Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle implicated in atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) levels have been recognized as a residual cardiovascular risk factor independent of low-density lipoprotein cholesterol. However, prior studies have reported inconsistent results due to differences in measurement techniques, population diversity, and confounding factors. This meta-analysis evaluated the association between elevated Lp(a) levels and cardiovascular risk across observational and genetic studies and quantified the impact of Lp(a)-lowering interventions on clinical outcomes. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to October 20, 2025, following PRISMA 2020 guidelines. Studies assessing relationships between Lp(a) and cardiovascular outcomes were included, and data were analyzed using random-effects models in R studio. Heterogeneity was measured using the I² statistic, and risk of bias was evaluated using the Newcastle-Ottawa scale (NOS) and ROBINS-I tool. Twenty-five studies encompassing 95,206 participants were included. Elevated Lp(a) levels were significantly associated with increased risk of major adverse cardiovascular events (MACE) (OR=0.81; 95% CI: 0.68-0.98; I²=54.9%), myocardial infarction (OR=0.86; 95% CI: 0.75-0.99), ischemic stroke (OR=0.87; 95% CI: 0.76-0.99), and cardiovascular mortality (OR=0.89; 95% CI: 0.87-0.91). PCSK9 inhibitors reduced Lp(a) by a pooled mean difference of -15.58 mg/dL, and anti-inflammatory therapies by -11.21 mg/dl. Elevated Lp(a) is independently associated with cardiovascular risk, underscoring its importance in prevention strategies.
Inflammatory myofibroblastic tumor and liposarcoma very rarely present as tumors of the chest wall. Never have both been reported together in the same lesion. We present a case wherein a 72-year-old man with a rapidly progressing lesion initially mistaken for a local infection underwent resection with diagnosis of inflammatory myofibroblastic tumor. He experienced recurrence less than 6 months before radical resection revealed well to dedifferentiated liposarcoma with areas of inflammatory myofibroblastic tumor. He is now doing well with over 4 years of follow-up.
BACKGROUNDDostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.METHODSWe conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed.RESULTSOf the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group.CONCLUSIONSDostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.).
Introduction/Background In the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (pA/rEC) dostarlimab+carboplatin/paclitaxel significantly improved PFS versus carboplatin/paclitaxel alone in the mismatch repair deficient/microsatellite instability-high (HR 0.28) and overall populations (HR 0.64) with a favourable OS trend (HR 0.64). Here, we report on safety for the RUBY trial. Methodology Patients with pA/rEC were randomised 1:1 to dostarlimab 500 mg, or placebo, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 Q3W for 6 cycles, followed by dostarlimab 1000 mg, or placebo, Q6W for up to 3 years. Adverse events (AEs) were assessed according to CTCAE v4.03. Results The safety population included 487 patients who received ≥1 dose of treatment (241 dostarlimab+carboplatin/paclitaxel; 246 placebo+carboplatin/paclitaxel). Treatment-emergent adverse events (TEAEs) were experienced by 100% of patients; 70.5% of the dostarlimab arm and 59.8% of the placebo arm experienced grade ≥3 TEAEs (table 1). Median time to TEAE was 2.0 days in the dostarlimab+carboplatin/paclitaxel arm and 2.5 days in the placebo+carboplatin/paclitaxel arm. TEAEs led to discontinuation in 23.7% of the dostarlimab+carboplatin/paclitaxel arm and 16.7% of the placebo+carboplatin/paclitaxel arm. Higher rates of discontinuation were reported during the chemotherapy phase (cycles 1–6) versus the monotherapy phase (cycles ≥7). TEAEs led to discontinuation of dostarlimab or placebo in 17.4% and 9.3% of patients (table 1). Discontinuation rates of carboplatin or paclitaxel were similar between arms. Immune-related AEs related to dostarlimab or placebo were reported in 38.2% of the dostarlimab arm and 15.4% of the placebo arm. Five deaths were reported in the dostarlimab arm; 2 were related to dostarlimab. Conclusion The safety profile of dostarlimab+carboplatin/paclitaxel was consistent with that of the individual components. The addition of dostarlimab did not compromise the completion rate of chemotherapy. Dostarlimab+carboplatin/paclitaxel has a favourable benefit-risk profile that makes it a valuable treatment option for patients with pA/rEC. Disclosures This study (NCT03981796) was sponsored by GSK, Waltham, MA, USA. Third-party medical writing support Writing and editorial support, funded and coordinated by GSK (Waltham, MA, USA), was provided by Shannon Morgan-Pelosi, PhD, and Mary Wiggin of Ashfield MedComms, an Inizio company.
There are a growing number of demands for liposuction each year and it is one of the most performed procedures in plastic surgery for aesthetic purposes. Bowel perforation and peritonitis are rare, but life-threatening complications following liposuction. However, there is a lack of awareness of these ill-fated outcomes which are underestimated and under-reported in the literature. We present the case of a 63-year-old male admitted to emergency department (ED) with the symptoms of abdominal pain and distension with anorexia and nausea. The patient stated that he had not been feeling well since the liposuction procedure which he received 6 days prior. During the physical examination, there was mild abdominal distension with tenderness and some guarding in all 4 quadrants. A computed tomography (CT) scan showed pneumoperitoneum. The patient underwent an exploratory laparotomy where multiple small bowel perforations were repaired and a part of the small bowel was resected. The patient eventually recovered well and was discharged on post-op day 12. Bowel perforation which can lead to peritonitis following liposuction is rare, but the risk increases in patients with a previous history of abdominal surgery such as hernia repair, as in this patient. Increased awareness of possible life-threatening complications and close follow-up in patients with risk factors are essential to prevent undesirable outcomes and promptly treat the patient.
