Event Rates Research Articles

Abbreviated Versus Standard Dual Antiplatelet Therapy Times After Percutaneous Coronary Intervention in Patients With High Bleeding Risk With Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P=0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Assessment of centanafadine in adults with ADHD: a matching adjusted indirect comparison versus methylphenidate hydrochloride extended release (Concerta)

Objective: To compare the safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD. Methods: In the absence of head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) were used to compare rates of adverse events reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER. Pooled patient-level data from two centanafadine trials (NCT03605680, NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e., above the 99th percentile). Results: Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: -11.95), initial insomnia (-11.10), decreased appetite (-8.05), anxiety (-5.39), palpitations (-5.25), and feeling jittery (-4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER. Conclusion: In this anchored MAIC, centanafadine had a better safety profile and possibly lower efficacy than methylphenidate hydrochloride ER. While the safety results were robust across analyses, there was no difference in efficacy between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern.

Clinical Outcomes After Definitive Treatment of Soft Tissue Sarcoma of the Hand: A Retrospective Cohort Study of 109 Patients

The purpose of this study was to provide updated data on oncologic outcomes following definitive surgical treatment of soft tissue sarcoma of the hand in a cohort of 109 patients, as well as to characterize risk factors for poor oncologic and functional outcomes. We analyzed data from 109 consecutive patients who had definitive surgical treatment for soft tissue sarcoma of the hand performed between 1996 and 2019 by a single surgeon at a sarcoma center. Primary outcomes included functional outcome (assessed by Musculoskeletal Tumor Society scores), disease-free survival (DFS), and overall survival (OS). We compiled descriptive data and used a multivariable linear model to identify factors associated with functional outcomes. Kaplan-Meier methods were used to estimate 5- and 10-year DFS and OS. Patients had a median age of 36 years at presentation. Median follow-up was 6.1 years among patients alive at the end of follow-up. The median Musculoskeletal Tumor Society score was 29; functional outcome was worse among patients with high-grade tumors or complications. Among the 107 patients who became disease-free, there were four local recurrences (one with metastasis), six distant recurrences, and one death without recurrence. All local recurrences were deep tumors (two myxofibrosarcoma and two myxoinflammatory fibrosarcoma). Estimated 5- and 10-year DFS rates were 89% (95% confidence interval [CI]: 83% to 96%) and 88% (95% CI: 80% to 95%). There were seven deaths, and the estimated 5- and 10-year OS rates were 95% (95% CI: 90% to 100%) and 92% (95% CI: 84% to 100%). Larger tumor size and higher stage at diagnosis were associated with shorter DFS and OS in univariable analyses; low event rates precluded multivariable analysis of survival. Aggressive disease-specific surgical and multidisciplinary treatment can yield long DFS and OS, and good functional outcomes. However, complications and high-grade tumors are associated with worse functional scores. Prognostic II.

Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis.

Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3years and a mean stricture length of 1.68 ± 0.84cm. The technical success rate was 96.4% (95% CI 92.5-98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2-70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption.

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes

Introduction: Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management. Methods: A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023. Results: Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS. Conclusions: Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients’ prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored.

Outcomes of endoscopic ultrasound-guided gallbladder drainage: A multicenter study from India (with video).

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) offers a safe and minimally invasive alternative for percutaneous cholecystostomy (PCC) in acute cholecystitis patients with high-surgical risk. Additionally, EUS-GBD serves as a rescue biliary drainage in malignant distal biliary obstruction. Despite its widespread application, data within the Indian context remains sparse. This study aims to report the outcomes of EUS-GBD through the first multi-center study from India. We retrospectively analyzed patients undergoing EUS-GBD at six tertiary care centers of India from March 2022 to November 2023. EUS-GBD was performed by free hand or over-the-guidewire technique with lumen-apposing metal stent (LAMS) or large caliber metal stent (LCMS). The primary outcome was technical success (defined as successful deployment of stent between gallbladder and stomach/duodenal lumen). The secondary outcomes were clinical success (defined as resolution of symptoms of acute cholecystitis and more than > 50% reduction in bilirubin level within two weeks in distal biliary obstruction), adverse event rate, 30-day mortality rate and 90-day reintervention rate. Total29 patients (mean age 65.86 ± 12.91, 11 female) underwent EUS-GBD. The indication for EUS-GBD were acute cholecystitis (79.31%) and rescue biliary drainage for malignant distal biliary obstruction (20.69%). LAMS was deployed in 92.86%, predominantly by free-hand technique (78.57%). Technical and clinical success rates were 96.55% and 82.75%, respectively. Adverse events occurred in 27.59% patients, with severe adverse events (bile leak and bleeding) being uncommon (10%). Both 30-day mortality rate and 90-day reintervention rate were 13.79% in patients. Cholecysto-duodenal fistula facilitated cholecystoscopic intervention and stone removal in one patient and transgastric EUS-GBD did not hamper bilio-enteric anastomosis during Whipple surgery in two patients. EUS-GBD is a safe and effective technique for managing acute cholecystitis in high-risk patients and for biliary drainage in cases with malignant distal biliary obstruction.

Obstructive Sleep Apnea and Its Cardiac Implications in the United States: An Age-Stratified Analysis Between Young andOlder Adults.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with cardiovascular risks. This study aimed to assess the prevalence of probable OSA and its relationship with cardiovascular risks and diseases focusing on age-stratified young adults (20-40 years) and older (>40 years). The study used a cross-sectional design, analyzing data from the National Health and Nutrition Examination Survey conducted between 2013 and 2018, comprising 9887 community-dwelling adults aged ≥20 years. Probable OSA was determined on the basis of self-report of OSA-related symptoms (eg, snoring, gasping/breath cessation while sleeping). Cardiovascular risk factors, including hypertension, diabetes, hyperlipidemia, and metabolic syndrome, were evaluated according to established guidelines. Cardiovascular diseases (CVDs) included self-reported heart conditions, including congestive heart failure, coronary heart disease, angina, heart attacks, and strokes. Individuals with probable OSA showed a significantly higher prevalence of health conditions, including hypertension (adjusted prevalence ratio [aPR], 1.19; P<0.001), diabetes (aPR, 1.17; P: 0.01), metabolic syndrome (aPR, 1.14; P<0.001), heart attack (aPR, 1.63; P<0.01), stroke (aPR, 1.41; P: 0.03), and any CVD event (aPR, 1.36; P: 0.01) after adjusting for relevant factors. Young adults with probable OSA showed higher prevalence rates of any CVD events (aPR, 3.44; P<0.001), hypertension (aPR, 1.45; P<0.001), metabolic syndrome (aPR, 1.25; P<0.001), and angina (aPR, 10.39; P<0.001). The study suggests early identification and management of OSA in individuals at risk for CVD. While cross-sectional, it emphasizes that health care providers should recognize OSA as significantly associated with CVDs and its precursor risks in young adults, stressing proactive care and screening to reduce CVD risk in this population.

Early outcomes from the pivotal trial of a four-branch off-the shelf solution to treat complex abdominal and type IV thoracoabdominal aortic aneurysms.

This study reports the 30-day outcomes of the primary arm of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis (TAMBE) pivotal trial for complex abdominal aortic aneurysm repair. This multicenter, nonrandomized, prospective study of the TAMBE device included patients enrolled in the primary study arm of extent IV thoracoabdominal aortic aneurysms and pararenal aneurysms. Technical success and major adverse events were analyzed per the Society for Vascular Surgery guidelines. The 102 patients of the primary arm who underwent endovascular repair using the TAMBE device were a mean age of 73± 6.4years (range, 58-82 years) and 84 (84.2%) were male. The mean body mass index was 28.3± 5.0kg/m2. Fifty-nine patients (57.8%) were treated for extent IV and 43 (42.2%) pararenal aneurysms; the mean maximum diameter of the aneurysms was 59.4± 7.8mm. A prophylactic cerebral spinal fluid drain was used in 10 patients (9.8%). Technical success was achieved in 99% of patients, with the single failure owing to unsuccessful cannulation of the left renal artery. Mean procedure time was 315± 103minutes (range, 163-944 minutes), estimated blood loss was 300± 296mL (range, 10-2000 mL), and contrast administration was 153.6± 73.5mL (range, 16-420 mL). The intensive care unit length of stay was 58.7± 52.7hours (range, 1-288 mL). In 28 patients (27.5%), a total of 32 additional endovascular components were deployed to manage procedural complications including aortic and target vessel dissections and injuries not related to access. Bridging stent grafts were deployed to incorporate 407 target vessels (mean 1.6/per vessel; range, 1-4). Postoperative transfusion was required in 14 patients (13.7%). Major adverse events occurred in seven patients (6.9%) through 30days. Events included respiratory failure (n= 2), disabling stroke (n= 1), new-onset renal failure requiring dialysis (n= 2), and paraplegia (n= 2). At 30days, there was one patient with intraoperative rupture; no severe bowel ischemia or lesion-related/all-cause mortality were reported. The Core lab-reported patency was 100% in the aortic component, superior mesenteric artery, and celiac artery, and 95.9% in the left renal and 99.0% in the right renal branch components through 30days of follow-up. Reinterventions through 30days were performed in 9 of 96 patients (9.4%) and were all minor. Early TAMBE device outcomes demonstrate a high technical success rate, no 30-day lesion-related mortality, and a low rate of safety events within 30days of the index procedure.

Impact of a tubeless, disposable insulin pump on emergency department visits and inpatient admissions among a Medicare population.

A tubeless, disposable insulin pump (Omnipod DASH Insulin Management System, Insulet Corporation) has demonstrated improved glycemic outcomes for people with diabetes who require insulin. The impact of the system on downstream health care events has not been studied. To assess health care resource utilization for a Medicare population before and after starting tubeless, disposable insulin pump therapy. This retrospective, observational analysis used data from the Centers for Medicare & Medicaid Services 100% Research Identifiable Files. Study outcomes included change in event rates for diabetes-related emergency department (DRED) visits, all-cause emergency department (ACED) visits, diabetes-related inpatient (DRIP) admissions, and all-cause inpatient (ACIP) admissions among Medicare beneficiaries who started the tubeless, disposable insulin pump in 2020 (postpump observation period) as compared with the same duration and calendar period in 2019 (prepump observation period) with no pump use. Subgroup analyses were performed based on Medicare entitlement reason, diabetes type, and diagnosis status for depressive disorder. A total of 811 users met the criteria for analysis: 46.2% had type 2 diabetes, a majority (59.2%) were aged 65 years or older, and 37.0% had a diagnosis for depressive disorder. Significant reductions were observed for DRED of -46.9% (95% CI = -63% to -23%); ACED of -29.0% (95% CI = -37% to -20%); ACIP of -19.9% (95% CI = -32% to -6%). DRIP rates declined notably (-36.6%; 95% CI = -61% to 4%). Event rates observed across subgroups demonstrated consistent downward trends; however, not all were statistically significant. These findings demonstrate that use of the tubeless, disposable insulin pump was associated with reductions in DRED, ACED, and ACIP. Our results provide real-world evidence to support the use of the tubeless, disposable insulin pump among Medicare beneficiaries who require insulin, regardless of diabetes type or Medicare entitlement reason. Additional studies are recommended to further evaluate the effect of insulin pumps on health care utilization among the Medicare population and other insurance populations.

Population-Based Study on the Implementation of Flash Glucose Monitoring and Severe Hypoglycemia in Adults With Type 1 Diabetes.

Objective: We analyzed the effect of implementing a flash glucose monitoring (FGM) technology in a public health care system with universal coverage on the rate of severe hypoglycemia requiring urgent care in adults with type 1 diabetes mellitus (T1DM). Methods: Using a comprehensive regional dataset, we extracted emergency care codes with hypoglycemia in individuals with T1DM who initiated the use of FGM in Andalucia, Spain, from January 1, 2020, to December 31, 2021. Severe hypoglycemia was defined as a confirmed blood glucose <70 mg/dL, which required the urgent dispatch of an emergency medical service (EMS) for onsite management. We compared hypoglycemic events reported in the 12 months before and after the initiation of FGM to determine the population incidence rates. Results: A total of 13,616 participants with a mean age of 43.7 ± 13.5 years were included. The follow-up periods were 23.4 and 24.8 months before and after FGM. There were 969 and 737 cases of hypoglycemia before and after the initiation of FGM. The baseline incidence rate was 358.58 episodes per 10,000 person-years, which decreased to 260.9 at the end of the follow-up (rate-ratio 0.72 [0.66; 0.80]). The reduction in hypoglycemia was significant in individuals aged ≥60 years (rate-ratio 0.40 [0.28; 0.55]) and males (0.64 [0.56; 0.72]). In addition, there was a reduction in the overall median HbA1c of -0.35% (95% CI [-0.38; -0.33], P < 0.001). Conclusion: The implementation of FGM systems in a public health care system as a provision for adults with T1DM was associated with significant reductions in the rate of severe hypoglycemic events that required urgent EMS care.

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation.

A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; P=0.046). The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed

ABSTRACT Objectives Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Methods NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs. Results NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (−44 [95% CI −328; −21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue. Conclusion Daridorexant 50 mg and 25 mg have a favorable benefit–risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.

LBA1001 Background: The combination of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard first line treatment for HR+, HER2- advanced breast cancer (ABC). While disease progression occurs in nearly all patients (pts) with ABC, the optimal treatment for pts who experience progression on a CDK4/6i + ET remains uncertain. Real-world evidence suggests that use of abemaciclib after disease progression on a prior CDK4/6i prolongs progression-free survival (PFS) in ABC; however, Phase 2 trials with other CDK4/6i have generated mixed results. Here we present the primary outcome analysis for the Phase 3 postMONARCH trial (NCT05169567) of fulvestrant + abemaciclib or placebo in pts with HR+, HER2- ABC following disease progression on prior CDK4/6i + ET. Methods: postMONARCH was a global, double-blind, placebo-controlled study with pts randomized 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant. Eligible pts had disease progression on a CDK4/6i + AI as initial therapy for ABC or relapse on/after a CDK4/6i + ET as adjuvant therapy for early breast cancer. No other prior treatment for ABC was permitted. Primary endpoint was investigator-assessed PFS; secondary endpoints included PFS by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety. Assuming a hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib, with a cumulative 2-sided type I error of 0.05. Kaplan-Meier method was used to estimate PFS curves and treatment effect was estimated using a stratified Cox proportional hazard model. Results: A total of 368 pts were randomized to abemaciclib + fulvestrant (n = 182) or placebo + fulvestrant (n= 186). Most pts (99%) enrolled directly after CDK4/6i + ET as initial therapy for ABC. Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib. At interim analysis, the study reached the pre-specified criteria for significantly improved investigator-assessed PFS with abemaciclib + fulvestrant compared to placebo + fulvestrant (169 events, HR = 0.66; 95% CI 0.48 – 0.91; p = 0.01). At primary analysis (258 events), the HR was 0.73 (95% CI 0.57 – 0.95), with PFS rates at 6 months of 50% vs 37% for the abemaciclib and placebo arms, respectively. Consistent effect was seen across major clinical and genomic subgroups, including pts with baseline ESR1 or PIK3CA mutations. ORR was improved with abemaciclib compared to placebo (17% vs 7%, respectively, in pts with measurable disease). PFS according to BICR was also improved with HR = 0.55 (95% CI 0.39 - 0.77). OS remains immature (20.9% event rate). Safety was consistent with the known profile of abemaciclib. Conclusions: Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy. Clinical trial information: NCT05169567 .

Characteristics and Usefulness of Neurophysiological Monitoring in Corrective Procedures for Abnormally Curved Spine in Young Patients.

To identify and characterize events of deterioration in intraoperative neuromonitoring data during correction procedures for thoracic and lumbar abnormal spinal curvature in young patients. Records of 1,127 cases were retrospectively reviewed to identify events with deterioration of the neuromonitoring data. General etiological and demographic variables were summarized, and neuromonitoring events were studied and characterized. Adolescent idiopathic cases were associated with female dominance and older age. Nonadolescent idiopathic cases were associated with a higher rate of neuromonitoring events. The neuromonitoring events evolved during the different procedural stages, were primarily reflected in the motor-evoked potential data and affected a range of neural structures to varying degrees. Most of the events were resolved, partially or completely, following a corresponding intervention by the surgical team, before the end of the procedure. Significant immediate weakness of the lower extremities was demonstrated in patients with unresolved neuromonitoring events, most of them were nonadolescent idiopathic patients. Neurophysiological monitoring enables the intraoperative assessment of the integrity of neural pathways and allows the detection of surgery-related impending neural injuries. Neuromonitoring contributes to intraoperative decision making, either when data are uneventful and allow confident continuation or when data deteriorate and lead to corresponding intervention. Further awareness should be paid to the vulnerable characteristics of the patient, surgery course, and neuromonitoring data. Proper interpretation of the neuromonitoring data, together with corresponding intervention by the surgeon when necessary, has the potential to reduce postoperative neurological insults and improve clinical outcomes.

A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo) adjuvant therapy in patients with early triple-negative breast cancer: Korean Cancer Study Group BR 15-1 PEARLY trial.

LBA502 Background: Triple-negative breast cancer (TNBC) is known for its high risk of early relapse and poor prognosis. Platinum agents have shown to increase pathological complete response (pCR) rates when added to neoadjuvant chemotherapy for TNBC. However, evidence regarding the survival benefit of platinum in this setting remains inconclusive. The PEARLY trial is a multicenter, randomized, open-label, phase 3 study designed to assess the efficacy and safety of carboplatin in combination with anthracycline/taxane therapy compared to standard anthracycline/taxane alone as either neoadjuvant or adjuvant treatment in early-stage TNBC. Methods: Patients with stage II or III TNBC were randomly assigned to either the carboplatin arm or the standard therapy arm, stratified by nodal status, institution, treatment setting (neoadjuvant vs adjuvant), and germline BRCA status. The standard therapy involved doxorubicin and cyclophosphamide (AC) followed by taxane treatment. The experimental arm included carboplatin in addition to taxane following AC. The primary endpoint was event-free survival (EFS), defined as disease progression or inoperable status for neoadjuvant therapy group, local or distant recurrence, occurrence of a second primary cancer, or death from any cause, while secondary endpoints encompassed overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety. With a planned enrollment of 878 patients, the trial aimed for 80% power to detect a hazard ratio of 0.70 for EFS at a two-sided alpha level of 0.05, anticipating 248 EFS events over a 5-year follow-up period. Results: Between Jan 2016 and Jun 2020, 868 patients across 22 institutions in South Korea were enrolled. At a median follow-up of 51.1 months, carboplatin significantly improved EFS compared to the control arm (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.50 to 0.93; p=0.017). The 5-year EFS rates were increased from 74.4% to 81.9%, demonstrating a 7.5% difference. Subgroup analysis showed consistent benefits across various patient categories. Secondary endpoints like IDFS and DRFS also favored carboplatin arm. OS data were immature, a total of 43 patients (10.2%) in the carboplatin arm and 57 patients (13.1%) in the control arm died (HR 0.66; 95% CI: 0.42 to 1.01). Grade ≥3 treatment-related adverse event rates were 74.6% (1 death due to infection) in the carboplatin arm and 56.7% (2 deaths due to infection and suicide) in the control arm. Conclusions: The addition of carboplatin to standard anthracycline followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. The safety profile was consistent with the known expectations for each regimen. Clinical trial information: NCT02441933 .

Fully ab-initio all-electron calculation of dark matter-electron scattering in crystals with evaluation of systematic uncertainties

We calculate target-material responses for dark matter–electron scattering at the all-electron level using atom-centered Gaussian basis sets. The all-electron effects enhance the material response at high momentum transfers from dark matter to electrons, q≳O(10αme), compared to calculations using conventional plane wave methods, including those used in ; this enhances the expected event rates at energy transfers E≳10 eV, especially when scattering through heavy mediators. We carefully test a range of systematic uncertainties in the theory calculation, including those arising from the choice of basis set, exchange-correlation functional, number of unit cells in the Bloch sum, k-mesh, and neglect of scatters with very high momentum transfers. We provide state-of-the-art crystal form factors, focusing on silicon and germanium. Our code and results are made publicly available as a new tool, called (“”). Published by the American Physical Society 2024

Effect of vigorous-intensity physical activity on incident cognitive impairment in high-risk hypertension.

We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9vs 19.7), probable dementia (6.3vs 9.0), and MCI/probable dementia (18.5vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.

Heart Failure and Edema Costs in Patiromer and SZC Users.

Previous work suggested differences between patients taking patiromer or sodium zirconium cyclosilicate (SZC) in real-world risk of heart failure (HF) hospitalizations and edema hospitalizations or emergency department (ED) visits (edema events). We further investigated these differences to assess economic importance. Retrospective study using published event rates and mean costs derived from Optum's de-identified Clinformatics® Data Mart (CDM) Database. We designed a model to estimate adjusted economic offsets that combined respective patiromer and SZC HF hospitalization (25.1 and 35.8; difference 10.7 [95% confidence interval [CI]2: 2.6-18.8]) and edema event (3.4 and 7.1; difference 3.6 [95% CI: 1.7-7.1]) rates/100 person-years from the original published work with costs from our parallel data extract spanning 2019-2021, adjusted to 2021 US dollars. In a base case of mean HF hospitalization, edema event, and 30-count potassium-binder prescription costs from our data extract, the estimated mean savings with patiromer was $1,428 per person per year (PPPY; 95% CI: -$1,508 to $4,652). Respective costs PPPY for patiromer vs SZC were $8,526 vs $12,622 (difference $4,096 [95% CI: $1,160-$7,320]) for HF hospitalization and edema events, and $10,649 vs $7,981 (difference -$2,668) for potassium binders, totaling $19,175 for patiromer vs $20,603 for SZC. With differing drug costs, hospitalization and ED costs offset this difference when event rates were numerically small. Model outcomes were driven by HF hospitalization cost and least influenced by edema ED visit cost. A limitation was that the CDM data extract may differ from the original work.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.