Cornerstone Research Group (United States)

Dysmenorrhea includes symptoms such as abdominal pain, nausea, and vomiting. It is a clinical diagnosis with typical treatment involving the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal therapy. Even with conventional treatment, many women deal with dysmenorrhea refractory to treatment. They are often subject to dealing with the adverse effects of those treatments, such as peptic ulcer disease. We present a case of a patient with severe refractory dysmenorrhea who was able to minimize symptoms with the use of semaglutide, a glucagon-like peptide-1 (GLP-1) agonist. With no changes in the patient's lifestyle and no additional medications added, the semaglutide therapy was able to minimize the patient's symptoms to where she was able to continue activities of daily living and minimize the use of NSAID therapy. Moreover, the patient experienced no changes in weight and only transient loss of appetite while onsemaglutide. We hypothesize that anti-estrogenic and anti-inflammatory properties are potential mechanisms of action in this case. This case brings to light the possible multifaceted applications of GLP-1 agonists beyond weight control and diabetes. The outcome of this case suggests that a controlled trial of GLP-1 agonist therapy is warranted to determine its potential for the management of dysmenorrhea.

BackgroundThe present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT).MethodsPropensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France.ResultsBefore matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted.ConclusionsPSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.

Background:Identification of AML patients at high risk of relapse after achieving a complete remission (CR) with induction chemotherapy enables the use of personalized post‐remission treatment strategies to prevent relapse. Detection of molecular measurable residual disease (mMRD) by conventional next‐generation sequencing (NGS) at a single time point post‐induction has previously been associated with a higher incidence of relapse and inferior overall survival (OS).Aims:In this study, we used error‐corrected NGS (EC‐NGS) to evaluate whether changes in mMRD levels between two time points during remission provide additional prognostic information over single time point assessments.Methods:88 AML patients who received standard induction chemotherapy and achieved a CR were evaluated. Targeted NGS of 54 genes associated with myeloid malignancies was performed at diagnosis. We collected peripheral blood (PB) samples upon count recovery following induction chemotherapy and each cycle of consolidation chemotherapy. To detect mMRD, we used a custom 37‐gene hybrid‐capture panel and EC‐NGS based on the Duplex Sequencing approach. PB samples collected at two different time points during remission were analyzed for each patient. The Cox proportional hazards model was used to relate predictor variables to time to relapse and OS. P‐values <0.05 were considered significant.Results:Sequencing analysis of diagnostic samples identified at least one putative oncogenic mutation in 82 of the 88 patients (93%). EC‐NGS of samples collected at the first remission time point (T1) identified at least one persistent mutation in 63 of the 82 patients (77%); 40% of the persistent mutations were in DNMT3A, TET2, and ASXL1 (DTA). The persistence of DTA or non‐DTA mutations, when considered separately, did not correlate with risk of relapse or OS. The co‐persistence of at least one DTA and one non‐DTA mutation was associated with a higher risk of relapse (HR: 2.61; 95% CI, 1.16 to 5.83; P = 0.02) but not OS (P = 0.56). To evaluate whether changes in mMRD level correlate with clinical outcomes, we analyzed the subset of mutations that were detected at diagnosis and persisted in both T1 and T2. We calculated the fold change (FC) in variant allele frequency (VAF) between T1 and T2 for each mutation and used the maximum FC among all mutations of each patient (maxFC) as a continuous variable for regression analysis. High maxFC values restricted to mutations found at diagnosis (maxFCD) were significantly correlated with a higher risk of relapse (P = 0.002) and inferior OS (P = 0.003). We extended the analysis to all non‐synonymous mutations that were detected in T1 and T2 including ones that were not identified at diagnosis. The mutations were predominantly in DNMT3A, TET2, ASXL1, and TP53. Higher maxFC values among mutations found in remission samples (maxFCR) was strongly associated with an increased risk of relapse (P < 0.0001; Fig 1A) and inferior OS (P < 0.0001; Fig 1B). In multivariable regression analysis, maxFCR remained an independent risk factor for relapse after adjustment for age, WBC, ELN 2017 risk group, maxFCD, MRD by flow cytometry, and persistence of mutations found at diagnosis (Table 1).Summary/Conclusion:Our analysis demonstrates that assessment of mMRD kinetics using EC‐NGS provides additional prognostic information over mMRD monitoring at a single time point. We developed an analytical framework to analyze mMRD results in remission and identified a novel parameter (maxFCR) that is independently associated with risk of relapse and OS.image

Abstract Background: Multiple sclerosis (MS) is a chronic neurodegenerative condition that severely impacts patient functioning and quality of life (QoL). Onset of MS typically occurs in adults and evidence is growing for onset in children and adolescents. Several studies describe the clinical burden of pediatric MS; however, to date, no systematic literature review summarizing the clinical burden of pediatric MS has been published. Objective: To conduct a systematic literature review to identify published data on the epidemiology, disease characteristics, QoL, and economic burden of pediatric MS in North America and Europe. Methods: Systematic searches were conducted in Ovid MEDLINE®, Embase, and Cochrane library to identify studies that enrolled patients with pediatric MS and reported at least one outcome related to the epidemiological, humanistic, and economic burden of pediatric MS. Only English-language studies were included. Results: In total, 7,447 unique records were identified, of which 103 met the study’s inclusion criteria. Of the included articles, 9 reported incidence and prevalence, 39 reported relapse rates, 15 reported QoL, 22 reported fatigue, 37 reported cognitive function, and 17 reported school performance. Incidence of pediatric MS ranged from 0.30 to 2.64 per 100,000 person-years, with few studies suggesting that incidence may increase with age. Prevalence was reported as high as 14.6 cases per 100,000 persons in the USA and 9.6% of all MS patients in European countries. The range of annualized relapse rates was similar across countries, at 0.36-2.76 in North America and 0.65-1.11 in European countries. Patients with pediatric MS experienced reduced QoL compared to healthy controls. Patients experienced reduced diminished cognitive functioning, worse school performance and increased fatigue. Limited information was identified for the mortality and economic burden of pediatric MS. Conclusions: Several studies describe the clinical burden of pediatric MS. Although incidence and prevalence rates for the disease are relatively low, the rate of relapse and burden to patients is considerable. Further studies are required to address gaps in the understanding of prognostic factors for relapse and the impact of QoL, fatigue, and cognitive function. Additional research on mortality and economic outcomes will be important to guide treatment pathways and reimbursement decisions.