Increased Serum Amylase Research Articles

Prospective Study on the Effects of Marijuana Smoking on Lipase and Amylase Activities among Adult Nigerians

Marijuana consumption is prevalent among young adults in Nigeria, and its effects on various physiological systems are of growing concern. This study investigates the impact of marijuana use on digestive enzymes, specifically serum amylase and lipase, to understand its potential implications on digestive health. This cross-sectional study was conducted in 120 participants comprising of 60 marijuana smokers and 60 non-smokers. Sociodemographic and lifestyle data were collected through structured questionnaires. Serum amylase and lipase activity levels were measured by spectrophotometric method and compared between the two groups. Statistical analysis was performed to assess differences and correlations. The study revealed that marijuana smokers had significantly higher serum amylase and lipase activities compared to non-smokers. Lipase activity correlated positively (r=0.425, p=0.019) with duration of marijuana use. Amylase activity was higher among males than females (r=-0.40, p=0.028). No significant correlation was found between the quantity of marijuana consumed and enzyme activities. Chronic marijuana consumption was associated with increased serum amylase and lipase activities, indicating potential alterations in pancreatic function. These findings suggest that marijuana use may have adverse effects on digestive health, warranting further investigation into the long-term implications. It is recommended that healthcare providers monitor digestive enzyme activities in marijuana users to detect early signs of pancreatic dysfunction.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study

The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Investigating the regulatory effect of Shen Qi Bu Qi powder on the gastrointestinal flora and serum metabolites in calves.

To investigate the effects of Shen Qi Bu Qi Powder (SQBQP) on the average daily gain, blood indexes, gastrointestinal microflora, and serum metabolites of calves. A total of 105 calves were randomly assigned to three groups (n = 35 per group): the control group (C, fed with a basal diet for 21 days) and two treatment groups (SQBQP-L and SQBQP-H, fed with the basal diet supplemented with 15 and 30 g/kg of SQBQP), respectively for 21 days. The active components of SQBQP were identified using LC-MS/MS. Serum digestive enzymes and antioxidant indices were determined by ELISA kits and biochemical kits, respectively. Serum differential metabolites were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), while flora in rumen fluid and fecal were analyzed by 16S rDNA sequencing. Further correlation analysis of gastrointestinal flora and serum metabolites of SQBQP-H and C groups were performed with Spearman's correlation. The principal active components of SQBQP mainly includes polysaccharides, flavonoids, and organic acids. Compared to the control group (C), calves in the SQBQP-H (high dose) and SQBQP-L (low dose) groups showed a significant increase in serum amylase (AMS) levels (P<0.001), while lipase content significantly decreased (P<0.05). Additionally, the average daily gain, T-AOC, and cellulase content of calves in the SQBQP-H group significantly increased (P<0.05). Proteobacteria and Succinivibrio in the rumen flora of the SQBQP-H group was significantly lower than that of the C group (P<0.05). The relative abundance of Proteobacteria, Actinobacteria, Candidatus_Saccharibacteria, Deinococcus_Thermus, Cyanobacteria, and Succinivibrio in the SQBQP-H group was significantly increased (P<0.05), while the relative abundance of Tenericutes and Oscillibacter was significantly decreased (P<0.05). Serum metabolomics analysis revealed 20 differential metabolites, mainly enriched in amino acid biosynthesis, β-alanine metabolism, tyrosine, and tryptophan biosynthesis metabolic pathways (P<0.05). Correlation analysis results showed that Butyrivibrio in rumen flora and Oscillibacter_valericigenes in intestinal flora were significantly positively correlated with average daily gain, serum biochemical indexes, and differential metabolite (-)-Epigallocatechin (R>0.58, P<0.05). SQBQP can promote calves weight gain and enhance health by modulating gastrointestinal flora and metabolic processes in the body.

The melatonin receptor agonist agomelatine protects against acute pancreatitis induced by cadmium by attenuating inflammation and oxidative stress and modulating Nrf2/HO-1 pathway

Pancreatitis is a serious effect of the heavy metal cadmium (Cd) and inflammation and oxidative stress (OS) are implicated in Cd-induced pancreatic injury. This study evaluated the effect of the melatonin receptor agonist agomelatine (AGM) on Cd-induced acute pancreatitis (AP), pointing to its modulatory effect on inflammation, OS, and Nrf2/HO-1 pathway. Rats were supplemented with AGM orally for 14 days and a single injection of cadmium chloride (CdCl2) on day 7. Cd increased serum amylase and lipase and caused pancreatic endocrine and exocrine tissue injury. Malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) were elevated, nuclear factor (NF)-kB p65, inducible NO synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and CD40 were upregulated, and antioxidants were decreased in the pancreas of Cd-administered rats. AGM ameliorated serum amylase and lipase and pancreatic OS, NF-kB p65, CD40, pro-inflammatory mediators and caspase-3, prevented tissue injury and enhanced antioxidants. AGM downregulated Keap1 and enhanced Nrf2 and HO-1 in the pancreas of Cd-administered rats. In silico findings revealed the binding affinity of AGM with Keap1, HO-1, CD40L and caspase-3. In conclusion, AGM protected against AP induced by Cd by preventing inflammation, OS and apoptosis and modulating Nrf2/HO-1 pathway.

Decreased syntaxin17 expression contributes to the pathogenesis of acute pancreatitis in murine models by impairing autophagic degradation.

Acute pancreatitis (AP) is an inflammatory disease of the exocrine pancreas. Disruptions in organelle homeostasis, including macroautophagy/autophagy dysfunction and endoplasmic reticulum (ER) stress, have been implicated in human and rodent pancreatitis. Syntaxin 17 (STX17) belongs to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) subfamily. The Qa-SNARE STX17 is an autophagosomal SNARE protein that interacts with SNAP29 (Qbc-SNARE) and the lysosomal SNARE VAMP8 (R-SNARE) to drive autophagosome-lysosome fusion. In this study, we investigated the role of STX17 in the pathogenesis of AP in male mice or rats induced by repeated intraperitoneal injections of cerulein. We showed that cerulein hyperstimulation induced AP in mouse and rat models, which was characterized by increased serum amylase and lipase activities, pancreatic edema, necrotic cell death and the infiltration of inflammatory cells, as well as markedly decreased pancreatic STX17 expression. A similar reduction in STX17 levels was observed in primary and AR42J pancreatic acinar cells treated with CCK (100 nM) in vitro. By analyzing autophagic flux, we found that the decrease in STX17 blocked autophagosome-lysosome fusion and autophagic degradation, as well as the activation of ER stress. Pancreas-specific STX17 knockdown using adenovirus-shSTX17 further exacerbated pancreatic edema, inflammatory cell infiltration and necrotic cell death after cerulein injection. These data demonstrate a critical role of STX17 in maintaining pancreatic homeostasis and provide new evidence that autophagy serves as a protective mechanism against AP.

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 Percutaneous Metallic Stent Insertion for Malignant Biliary Obstruction: A Retrospective 2-Center Study.

The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM).

8004 Background: B cell maturation antigen (BCMA) targeted CAR-T cells are approved for RRMM. Long manufacturing time and high clinical demand limit access. T-Charge, an innovative platform that reduces manufacturing time to &lt;2 days and preserves T cell stemness, results in robust expansion and prolonged CAR T cell persistence. Here we report updated results from the Phase I trial of T-Charge manufactured, fully human, BCMA CAR-T PHE885 (NCT04318327). Methods: Eligible pts had RRMM after ≥2 prior lines of therapy (tx). Pts received fludarabine and cyclophosphamide (or bendamustine) for lymphodepletion (LD) prior to PHE885 infusion. Primary objective was safety. Secondary objectives were clinical response and cellular kinetics. Results: As of December 22, 2022, 46 pts received PHE885 at the following doses: 2.5e6 (n=4), 5e6 (n=13), 10e6 (n=20), 14.3e6 (n=1), and 20e6 (n=8) CAR T cells. PHE885 was manufactured for 61% of pts at a single academic institution; these pts proceeded from apheresis to LD in a median of 16 days. Median age at enrollment was 65 y (range [R] 45-81), median prior lines of tx was 4 (R 2-10). 37% of pts had extramedullary disease; 96% were triple refractory. Despite aggressive disease, only 28% of pts required bridging chemotherapy, predominantly influenced by quick production time. 96% of pts experienced any gr cytokine release syndrome (CRS); 11% had gr 3 CRS. Median time to CRS onset was 8 (R 2-16) days and median duration was 4 (R 1-19) days. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 22% of pts; 7% had gr 3 ICANS. Dose limiting toxicities were experienced by 13% of pts and included gr 4 neutropenia, gr 4 lipase increase, gr 3 serum amylase increase, gr 3 neurotoxicity, gr 3 transaminitis, and gr 3 ejection fraction reduction. The most common tx-related gr ≥3 AEs included anemia (54%), neutropenia (50%), and thrombocytopenia (37%). Geo-mean peak PHE885 expansion (Cmax) was 276,000 copies/µg by qPCR and 70.6% of CD3+ T cells by flow cytometry (n=41). The PHE885 transgene was detected in 13/14 (93%) pts at 6 mo and 5/7 (71%) at 12 mo post infusion. T cells with early memory phenotype were preserved in the final product and persisted in pts post infusion. In 43 efficacy-evaluable pts, the ORR was 98%. At 10e6 dose (n=19), ORR was 100% and CRR was 42% (median follow-up of 4.9 mo [R 1.4-11.8]); 60% of 10 evaluable pts were MRD negative at 10-5 by NGS. Initial efficacy data at 20e6 and longer follow-up at active doses will also be presented. Conclusions: T-Charge manufactured PHE885 produced high response rates with no unexpected safety findings in heavily pretreated RRMM pts with aggressive disease. PHE885 expanded rapidly and showed durable persistence in vivo. Since conversion to CR/sCR has occurred as late as 18 months after infusion in this study, longer follow-up is ongoing to identify a recommended dose for future development. Clinical trial information: NCT04318327 .

Acute pancreatitis, a significant mortality predictor in acute organophosphate poisoning: an observational study in a tertiary care centre in north India

Background: Organophosphate compounds are one of the most common agents used as poison and acts by accumulation of acetylcholine hormone at neuronal synapses resulting in the symptoms like excessive salivation, vomiting, urination, and increased serum amylase and lipase levels. APACHE 2 score along with ultrasound modality can be used to assess the acute pancreatitis. The primary aim of the study is to find correlation of serum amylase and lipase levels with duration of ICU stay and with radio-logical variables like bulky pancreas. Methods: This observational study conducted at GSVM medical college, Kanpur from December 2020 to October 2022 included 58 out of total 94 admitted patients with acute organophosphate intoxicationn on the basis of inclusion and exclusion criteria. Patients were divided in 3 groups as mild, moderate and severe using q SOFA score at the time of admission. Results: Acute organophosphate poisoning was more prevalent among 20-40 years of age group. Mean serum amylase level values in q SOFA category 0, 1, 2, 3 were 65.2, 82.0, 118.4, 329.9 IU/l respectively and that of mean serum lipase levels on day 1 of admission values were 42.0, 44.3, 38.6 and 115.5 IU/l respectively. Serum amylase levels were positively correlated with duration of ICU stay and were better predictor for acute pancreatitis. Conclusions: In this study we concluded that serum amylase is a better predictor of duration of ICU stay and acute pancreatitis in patients admitted with acute organophosphate poisoning.

Association between serum amylase levels and CD4 cell counts in newly diagnosed people living with HIV: A case-control study.

Serum amylase is a direct reflection of pancreatic injury. Several clinical studies have indicated that antiretroviral therapy may be the main cause of increased serum amylase in people living with human immunodeficiency virus (PLWH). However, other probable causes including direct human immunodeficiency virus infection, opportunistic infections and neoplasms, alcohol abuse, and use of illicit drugs, which can also affect pancreatic amylase levels were not considered in these studies. In our study, we collected clinical data from newly diagnosed PLWH who had not received antiretroviral therapy, and examined the association between serum amylase levels and CD4 cell counts. Between November 2018 and September 2021, a total of 344 newly diagnosed PLWH and 344 healthy controls were recruited at Ningbo Yinzhou No 2 Hospital. Serum amylase levels, CD4 cell counts and other clinical features were measured. Relationships between serum amylase levels and clinical parameters were evaluated using correlation analysis. Multiple linear regression analyses were performed to identify the independent risk factors. Newly diagnosed PLWH had lower CD4 cell counts and higher serum amylase levels than healthy controls (P < .05). Serum amylase levels were negatively correlated with CD4 cell counts (r = -0.506, P < .001). In multiple linear regression analyses, CD4 cell counts (β = -0.327, 95% confidence interval = -0.051--0.022, P < .001) were independently associated with serum amylase levels. CD4 cell counts were independently associated with serum amylase levels in newly diagnosed PLWH. Thus, close monitoring of serum amylase may be significant in preventing opportunistic infections of PLWH, since low CD4 cell counts are associated with an increased risk of opportunistic infections.

Secondary iron overload induces chronic pancreatitis and ferroptosis of acinar cells in mice.

Disruption of iron homeostasis is associated with multiple diseases. It has been found that patients with genetic iron overload develop massive iron deposition in the pancreas. However, few studies have focused on the effect of secondary iron overload on the pancreas. The objective of the present study was to investigate the pathogenic consequences of secondary iron overload in mice. An iron overload mouse model was constructed by intraperitoneal injection of 120mg/kg body weight of iron dextran every other week for 12weeks. Iron deposition, immunocyte infiltration, fibrosis, oxidative stress and ferroptosis were assessed using Prussian blue staining, immunohistochemical analysis, Masson staining, Sirius red staining, RT‑qPCR analysis and western blot analysis. It was found that iron‑overloaded mice showed pancreatic iron overload, together with elevated gene expression of the iron storage factor ferritin H, and decreased expression of the iron transportation mediator divalent metal transporter 1, ferroportin 1 and transferrin receptor. Iron‑overloaded mice developed mild pancreatitis with increased serum amylase and lipase activities, as well as elevated gene expression levels of pro‑inflammatory cytokines, including interleukin (IL)‑1β, IL‑6 and inducible nitric oxide synthase. Acinar atrophy, massive immunocyte infiltration and pancreatic fibrosis were noted in the iron‑overloaded mice. As an underlying mechanism, iron‑overloaded mice showed increased pancreatic oxidative stress, with an elevated malondialdehyde level, and decreased SOD and glutathione peroxidase activity. Furthermore, iron overload led to ferroptosis with promoted expression of cytochrome c oxidase subunit II, and decreased transcripts of glutathione peroxidase 4 and solute carrier family 7 member 11. These results provided evidence that multiple intraperitoneal injections of iron dextran in mice lead to iron overload‑induced chronic pancreatitis, which suggested that secondary iron overload is a risk factor for pancreatitis and highlights the importance of iron in maintaining the normal functions of the pancreas.

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504

Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).

The Elevation of Pancreatic Enzymes in Serum and Their Distribution at Different Stages of Renal Insufficiency Among Diabetic Patients Attending Goba Referral Hospital.

IntroductionAcute pancreatitis is auto-cell destruction that is manifested by increased leakage of amylase and lipase into circulation. During pancreatitis, the activity of serum amylase and lipase is elevated three times above the upper limit of the normal range. This elevation was observed in both prediabetic and diabetic patients. Severe acute pancreatitis can result in acute kidney injury and other multi-organ dysfunction, which is one of the reasons for death.ObjectiveThis study aimed to evaluate the elevation of serum amylase and lipase and their distribution at different stages of renal insufficiency among diabetic patients.MethodsThis study included 286 diabetic patients (36 type 1 and 250 type 2), and data were collected from May 1 to June 30, 2019. The study design used was an institution-based cross-sectional study. A face-to-face interview was used to collect data, and serum creatinine, amylase, and lipase levels were measured using a chemistry analyzer. For data entry and statistical analysis, respectively, Epidata software version 3.02 and SPSS version 21 were used.ResultsThe mean serum amylase among diabetic patients suffering from G3b and G4 was 106.79 IU/L ± 118.18 IU/L and 104.85 ± 90.42 IU/L, respectively. Their mean serum lipase activity was 105.07 IU/L ± 127.54 IU/L and 106.98 IU/L ± 88.35 IU/L, respectively. Serum lipase activity was elevated above the normal range and three times above the upper limit of the normal range with a magnitude of 11.2% and 4.2%, respectively. Similarly, 9.1% and 0.7% of diabetic patients had increased serum amylase above the normal range and three-fold above the normal range, respectively.ConclusionAs glomerular filtration decreases, particularly in moderate-to-severe chronic kidney disease, serum amylase and lipase activity rise above the upper limit.

Predisposing Factors in Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Objective: To ascertain the prevalence of risk factors in pancreatitis after endoscopic retrograde cholangiopancreatography at Isra University Hospital in Hyderabad. Methodology: This descriptive case series study was done at the gastroenterology department of Isra University Hospital, Hyderabad, from September 2018 to March 2020. Patients aged 18 to 50 years, both genders, and diagnosed with post-ERCP pancreatitis were included. All the patients were undergoing an ERCP procedure. The procedure was done under conscious sedation or propofol where needed. The serum amylase level was assessed in all patients at 4 hours. Patients had been considered to have post-ERCP pancreatitis if they developed new or worsening pain of abdomen and had a threefold increase in serum amylase. All the cases were assessed regarding risk factors in pancreatitis after endoscopic retrograde cholangiopancreatography. All the data was recorded in the proforma. Results: The mean age of the patients was 42.7 years. The majority of the patients (65.47%) were females and 32.90% were males. The mean duration of pancreatitis was 3.1 days. Sphincter of Oddi dysfunction was found in 17.1% of cases. Precut papillotomy was done in 18(23.7%) cases. Repeated pancreatic duct injury was seen in 10(13.2%) cases. No significant difference was found in the effect of modifiers on predisposing factors in post-endoscopic retrograde cholangiopancreatography pancreatitis, p-values were almost insignificant. Conclusion: Cannulation attempts, Sphincter of Oddi dysfunction, precut papillotomy, repeated pancreatic duct injection, and female gender were observed to be the predisposing factors in post-endoscopic retrograde cholangiopancreatography pancreatitis.

Ginsenoside Rg3 ameliorates acute pancreatitis by activating the NRF2/HO‑1‑mediated ferroptosis pathway.

Acute pancreatitis (AP) is an inflammatory disorder that has been associated with systemic inflammatory response syndrome. Ginsenoside Rg3 is a major active component of Panax ginseng, which has been demonstrated to exert potent protective effects on hyperglycemia and diabetes. However, it remains to be determined whether Rg3 ameliorates AP. Thus, an in vitro AP cell model was established in the present study by exposing AR42J cells to cerulein (Cn). AR42J cell viability was increased in the Rg3-treated group as compared with the Cn-exposed group. Simultaneously, the number of dead AR42J cells was decreased in the Rg3-treated group compared with the group treated with Cn only. Furthermore, following treatment with Rg3, the production of malondialdehyde (MDA) and ferrous ion (Fe2+) in the AR42J cells was reduced, accompanied by increased glutathione (GSH) levels. Western blot analysis revealed that the decrease in glutathione peroxidase 4 (GPX4) and cystine/glutamate transporter (xCT) levels induced by Cn were reversed by Rg3 treatment in the AR42J cells. Mice treated with Cn exhibited increased serum amylase levels, as well as increased levels of TNFα, IL-6, IL-1β, pancreatic MDA, reactive oxygen species (ROS) and Fe2+ production. Following Rg3 treatment, ROS accumulation and cell death were decreased in the pancreatic tissues compared with the AP group. Furthermore, in the pancreatic tissues of the AP model, the expression of nuclear factor-erythroid factor 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1)/xCT/GPX4 was suppressed. In comparison, the NRF2/HO-1/xCT/GPX4 pathway was activated in pancreatic tissues following Rg3 administration. Taken together, the present study, to the best of our knowledge, is the first to reveal a protective role for Rg3 in mice with AP by suppressing oxidative stress-related ferroptosis and the activation of the NRF2/HO-1 pathway.

Efficacy of platelet rich plasma on pancreatic injury induced by renal ischemia reperfusion in adult male rats

ABSTRACT Renal ischemia-reperfusion (I-R) injury is the main cause of acute renal failure. Acute pancreatitis is one of the fatal remote lesions that occurs in patients with renal I-R injury. Platelet-rich plasma (PRP) is a hopeful aiding therapy for tissue injuries. Forty adult rats were utilized in this study, ten for PRP preparation and thirty were divided into three groups; Control: subdivided into three equal subgroups, I-R group: exposed to bilateral renal pedicles clamping and I-R+ PRP group: were experienced identical procedures as I-R group then subcutaneously (S.C) injected with 0.5 ml PRP two times weekly for three weeks. Blood samples were taken for detection of serum urea and creatinine, blood glucose level and serum amylase. The pancreas was dissected and prepared for histopathological examination by light and electron microscope. Statistical analysis of all collected results was performed. Our biochemical results revealed deleterious effects of renal I-R on the pancreas as evidenced by a highly significant increase in serum amylase and blood glucose level. In I-R group, histopathological examination revealed wide septa and congested blood vessels, acinar cells showed disrupted rough endoplasmic reticulum and few secretory granules. Some islet cells showed pyknotic nuclei and vacuolated cytoplasm. PRP treated group showed nearly normal structure in the form of numerous acinar cells’ granules, extensive rough endoplasmic reticulum and mitochondria. Most of Beta cells had euchromatic nuclei and numerous secretory granules. Accordingly, PRP treatment reduced the pancreatic biochemical and histopathological alterations caused by renal I-R injury and so considered a promising therapy for pancreatic damage.

A first-in-human phase 1b study of a novel allosteric extracellular FGFR2 inhibitor alofanib in patients with refractory metastatic gastric cancer.

304 Background: FGFR2 promotes gastric cancer progression, suggesting that inhibition of FGFR2 may be an important therapeutic strategy. Alofanib (RPT835) is a small molecule, allosteric inhibitor that binds to the non-active extracellular site of IIIc and IIIb FGFR2 isoforms with IC50 &lt; 10 nM. Methods: RPT835GC1B is a Phase 1b open-label study evaluating the safety and preliminary efficacy of alofanib in patients with metastatic gastric adenocarcinoma pretreated with ≥ 1 previous lines of therapy. The standard dose-escalation part (design 3+3) aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) as a primary endpoint. Secondary endpoints included pharmacokinetic (PK) parameters, rate of adverse events, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Alofanib was administered daily intravenously for 5-days followed by a 2-day interval (rest). There were five dose levels: 50, 100, 165, 250, and 350 mg/m2. All patients received alofanib until disease progression or unacceptable toxicity. Results: As of 20 September 2021, 21 patients have been enrolled in the study. Patients were Caucasian (100%), predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 14% had ECOG PS 2, and were heavily pretreated (86% had previous 3 and more lines of therapy). All enrolled patients have been studied for safety and have not experienced any dose-limiting toxicities (DLTs) within the 28-day DLT-assessment window. 17 (81%) patients had at least one treatment-related adverse event (trAE). Grade 3 or higher trAEs (5/23.8%) have included raised ALT/AST at 50 mg/m2, neutropenia at 50 mg/m2, diarrhea at 165 mg/m2, headache at 165 mg/m2, increased serum amylase at 350 mg/m2, and reactions immediately after intravenous injections (facial flushing, dizziness, weakness, sweating, and sinus tachycardia) at 350 mg/m2. Three (14.3%) patients discontinued treatment due to trAEs. Most common Grade 1-2 adverse events included reactions immediately after intravenous injections, diarrhea, thrombocytopenia, arthralgia, and headache. Grade 1 hyperphosphatemia was found in 1 (4.8%) patient. Table summarizes efficacy data. Conclusions: The MTD has not been reached and dose of 350 mg/m2 has been declared as RP2D. Alofanib showed acceptable tolerability and preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer. Clinical trial information: NCT04071184. [Table: see text]

Positive Predictive Value of Serum Amylase in Predicting Acute Appendicitis taking Histopathology as Gold Standard

Background: Worldwide acute appendicitis is one of the most commonly encountered abdominal emergencies. Despite recent advances in imaging and laboratory parameters, the diagnosis still remains clinical. This study was carried out to determine positive predictive value of serum amylase in diagnosing acute appendicitis taking into account histopathology as gold standard. Methods: Total 103 patients of both genders aged between 15-40 years presenting with pain and tenderness in right iliac fossa and vomiting having raised serum amylase &gt; 85U/L were included. These patients underwent appendectomy followed by histopathology of excised tissue. Diagnosis of appendicitis was confirmed on histopathology postoperatively and results of increased serum amylase levels were interpreted accordingly as true positive/ false positive. Informed consent was taken from all enrolled patients. Results: Mean age of the enrolled patients was 27.8±7.5 years. There were 59 (57.3%) male and 44 (42.7%) female patients, with a male to female ratio of 1.3:1. The BMI of enrolled patients ranged from 22.0 Kg/m2 to 34.4 Kg/m2 with a mean of 26.9±3.4 Kg/m2. Diagnosis of appendicitis was confirmed in 93 (90.3%) patients on histopathology. Thus there were 93 true positive and 10 false positive cases. It yielded a positive predictive value of 90.3% for serum amylase in predicting acute appendicitis taking histopathology as gold standard. Similar positive predictive value was noted across various subgroups based on age, gender and BMI. Conclusion: In the present study, the positive predictive value of raised serum amylase was found to be 90.3% in predicting acute appendicitis which along with simplicity and routine availability of the test and low cost advocate the preferred use of this novel biomarker in the diagnostic workup of such patients in future surgical practice. Keywords: Appendicitis, Serum Amylase, Positive Predictive Value

Systemic lupus erythematous presenting with hemorrhagic shock caused by gastric penetration of pancreatic pseudocyst: a case report

BackgroundSystemic lupus erythematous that causes various organ damage is rarely associated with pancreatic lesion. To the best of our knowledge, no cases presenting with hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis have been reported. Herein, we report a case of hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis.Case presentationA 53-year-old Japanese man with a history of systemic lupus erythematous, pancreatic pseudocyst, and chronic pancreatitis complained of epigastric pain and had hematemesis. He visited our emergency room and was admitted in our hospital. Upper endoscopy showed that hemostasis was obtained; however, computed tomography scan was performed since he was suspected to have gastric penetration into hollow viscera. The computed tomography revealed accumulation of fluid around the pancreas and gastric penetration of pancreatic cyst. Blood test showed increased serum amylase level. These results suggest that the exacerbation of chronic pancreatitis causes the penetration. Surgery was considered; however, we took a wait-and-see approach since hemostasis was obtained. After that, he was in stable condition, although he suffered from fever and accumulation of left pleural effusion was observed by computed tomography. However, he had massive hematemesis and melena 9 days after hospitalization and died in spite of several treatments including blood transfusion. Autopsy revealed that he actually had pleural thickening, which is not caused by accumulation of left pleural effusion but by severe pleural inflammation. We therefore performed additional blood and urinary tests on the same day. The test results showed that he had a high titer of anti-double-stranded deoxyribonucleic acid (DNA) antibody, hypocomplementemia, and erythrocyturia, indicating that he had systemic lupus erythematous with high disease activity considering his fever and pleural inflammation.ConclusionsPatients who have systemic lupus erythematous with high disease activity have the potential to develop fatal complications due to pancreatitis, so appropriate treatments are required for such patients.

Activity of Ligustrum vulgare L extracts against acute pancreatitis in murine models by regulation of p38 MAPK and NF-κB signaling pathways.

Pancreatitis is a fatal disease associated with significant mortality and morbidity. At present, no specific treatment is available for pancreatitis and the patients are mainly treated with supportive medication. The need for specific antipancreatitic chemotherapy is an urgent medical obligation. In the current study, protective effects of the methanolic extract of the Ligustrum vulgare berries were investigated in the rat model of acute pancreatitis. Acute pancreatitis (AP) was induced in the male Sprague-Dawley (SD) rats by cerulein injection. Fruit extract of L. vulgare L extract was prepared using the methanol. Treatment effects of L. vulgare were evaluated in AP rats. Serum levels of lipase, amylase, proinflamatory cytokines (TNF-α, IL-6, TL-1β), lipid peroxidase (LPO), myeloperoxidase (MPO) were determined. Histological changes in the pancreas were assessed. L. vulgare treatment prevented the increase in serum amylase and lipase levels, reduced the disease progression in pancreas, and reduced the serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in AP rats. Moreover, L. vulgare significantly suppressed pancreatic edema, inhibited oxidative damage (MPO activity and SOD activity), and inhibited the expression of NF-κB/p65 and activation (phosphorylation) of the inhibitor of NF-κB (IκBα) and p38 MAPKs. Histological examinations showed that L. vulgare significantly reduced the inflammatory and fibrotic changes. The results indicated the potent pancreato-protective effects of L. vulgare in AP.