Emergency Nursing Care of a Pregnant Patient With Acute Abdomen Owing to Acute Pancreatitis: A Case Report.

We analyzed national mortality from Acute pancreatitis (AP) in United States (US) adults from 2006-2023 using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database to compare alcoholic AP (AAP) and non-alcoholic AP (non-AAP) across demographic and geographic groups. During this period, there were 52,904 AP deaths, including 6,759 AAP deaths and 46,145 non-AAP deaths. Overall, AP age-adjusted mortality rate (AAMR) declined from 1.54 to 1.19 per 100,000, and non-AAP AAMR declined from 1.38 to 0.99 per 100,000. In contrast, AAP AAMR increased from 0.13 to 0.23 per 100,000, and AAP deaths rose by more than 60 percent. Crude mortality fell in adults aged 75 years and older but increased in adults aged 25 to 44 years, especially for AAP. AAP deaths increased in both males and females and in both metropolitan and nonmetropolitan areas. These findings show that while non-AAP mortality continues to decline, AAP mortality is increasing and represents a growing, largely preventable source of premature death that warrants targeted prevention, improved access to alcohol use treatment, and community-level policies addressing harmful drinking behaviors, with particular concern for younger adults entering their peak working years.

BackgroundThe National Institute for Health and Care Excellence, the Association of Upper Gastrointestinal Surgeons, and the Tokyo Guidelines advocate early laparoscopic cholecystectomy (LC) as the standard of care for patients presenting with acute cholecystitis (AC). This study evaluates the implementation of a hybrid Hot Gallbladder (HGB) pathway, incorporating both inpatient index admission and fast-tracked outpatient management at a district general hospital in the United Kingdom with a 550-bed capacity, analysing its impact on service efficiency, early surgery rates, and alignment with guideline standards.MethodologyA retrospective review was performed over a 15-month period (January 2023 to March 2024) following the introduction of the HGB service. Patients presenting with acute biliary pathology were identified from the Surgical Acute Care Unit (SACU) database. Patients meeting the defined eligibility criteria were included. Data were cross-verified across the SACU database, the HGB service list, and electronic patient records to ensure accuracy before analysis. Patients were grouped into pre-HGB (n = 84) and post-HGB (n = 202) cohorts. Statistical analysis was performed using chi-square testing, with significance set at p-values <0.05.ResultsA total of 286 patients were included (80.4% female; mean age of 45 years). The most common diagnosis was biliary colic (62.2%), followed by AC (27.3%) and gallstone pancreatitis (10.5%). Introduction of the HGB pathway significantly increased the rate of early LC from 13.1% to 30.2% (χ² = 9.19; p = 0.0024). The complication and 30-day readmission rates remained low.ConclusionsImplementation of a hybrid HGB service significantly facilitated early LC, nearly doubling the proportion of patients receiving early LC. Although performance improved further as the service matured, the verified overall increase from 13.1% to 30.2% represents the key finding. These results support the feasibility of guideline-aligned, structured HGB pathways within district general hospital settings and provide a foundation for prospective multi-centre validation.

Cholelithiasis, characterized by the presence of gallstones, is a common condition in the United States, with 80% of affected individuals having no symptoms. Symptomatic gallstone disease encompasses symptomatic cholelithiasis, biliary dyskinesia, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and acute cholangitis. It often manifests as sharp, stabbing right upper quadrant or epigastric pain as well as nausea and vomiting. History, physical examination, and laboratory evaluation alone are insufficient to make an accurate diagnosis. Ultrasonography should be the first-line imaging modality for evaluating right upper quadrant pain. Symptomatic cholelithiasis is diagnosed with the confirmation of gallstones on imaging in patients presenting with classic symptoms. Clinical prediction tools such as the 2018 Tokyo guidelines for acute cholecystitis or pretest probability calculation for choledocholithiasis should be used to aid diagnosis and determine the need for further imaging. Laparoscopic cholecystectomy is the standard treatment for most forms of symptomatic gallstone disease. In cases of choledocholithiasis, intraoperative common bile duct exploration at the time of cholecystectomy or endoscopic retrograde cholangiopancreatography performed before, during, or after cholecystectomy is needed.

Pancreatic polypeptide in patients with type 1 diabetes and exocrine failure or chronic pancreatitis. The DIAPP study.

Anti-AT1R autoantibodies in pancreas transplantation.

Abstract Aim This study evaluates Key Performance Indicators (KPIs) in cholecystectomy at our Trust, assessing adherence to the British Benign Upper Gastrointestinal Society (BBUGSS) standards. Objectives included monitoring procedural volume, day-case rates, readmissions, index laparoscopic cholecystectomy rates for acute cholecystitis and Gallstone pancreatitis, conversion rates, complications, and mortality in alignment with national benchmarks. Method A retrospective cohort analysis included 599 patients randomised from 983 elective and emergency cholecystectomies performed trust-wide between April 2023 to April 2025. Data were obtained from electronic health records and theatre logs. Assessed KPIs included day-case rates, 30-day readmissions, index laparoscopic cholecystectomy for acute cholecystitis and gallstone pancreatitis, conversion rates, morbidity, bile leak, retained common bile duct (CBD) stones, major bile duct injury, and mortality. Descriptive statistics and chi-square tests were used for analysis. Results No mortality (0%) or major bile duct injuries (0%) were recorded. proportion of index or within two weeks laparoscopic cholecystectomy for gallstone pancreatitis was performed on 16.7% of cases and in 7.5% of those with cholecystitis. The 30-day readmission rate was 6.3%. Retained CBD stones were reported in 0.7%, and bile leaks in 1.5%. Overall morbidity was 11.7%. Subtotal cholecystectomy was performed in 2.3% and conversion to open surgery in 0.2%. Conclusions Outcomes largely align with national KPIs, with no mortality or bile duct injury and low rates of bile leak, retained stones, and conversion. However, the readmission and morbidity rates slightly exceed benchmarks in addition to lower proportion of index operations for cholecystitis and gallstone pancreatitis, indicating potential areas for improvement.

Abstract Aim To evaluate adherence to the 2019 World Society of Emergency Surgery (WSES) guidelines in the diagnosis and management of gallstone pancreatitis at South Tyneside District Hospital. The primary aim was to assess the adequacy of severity scoring using the Glasgow-Imrie score. A secondary aim was to examine the timing and appropriateness of imaging—particularly MRCP and ERCP—as well as the scheduling of laparoscopic cholecystectomy in accordance with guideline standards. Method A retrospective review was conducted on 192 patients admitted with gallstone pancreatitis between January 2022 and December 2023. Data on patient demographics, Glasgow-Imrie score documentation, imaging modalities (USS, MRCP, ERCP), biochemical trends, and surgical timing were analysed and compared to WSES recommendations. Results Of 192 patients, 62.5% were female, with a mean age of 61.8 years. All parameters of the Glasgow-Imrie score were completed in only 18 patients (9.4%), but no full score was documented in any case. Repeat ultrasound was unnecessarily performed in 41.4% of patients with previously confirmed gallstones. MRCP was conducted in 115 patients (59.9%), with 80 (69.6%) performed within 48 hours. Of these, 80 patients (69.6%) showed a downward bilirubin trend, yet 14 (17.5%) still underwent ERCP. ERCP was performed in 28 patients overall (14.6%), with 9 (32.1%) showing no stones. Early laparoscopic cholecystectomy was inconsistently achieved, often exceeding the two-week post-discharge window. Conclusions Adherence to WSES guidelines was variable. The proposed action plan is to integrate the Glasgow-Imrie scoring template into Meditech V6 to support timely, standardised assessment and improve patient outcomes.

Abstract Aim This study aimed to evaluate the clinical outcomes and implications of prolonged waiting times for elective cholecystectomy, focusing on complication rates, healthcare utilization, and the association with wait duration. Method A retrospective analysis was conducted on 697 patients listed for elective cholecystectomy. Data were collected on the duration of waiting time, incidence of gallstone-related complications, hospital admissions, and the need for additional diagnostic or interventional procedures. Statistical analysis was performed using the chi-square test to assess associations between waiting time and clinical outcomes, with significance set at p &amp;lt; 0.05. Results The waiting time ranged from 0 to 2943 days, with a mean of 801.3 days. A total of 94.7% of patients developed complications while awaiting surgery. The most frequent complications were biliary colic (77.6%), acute cholecystitis (43.2%), obstructive jaundice (22.7%), and gallstone pancreatitis (7.6%). Of those with complications, 64% required hospital admission. A significant association was observed between longer waiting times and the need for hospital admission (p = 0.001), ultrasound (p = 0.001), MRCP (p = 0.003), and ERCP (p = 0.001). No significant association was found between waiting time and overall complication rate (p = 0.297) or CT utilization (p = 1.000). Conclusions Prolonged waiting for cholecystectomy is associated with a high burden of complications and increased healthcare resource utilization, particularly hospital admissions and advanced imaging or interventions. Strategies to reduce surgical waiting times may significantly improve patient outcomes and decrease system strain.

Abstract Aim To evaluate the safety, efficacy, and technical approach of laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis at a UK tertiary centre. Method A retrospective analysis from a prospectively maintained database was performed on 36 patients undergoing LCBDE between November 2024 and June 2025. The primary endpoint was successful stone clearance; secondary endpoints included complications, operative time, length of stay, and readmissions. Results Mean age was 55 years (range 21–79), with 67% female. Emergency cases constituted 69%; 72% had deranged liver function tests and 14% had a bilirubin &amp;gt;51 μmol/L. The most common indication was confirmed CBD stones (84%) on preoperative imaging, with 28% having gallstone pancreatitis. A transcystic approach was used in 94%, involving an ultra-slim 2.7 mm scope in 75%. Electrohydraulic lithotripsy was required in one case. Mean operative time was 110 minutes. Ductal clearance was achieved in 94% of patients. Postoperative complications included bile leak (5.6%) and retained stones (8.3%), disproportionately affecting older males. There were no cases of post-operative pancreatitis. Average post-operative stay was 2 days (range 0–9), with two readmissions and no conversions to open surgery. Conclusions LCBDE is a safe and effective single-stage approach for choledocholithiasis, with high success rates and low complication rates in this early cohort. The transcystic route, combined with an ultra-slim scope, was successful in most cases, reducing the need for more invasive transductal exploration. These results support broader adoption of LCBDE in general surgical practice, improving access and potentially reducing reliance on ERCP.

Abstract Aim To evaluate practice and outcomes of laparoscopic cholecystectomy across a large NHS Trust, assessing indications, imaging pathways, surgical approach, and complications. Method A retrospective audit was conducted on all patients listed for cholecystectomy between January 2024 and January 2025 across three sites. Data included demographics, imaging, surgical modality, complications, and 90-day readmission. Results 675 patients underwent cholecystectomy (73% female, mean age 53.6 years). The most common indication was symptomatic biliary colic (46%), followed by gallstone cholecystitis (28%) and gallstone pancreatitis (14%). Most cases were elective (79%), with CholeQuIC (13%) and emergency (8%) pathways. Laparoscopic surgery was performed in 89.5%, with robotic and subtotal approaches in 3.0% and 4.1%, respectively. Pre-operative ultrasound was performed in 93%, and 36% underwent MRCP. Of those, 31% proceeded to ERCP for stone retrieval. A drain was inserted intra-operatively in 14% of cases. The overall complication rate was 2.2%, including retained stones (1.3%), wound infections (1.3%), and bile leaks (0.9%), with no significant variation based on pre-operative imaging modality. Complication rates were higher in emergency presentations (5.6%) compared to elective cases (2.0%). Readmission rate was 3.9%. Elective cases achieved an 87% day-case rate, exceeding NICE targets. Conclusions Laparoscopic cholecystectomy is delivered safely and consistently across the Trust with excellent outcomes. However, MRCP was used in over one-third of cases, often without influencing complication rates, and may contribute to delays and additional costs. A more selective, evidence-based imaging strategy incorporating intraoperative ultrasound may reduce unnecessary MRCP use, streamline patient care pathways, and improve cost-effectiveness while maintaining clinical safety and outcomes.

Abstract Aim An emergency surgery ambulatory care (ESAC) pathway can be adopted to facilitate early laparoscopic cholecystectomy (LC) for acute cholecystitis and gallstone pancreatitis. Common challenges to achieving early intervention include high workload, limited theatre resources and unexpected post-operative admissions. This study aims to report our experience in performing LC through a dedicated ESAC pathway in a single district general hospital. Method Data was collected retrospectively on ESAC patients undergoing LC consecutively from 11/06/2024- 31/12/2024. Patients who were admitted post-operatively were compared to those discharged the same day. Patient characteristics including pre-operative diagnosis, presence of biliary obstruction and operative complexity (Nassar scale 3 or 4) were compared using Fisher exact test. Results 75 patients were included. 42 (56.0%) underwent LC for acute cholecystitis, 12 (16.0%) for acute pancreatitis and 21 (28.0%) for biliary colic. The median time from presentation to surgery was 62.3 (IQR 42-67) days. One patient (1.3%) underwent LC within 7 days of presentation. 24 patients (32.0%) were admitted for ≥1 night in hospital. Patients who had unplanned inpatient admissions were more likely to have gallbladder thickening on ultrasound preoperatively [20 (39.2%) vs 16 (66.7%), p=0.0464] and had more challenging procedures (Nassar scale 3 or 4) [15 (62.5%) vs 3(5.8%), p≤0.00001]. 4 patients (5.3%) were readmitted within 30 days due to complications. Conclusions A dedicated ESAC pathway for LC can ensure shorter waiting times for ambulatory patients with acute gallstone disease, however, facilitating early cholecystectomy remains challenging. A large proportion of patients require unplanned inpatient stay due to operative complexity.

Abstract Aim To evaluate the effectiveness of Laparoscopic Cholecystectomy Pathway for patients with mild gallstone pancreatitis at Hull Royal Infirmary. Method A retrospective closed-loop audit conducted over 7-month period (September 2023-March 2024). The audit was registered on AMAT and approvals obtained. Data were gathered and compiled into spreadsheet capturing basic demographics (age, gender, date of admission), imaging findings, surgical intervention, re-admissions, amylase levels, and timing of surgery. The audit standard: all patients with biliary pancreatitis should receive definitive gallstone management during the same hospital admission, unless a clear plan exists for treatment within two weeks of discharge. Results 46 patients met the inclusion criteria, age range:22-92 years (median age:58). Of these, 61% were male. Case stratification showed that 7 patients (11%) were unfit for surgery, 21 patients (54%) underwent surgery during the index admission, 1 patient (3%) had surgery within two weeks of discharge, 6 patients (15%) underwent delayed laparoscopic cholecystectomy, and 11 patients (28%) did not receive surgery. There were 2 mortalities (4%) during the index-admission and 1 re-admission (2%). Regarding imaging, 67% of patients had an ultrasound scan, 43% had a CT-AP, and 59% underwent MRCP. Compliance with the pathway was compared to previous audit cycles: 21.3% in 2014–2015, 33% in 2016, 83% in 2019, and 56% in the current cycle. Conclusions This reflects a decline in adherence since the last audit. The findings support the benefit of providing definitive treatment during the acute admission, which is clinically advantageous for patients by improving symptom relief, reducing re-admissions, and minimizing loss to follow-up.

Abstract Aim To review current management of patients with common bile duct (CBD) stones who are awaiting cholecystectomy. To assess if biodegradable stents would be a viable alternative to plastic. Method Retrospective data from operating theatre software was obtained for patients undergoing cholecystectomy (1/1/22-31/12/22). This was cross referenced with endoscopy reporting software to see if they had undergone ERCP before their procedure (n=82) Results 58 patients (70%) had a plastic stent placed prior to surgery. Their median time to cholecystectomy was 103.5 days (IQR 47.5-232). Their median time to stent removal was 138 days (IQR 71-184.5). 7 patients were waiting more than 1 year for stent removal and one more than 2 years. Pre-cholecystectomy there were 8 admissions with cholecystitis, 3 cholangitis, 2 gall bladder perforations, 1 ERCP pancreatitis and 1 with a blocked CBD stent. Post-cholecystectomy there were 5 patients with blocked/infected stents admitted for an average of 5 days. 1 patient died shortly post-ERCP and stent removal. 24 patients (30%) had ERCP with sphincterotomy only. Their median time to cholecystectomy was 57.5 days (IQR 24-118.5). Only 1 patient required further ERCP before surgery for gallstone pancreatitis. Conclusions It is likely that our hospital is not alone regarding its reliance on two stage ERCP for the management of CBD stones. Biodegradable stents would provide an opportunity to eliminate the risk &amp; cost of a second ERCP; however, a significant improvement in time to cholecystectomy would be required to make it a success. Further information regarding sphincterotomy only management &amp; outcomes is required.

Pigment gallstones represent a heterogeneous group of concretions, classically divided into black and brown types, whose morphology and microstructure offer critical clues about their underlying pathogenesis. Gallstone formation (lithogenesis) is a complex process triggered when the physicochemical equilibrium of bile is disrupted. Background/Objectives: The spicules observed on the surface of certain black pigment gallstones have traditionally been attributed to the branching capacity of cross-linked bilirubin polymers. However, a growing body of experimental and spectroscopic evidence suggests that inorganic calcium salts, particularly calcium carbonate and calcium phosphate, play a central role in the formation of the distinctive spiculated or “coral-like” architecture. Materials and Methods: In our study, we examined a case series of 1350 consecutive patients with gallstone disease, identifying 81 patients who presented with solitary black pigment stones. We systematically explored the association between high calcium content, specifically calcium carbonate, and the occurrence of spiculated morphology. Our analyses demonstrated a robust correlation between an elevated concentration of calcium carbonate and the presence of well-defined spicules. Results: These results support the hypothesis that mineral elements, rather than organic bilirubin polymers, act as crucial determinants of the peculiar crystalline structure observed in a significant subset of pigment stones. Spiculated stones, due to their small size and sharp projections, have a higher likelihood of migrating, increasing the risk of potentially life-threatening complications, such as acute cholangitis and gallstone pancreatitis. Conclusions: Our findings, consistent with recent advanced crystallographic analyses, underscore the importance of considering mineral composition in the diagnosis and management of cholelithiasis. Understanding the factors that drive calcium carbonate precipitation is essential for developing new preventive and therapeutic strategies, aiming to modulate bile chemistry and reduce the risk of calcium-driven lithogenesis.

This study aimed to investigate the relationship between non-alcoholic fatty pancreas disease (NAFPD) and metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the effects of pancreatic steatosis on clinical and laboratory parameters in patients aged 40-49 years. The secondary aim was to identify independent predictors of pancreatic steatosis and discuss their clinical relevance for early detection and prevention. This retrospective single-center study included 132 patients aged 40-49 years who underwent abdominal magnetic resonance imaging (MRI). Pancreatic and hepatic fat fractions were measured using a chemical shift-based MRI technique. Demographic data, comorbidities, and laboratory parameters were analyzed. Patients with a history of alcohol intake, pancreatitis, or incomplete data were excluded. Pancreatic steatosis was present in 35.6% of participants. Patients with pancreatic steatosis had significantly higher rates of diabetes mellitus (59.6% vs. 21.2%), obesity (61.7% vs. 14.1%), hypertension (38.3% vs. 17.6%), and hyperlipidemia (44.7% vs. 20%) (all P<0.01). Pancreatic steatosis was strongly associated with hepatic steatosis (80.9% vs. 11.8%, P<0.001). Fasting glucose, HbA1c, HOMA-IR, and triglycerides were higher, whereas HDL and amylase were lower in the steatosis group. In multivariate logistic regression, diabetes mellitus (OR 8.06, 95% CI: 1.15-56.76, P=0.036) and HOMA-IR (OR 1.54, 95% CI: 1.19-1.99, P=0.001) were identified as independent predictors of pancreatic steatosis. Among patients with pancreatic steatosis, 80.9% also had hepatic steatosis, demonstrating a significant association between pancreatic and hepatic fat accumulation. A significant association was found between pancreatic steatosis and metabolic risk factors such as diabetes, obesity, insulin resistance, and MASLD. MRI-based quantification provided accurate detection, supporting its value as the most reliable imaging modality for assessing pancreatic fat. Lifestyle interventions such as weight loss and physical activity may help mitigate pancreatic steatosis and related metabolic consequences. Further studies are needed to clarify causality and underlying pathways, such as lipotoxicity, inflammation, and β-cell dysfunction.

Abstract Introduction: The increasing incidence of early-onset pancreatic ductal adenocarcinoma (PDAC), defined as diagnosis before age 50, coincides with rising global exposures to carcinogens such as alcohol and tobacco during critical developmental windows. Emerging evidence suggests these exposures reprogram epithelial and stromal compartments early in life, priming the pancreas for oncogenic transformation. However, the molecular events linking these exposures to early tumorigenesis remain underexplored. Methods: To investigate alcohol- and tobacco-driven mechanisms of early-onset pancreatic carcinogenesis, we utilized both syngeneic orthotopic models and genetically engineered mouse models (GEMMs), including Ptf1aCreERTM/+, Ptf1aCreERTM/+;LSL-KrasG12D/+ (KC), KPC (KC with mutant p53) and Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) lines (both tumor-bearing and non-tumor). Chronic cigarette smoke exposure and alcoholic chronic pancreatitis (ACP) were initiated in early adulthood. single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, immunophenotyping, and histopathology were performed to delineate epithelial, stromal, and immune cell changes. Acinar lineage tracing using Rosa26tdTomato/+ was integrated to track acinar-to-ductal metaplasia (ADM). Human PDAC (smokers and non-smokers) and chronic pancreatitis tissues were used for cross-species validation. Results: Both alcohol and tobacco exposure accelerated neoplastic progression and induced pronounced fibroinflammatory transformation of the tumor microenvironment (TME). scRNA-seq revealed the early emergence of ductal-like epithelial clusters with elevated Sox9, Pdx1, and Hnf1b-hallmarks of ADM. Ethanol- and smoke-exposed mice showed impaired acinar regeneration, persistent epithelial reprogramming, and an augmented PanIN burden. Immune profiling showed expanded MDSCs, M2 macrophages, and regulatory T cells in exposed models, mirroring immune-suppressive signatures seen in early-onset human PDAC samples. We show the molecular mechanism involved and the differences in cellular signaling between tobacco-induced and alcohol-induced carcinogenesis. Lineage tracing confirmed that acinar cells serve as a source for ductal lesions under repeated inflammatory insults, especially in the presence of oncogenic Kras. Conclusions: Early exposure to carcinogens from external sources, like tobacco and alcohol, triggers molecular changes in pancreatic epithelium and immune stroma, which accelerate neoplastic transformation. Such exposures result in persistent fibroinflammatory damage, encourage ADM, and establish a pro-tumorigenic microenvironment. Our research provides a mechanistic understanding of the increase in early-onset PDAC and advocates for using integrated technologies-GEMMs, scRNA-seq, and lineage tracing-to model early-life exposures as crucial for intervention targets. These findings emphasize the importance of prevention strategies aimed at modifiable exogenous risk factors during the critical stages of PDAC development. Citation Format: Nagaraj Nagathihalli. Exogenous carcinogenic exposures in early-onset pancreatic carcinogenesis: Insights from alcohol and tobacco-driven models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr C017.

Insulin resistance and pancreatic β-cell failure are key characteristics of type 2 diabetes (T2D). Impaired β-cell function is associated with loss of β-cell identity, resulting in β-cell dedifferentiation or trans-differentiation to other endocrine cells. We have shown that β-cell dedifferentiation can be reversed, restoring insulin secretion. The aim of this study was to investigate whether semaglutide or tirzepatide treatment can reverse early stages of β-cell dedifferentiation in db/db mice independent of their effect on body weight. After 4 weeks of treatment, 12-week-old db/db mice were assessed by oral glucose tolerance test and immunofluorescence to evaluate glucose clearance capacity and effects on pancreatic β-cell. Body weight, fasting blood glucose, and plasma insulin levels were monitored weekly. Bulk RNA sequencing from islets was performed to identify potential targets. At the doses employed, tirzepatide stabilized, whereas semaglutide was unable to reverse the weight gain of db/db mice. After a 4-week course, both groups showed comparable glucose lowering and increased insulin levels. However, both treatments failed to reverse pancreatic β-cell dedifferentiation, as assessed by either the percentage of cells expressing the dedifferentiation marker ALDH1A3+ or FOXO1 translocation. Furthermore, the number of β-cells expressing low levels of PDX1 was higher in both treatment groups than in controls. Gene expression analyses showed a muted transcriptional response in overlapping patterns in islets treated with either compound but no obvious candidate target genes. The findings highlight that the early glucose-lowering effects of semaglutide and tirzepatide in db/db mice occur independently of changes to β-cell identity.

Type 2 Diabetes Mellitus (T2DM) is a chronic, progressive metabolic dysregulation characterized by the dual defects of peripheral insulin resistance and pancreatic β-cell failure. The global escalation of T2DM correlates strongly with shifting lifestyle patterns, urbanization, and the obesity epidemic, posing a substantial challenge to healthcare systems. Pathophysiologically, the disease involves complex molecular disruptions, including impaired insulin signaling pathways, lipotoxicity, glucotoxicity, and systemic inflammation, which collectively compromise glucose homeostasis. Persistent hyperglycemia precipitates a wide spectrum of systemic sequelae, categorized into microvascular pathologies such as nephropathy, retinopathy, and neuropathy and macrovascular complications, including coronary artery disease and cerebrovascular accidents. Early diagnosis remains challenging due to the frequent asymptomatic clinical presentation, necessitating rigorous screening protocols using glycated hemoglobin and fasting plasma glucose metrics. Contemporary management paradigms have evolved beyond mere glycemic control to prioritize cardiorenal protection. Therapeutic strategies now integrate lifestyle modifications with a diverse pharmacopeia, ranging from foundational biguanides to novel sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. This review explains the etiological mechanisms, epidemiological trends, diagnostic standards, and multifaceted therapeutic approaches essential for optimizing clinical outcomes and mitigating the long-term burden of the disease

Gallstone Pancreatitis: Clinical outcomes and economic impact at a tertiary UK Hepatobiliary centre.