The impact of sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on insulin utilisation and costs in Australia: a national retrospective observational cross-sectional study.

Background: Global insulin requirements for type 2 diabetes were predicted to increase by more than 20% from 2018 to 2030. However, this did not anticipate the rapid increase in use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors that has occurred over recent years. The current study aims to examine changes in insulin utilisation and costs in Australia from 2003 to 2023. Methods: We conducted a large-scale observational study of national insulin utilisation and expenditure in Australia from 2003 to 2023 using the Australian Pharmaceutical Benefits Scheme. The proportion of insulin-treated people with type 2 diabetes between 2013 and 2023 was estimated using National Diabetes Services Scheme data. Joinpoint models and interrupted time series analysis were used to examine utilisation trends. Findings: Insulin utilisation (units of insulin per person with diabetes) increased by an average of 2.71% per annum (95% CI 1.97, 3.73) from 2003 to 2015, then fell by 2.70% per annum (95% CI -4.55, -1.39) from 2015 to 2023. The proportion of insulin-treated people with type 2 diabetes increased by 1.00% per annum (95% CI 0.81, 1.25) from 2013 to 2020, then fell by 0.66% per annum (95% CI -1.62, -0.04) from 2020 to 2023. A 43% reduction in inflation-adjusted insulin expenditure was observed between 2015 and 2023 due to a combination of reduced utilisation and reduction in the price of insulin glargine. Interpretation: Projected global insulin requirements and costs may be less than previously anticipated if reduced use of insulin in Australia is similarly observed in other countries. Funding: No funding was received for this study.

Targeting the serum marker interleukin 9 improves the underlying characterization and immune homeostasis in rheumatoid arthritis.

Introduction: Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA). Material and methods: The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed. Results: We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues. Conclusions: These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation.

Difficult-to-treat rheumatoid arthritis: what have we learned and what do we still need to learn?

Difficult-to-treat rheumatoid arthritis (D2T RA) is an area of high unmet need. The prevalence reported in the first D2T RA cohort studies ranged from 5.5-27.5%. Key to the definition is a conviction by patient and/or rheumatologist that disease management has become problematic and failure of at least two biological or targeted synthetic disease-modifying antirheumatic drugs. D2T RA is a multifactorial disease state which was reflected in data from D2T RA cohort studies: these pointed towards high prevalence of co-morbidities and/or lower socioeconomic status in D2T RA subgroups, while others had persistent symptoms without these factors being present. A holistic approach is necessary to identify the root problems underlying D2T RA in individual patients. In this review, biological and non-biological drivers that should be considered to be optimized will be discussed in view of what we have learned from patient data emerging from the first D2T RA cohort studies.

Relationship between type 1 diabetes and autoimmune diseases in european populations: A two-sample Mendelian randomization study.

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Real-World Utilization and Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists Dosed Weekly and Daily in Patients with Type 2 Diabetes Mellitus: Results from Retrospective Electronic Medical Records in China.

Aim: This study aimed to conduct a retrospective observational study in China to investigate the real-world utilization of glucagon-like peptide-1 receptor (GLP-1RA) in China. Methods: Type 2 diabetes mellitus (T2DM) patients were retrieved from the electronic medical records of 18 hospitals from 2016 to 2020. A descriptive analysis detailed patient characteristics and clinical outcomes. Multivariate logistic regression analysed the factors associated with daily and weekly GLP-1RA. Results: Fifteen thousand one hundred and seventy-six individuals were included. At the 6-month follow-up, the overall estimated mean change from baseline in HbA1c was -1.26±1.91% (p < 0.001), the "Weekly GLP-1RA" group was -1.58±2.03% (p < 0.001), and the "Daily GLP-1RA" group was -1.25±1.90% (p < 0.001). At the 12-month follow-up, the overall estimated mean change from baseline in HbA1c was -0.95±1.80% (p < 0.001), the "Weekly GLP-1RA" group was -1.05±1.93% (p < 0.001), and the "Daily GLP-1RA" group was -0.95±1.80% (p < 0.001). At 6 months following GLP-1RA initiation, there were statistically significant improvements in the mean TC, LDL-C, and TG at 6 months or 12 months separately following GLP-1RA initiation. Statistically significant improvements were observed in the mean HDL-C after 6 months. Compared with the baseline (11.92%), the proportion of patients who had an incidence of all hypoglycemia was lower at the 6-month follow-up (9.73%). Patients with dyslipidemia were more likely to use weekly GLP-1RA (OR =1.61, 95% CI: 1.27-2.06, p < 0.001). Conclusion: In China, weekly GLP-1RA demonstrated better effectiveness compared to the daily GLP-1RA. The results confirmed the efficacy of GLP-1RA in clinical trials.

[Management of pediatric immune thrombocytopenia].

The new guidelines for pediatric immune thrombocytopenia (ITP) not only include changes to the name and staging of the disease, but also introduce the modified Buchanan's bleeding score for the assessment of bleeding symptoms. Treatments should aim to improve patients' health-related quality of life (HRQoL) based on a multidimensional assessment of not only platelet counts but also bleeding symptoms, as well as activity level, lifestyle, and access to healthcare. First-line therapy includes intravenous immunoglobulin therapy (IVIG) and short-term corticosteroids. Second-line therapy includes thrombopoietin receptor agonists, rituximab, and splenectomy. Many novel agents are also in development, with splenic-derived tyrosine kinase (Syk), Bruton's kinase (BTK), and fetal Fc receptor (FcRn) attracting attention as target molecules. Future developments in the treatment of pediatric ITP are eagerly awaited.

Glucagon-like peptide-1 receptor agonists in neoplastic diseases.

Glucagon-like peptide-1 receptor agonist (GLP-1RA), a novel hypoglycemic agent for the treatment of type 2 diabetes, has well-known effects such as lowering blood sugar, ameliorating inflammation, reducing weight, and lowering blood lipids. It has also been shown that it can influence the proliferation and survival of cells and has a certain effect on the prognosis of some neoplastic diseases. In this study, the potential effects of GLP-1RAs on the occurrence and development of tumors were reviewed to provide new ideas for the prevention and treatment of tumors in patients.

Trends in Glucagon-Like Peptide-1 Receptor Agonist Social Media Posts Using Artificial Intelligence.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have surged in popularity in recent years, with discussions about their on-label and off-label use spilling into the public forum. No study has analyzed online discussions about GLP-1RAs. Objectives: The purpose of this study was to analyze perceptions of GLP-1RAs on social media. Methods: We analyzed GLP-1RA-related posts on Reddit between May 28, 2013, and June 1, 2023. All posts were identified that included generic or brand names of GLP-1RAs. Post volume on Reddit was compared to search interest on Google over time. An artificial intelligence (AI) pipeline consisting of a semi-supervised natural language processing model (Bidirectional Encoder Representations from Transformers [BERT]), a dimensionality reduction technique, and a clustering algorithm was used to cluster posts into related topics. Discussion sentiment was classified using a pretrained BERT model and assessed qualitatively. Results: 14,390 GLP-1RA-related Reddit posts by 8,412 authors were identified. Ninety-four percent of posts were created after 2021, consistent with search interest trend on Google. We used the AI model to categorize posts into 30 topics which were hierarchically grouped by the model based on shared content. Posts were identified among communities for individuals with diabetes and obesity, as well as for diseases without a Food and Drug Administration-approved indication. Most posts had a negative sentiment using the pretrained model, acknowledging the pretrained model is at risk for misclassifying posts. Conclusions: AI can generate insights on perceptions of GLP-1RAs on social media. Common themes included success stories of improving diabetes and obesity management, struggles with insurance coverage, and questions regarding diet, side effects, and medication administration.

Diagnostic Complexities and Management of Gouty Arthritis With Suspected Seronegative Rheumatoid Arthritis and Malignancy in an Elderly Male.

Rheumatoid arthritis (RA) and gout are two distinct types of inflammatory arthritis with significant morbidity. While RA is characterized by autoimmune synovitis, gout is defined by the deposition of urate crystals. Diagnosing these conditions becomes particularly challenging in patients with negative serological markers for RA, compounded by the patient's advanced age and potential for malignancy. This case involves a 77-year-old male with chronic gout, hypertension, chronic atrial fibrillation on edoxaban, diastolic congestive heart failure, and chronic kidney disease stage 3B, presenting with left knee pain and limited mobility. Despite negative serology for RA (rheumatoid factor (RF) <20.0 IU/ml, anti-CCP2 antibodies 1.2 U/mL), the clinical presentation raised suspicion for RA. Imaging revealed significant synovial hypertrophy and multiple periarticular lesions suggestive of chronic gouty tophi rather than RA or malignancy. The patient was managed with allopurinol, prednisolone, and colchicine and referred to rheumatology for further evaluation. Approximately 30% of RA patients may present with negative serological markers, complicating the diagnosis. Differentiating RA from gout is crucial due to differences in management strategies. Imaging modalities such as MRI and CT are essential in identifying characteristic changes of both conditions, such as synovial hypertrophy in RA and tophi in gout. In elderly patients, the possibility of malignancy should also be considered. This case highlights the complexity of diagnosing gouty arthritis mimicking seronegative RA, especially in elderly patients where the risk of malignancy must be considered. It underscores the need for comprehensive clinical and imaging evaluations and personalized treatment plans in managing patients with multiple comorbidities.

Brief Version of the Revised-Abbreviated Eysenck Personality Questionnaire in a Spanish Young Adult Population.

Eysenck's PEN model is one of the most relevant and fruitful models with empirical support, and continues eliciting a large research corpus. Neverthe less, the systematic limitations regarding the psychoticism dimension and questionable inclusion of social desirability as a personality dimension have limited the model. The current research aimed to estimate an alternative PEN model including social desirability as a control and test its validity and reliability. This sample consists of 2969 Spanish young adults. Confirmatory factor analysis was carried out to test the fitting of four different models to the data. Once the best-fitting model was obtained, multiple-group analyses were carried out to assess the configural, metric, and scalar invariance of the model across sexes. The results showed that the three-dimension PEN model and two-dimension EN model controlling social desirability best fit the data and were invariant across sexes. Despite the apparent appropriateness of both models, the EN model controlling for social desirability is more appropriate due to the weakness of the P dimension.

El modelo PEN de Eysenck es uno de los modelos con evidencia empírica más relevantes y fructíferos que sigue suscitando investigación. Sin embargo, las limitaciones sistemáticas del modelo relacionadas con la dimensión de psicoticismo y la inclusión de la deseabilidad social como dimensión de personalidad han limitado al modelo. El objetivo de la investigación actual fue estimar un modelo PEN alternativo, incluyendo la deseabilidad social como control, y testar su validez y fiabilidad. La muestra estuvo compuesta por 2962 españoles adultos jóvenes. Se evaluó el ajuste de cuatro modelos diferentes a los datos. Una vez establecido el mejor ajuste, se llevó a cabo un análisis multigrupo para evaluar la invarianza configural, métrica y escalar por sexos. Los resultados indicaron que el modelo PEN de tres dimensiones y el modelo EN de dos dimensiones, controlando la deseabilidad social, tenían el mejor ajuste a los datos y eran invariantes entre sexos. A pesar de la aparente adecuación de los modelos, el modelo EN, controlando la deseabilidad social, se consideró más apropiado atendiendo a las debilidades de la dimensión P.

Cardiovascular effectiveness of newer glucose-lowering agents, with and without baseline lipid-lowering therapy in type 2 diabetes: A systematic meta-analysis of cardiovascular outcome trials and real-world evidence.

BACKGROUND: Whether the cardiovascular treatment benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D). METHODS: We identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95 % confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial. RESULTS: Twenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95 % CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95 % CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs. CONCLUSIONS: Aggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status. PROSPERO Registration: CRD42024498939.

Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System.

Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an increasingly prevalent class of drugs for managing overweight/obesity and type 2 diabetes mellitus. Postmarket surveillance is essential for characterizing their risk profiles in real-world patient populations as clinical use increases. This study investigated the association of GLP-1RAs with mortality and serious adverse events (AEs) reported to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods A disproportionality analysis was conducted utilizing FAERS data from Q2 2005 to Q1 2024 to identify AEs listing an approved GLP-1RA as the primary suspect drug. The reporting odds ratio (ROR) was calculated for mortality and serious AEs associated with each GLP-1RA compared to the combined group of all other GLP-1RAs. A signal of disproportionate reporting indicating a potential safety concern was defined as a lower bound of the 95% CI for the ROR exceeding 1.0. Results The analysis identified 287,201 AEs associated with GLP-1RAs during the study period. Disproportionality analyses revealed statistically significant elevated signals for mortality with the earliest approved GLP-1RAs: Byetta (ROR = 2.20, 95% CI: 2.06-2.34) and Victoza (ROR = 2.12, 95% CI: 1.98-2.28). Significant elevated signals for serious AEs were identified with the semaglutide products Ozempic (ROR = 2.77, 95% CI: 2.69-2.85), Rybelsus (ROR = 2.42, 95% CI: 2.26-2.60), and Wegovy (ROR = 1.30, 95% CI: 1.22-1.39); the liraglutide products Victoza (ROR = 2.10, 95% CI: 2.04-2.15) and Saxenda (ROR = 2.21, 95% CI: 2.09-2.33); and Byetta (ROR = 1.11, 95% CI: 1.08-1.14) compared to other GLP-1RAs. The newer GLP-1RAs were associated with a higher proportion of serious AEs reported in younger patients (p < 0.001) and females (p < 0.001). Conclusion This pharmacovigilance study utilizing the FAERS database identified potential safety signals of increased mortality and serious AE reporting associated with certain GLP-1RAs, particularly the earlier approved liraglutide agents Byetta and Victoza. These findings highlight the importance of proactive postmarket surveillance to characterize the real-world safety profiles of individual GLP-1RA drugs.

Standard Safety Procedure Before Therapeutic Administration of 223Ra-Dichloride.

223Ra-dichloride is an α-emitter therapy approved for the treatment of castration-resistant prostate cancer with symptomatic bone metastases. 223Ra-dichloride is the first targeted α-therapy for this indication with evidence of benefit in overall survival. The administration is intravenous, and extravasation can cause severe injuries such as tissue necrosis. To prevent this side effect, some procedures can be performed according to the guideline of the European Association of Nuclear Medicine. Ionizing radiation is a well-established risk factor for the development of cutaneous squamous cell carcinoma, but surprisingly there are few reports of local adverse effects related to extravasation of radiotherapies at the injection sites. Recently, a possible case of cutaneous cancer was observed after 223Ra-dichloride extravasation. Methods: To complement the prevention of extravasation, we developed a standardized technique to be performed before the injection of 223Ra. Results: Our technique was successfully applied to the study population, and no apparent extravasation was seen. Conclusion: Our study suggests that use of this standardized technique before administration of 223Ra is helpful in preventing extravasation during this treatment.

Impact of Visceral and Hepatic Fat on Cardiometabolic Health.

PURPOSE OF REVIEW: Body fat distribution plays a significant role in the cardiometabolic consequences of obesity. We review the impact of visceral and hepatic fat and highlight important interventions. RECENT FINDINGS: Several epidemiologic studies have established a clear association between visceral fat and cardiovascular disease. The association between hepatic fat and cardiovascular disease is less clear with discordant results. Novel evidence demonstrates sodium glucose co-transporter-2 (SGLT2) inhibitors facilitate modest weight loss and reductions in ectopic fat depots in patient with type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with decreased visceral/hepatic fat and reductions in MACE in populations with type 2 diabetes and with overweight/obesity. Clear associations between visceral fat and cardiometabolic outcomes have been established, whereas the impact of hepatic fat remains less clear. Lifestyle modification and pharmacologic interventions remain the initial therapies, while surgical intervention is associated with improved long-term outcomes. Emerging therapies have demonstrated a profound impact on body fat distribution and cardiometabolic risk.

Advancements in extracellular vesicle targeted therapies for rheumatoid arthritis: insights into cellular origins, current perspectives, and emerging challenges.

Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome.

Frequently asked questions to the 2023 obesity medicine association position statement on compounded peptides: A call for action.

Background: In 2023, the Obesity Medicine Association (OMA) published "Compounded peptides: An Obesity Medicine Association Position Statement." Since this publication, the use of compounded peptides for the treatment of obesity has continued to evolve, leading to additional confusion and questions from obesity medicine clinicians and their patients. Methods: This frequently asked questions (FAQ) document and "Call for Action" commentary is based upon the existing evidence and practical clinical experiences of the authors. Results: This FAQ is intended to provide insights beyond the original 2023 OMA Position Statement regarding the use of "compounded peptides" for treating obesity. Three obstacles impair patient access to highly effective peptide anti-obesity medications: insufficient production especially during times of high demand, high costs, and lack of clarity surrounding the role of compounded peptides. Solutions to enhance patient access to these medications lie within the existing legal and regulatory framework and Food and Drug Administration policies. Implementing these solutions necessitates dispelling misinformation and providing clear guidance on the appropriate prescribing and administration of compounded peptides, particularly during times of acknowledged shortage. Conclusion: Among stakeholders with aligned priorities, challenges can often be overcome by collaboration and communication. Towards the goal of providing patient-centered care, the OMA calls on applicable stakeholders (e.g., pharmaceutical companies, compounding pharmacy organizations, health insurance companies, and the Food and Drug Administration) to work collaboratively to achieve a consensus that improves patient access to safe anti-obesity medications. The purpose of this "Call to Action" is to ask stakeholders to provide clinicians and their patients clarity regarding the role of compounded peptide anti-obesity medications during times of FDA-acknowledged shortages. Finally, this FAQ review provides clinicians with a simple and practical checklist respective to the potential use of compounded peptides.

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Adolescents Without Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have become the leading anti-obesity drugs for adults, and a similar trend may follow in adolescents with its recent approval for this age group. However, there is a lack of comparative analysis on the weight loss effects and safety of GLP-1 RAs in obese or overweight pediatric and adolescent populations, especially those who are non-diabetic. This systematic review and meta-analysis aim to provide current evidence on the efficacy and safety of GLP-1 RAs as an anti-obesity treatment in obese or overweight non-diabetic pediatric and adolescent populations. METHOD:  We searched electronic databases from inception until January 2024 for randomized controlled trials (RCTs) that analyzed the weight loss effect of GLP-1 receptor agonists in adolescents with obesity or overweight without diabetes mellitus. Search results were screened, and eligible studies were included to perform a systematic review and meta-analysis using the Review Manager (RevMan) computer program Version 5.4.1 (The Cochrane Collaboration, 2020) with a random-effects model. The primary efficacy outcomes were changes in body weight, BMI, and BMI Z-score, while the secondary outcomes were the incidence of gastrointestinal adverse events, treatment discontinuation rate due to adverse events, and incidence of serious adverse events. The mean difference, odds ratio, and 95% confidence interval (CI) were used to present the meta-analysis results. Publication bias was visualized using a funnel plot. The quality of the studies was analyzed using Cochrane's Risk of Bias tool (RoB2). RESULTS: A total of seven RCTs with 576 adolescent participants were included in the analysis. GLP-1 RAs significantly achieved greater weight loss than placebo, with a mean difference of -4.98 kg (-8.49, -1.46), I² = 99%, p = 0.006. Subgroup analysis showed that semaglutide had the most pronounced anti-obesity effect (mean difference of -17.70 kg (-18.89, -16.51), p < 0.00001), compared to liraglutide (mean difference of -2.26 kg (-5.17, 0.65), I² = 99%, p = 0.13) and exenatide (mean difference of -3.17 kg (-4.45, -1.90), I² = 0%, p < 0.0001). Similar results were obtained for other efficacy parameters such as BMI and BMI z-score. However, GLP-1 RA was associated with more gastrointestinal adverse events (such as nausea and vomiting) than placebo (3.06 (2.12, 4.42), I² = 0%, p < 0.00001), with incidence comparable among all GLP-1 RAs in the subgroup analysis. The overall risk of bias among included studies was either of 'some concern' or 'high risk.' CONCLUSIONS: Our meta-analysis demonstrated that GLP-1 RAs had a superior anti-obesity effect compared to placebo or lifestyle modification in obese or overweight non-diabetic adolescents, particularly semaglutide, which had a more pronounced anti-obesity effect than liraglutide and exenatide, with tolerable gastrointestinal adverse effects.

Risk of Aspiration Pneumonitis After Elective Esophagogastroduodenoscopy in Patients on Glucagon-Like Peptide-1 Receptor Agonists.

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining popularity in the management of diabetes mellitus and obesity. It has been suggested that this class of medications causes delayed gastric emptying which raised concerns about the potential for aspiration of gastric contents in patients undergoing sedation. This led to a statement by the American Society of Anesthesiologists about their preoperative use. Nevertheless, there is minimal evidence regarding the effects of GLP-1RAs on the risk of aspiration post-esophagogastroduodenoscopy (EGD). In this study, we sought to evaluate the incidence of aspiration and pneumonia in patients receiving GLP-1RAs who underwent EGD. Methodology We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. The primary outcome was the development of aspiration post-EGD. Secondary outcomes were the development of aspiration pneumonia and requiring antibiotics post-EGD. One-to-one propensity score matching was performed for age, sex, diabetes mellitus, obesity, and other comorbidities between the cohorts. Results Our analysis showed a small but significant risk of aspiration pneumonitis in patients on GLP-1RAs undergoing elective EGD compared to non-GLP-1RA-receiving patients. However, there was no increased risk of the composite outcome of respiratory failure or intensive care unit (ICU) admission; however, this did not reach statistical significance. Conclusions GLP-1RA use was associated with an increased risk of aspiration in patients undergoing elective upper endoscopy. However, this did not translate to an increased risk of respiratory failure or ICU admission. Our findings highlight the importance of following an individualized approach to preoperative management that takes into consideration GLP-1RA indications and other aspiration risk factors, including advanced age, impaired gag reflex, and gastrointestinal symptoms such as nausea and abdominal distention.

Is There a Correlation Between Immune Thrombocytopenia and Immunoglobulin G4-Related Disease?

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition causing organ swelling and fibrosis. Rarely, it coexists with primary immune thrombocytopenia (ITP), characterized by low platelet count (< 100 × 106/L) without an underlying cause. We present a case of a 56-year-old woman diagnosed with ITP in 2005, successfully treated with dexamethasone and intravenous immunoglobulins (IVIG). In 2011, she was diagnosed with IgG4-RD, type I autoimmune pancreatitis, initially treated with steroids then azathioprine with no response. ITP relapses were managed with prednisone/IVIG, rituximab, and thrombopoietin-receptor agonist therapy. Fostamatinib provided temporary relief, but platelet count dropped again in 2023. Combination therapy with small doses of prednisone and mycophenolate showed a partial response, maintaining platelet count over 50 × 106/L. Further investigation is warranted to explore any correlation between these two conditions, especially considering the patient's prolonged response to immunosuppressors.

Evaluating Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in Type 2 Diabetes Mellitus: A Systematic Review.

Cardiovascular risks and complications remain elevated in patients with type 2 diabetes even after appropriate control of contributing factors like glycemic control, hypertension, and lipid profile. More efficient methods are needed to address this issue in type 2 diabetics. Newer drugs like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a cardioprotective effect in addition to glycemic control. This systematic review aims to study the latest literature findings on the cardiovascular effects of GLP-1 RAs in patients with type 2 diabetes. We used PubMed, Google Scholar, Science Direct, and Biomed Central databases for our data collection. Our review adheres to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The outcomes evaluated in the review include major adverse cardiovascular events (MACE), heart failure, stroke, all-cause mortality, and effects on cardiovascular risk factors. After careful inspection and quality check, we included 14 articles in the systematic review. GLP-1 RAs were associated with a significant reduction in cardiovascular mortality, all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal stroke, especially in patients with existing cardiovascular risk factors. However, more evidence is required to determine if these benefits extend to those without such risk factors. Limited data suggest that GLP-1 RAs might have a protective effect on arrhythmias, but this area needs further investigation. Despite their potential, several barriers hinder the widespread use of GLP-1 RAs. In conclusion, GLP-1 RAs significantly reduce cardiovascular mortality, all-cause mortality, nonfatal MI, and stroke, with minor effects on hospitalization due to heart failure. Benefits are greater in patients with cardiovascular risk factors. A comprehensive, multilevel approach to policy development and implementation is necessary to optimize the use of these medications in eligible populations.