced by the TSST.

Analysis of risk factors associated with postoperative pancreatic fistula after robotic-assisted distal pancreatectomy

Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI: 0.112 to 0.623), manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying (P=0.020, 95%CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

Improvement of laparoscopic interventions on the bile ducts in choledocholithiasis

Objective. To improve the technique of laparoscopic choledocholithotomy to improve the results of choledocholithiasis treatment. Materials and methods. The study covers the period from 2012 to 2022, during which 144 patients with choledocholithiasis were treated. In 120 patients, the surgical intervention was successfully performed using a fully laparoscopic approach: in 48 patients (group 1), the common bile duct was drained with a T-shaped drainage; in 34 patients (group 2), the intervention on the common bile duct was completed with a primary suture of the duct; in 38 patients (group 3), a biliary stent was inserted integrally with subsequent suturing of the choledochotomy opening. Results. In group 1, 5 (10.4%) patients had serious complications that required repeated surgical interventions: dislocation of the T-shaped drainage in 1 (2.1%) patient, development of biliary peritonitis in 4 (8.3%) patients. In the treatment of patients in group 2, a number of advantages were noted compared to the treatment of patients with T-shaped drains. The majority of patients with primary common bile duct suture were discharged on the 3rd day after surgery, and they returned to active work in 2 to 3 weeks. At the same time, 3 (8.8%) patients in this group had complications that required repeated surgical interventions: in 1 patient with multiple choledocholithiasis, bile leakage into the abdominal cavity was caused by a residual stone, in 2 patients - by papillitis and partial inflammatory stenosis of the large duodenal papilla. They underwent endoscopic papillotomy. Of the 38 patients in group 3, 32 had biliary stents that migrated to the intestine on their own. These patients had no complaints in the long term. In 6 patients, the stents remained in the ducts for 30 days after surgery. In 5 of them, endoscopic dosed papillotomy with a needle papillotome was performed, after which the stents were easily removed from the ducts. In 1 patient, a stone up to 6 mm in diameter fell out of the common bile duct along with the stent. None of the patients had signs of pancreatitis or elevated blood amylase levels. Conclusions. Laparoscopic interventions on the common bile duct allow successful removal of large and numerous calculi in one stage. Primary suturing of the common bile duct has significant advantages over the installation of T-shaped drains and allows to reduce the treatment time. In case of multiple choledocholithiasis and suspected stenosis of the duodenal papilla, it is advisable to combine primary common bile duct suture with antegrade stenting of the bile ducts.

Reasonability of Frequent Laboratory Analyses during Therapy with Nivolumab and Nivolumab+Ipilimumab in Patients with Advanced or Metastatic Renal Cell Carcinoma during the Phase 2 Clinical Trial TITAN-RCC.

In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in laboratory values would have been missed if laboratory values had been assessed less frequently. Patients with metastatic renal cell carcinoma (n = 207) received a response-based approach with nivolumab and nivolumab+ipilimumab boosts for non-response. We simulated that laboratory values were obtained before every second dose instead of every dose of the study drug(s). We assessed elevated leukocyte counts, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, amylase, lipase, and thyroid-stimulating hormone. Dose delay and discontinuation criteria were defined according to the study protocol. With the reduced frequency of laboratory analyses, dose delay criteria were rarely missed: in a maximum of <0.1% (3/4382) of assessments (1% [2/207] of patients) during nivolumab monotherapy and in a maximum of 0.2% (1/465) of assessments (1% [1/132] of patients) during nivolumab+ipilimumab boosts. An exception was lipase-related dose delay which would have been missed in 0.6% (25/4204) of assessments (7% [15/207] of patients) during nivolumab monotherapy and in 0.8% (4/480) of assessments (3% [4/134] of patients) during nivolumab+ipilimumab boosts, but would have required the presence of symptoms. Discontinuation criteria would have only been missed for amylase (<0.1% [1/3965] of assessments [0.5% (1/207) of patients] during nivolumab monotherapy, none during nivolumab+ipilimumab boosts) and lipase (0.1% [5/4204] of assessments [2% (4/207) of patients] during nivolumab monotherapy; 0.2% [1/480] of assessments [0.7% (1/134) of patients] during nivolumab+ipilimumab boosts). However, only symptomatic patients would have had to discontinue treatment due to amylase or lipase laboratory values. In conclusion, a reduced frequency of laboratory testing appears to be acceptable in asymptomatic patients with metastatic renal cell carcinoma treated with nivolumab or nivolumab+ipilimumab.

Pancreatitis-induced prediabetes and hepatic lipidosis in a mixed breed cat

Pancreatitis can lead to decreased insulin production and elevated blood glucose levels. Reduced insulin levels can cause excessive lipolysis, leading to hepatic lipidosis. This report aimed to illustrate how pancreatitis can result in prediabetes and hepatic lipidosis, providing insight into selecting appropriate and causal therapies. This case report discusses a 5-year-old male mixed-breed cat weighing 3.9 kg presented with anorexia and hypersalivation. Despite a routine physical examination, blood tests revealed decreased creatinine and Ca2+ levels and elevated blood glucose, SGPT, cholesterol, and amylase levels. These findings suggested a diagnosis of pancreatitis accompanied by prediabetes and hepatic lipidosis. The treatment administered included intravenous Ringer’s Lactate, subcutaneous Ornipural® injection, oral cephalexin (Rilexine®) and Samylin®, and dietary management with specialized renal wet food.

Effects of prolonged hydroxychloroquine use on the pancreatic tissue and expected ameliorative effect of lactoferrin in rats (biochemical, histological, and morphometric study)

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration.

Clinical characteristics, treatment and outcome of pembrolizumab-induced acute pancreatitis.

Acute pancreatitis (AP) is a rare adverse event of pembrolizumab with unclear clinical features. This study investigated the clinical features of pembrolizumab-induced AP to provide a reference for prevention and treatment. Case reports, case series and clinical studies of pembrolizumab-induced AP were collected by searching Chinese and English databases up to January 31, 2024. Thirty-one patients were included, with a median age of 59 years (range 39, 82). The median time from administration to onset of AP was 5.05 months (range 0.5, 16) and the median cycle was 7 cycles (range 1, 35). Twenty-two (71.0%) patients had elevated pancreatic amylase with a median value of 860 IU/L (range 105-12562), and 16 (51.6%) patients had elevated lipase with a median value of 282 IU/L (range 153-1034). Pancreatic biopsy showed neutrophil infiltration (9.7%) and lymphocyte infiltration (6.5%). Immunohistochemical staining showed CD8 dominated inflammatory infiltration (6.5%). The computed tomography showed diffuse enlargement (51.6%) and focal enlargement (51.6%) of the pancreas. Endoscopic ultrasound showed enlarged hypoechoic pancreas(16.1%). PET/CT showed increased FDG uptake (16.1%). The magnetic resonance cholangial pancreatography showed narrowing of main pancreatic duct (12.9%). AP symptoms and pancreatic enzymes improved after discontinuation of pembrolizumab and administration of steroids and infliximab. Clinicians should be aware that AP is a rare adverse reaction to pembrolizumab. Pembrolizumab induced AP can be initiated with steroids for control, and infliximab can be initiated with steroid-refractory AP.

A phase II study of anlotinib and an anti-PDL1 antibody in patients with alveolar soft part sarcoma: Results of expansion cohorts.

11515 Background: The combination of the anti-angiogenesis tyrosine kinase inhibitor (TKI), anlotinib, with the anti-programmed death-ligand 1 (PDL1) antibody (TQB2450) demonstrated commendable antitumor efficacy in a phase II clinical trial for pan-sarcoma patients, particularly within the alveolar soft part sarcoma (ASPS) cohorts (Liu et al., 2022, PMID: 35675031). An expansion of the ASPS cohort has been underway since 2019. Herein, we present the observed efficacy within this ASPS-specific expansion cohort. Methods: ASPS patients naïve to TKIs or immunotherapy received TQB2450 (1200mg) intravenously on day 1, in combination with oral administration of anlotinib (12mg) from day 1 to 14, repeated every 3 weeks. The primary endpoint was best objective response rate (ORR, per RECIST v1.1). Secondary endpoints comprised median progression free survival (PFS), median overall survival (OS), duration of response (DOR), and adverse events (AEs). Formalin-fixed paraffin-embedded (FFPE) slides were taken for immunohistochemistry and examined for lymphocyte marker expression. Results: Twenty-nine patients were enrolled in the phase II trial. The median age was 29 years (range: 19-46), with female 48.3%. A subset of patients (20.7%) had undergone prior lines of chemotherapy. Twenty-eight patients were evaluable for efficacy (one withdrew). The ORR for evaluable patients reached 79.3%, characterized by 3 complete responses and 20 partial responses. The median PFS (months) was not reached (95%CI: 20.7, not-reached). The median DOR (months) for responders was not reached (95%CI: 18.0, not-reached). No mortalities occurred during the follow-up. Treatment demonstrated favorable tolerability, with predominant grade 1 and 2 AEs. Thirteen patients (44.83%) experienced grade ≥3 AEs, principally hypertriglyceridemia (13.79%), lipase elevation (6.90%), amylase elevation (3.45%), and hypertension (3.45%). A detailed analysis of the tumor microenvironment in 7 patients, including 3 good responders and 4 poor responders, revealed a significant discrepancy in the presence of tertiary lymphoid structures (TLS) between the two groups (refer to Table). Conclusions: The combination of anlotinib and TQB2450 exhibits promising efficacy in ASPS patients, markedly enhancing ORR and extending PFS with favorable tolerability. Notably, TLS emerges as a potential predictive indicator of immunotherapeutic efficacy in ASPS. Clinical trial information: CTR20190938 . [Table: see text]

A Phase II Study of ERK Inhibition by Ulixertinib (BVD-523) in Metastatic Uveal Melanoma.

Uveal melanoma is a rare and aggressive subset of melanoma that is minimally responsive to traditional therapies. Greater than 80% of uveal melanomas have a mutation in GNAQ or GNA11 which lead to downstream signaling through the MAPK pathway. Ulixertinib (BVD-523) is a potent and reversible small-molecule ATP-competitive inhibitor of both ERK1 and ERK2 protein kinases. We performed a phase II study to determine the efficacy and safety of BVD-523 in patients with metastatic uveal melanoma. This was conducted as a Simon two-stage design with a sample size of 25 patients and an initial evaluation of efficacy after 13 patients. From April 2018 to April 2019, 13 patients were enrolled. Patients were predominantly female (69%) with a median age of 64 years (34-76). Sites of metastases included liver (84.6%) and lung (30.8%). Grade 3 and 4 toxicities associated with therapy were consistent with ERK inhibitors and included liver function test (LFT) elevation, hyponatremia, pruritis, amylase elevation, anemia, and rash. The best response, per RECIST 1.1, was stable disease in 4 patients, and disease progression in 7 patients. Two patients were unevaluable for response due to withdrawal from study. Median time to progression was 2.0 months. There were eight deaths due to disease progression with a median overall survival of 6.9 months. ERK inhibition with ulixertinib (BVD-523) did not demonstrate activity in patients with metastatic uveal melanoma. The toxicities observed were consistent with what would be expected with MAPK pathway inhibition. Uveal melanoma is a difficult to treat disease with minimal therapy options. The majority of uveal melanomas have mutations in GNAQ or GNA11 leading to activation of the MAPK pathway. Efforts to target MEK in uveal melanoma has had mixed results. This phase II trial of ERK inhibition with BVD-523 examined the potential role of this agent in uveal melanoma therapy.

CORONARY ARTERY ANEURYSM IN IGG4–RELATED DISEASE

Abstract Introduction Coronary artery ectasia is a rare disease defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adiacent normal segment. The etiology is diverse and can be rarely associated with immunoglobulin G4 (IgG4)–related disease. The high levels of serum IgG4 may promote the development of low–density plaques, intimal thickening due to pericoronitis and subsequent coronary ectasia. Case Report We present the case of a 72–year–old male patient with arterial hypertension, dyslipidemia, chronic renal insufficiency, and a family history of cardiovascular diseases. In the previous year, he suffered a cerebral hemorrhage attributed to an unspecified cerebral vascular malformation, which was managed with an endovascular approach. The patient was admitted for Non–ST–segment Elevation Myocardial Infarction (NSTEMI). Coronary angiography revealed widespread ectasia of the coronary vessels, a chronically occluded marginal branch, and an aneurysmatic proximal right coronary artery with the presence of a thrombus on the aneurysmal segment, dissolved following administration of intracoronaric heparin. Furthermore a critical stenosis at the crux involving the posterior interventricular branch was detected and angioplasty with drug–eluting stent implantation was performed on the affected vessel. Given the coronary artery ectasia, aortic ectasia revealed by echocardiography, renal insufficiency and persistently elevated amylase and lipase levels, further diagnostic investigation was conducted suspecting IgG4–related disease. Hematological tests revealed elevated IgG and IgG4 subclass levels (882 mg/dL and 1438 mg/L, respectively), C3 117 mg/dL, C4 30 mg/dL, and total IgE 130 KU/L. The diagnosis of IgG4–related disease was confirmed and the patient was advised to continue cardiological and rheumatological follow–up. Conclusion When the coronary arteries are involved in the IgG4–related disease, risk of acute events such as heart attack may increase and the prognosis is poor. Coronary thickening and ectasia, typical imaging features, other aortic involvement and inflammation indicators, like elevated serum IgG4, should be considered as red flags for an early investigation and subsequent early intervention.

How They Eat: An Examination of Digestive Physiology of Sympatric Prickleback Fishes

How fishes thrive on different diets is not understood as well as for terrestrial animals. Thus, examining the flexibility of gut function in fishes with different diets provides insight into dietary specialization in the largest vertebrate class. In this study, we measured the amylolytic activities in the guts of closely related, sympatric species: Xiphister mucosus (herbivore), X. atropurpureus (omnivore), Phytichthys chirus (omnivore), and Anoplacharus purpurescens (carnivore). For all species, the amylase activity decreased moving distally along the intestine, but less so for the carnivorous A. purpurescens. Overall, our results—more elevated amylase activity in those fish eating more algae—agree with the Adaptive Modulation Hypothesis (AMH), which suggests that there should be a match between enzymatic activity and dietary substrate intake. Measurements of proteases and lipases are in progress, but we anticipate some support for AMH in other enzyme classes. Moreover, we are also measuring these same enzyme activities in these same species fed omnivorous or carnivorous diets in the laboratory. The flexibility of the intestines of the fish species to accommodate different food types provides insight into their roles in the ecosystems and how fixed the vertebrate digestive system can be. NSF IOS 1355224 Undergraduate Research Opportunity Program at University of California, Irvine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Complex Presentation of Lung Cancer with Obstructive Jaundice

Background: Lung cancer, particularly small-cell lung carcinoma (SCLC), often presents with respiratory symptoms. However, atypical manifestations including jaundice and abdominal pain can obscure the diagnosis, leading to challenges in early detection and treatment. Case Presentation: A 49-year-old male, with a history of smoking and diagnosed with Chronic Obstructive Pulmonary Disease (COPD), presented to the emergency department with a 3-day history of jaundice and a 3-week duration of mild abdominal pain. Initial investigations, including blood tests, showed hyperbilirubinemia and elevated lipase and amylase levels. An abdominal ultrasound was performed and revealed a hypoechoic, inhomogeneous mass in the head of the pancreas and multiple liver masses, suggesting a cephalo-pancreatic formation with liver metastasis. Further diagnostic procedures, including upper endoscopy and ERCP, followed by a TAP CT scan, identified a large mediastinal-pulmonary mass with invasion into major vessels and extensive metastasis. The immunohistochemical analysis of a duodenal ulcer biopsy confirmed a diagnosis of duodenal metastasis from a small-cell neuroendocrine lung carcinoma. Conclusion: Our case highlights that while rare, the possibility of metastatic spread should be included in the differential diagnosis when obstructive jaundice occurs in the context of high-risk factors for lung cancer.

Cabozantinib in patients with unresectable and progressive metastatic phaeochromocytoma or paraganglioma (the Natalie Trial): a single-arm, phase 2 trial

Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs. The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting. From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study. Cabozantinib shows promising activity in patients with MPPGs. Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot.