Exploratory Subgroup Analysis Research Articles

Association between stress hyperglycemia ratio and postoperative major adverse cardiovascular and cerebrovascular events in noncardiac surgeries: a large perioperative cohort study

BackgroundThere has been a concerning rise in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) following noncardiac surgeries (NCS), significantly impacting surgical outcomes and patient prognosis. Glucose metabolism abnormalities induced by stress response under acute medical conditions may be a risk factor for postoperative MACCE. This study aims to explore the association between stress hyperglycemia ratio (SHR) and postoperative MACCE in patients undergoing general anesthesia for NCS.MethodsThere were 12,899 patients in this perioperative cohort study. The primary outcome was MACCE within 30 days postoperatively, defined as angina, acute myocardial infarction, cardiac arrest, arrhythmia, heart failure, stroke, or in-hospital all-cause mortality. Kaplan-Meier curves visualized the cumulative incidence of MACCE. Cox proportional hazard models were utilized to assess the association between the risk of MACCE and different SHR groups. Restricted cubic spline analyses were conducted to explore potential nonlinear relationships. Additionally, exploratory subgroup analyses and sensitivity analyses were performed.ResultsA total of 592 (4.59%) participants experienced MACCE within 30 days after surgery, and 1,045 (8.10%) within 90 days. After adjusting for confounding factors, compared to the SHR T2 group, the risk of MACCE within 30 days after surgery increased by 1.34 times (95% CI 1.08–1.66) in the T3 group and by 1.35 times (95% CI 1.08–1.68) in the T1 group respectively. In the non-diabetes group, the risk of MACCE within 30 days after surgery increased by 1.60 times (95% CI 1.21–2.12) in the T3 group and by 1.61 times (95% CI 1.21–2.14) in the T1 group respectively, while no statistically significant increase in risk was observed in the diabetes group. Similar results were observed within 90 days after surgery in the non-diabetes group. Additionally, a statistically significant U-shaped nonlinear relationship was observed in the non-diabetes group (30 days: P for nonlinear = 0.010; 90 days: P for nonlinear = 0.008).ConclusionIn this large perioperative cohort study, we observed that both higher and lower SHR were associated with an increased risk of MACCE within 30 and 90 days after NCS, especially in patients without diabetes. These findings suggest that SHR potentially plays a key role in stratifying cardiovascular and cerebrovascular risk after NCS.

A descriptive survey of patient experiences and access to specialty medicines with alternative funding programs.

Alternative funding programs (AFPs) seek to reduce health plan sponsor costs, for example by excluding specialty drugs from a beneficiary's plan coverage and requiring patients to obtain medications through alternative sources (typically, the manufacturer's patient assistance programs) via an AFP vendor as a third-party. To describe patients' experiences and specialty medication access with AFPs. A survey method consisting of 26 optional single-choice and multiple-choice questions with branching logic divided across 5 sections (related to patient challenges with AFPs) was administered to patients recruited from an experienced AFP online patient panel and a patient advocacy group. The survey assessed patients' awareness of AFPs from their employers, experience with the patient assistance program application process via the AFP vendor, timeliness of medication access (if granted), and/or the health impact of delay in access. All descriptive and exploratory subgroup analyses were conducted by disease area and reported income levels; statistical analyses were carried out for the exploratory analyses. The final sample included 227 patients. Most patients (61% [136/223]) first heard of the AFP as part of their health benefit when trying to obtain their medication. Of 198 patients, 88% reported being stressed because of the medication coverage denial and the uncertainty of obtaining their medication. More than half of patients (54% [115/213]) reported being uncomfortable with the benefits manager from the AFP vendor. On average, patients reported waiting to receive their medication for 68.2 days (approximately 2 months); 24% (51/215) reported the wait for the medication worsened their condition and 64% (138/215) reported the wait led to stress and/or anxiety. Patients who indicated the wait time negatively affected them had considered a job change or left their job at a 3-5-fold higher rate than those who reported no impact from wait time. A significantly higher proportion of patients with hemophilia and other bleeding disorders reported receiving their prescribed medication less often than patients with other conditions (63% [19/30] vs 81% [52/64]; P = 0.022), whereas more patients with lower incomes (<$50,000 vs >$50,000) reported not receiving any medication (12% [7/57] vs 5% [7/129]; P = 0.657), although these differences were not significant. Most patients who obtain their specialty medicines via AFPs reported being uncomfortable with the process and experiencing treatment delays, which may have been linked to disease progression, worsened mental well-being, and consideration of a job change. Employers should be aware of the potential downstream impacts on employee health, retention, and the employee-employer relationship when considering implementing an AFP into their health plan.

Pharmacological interventions for co-occurring psychopathology in people with borderline personality disorder: secondary analysis of the Cochrane systematic review with meta-analyses.

Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD). To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities. Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific ('co-occurring') psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty. Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) -0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic-dissociative symptoms (SMD -0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD -0.44, P = 0.02; LCE) and anxious symptoms (SMD -1.11, P < 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic-dissociative symptoms (P = 0.001). Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.

The efficacy of socially assistive robots in improving children’s pain and negative affectivity during needle-based invasive treatment: A systematic review and meta-analysis

BackgroundThe ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots.ObjectiveThis study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures.DesignThis study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines.MethodsThe PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence.ResultsTen RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use.ConclusionsThe use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions.Trial registrationThe protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Prognostic and predictive factors in advanced upper gastrointestinal cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis of the current evidence

BackgroundImmune checkpoint inhibitors (ICIs) have shown encouraging treatment efficacy for upper gastrointestinal cancers (UGICs). However, durable clinical responses only existed in a minority of patients. We evaluated evidence predicting survival benefits to identify the optimal population followed by ICI-based therapy.MethodsA comprehensive search was performed using PubMed, Embase, Cochrane Library, and Web of Science to identify clinical trials for UGICs with ICI-based therapy. The outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE).ResultsThirty-six studies comprising 12,440 patients were included for quantitative synthesis. Patients with PD-L1-positive (OR = 2.08, p < 0.00001), EBV+ (OR = 8.47, p = 0.003) tumors were more likely to respond to ICI treatment. Moreover, OS was significantly improved with the statistical subgroup difference concerning sex (p = 0.02) and region (p = 0.02). An exploratory subgroup analysis showed significantly improved OS with ICI plus chemotherapy in patients with CPS ≥ 10 (HR = 0.66, p = 0.001) and CPS ≥ 1 (HR = 0.75, p < 0.00001).ConclusionUGIC patients with PD-L1-positive, EBV + status are associated with a better therapeutic response to ICI-based therapy. The male patients and Asian patients could derive more survival benefits following ICI treatment than female and non-Asian ones. A combination of prognostic and predictive factors was suggested to help guide immunotherapy decision-making in UGIC patients.

The association between novel negative pressure ureteroscopic lithotripsy combined with flexible ureteroscopy versus percutaneous nephrolithotomy on stone-free rates: implications for clinical practice and policy

The correlation between novel negative pressure ureteroscopic lithotripsy (NP-URL) combined with flexible ureteroscopy (FU) and percutaneous nephrolithotomy (PCNL) on stone-free rates (SFR) remains unclear. There is a lack of evidence from Chinese populations regarding the relationship between SFR and NP-URL combined with FU (NP-URL-FU) versus PCNL. We aimed to assess the association between NP-URL-FU and PCNL on SFR. We conducted a cohort study involving 166 participants with 2–4 cm kidney stones. Data on SFR (7 days and 2 months) were collected from all participants. Logistic regression analysis was used to substantiate the research objectives. NP-URL-FU versus PCNL showed an 86% decrease in the 7-day SFR (OR = 0.14, 95% CI 0.07–0.29). The results remained stable even after adjusting for potential confounders. However, no statistically significant association was found between the surgical method and the 2-month SFR. Further exploratory subgroup analyses showed no significant interactions, with all P values > 0.05. Among patients with 2–4 cm kidney stones, NP-URL-FU was associated with a lower risk of incident 7-day SFR than PCNL. However, no statistically significant difference was found in the long-term stone removal rate. Therefore, NP-URL-FU may be a viable alternative surgical option for patients seeking minimally invasive procedures.

Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial.

In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population. In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1-21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71-1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73-1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results. Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood.

Association between renal function and fracture incidence during treatment with teriparatide or alendronate: an exploratory subgroup analysis of the Japanese Osteoporosis Intervention Trial-05.

Incidence rate of morphometric vertebral fracture was lower under treatment with once-weekly teriparatide (TPTD) followed by alendronate (ALN) than under treatment with ALN throughout the study among elderly Japanese women at high fracture risk in JOINT-05. This is an exploratory subgroup analysis according to chronic kidney disease (CKD) status at baseline. Participants received sequential therapy with TPTD for 72weeks, followed by ALN for 48weeks (TPTD-ALN group, N = 483) or ALN monotherapy for 120weeks (ALN group, N = 496). Baseline CKD status was classified by the estimated glomerular filtration rate (eGFR) and categorized as: CKD 1/2 (eGFR ≥ 60mL/min/1.73 m2), CKD 3a (eGFR 45-59mL/min/1.73 m2), or CKD 3b/4 (eGFR < 45mL/min/1.73 m2). Incidences of vertebral fractures including morphometric fractures, non-vertebral fractures, and all fractures were evaluated during follow-up. Baseline characteristics were not different between treatment groups. Higher stages of CKD were associated with age and number of prevalent vertebral fracture. In CKD 1/2 patients (N = 556 with 90 incidents of morphometric vertebral fracture), the incidence of vertebral fractures was lower in the TPTD-ALN group than in the ALN group (p = 0.01). In CKD 3b/4 patients (N = 112 with 10 incidents of non-vertebral fracture), the incidence of non-vertebral fractures was lower in the ALN group than in the TPTD-ALN group, although the number of fractures was small. In the ALN group, the incidences of vertebral fractures, non-vertebral fractures, and all fractures remained constant across CKD stages. This exploratory analysis showed that fracture incidence on ALN was constant regardless of renal function. It also suggested that the incidence of vertebral fractures on TPTD-ALN was lower than ALN monotherapy in CKD 1/2 patients. These results provide important information for drug selection in the clinical practice of osteoporosis.

Association between toxicity-index of diquat and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study

Background This study investigates the impact of diquat toxicity levels on in-hospital mortality rates among patients with acute diquat poisoning. It aims to clarify the relationship between diquat toxicity scores and the likelihood of death during hospitalization. Methods A retrospective cohort study was conducted on 98 individuals with acute diquat poisoning. Data on post-ingestion time, initial diquat plasma concentration, and clinical outcomes were systematically collected for all participants. The toxicity-index of diquat was calculated based on post-ingestion time and initial diquat plasma concentration. Logistic regression analysis was utilized to assess the association between the toxicity-index of diquat and in-hospital mortality rates, adjusting for potential confounding variables such as age, comorbidities, and treatment interventions. Results The study found that the overall prevalence of in-hospital mortality was 34.7%, with 58.2% in males. The multivariable-adjusted regression coefficient for in-hospital mortality associated with the toxicity-index was 1.09, with a 95% confidence interval (CI) of 1.01–1.17. Subsequent exploratory subgroup analysis indicated that there were no significant interactions (all p values for interaction were >0.05). Conclusions The study found that higher diquat toxicity-index values correlate with increased in-hospital mortality in acute diquat poisoning cases, indicating that the toxicity-index could be a useful biomarker for assessing mortality risk.

Effects of antiseizure medication withdrawal during the first trimester of pregnancy on seizure control and offspring outcomes.

To explore seizure control and offspring outcomes associated with antiseizure medication (ASM) withdrawal during the first trimester of pregnancy. Based on a prospective multicenter study in China, pregnancies followed up between 2009 and 2023 at the neurology outpatient clinic of 50 hospitals were included in this study. Information on demographics, epileptic characteristics, treatment during pregnancy, and offspring outcomes was collected. Pregnancies were categorized into an ASM withdrawal group and an ASM continuation group. Balance tests and univariate log-binomial regression analysis were conducted to identify imbalanced factors between groups and potential risk factors for seizure deterioration during pregnancy. Multivariate log-binomial regression was then used to estimate the adjusted effects of ASM withdrawal on seizure deterioration during pregnancy and fetal outcomes. In addition, exploratory subgroup analysis was conducted to identify high-risk patients who should avoid ASM withdrawal. Of the 695 pregnancies enrolled, 14.2% withdrew ASMs in the first trimester of pregnancy. ASM withdrawal during this period was associated with a risk of seizure deterioration during pregnancy (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.009-1.876). Subgroup analysis revealed a significant risk of seizure deterioration in pregnancies with seizures in 9 months (aRR 1.590, 95% CI 1.079-2.344). After adjusting the folic acid dose, no evidence of protective effects on fetus after ASM withdrawal was observed compared to patients with continued treatment, whereas seizure deterioration during pregnancy increased the risk of fetal death (aRR 3.577, 95% CI 1.086-11.651). ASM withdrawal in the first trimester of pregnancy did not show a protective effect on fetal outcomes but rather resulted in increased seizure frequency during pregnancy. However, this finding requires a larger sample for validation. Furthermore, seizure deterioration during pregnancy was associated with an increased risk of fetal death.

Whole Lung Irradiation in Rhabdomyosarcoma With Lung Metastases: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases. Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed. Event-free survival (EFS) and overall survival (OS) were compared between patients who received and did not receive WLI. In 143 patients with rhabdomyosarcoma with lung metastases, 65 patients (45.5%) received WLI and 78 patients (54.5%) did not receive WLI despite protocol requirements. The 5-year EFS was 38.3% (95% CI, 24.8 to 51.8) in patients who received WLI and 25.2% (95% CI, 13.8 to 36.6) in patients who did not receive WLI (P = .0496). The 5-year OS was 45.5% (95% CI, 31.8 to 59.3) in patients who received WLI and 32.4% (95% CI, 20.4 to 44.4) in patients who did not receive WLI (P = .08). In exploratory subgroup analyses, the benefit of WLI on EFS and OS was significant in patients 10 years and older. Other clinical factors associated with EFS on univariable analysis included age, histology FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin Score. WLI is associated with improved EFS in patients with rhabdomyosarcoma with lung metastases. These results highlight the potential importance of WLI and need for more stringent protocol compliance for administering WLI.

Do DanGer-SHOCK-like patients benefit from VA-ECMO treatment in infarct-related cardiogenic shock? results of an individual patient data meta-analysis.

In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial. Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56-1.26], while major bleeding (OR, 2.24; 95% CI, 1.08-4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15-11.56) were increased with the use of VA-ECMO. In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions.

Negative Association of GNRI with All-Cause Mortality in Chinese Atrial Fibrillation Patients: A Multicenter Retrospective Cohort Study

Introduction: Malnutrition is common in older atrial fibrillation (AF) patients and results in poor clinical outcomes. The Geriatric Nutritional Risk Index (GNRI) is a straightforward method for evaluating nutritional health. However, its prognostic value in AF patients is unclear. This research focused on examining the correlation between GNRI and overall mortality in Chinese individuals with AF. Methods: We performed a multicenter retrospective study at four Chinese hospitals involving patients diagnosed with AF between January 2019 and August 2023. Using GNRI, nutritional status was evaluated, classifying patients into three categories. Multivariable logistic regression and restricted cubic spline analysis assess the relationship between GNRI and mortality, with exploratory subgroup analyses investigating potential effect modifiers. Results: The study included 4,878 AF patients with a median follow-up of 19 months. The mean age was 71 (63–78), and the mean GNRI was 102 (95–108). Malnutrition was identified in 1,776 patients (36.41%). During the study, 419 (8.59%) deaths occurred. After controlling for confounders, moderate to severe malnutrition was linked to an increased risk of all-cause mortality compared to no malnutrition (odds ratio 1.50; 95% CI, 1.17–1.94). The relationship between GNRI and mortality risk was approximately linear, with consistent associations across subgroups. Conclusion: Malnutrition, as assessed by GNRI, is prevalent among Chinese AF patients and is independently linked to higher all-cause mortality risk.

Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence.

The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens. A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to P-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement). Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72-.97]) and EFS (HR .79 [.69-.91]) than observation, as any monotherapy did (HR .84 [.74-.96]; HR .79 [.70-.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49-.98]) while fluoropyrimidines achieved the best P score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size. Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.

Triglyceride glucose index is a risk factor for heart failure: A prospective cohort study.

This study aimed to investigate the relationship between the triglyceride glucose (TyG) index and all-cause mortality in patients with heart failure (HF). A total of 1274 patients with HF diagnosed at Hebei General Hospital were enrolled in this study. The patients were divided into four groups by quartiles based on the TyG index. The endpoint was all-cause mortality during the follow-up period. The median follow-up period was 1079days, with a total of 543 (42.7%) patients experiencing all-cause mortality. The survival curves showed no significant difference in endpoint events among the four groups (log-rank P=0.329). The adjusted survival curves revealed that after adjusting for the variables in Model 3, the group with a higher TyG index exhibited a higher risk of death (log-rank P<0.001). The multivariate-adjusted Cox proportional hazard models revealed a positive correlation between the TyG index and all-cause mortality. After complete adjustment, patients with the highest TyG index exhibited a higher risk of all-cause mortality than those in the lowest quartile [hazard ratio (HR)=1.6, 95% confidence interval (CI): 1.22-2.09; P=0.001]. Restricted cubic spline analysis showed that the risk of all-cause mortality increased linearly with the TyG index (P for non-linear=0.207). Exploratory subgroup analyses revealed that, as a continuous variable, the TyG index was significantly associated with all-cause mortality in female patients (HR=1.31, 95% CI: 1.08-1.58, P=0.029) and older patients (HR=1.25, 95% CI: 1.1-1.43, P=0.027). The TyG index was positively associated with increased all-cause mortality in hospitalized patients with HF. Subgroup analyses indicated that the TyG index was strongly associated with all-cause mortality in older and female patients.

The Relationship between Low-Sodium Salt Intake and Both Blood Pressure Level and Hypertension in Chinese Residents.

Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose-response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1: <4.72 g/d, Q2: ≥4.72 g/d, and <6.88 g/d, and Q3: ≥6.88 g/d). The restricted cubic spline results indicated that low-sodium salt intake decreased linearly with SBP and DBP, while low-sodium intake demonstrated a non-linear, L-shaped relationship with the risk of hypertension, with a safe range of 5.81 g to 7.66 g. The multiple linear regression analysis revealed that compared with group Q1, the DBP in group Q2 decreased by 2.843 mmHg (95%CI: -5.552, -0.133), and the SBP in group Q3 decreased by 4.997 mmHg (95%CI: -9.136, -0.858). Exploratory subgroup analyses indicated that low-sodium salt intake had a significant impact on reducing SBP in males, DBP in females, SBP in rural populations, and DBP in urban populations. The intake of low-sodium salt adheres to the principle of moderation, with 5.81-7.66 g potentially serving as a pivotal threshold.

Outcomes with perioperative durvalumab (D) in pts with resectable NSCLC and baseline N2 lymph node involvement (N2 R-NSCLC): An exploratory subgroup analysis of AEGEAN.

8011 Background: In the phase 3 AEGEAN study (NCT03800134), perioperative D + neoadj chemotherapy (CT) vs neoadj CT alone significantly improved the primary EPs of event-free survival (EFS) and pathological complete response (pCR; absence of residual viable tumor [RVT] in resection specimen, incl. primary tumor and sampled lymph nodes) with manageable safety in pts with R-NSCLC (modified ITT [mITT] population). Here, we report exploratory analyses of pts in AEGEAN with baseline N2 nodal status. Methods: Pts with Tx-naïve R-NSCLC (stage II–IIIB[N2]; AJCC 8th ed) were randomized (1:1) to 4 cycles of platinum-based CT plus D 1500 mg IV or placebo (PBO) Q3W before surgery (Sx), followed by D or PBO (Q4W, 12 cycles) after Sx. The mITT population excluded pts with known EGFR/ ALK alterations. Efficacy was assessed in an mITT subpopulation with baseline N2 nodal status (per investigator). Safety was assessed in all N2 R-NSCLC pts who had ≥1 Tx dose. Results: Of 740 pts in the mITT population, 366 (49.5%) had baseline N2 nodal status (D, n = 181; PBO, n = 185). In the N2 subgroup, 83.4% in the D arm and 84.9% in the PBO arm completed 4 cycles of platinum-doublet CT; 77.9% and 77.8%, respectively, had Sx; and 73.5% and 71.9% completed Sx. In the N2 subgroup, similar to the overall mITT population, EFS was prolonged in the D vs PBO arm (HR, 0.63 [95% CI: 0.43–0.90]); rates of pCR (16.6% vs 4.9%; difference, 11.7% [95% CI: 5.6–18.4]) and major pathological response (MPR, ≤10% RVT in primary tumor; 32.6% vs 15.1%; difference, 17.5% [95% CI: 8.8–26.0]) were higher in the D vs PBO arm. While EFS benefit in the D vs PBO arm was similar among pts with single- (HR, 0.61 [95% CI: 0.39–0.94]) or multi-station N2 (HR, 0.69 [95% CI: 0.33–1.38]), pCR benefit was less pronounced in multi-station pts (difference in pCR rate, 13.9% [95% CI: 6.6–21.7] for single-station N2 vs 3.8% [95% CI: –9.2–18.8] for multi-station N2). Among pts in the N2 subgroup who had Sx, similar proportions in the D and PBO arms had open (47.5% vs 50.0%) and minimally invasive procedures (50.4% vs 46.5%); 9.2% vs 11.1% had pneumonectomy (9.2% vs 9.6% in the overall mITT population). Of pts in the N2 subgroup who completed Sx, the proportion with R0 resection in the D vs PBO arm (94.7% vs 91.7%) was similar to that in the overall mITT population. Sx was delayed in a similar proportion who had Sx in the D vs PBO arm (19.9% vs 23.6%, respectively), most commonly for logistical reasons (e.g., scheduling issues). Among 394 pts who received Tx (N2 safety analysis subset; D, n = 200; PBO, n = 194), max grade 3/4 any-cause AEs occurred in 38.5% vs 41.8% in the D and PBO arm, respectively, similar to rates in the overall safety analysis set. Conclusions: With clinically meaningful improvement in efficacy, no adverse impact on Sx outcomes and a manageable safety profile, the addition of perioperative D to neoadj CT remains a potential new Tx option for pts with N2 R-NSCLC. Clinical trial information: NCT03800134 .

Long-term survival outcomes of patients (pts) with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with brexucabtagene autoleucel (brexu-cel) in ZUMA-3.

6531 Background: Brexu-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for pts ≥18 y with R/R B-ALL in the US (≥26 y in the EU). In the 3-y follow-up of ZUMA-3, median overall survival (OS) was 25.6 mo (N=78). Survival benefit was seen regardless of age, prior treatment, or subsequent allogeneic stem cell transplant (sub alloSCT) status (Shah et al. ASCO 2023. #7023). Here we report 4-y survival outcomes for ZUMA-3. Methods: Eligible pts (≥18 y) had R/R B-ALL and received brexu-cel (1×106 CAR T cells/kg) after leukapheresis and lymphodepleting chemotherapy. The primary endpoint was overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate per independent review with OS as a key secondary endpoint. Descriptive statistics are reported for post hoc exploratory subgroup analyses. Results: As of July 23, 2023, median follow-up time in Phase 1 and 2 pts who received the pivotal dose of brexu-cel (N=78) was 53.6 mo (range 44.7-82.3). Median OS (95% CI) was 25.6 mo (16.2-60.4) in all treated pts and 47.0 mo (23.2-not estimable [NE]) in pts with CR/CRi (n=57). In pts &lt;26 y (n=15), median OS (95% CI) was 23.2 mo (9.0-NE) and was 26.0 mo (15.9-NE) in pts ≥26 y (n=63). Median OS (95% CI) in pts with 1 prior therapy (n=15) was 60.4 mo (7.6-NE) and was 25.4 mo (15.9-47.0) in pts with ≥2 prior therapies (n=63). Medians for OS (95% CI) in pts with (n=38) and without (n=40) prior blinatumomab (blina) were 15.9 (8.3-26.0) and 60.4 mo (18.6-NE), respectively. Median OS (95% CI) was 36.3 mo (10.2-NE) in responders who went on to sub alloSCT (n=14) and 60.4 mo (23.2-NE) in those who did not (n=43). The 48-mo OS rate was 40% (95% CI, 28-52) in all pts but appeared lower in pts with prior blina (24%; Table). No new adverse events or deaths occurred since the prior analysis. Grade ≥3 infection rates since the start of study appeared higher in pts &lt;26 y and in pts with prior blina (Table). Rates of non-relapse mortality (NRM) and relapse-related mortality (95% CI) at 48 mo were 25% (15-37) and 34% (24-45; N=78), respectively. Of note, 6/17 NRM events (35%) occurred in pts with sub alloSCT. Conclusions: After &gt;4 y follow-up, pts in ZUMA-3 continued to experience OS benefit regardless of age, prior therapy, or sub alloSCT status, though pts with prior blina had a numerically lower 48-mo OS rate. Small subgroups and unbalanced pt characteristics limit interpretation of these results. No new safety signals were observed. Further studies are needed to fully assess the impact of age, prior therapies, and sub alloSCT on outcomes after brexu-cel. Clinical trial information: NCT02614066 . [Table: see text]

Domain-Specific Physical Activity and Stroke in Sweden

Associations of domain-specific physical activity with stroke incidence and poststroke outcomes have not been extensively studied using long-term, population-based data. To investigate associations of leisure time, work time, transport, and household physical activity with stroke incidence and death or dependency in activities of daily living (ADL) 3 months after stroke. The prospective, population-based Interplay Between Genetic Susceptibility and External Factors (INTERGENE) cohort study was conducted among a random sample of individuals from an urban-rural area covering western Sweden; 3614 individuals aged 24 to 77 years were examined in 2001 to 2004, and 1394 individuals were reexamined in 2014 to 2016. The median (range) follow-up was 20.0 years (56 days to 21.9 years). Data were analyzed from September through October 2023. Physical activity levels were self-reported for leisure time, work time, transportation, and household domains. The mean number of steps taken over a 6-day period was collected in a subgroup of participants using a sealed pedometer. Follow-up for stroke incidence and mortality rates continued until December 31, 2022. The composite outcome of death or ADL dependency was assessed at 3 months after stroke. Among 3614 individuals (mean [SD] age, 51.4 [13.1] years; 1910 female [52.9%]); 269 individuals (7.4%) developed stroke, of whom 120 individuals (44.6%) were dead or ADL dependent at 3 months. Intermediate (adjusted hazard ratio [aHR], 0.54; 95% CI, 0.38-0.77) and high (aHR, 0.47; 95% CI, 0.31-0.73) levels of leisure time physical activity were associated with a reduced incidence of stroke compared with low levels, as was an intermediate level of physical activity in transportation (aHR, 0.69; 95% CI, 0.52-0.93). High levels of leisure time physical activity were also associated with a reduced risk of poststroke death or ADL dependency (adjusted odds ratio, 0.34; 95% CI, 0.16-0.71) compared with low levels. Work time and household physical activity were not associated with stroke incidence or stroke outcomes. In exploratory subgroup analyses, there were interactions between physical activity and smoking (current smoking or smoking in the past year associated with stroke risk only in participants with low or intermediate physical activity: aHR, 2.33; 95% CI, 1.72-3.15) and family history of stroke (first-degree relative with a history of stroke associated with stroke risk only in participants with low or intermediate physical activity: aHR, 1.73; 95% CI, 1.27-2.38). In this study, leisure time and transport-related physical activities were associated with a reduced risk of stroke. A high level of leisure time physical activity was also associated with a lower risk of death or ADL dependency 3 months after stroke.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects

Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. ClinicalTrials.gov Identifier: NCT02133573.