American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of chronic pancreatitis: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the management of chronic pancreatitis (CP). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses effectiveness of endoscopic therapies for the management of pain in CP, including celiac plexus block, endoscopic management of pancreatic duct (PD) stones and strictures, and adverse events such as benign biliary strictures (BBSs) and pseudocysts. In patients with painful CP and an obstructed PD, the ASGE suggests surgical evaluation in patients without contraindication to surgery before initiation of endoscopic management. In patients who have contraindications to surgery or who prefer a less-invasive approach, the ASGE suggests an endoscopic approach as the initial treatment over surgery, if complete ductal clearance is likely. When a decision is made to proceed with a celiac plexus block, the ASGE suggests an EUS-guided approach over a percutaneous approach. The ASGE suggests indications for when to consider ERCP alone or with pancreatoscopy and extracorporeal shock wave lithotripsy alone or followed by ERCP for treating obstructing PD stones based on size, location, and radiopacity. For the initial management of PD strictures, the ASGE suggests using a single plastic stent of the largest caliber that is feasible. For symptomatic BBSs caused by CP, the ASGE suggests the use of covered metal stents over multiple plastic stents. For symptomatic pseudocysts, the ASGE suggests endoscopic therapy over surgery. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

TEMPORARY REMOVAL: American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations.

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American College of Gastroenterology Guidelines: Management of Acute Pancreatitis.

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.

Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis.

BACKGROUND: Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. METHODS: This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). RESULTS: Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7 years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. CONCLUSIONS: Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.

Impact of Geospatial Food Access on Acute Pancreatitis Outcomes.

BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access. METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access. RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR 1.88 (95%CI 1.21-2.92); p = 0.005], and 30-day AP-related readmission [OR 1.78(95%CI 1.11-2.86); p = 0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p = 0.40) and length of stay (LOS: p = 0.99). CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.

Innovative pathways allow safe discharge of mild acute pancreatitis from the emergency room.

Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States, resulting in 300000 admissions per year with an estimated cost of over $2.6 billion annually. The severity of AP is determined by the presence of pancreatic complications and end-organ damage. While moderate/severe pancreatitis can be associated with significant morbidity and mortality, the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%. Despite favorable outcomes, the majority of mild AP patients are admitted, contributing to healthcare cost and burden. In this Editorial we review the performance of an emergency department (ED) pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations, resource utilization, and costs after several years of implementation of the pathway. We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital, and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway. We conclude that by implementing innovative clinical pathways which are established and reproducible, selected AP patients can be safely discharged from the ED, reducing hospitalizations and healthcare costs, without compromising clinical outcomes. We also identify a subset of patients most likely to succeed in this pathway.

Optimization of fungal chitosan production from Cunninghamella echinulata using statistical designs.

Fungal chitosan (FCH) is superior to crustacean chitosan (CH) sources and is of immense interest to the scientific community while having a high demand at the global market. Industrial scale fermentation technologies of FCH production are associated with considerable challenges that frequently restrict their economic production and feasibility. The production of high quality FCH using an underexplored fungal strain Cunninghamella echinulata NCIM 691 that is hoped to mitigate potential future large-scale production was investigated. The one-factor-at-a-time (OFAT) method was implemented to examine the effect of the medium components (i.e. carbon and nitrogen) on the FCH yield. Among these variables, the optimal condition for increased FCH yield was carbon (glucose) and nitrogen (yeast extract) source. A total of 11 factors affected FCH yield among which, the best factors were screened by Plackett-Burman design (PBD). The optimization process was carried out using the response surface methodology (RSM) via Box-Behnken design (BBD). The three-level Box- Behnken factorial design facilitated optimum values for 3 parameters-glucose (2% w/v), yeast extract (1.5% w/v) and magnesium sulphate (0.1% w/v) at 30˚C and pH of 4.5. The optimization resulted in a 2.2-fold higher FCH yield. The produced FCH was confirmed using XRD, 1H NMR, TGA and DSC techniques. The degree of deacetylation (DDA) of the extracted FCH was 88.3%. This optimization process provided a significant improvement of FCH yields and product quality for future potential scale-up processes. This research represents the first report on achieving high FCH yield using a reasonably unfamiliar fungus C. echinulata NCIM 691 through optimised submerged fermentation conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03919-6.

Long-Term Follow-up of Disabled Patients With Chronic Pancreatitis: Evaluation of Clinical Characteristics, Outcomes, and Predictors.

BACKGROUND/AIMS: Patients with chronic pancreatitis (CP) often report a poor quality of life and may be disabled. Our study identifies clinical characteristics, predictors and outcomes in CP patients with disability. METHODS: A review of established CP patients followed in our Pancreas Center between January 1, 2016 and April 30, 2021. Patients were divided into 2 groups based on disability. Univariate analysis was performed to identify differences in demographics, risk factors, comorbidities, complications, controlled medications, and resource utilization. Multivariate analysis was conducted to identify predictors for disability. RESULTS: Out of 404 CP patients, 18% were disabled. These patients were younger (53.8 vs. 58.8, P =0.001), had alcoholic CP (54.1% vs. 30%; P <0.001), more recurrent pancreatitis (83.6% vs. 61.1%; P =0.001), chronic abdominal pain (96.7% vs. 78.2%; P =0.001), exocrine pancreatic insufficiency (83.6% vs. 55.5%; P <0.001), concurrent alcohol (39.3% vs. 23.3%; P =0.001) and tobacco abuse (42.6% vs. 26%; P =0.02), anxiety (23% vs. 18.2%; P <0.001), and depression (57.5% vs. 28.5%; P <0.001). A higher proportion was on opiates (68.9% vs. 43.6%; P <0.001), nonopiate controlled medications (47.5% vs. 23.9%; P <0.001), neuromodulators (73.3% vs. 44%; P <0.001), and recreational drugs (27.9% vs. 15.8%; P =0.036). Predictors of disability were chronic pain (OR 8.71, CI 2.61 to 12.9, P < 0.001), celiac block (OR 4.66, 2.49 to 8.41; P <0.001), neuromodulator use (OR 3.78, CI 2.09 to 6.66; P <0.001), opioid use (OR3.57, CI 2.06 to 6.31; P < 0.001), exocrine pancreatic insufficiency (OR3.56, CI 1.89 to 6.82; P <0.001), non-opioid controlled medications (OR 3.45, CI 2.01 to 5.99; P <0.001), history of recurrent acute pancreatitis (OR 2.49, CI 1.25 to 4.77; P <0.001), depression (OR 2.26, CI 1.79 to 3.01; P <0.001), and active smoking (OR1.8, CI 1.25 to 2.29; P <0.001). CONCLUSION: CP patients with disability have unique characteristics and predictors, which can be targeted to reduce disease burden and health care expenditure in this population.

Prospective Evaluation of Sexual Dysfunction in Men With Chronic Pancreatitis: A Pilot Study.

OBJECTIVE: Our study aimed to determine the prevalence of sexual dysfunction (SD) and its association with quality of life (QOL) in men with chronic pancreatitis (CP). MATERIALS AND METHODS: Male patients with CP were prospectively enrolled in our pancreas center and completed the following 4 validated questionnaires: International Index of Erectile Function 5, Erectile Hardness Score, Pancreatitis Quality of Life Instrument, and Short Form Survey. Patients were classified as having mild, moderate, or severe SD based on review of questionnaires. RESULTS: Thirty patients were enrolled in the study, of which 18 patients had SD (mild in 9, moderate in 1, and severe in 8 patients). No significant differences were seen demographic or clinical characteristics in patients with and without SD. Patients with SD had more abdominal pain compared with those without SD (94.4% vs 83.3%, P = 0.001). No significant differences were noted in QOL metrics between the 2 groups. CONCLUSIONS: This pilot study shows that SD is present in 60% males with CP. No difference was noted in the QOL of patients with and without SD, albeit limited by our small sample size. Physicians caring for CP patients should routinely inquire for symptoms of SD and offer a urology referral if indicated.

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

OBJECTIVE: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. METHODS: C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. RESULTS: Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. CONCLUSION: Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

GlycA: Evaluation of a New Biomarker of Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate-severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP. METHODS: We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera® Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 µmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity. RESULTS: Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m2; p < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 µmol/L, p < 0.001) and at discharge (655 vs. 376 µmol/L, p < 0.001). GlycA levels were significantly higher in patients with moderate-severe AP than in those with mild AP at discharge (533 vs. 757 µmol/L, p = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 µmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07-32.2; p = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48-42.0; p = 0.025) than controls. CONCLUSION: Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.

Design, Docking, Characterisation, and Synthesis of Pyrimidine Derivatives for Antidepressant Activity.

BACKGROUND: According to the report, in 2022, the prevalence rate of depression in India was 4.50%, and the cases stood at 56,675,969. The development of antidepressant agents has reduced the number of depressant and suicidal cases. Many researchers have found that pyrimidine possesses antidepressant activity. With this background, we thought of synthesizing pyrimidine derivatives. OBJECTIVE: The objective of this study is to carry out molecular docking, synthesis, characterization, and evaluation of 2-((4,6-diphenylpyrimidin-2-yl)oxy)-N-phenylacetamide derivatives (17-26) as in vivo antidepressant agent. METHOD: The designed compounds were checked for their activity using Molegro virtual docker (MVD) and were further synthesized. Benzaldehyde reacted with acetophenone to give compound (3), which gave compound (4) upon reaction with urea. In another reaction, substituted anilines (5) were reacted with chloroacetyl chloride (6) to yield compounds (7-16), which upon further reaction with compound (4) yielded the final derivatives (17-26). The synthesized compounds were characterized by spectral analysis and checked for their antidepressant activity. RESULT: The MolDock scores of the derivatives ranged from -147.097 to -182.095, whereas of active ligand IXX_801 was -115.566. All the synthesized pyrimidine derivatives showed better affinity towards the Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine, and 15B8 Fab protein (PDB ID: 7LWD) as compared to standard drug clomipramine (-101.064). All the synthesized derivatives were screened for antidepressant activity at a 100mg/kg dose level compared to the standard clomipramine HCl at a dose level of 20mg/kg. Among all the synthesized derivatives, compound 24 showed the most potent antidepressant activity, and Compound 20 showed moderate antidepressant activity, which reduced the duration of immobility times to 35.42% and 31.97% at 100mg/kg dose level when compared to the control, respectively. CONCLUSION: Compound 24 showed the highest MolDock score as well as found to be the most potent antidepressant agent.

Racial and Ethnic Disparities in Opioid Prescriptions for Patients with Abdominal Pain: Analysis of the National Ambulatory Medical Care Survey.

BACKGROUND: Disparities in pain control have been extensively studied in the hospital setting, but less is known regarding the racial/ethnic disparities in opioid prescriptions for patients with abdominal pain in ambulatory clinics. METHODS: We examined opioid prescriptions during visits by patients presenting with abdominal pain between the years of 2006 and 2015, respectively, in the National Ambulatory Medical Care Survey database. Data weights for national-level estimates were applied. RESULTS: We identified 4006 outpatient visits, equivalent to 114 million weighted visits. Rates of opioid use was highest among non-Hispanic White patients (12%), and then non-Hispanic Black patients (11%), and was the lowest in Hispanic patients (6%). Hispanic patients had lower odds of receiving opioid prescriptions compared to non-Hispanic White patients (OR = 0.49; 95% CI, 0.31-0.77, p = 0.002) and all non-Hispanic patients (OR 0.48; 95% CI 0.30-0.75; p = 0.002). No significant differences were noted in non-opioid analgesia prescriptions (p = 0.507). A higher frequency of anti-depressants/anti-psychotic prescriptions and alcohol use was recorded amongst the non-Hispanic patients (p = 0.027 and p = 0.001, respectively). CONCLUSIONS: Rates of opioid prescriptions for abdominal pain patients were substantially lower for the Hispanic patients compared with the non-Hispanic patients, despite having a decreased rate of high-risk features, such as alcohol use and depression. The root cause of this disparity needs further research to ensure equitable access to pain management.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence.

This document from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used in the review of the evidence used to inform the final guidance outlined in the accompanying Summary and Recommendations document regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. This guideline used the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, the ASGE suggests surgical evaluation over endosic approaches.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based summary and recommendations regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. It is accompanied by the document subtitled "Methodology and Review of Evidence," which provides a detailed account of the methodology used for the evidence review. This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well- or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, we suggest surgical evaluation over endoscopic approaches.

Discovery of IACS-52825, a Potent and Selective DLK Inhibitor for Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet medical need with limited treatment options. Despite different mechanisms of action, diverse chemotherapeutics can cause CIPN through a converged pathway─an active axon degeneration program that engages the dual leucine zipper kinase (DLK). DLK is a neuronally enriched kinase upstream in the MAPK-JNK cascade, and while it is dormant under physiological conditions, DLK mediates a core mechanism for neuronal injury response under stress conditions, making it an attractive target for treatment of neuronal injury and neurodegenerative diseases. We have developed potent, selective, brain penetrant DLK inhibitors with excellent PK and activity in mouse models of CIPN. Lead compound IACS-52825 (22) showed strongly effective reversal of mechanical allodynia in a mouse model of CIPN and was advanced into preclinical development.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the role of fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic workup of these patients, we suggest the use of fluoroscopic-guided biopsy sampling in addition to brush cytology over brush cytology alone, especially for hilar strictures. We suggest the use of cholangioscopic and EUS-guided biopsy sampling especially for patients who undergo nondiagnostic sampling, cholangioscopic biopsy sampling for nondistal strictures and EUS-guided biopsy sampling distal strictures or those with suspected spread to surrounding lymph nodes and other structures.