Specific Subgroups Research Articles

Disparities in stage of diagnosis of colon cancer: Differences by Hispanic background, race, and ethnicity.

24 Background: Given noted heterogeneity in Hispanic adults, cancer outcomes reported in aggregate may not detect disparities within specific Hispanic subgroups. The objective was to assess whether any potential differences in colon cancer (CC) stage at diagnosis among patients with Hispanic background (HBackground) could be explained by differences in socio-economic determinants of health (SDOH) including income, education and insurance status. Methods: The National Cancer Database was queried for patients diagnosed with CC from 2004 to 2021. Two logistic regression models generated adjusted odds ratios of late-stage (III-IV) vs early-stage (I-II) CC at diagnosis, disaggregated either by HBackground or R&E, compared to non-Hispanic White (NHW) patients. Model 1 controlled for patient/facility characteristics; Model 2 controlled for additional SDOH. Results: Of the 442,742 CC patients identified, 6% were Hispanics. Compared to NH adults, Hispanic patients were more likely (6% higher odds, p<0.0001) to present with late-stage CC. When Hispanic patients were disaggregated by HBackground, some were more likely (Mexicans 16%; Cubans 20% and South/Central Americans 12%) than NHW adults to present with late-stage CC while others (Puerto Ricans and Dominicans) were not. Disaggregation by R&E indicated that only Hispanic-White patients were more likely (12%) to present with late-stage disease than NHW patients. Controlling for SDOH, R&E differences in stage at diagnosis persisted but HBackground differences became insignificant (Table). Conclusions: Disaggregation of Hispanic adults by HBackground identifies specific subgroups at increased risk for late-stage CC at diagnosis. Understanding modifiable SDOH may identify opportunities for improving early detection of CC and outcomes in specific Hispanic subgroups. Odds of presenting with late-stage colon cancer of “Hispanic” patients disaggregated by race and ethnicity or Hispanic background compared to non-Hispanic Whites. Disaggregation based on: Model 1: Adjusted for age, facility type, year of diagnosis, and Charlson-Deyo comorbidity Model 2: Adjusted for age, facility type, year of diagnosis, Charlson-Deyo comorbidity, neighborhood income, neighborhood education, and insurance status aOR (95% CI) p-value aOR (95% CI) p-value Non-Hispanic White (n=418,046) (ref) (ref) Hispanic White (n=24,058) 1.12 (1.09, 1.15) <.0001 1.04 (1.01, 1.07) 0.01 Hispanic Background Mexican (n=3,612) 1.16 (1.08, 1.24) <.0001 1.05 (0.97, 1.13) 0.25 South/Central American (n= 1,734) 1.12 (1.02, 1.24) 0.02 1.01 (0.91, 1.12) 0.83 Cuban (n=937) 1.20 (1.05, 1.36) 0.001 1.11 (0.97, 1.27) 0.13 Puerto Rican (n=1,280) 1.07 (0.95, 1.19) 0.28 1.01 (0.90, 1.14) 0.88 Dominican (n=465) 1.14 (0.94, 1.39) 0.18 1.02 (0.83, 1.25) 0.85 aOR, Adjusted odds ratio; CI, confidence Interval.

Associations between prenatal exposure to PFAS and cardiometabolic health in preadolescents.

While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration. This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France). Nine PFAS were measured in umbilical cord blood, and the children attended a clinical examination at age 12. Anthropometry, blood metabolic markers, and blood pressure were measured and used to build an internal cardiometabolic score. Linear regression and Quantile G-computation models were used to evaluate individual and mixture PFAS effects, adjusting for confounders and stratifying by sex and pubertal stage. No statistically significant association was observed between prenatal exposure to PFAS and cardiometabolic score at age 12. In post-menarche girls, perfluorohexane sulfonate (PFHxS) and perfluorodecanoic acid (PFDA) were statistically significantly associated with a decrease in a number of adiposity parameters (e.g., Body mass index z-score: beta [95%CI]=-0.37 [-0.67; -0.07]), as well as a decrease in low-density lipoproteins (LDL) and leptin levels. Similar results were observed with PFAS mixture, with statistically significantly decreased tricipital skinfolds (beta [95%CI]=-1.30 [(-2.54;-0.06)]). Isolated associations, including higher systolic blood pressure, changes in cholesterol levels, and lower adiponectin levels were observed in specific subgroups. There is no clear evidence of an association between prenatal exposure to PFAS and the cardiometabolic health at earlier stage of pubertal development. However, inverse associations between PFAS and anthropometric measures have been observed in post-menarche girls. While the literature on this topic is scarce in pre-adolescents, these results suggest the importance of considering sex and pubertal stage in these associations.

Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigated. To assess the beneficial impact of SGLT2 inhibitors on VAs in patients at various stages of HF, a systematic review and meta-analysis of randomized controlled trials involving SGLT2 inhibitors in this patient population was performed.MethodsA comprehensive search of the PubMed, Embase, Ovid, ProQuest, Scopus, and Cochrane databases was performed for clinical trials published up to November 21, 2024. The primary outcomes of interest were incidences of VAs and sudden cardiac death (SCD) between the groups receiving SGLT2 inhibitors and the control drugs. For the outcomes observed in the populations of the included trials and in specific subgroups, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled and meta-analysed across the analyses.ResultsA total of 23 randomized trials (22 placebo-controlled trials and 1 active-controlled trial) involving 74,380 patients (37,372 receiving SGLT2 inhibitors and 37,008 in the control group) were included. The analysed SGLT2 inhibitors included canagliflozin, dapagliflozin, empagliflozin, bexagliflozin, sotagliflozin, and ertugliflozin. The participants were non-advanced HF patients, including at-risk for HF, pre-HF, and symptomatic HF, with follow-up duration ranging from 12 to 296 weeks. Compared with the control, treatment with SGLT2 inhibitors was associated with significantly reduced risk of VAs (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74–0.98; P = 0.02) and SCD (RR 0.79, 95% CI 0.64–0.98; P = 0.03). Subgroup analyses indicated that longer follow-up (≥ 1 year) taking SGLT2 inhibitors can still reduce the risk of VAs (RR 0.79, 95% CI 0.65–0.96; P = 0.02) and SCD (RR 0.80, 95% CI 0.65–0.99; P = 0.04).ConclusionSGLT2 inhibitors have beneficial effects on lowering risks of VAs and SCD in patients with type 2 diabetes, cardiovascular diseases, heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mildly reduced ejection fraction (HFmrEF), with longer follow-up duration reinforcing these findings. However, future prospective trials are needed to verify the effects of SGLT2 inhibitors on VAs and SCD.Systematic review registrationPROSPERO (CRD42024601914)

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of infertility among US adults: A cross-sectional NHANES study.

Infertility affects millions worldwide, with a significant proportion of cases remaining unexplained. Recent evidence suggests a potential link between lipid metabolism and reproductive health, prompting investigations into novel biomarkers like the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) for assessing infertility risk. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional analysis of 5,524 women aged 20-45 in the United States. NHHR was calculated from lipid profiles, and infertility was determined via the Reproductive Health Questionnaire. Multivariate logistic regression and restricted cubic spline (RCS) analyses were performed to examine the relationship between NHHR and infertility, adjusting for confounding factors such as age, BMI (body mass index), and lifestyle habits. The study found a nonlinear association between NHHR and infertility risk, with the risk peaking in the second and third quartiles of NHHR levels. Notably, women in the higher NHHR quartiles exhibited a 2.15 to 2.36 odds ratio for infertility compared to those in the lowest quartile, suggesting a significant increase in risk. Subgroup analyses revealed that this association was particularly strong in younger women and those with a higher BMI. Moreover, the RCS analysis confirmed the nonlinear pattern of the relationship, highlighting a more pronounced risk at moderate NHHR levels, which plateaued or varied at higher levels. The interaction analyses further suggested that the relationship between NHHR and infertility risk could be influenced by age and BMI, pointing to differential effects in various subpopulations. Elevated NHHR levels are associated with increased infertility risk, especially in specific subgroups, suggesting a complex link between lipid metabolism and reproductive health. Further research is needed to validate these findings and explore the potential of NHHR as a biomarker for infertility risk.

Selecting systemic treatment for metastatic neuroendocrine tumors of the lung-current evidence and clinical implications.

Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC). Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT). However, there is no clear treatment sequence, and the therapy of choice may depend on several factors such as tumor grade / growth rate, tumor burden / symptoms, disease progression status, and somatostatin receptor (SSTR) expression. In order to tailor treatment to each individual patient, the latest scientific findings and patient-specific clinical features must be considered together. This review critically evaluates the available evidence with regards to relevant patient characteristics, inclusion and exclusion criteria, and outcome metrics of clinical trials given the presumed natural disease course. Specific patient subgroups with an unmet therapeutic need are identified and discussed in the context of ongoing clinical trials.

Risk of peritoneal recurrence following laparoscopic versus open surgery for stage II or III colorectal cancer (JCOG2310A): An integrated analysis of three phase III randomized controlled trials.

161 Background: Peritoneal recurrence in colorectal cancer (CRC) has long been a concern. Although studies have examined the higher risk of peritoneal recurrence following laparoscopic (LAP) compared with open (OP) surgery, the issue remains unresolved, largely due to the heterogeneity of existing data and the limited number of observed peritoneal recurrence events, preventing any definitive conclusions. This study aimed to evaluate whether LAP for pStage II/III CRC presents a potential risk factor for peritoneal recurrence compared with OP. Methods: Data from three phase III trials (JCOG0404, JCOG0910, JCOG1006) were extracted from an ancillary research database (JCOG2310A). From this cohort, patients with pStage II or III CRC who underwent curative surgery were included, and the incidence of peritoneal recurrence was compared between LAP and OP. A multivariate analysis was conducted to adjust covariates between the two groups. The primary outcome was the cumulative incidence of peritoneal recurrence, and the secondary outcome was recurrence in specific high-risk subgroups identified through a univariate analysis. Results: From 3061 patients (OP: 1734; LAP: 1327), pT4 (25% vs. 17%), pStage III (65% vs. 83%), and right-sided tumor (63% vs. 70%) were different between OP and LAP, respectively. With a median follow-up for peritoneal recurrence of 6.2 years, the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 2.9% in the LAP group (hazard ratio (HR): 0.940, 95% confidence interval (CI): 0.621-1.425 in the univariate analysis, and HR: 1.086, 95% CI: 0.683-1.727 in the multivariate analysis. The univariate analysis identified pT4, pN2, pStage III, right-sided tumor, poorly differentiated (por/sig/muc), and ECOG-PS 1 as risk factors for peritoneal recurrence. No significant difference was observed in the subgroups (see table). An exploratory propensity score matching analysis with 1066 patients in each group also showed no difference between the groups (the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 3.0% in the LAP group [HR: 1.002, 95% CI: 0.625-1.607]). Conclusions: This study revealed that LAP was not a risk factor regarding peritoneal recurrence following curative surgery for Stage II/III CRC. Subgroup analysis of cumulative incidence of peritoneal recurrence. OutcomeMeasures Subgroups pT4 pN2 pStage III Right-sided Poorly differentiated ECOG PS 1 N(OP vs. LAP) 428 vs. 229 274 vs. 184 1133 vs. 1105 635 vs. 403 122 vs. 66 56 vs. 25 Event(OP vs. LAP) 31 vs. 23 13 vs. 10 45 vs. 32 28 vs. 18 10 vs. 2 7 vs. 2 5-year peritoneal recurrence rate (OP vs. LAP)(%) 6.8 vs. 10.1 4.8 vs. 5.4 3.6 vs. 2.9 4.1 vs. 4.5 7.5 vs. 3.0 9.1 vs. 8.0 HR (95% CI) 1.403(0.819-2.402) 1.144(0.503-2.603) 0.725(0.461-1.139) 1.014(0.562-1.829) 0.372(0.081-1.699) 0.609(0.130-2.862)

Age estimation by radiomics analysis of mandibular condylar cone beam computed tomography images.

The aim of this study was to estimate the legal age using the parameters obtained from radiomic analysis of the mandibular condyle in cone beam computed tomography (CBCT) images. The study group consisted of 300 mandibular condyles, which were categorized into six groups based on the age of the patients: 8-11years, 12-14years, 15-17years, 18-20years, 21-23years, and over 24years. Each patient's condyle was segmented individually using the 3D Slicer program. Radiomic features were extracted from the segmented images using the SlicerRadiomics plugin. Subsequently, three distinct models were developed with reference to three specific subgroups of the 12-14 age group, 15-17 age group, 18-20 age group and the efficacy of radiomic features in predicting the age of the patient was evaluated. The ROC analysis of the three radiomics scores (RS) yielded AUC values of 0.927, 0.860, and 0.769 for RS12-14, RS15-17, and RS18-20, respectively. The RS12-14 model exhibited the highest sensitivity and specificity values among the models, with 88% and 84.4%, respectively. Among the radiomic features extracted from the mandibular condyle in CBCT images, the most significant features, identified based on developed models and their respective coefficients, can be applied to estimate patients' ages. Future studies hold substantial potential for advancing this method, particularly in automating both the segmentation process and the derivation of formulae for age estimation. The use of radiomic features for age prediction presents a promising alternative method for developing fully automated systems in clinical practice.

Policies, programmes and research on adolescent and youth sexual and reproductive health in South Sudan: a systematic scoping review

ObjectivesTo provide an overview of research, policies and programmes related to the sexual and reproductive health (SRH) needs of adolescents and youth (AY) in South Sudan in order to identify...

P-1211. Early Infections Predict Weight Gain and Obesity in US Children

Abstract Background An unexplained link between early viral infection and later weight gain has been observed in the US and internationally. In our population of children at Kaiser Permanente Southern California, we seek to confirm this association and determine the magnitude of the absolute weight increase. Methods In a retrospective cohort of children born 2008 – 2012, frequency of infection in infancy (≤12m), timing of first infection (< 6m vs 6-12m), and antibiotic use, class, timing, and frequency were assessed relative to absolute weight and body mass index (BMI) at age 4-6 and 10 years. Patients with low birthweight and prematurity were excluded. Maternal BMI, breastfeeding, birthweight, delivery type, and race/ethnicity were included in multivariable regression; height was also included when absolute weight was the outcome variable. Weight outcomes were compared in uninfected vs infected without antibiotic treatment in infancy (IWOT); and IWOT vs those infected who received antibiotic treatment (IWAT), using logistic regression analysis for obesity outcomes and linear regression for absolute weight. Results We identified N=66,687 children at 4-6y and N= 46,462 at 10y for analysis. Of the latter, 7,918 had been uninfected, 18,144 had IWOT, and 20,400 had IWAT. The IWOT group had higher rates of obesity vs uninfected (24% vs 19% at 10y; see figure 1), reflected in multivariable analysis at 4-6y (OR 1.11 [1.03-1.2]; p=0.004) and 10y (OR 1.14 [1.06-1.22]; p < 0.001), in a "dose-dependent" manner (Figure 2). The corresponding absolute weight increase (+0.55 kg [+0.3-0.8] at 10y; p< 0.001) was also dose-dependent (Figure 3). Compared to untreated infections, the additional contribution of antibiotic use to future obesity was minimal (OR 1.05 [0.99-1.1]; p=0.09) and not dose-dependent. Of the 10 year olds, most had upper respiratory infections (27,562 patients had at least one URI; 59%), ear infections (16,404 patients; 35%), or infections without a specified site (including viral syndromes; 11,822; 25%) in infancy. Conclusion A significant (14% at 10y) increase in obesity after early infection is confirmed, with a small (+0.55kg) corresponding increase in average weight. Prospective study in specific subgroups or with specific viruses of interest would be warranted. Disclosures All Authors: No reported disclosures

The disparities of PrEP adherence among men who have sex with men between the Global South and the Global North: An updated determinantal global meta-analysis.

Suboptimal adherence to PrEP limits its global impact, with current evidence mostly from the Global North and lacking Global South perspectives. This meta-analysis synthesises the rates and determinants of suboptimal adherence to oral PrEP among MSM in both regions. We searched for literature describing PrEP adherence and its determinants among MSM globally up until October 2024 to conduct a meta-analysis on the rate and determinants of suboptimal adherence in both regions. The definition of (sub-)optimal adherence were study-based. We included 82 studies in the meta-analysis, with 24, 53, and 5 stemmed from the Global South, North, and global multicentre studies, respectively. Oral PrEP suboptimal adherence is prevalent among MSM PrEP-users globally (rate=0.33, 95%CI:0.28-0.38) with a significantly higher rate (p=0.021) in the Global South (rate=0.41, 95%CI:0.33-0.50) compared to the Global North (rate=0.29, 95%CI:0.23-0.35). In the Global South, older age (OR=0.57, 95%CI:0.37-0.87), alcohol use (OR=1.28, 95%CI:1.02-1.60) and presenting depressive symptoms (OR=1.47, 95%CI:1.01-2.16) were associated with suboptimal adherence. In the Global North, MSM self-identified as Black (OR=2.27, 95%CI:1.31-3.95) or Other (OR=1.36, 95%CI:1.02-1.81), having a university degree (OR=0.50, 95%CI:0.34-0.73), and presenting depressive symptoms (OR=2.26, 95%CI:1.35-3.78) were associated with suboptimal adherence. On-demand PrEP-users globally demonstrated a higher likelihood of suboptimal adherence (OR=1.59, 95%CI:1.18-2.14). Suboptimal adherence to oral PrEP is prevalent among MSM globally, particularly higher in the Global South. Regional differences in determinants highlight the need for tailored interventions. Tailored interventions are required to address mental health with tailored efforts to younger MSM in the Global South, while interventions in the Global North should be tailored to specific sub-groups.

P-1691. Palliative medicine consultation does not reduce antimicrobial use during end-of-life care

Abstract Background The role of antimicrobial drugs in end-of-life (EOL) care is uncertain, with the potential palliative benefit of antimicrobials in some settings being outweighed by potential limited benefit and added toxicity. In this study, we aimed to analyze the roles of palliative care consultation and code status change on antimicrobial prescribing practices at the EOL. We hypothesized that palliative medicine consultation (PMC) reduces antimicrobial use in patients receiving EOL care. Methods This was a retrospective cohort study conducted on adult patients who were admitted to Wake Forest Baptist Health facilities between January-December 2019 and who were either transitioned to comfort care or discharged to hospice. Patients were stratified based on the presence or absence of PMC during their hospitalization. The primary outcome was the mean days of therapy (DOT) per patient before and after EOL care. DOTs were defined as a calendar day when a single systemic antimicrobial was administered. Antimicrobials given topically or prescribed solely for Pneumocystis or herpesvirus prophylaxis were excluded. Results A total of 2242 patients were identified, of whom 621 received PM consultation during their hospitalization. Among those receiving PMC, there were a total of 3301 days of hospitalization and 4560 DOTs prior to the transition to EOL care, for a mean DOT/hospital day of 1.38 (95% CI 1.34-1.42). There were 6,563 hospital days and 11,466 DOTs among the non-PMC group, for a mean DOT/hospital day of 1.75 (1.72-1.78). Following transition to EOL care, antimicrobial use decreased rapidly, with 0.087 DOTs/hospital day in the PMC group (0.077-0.097) and 0.051 DOTs/hospital day (0.044-0.056) in the non-PMC group. Conclusion In this observational study, antimicrobial drug use decreased markedly in patients transitioning to EOL care. However, the rate of antimicrobial use in EOL patients was not reduced by PMC and was greater than in those patients not receiving PMC, although this difference was not clinically substantial. Antimicrobial use was infrequent in EOL patients in our cohort. Future studies should evaluate the palliative benefit of antimicrobials in specific subgroups of patients receiving EOL care. Disclosures Ryan C. Maves, MD, AiCuris: Grant/Research Support|Biotest: Grant/Research Support|GeoVax: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Sound Pharmaceuticals: Grant/Research Support

P-226. Assessing the Risk Factors for Catheter Related Bloodstream Infections (CRBSI) among Cancer Patients with Long Term Central Venous Catheters (LCVC) for Implementing Preventive Interventions

Abstract Background Catheter Related Bloodstream Infection (CRBSI) remains a leading cause of morbidity, mortality, and escalating costs in cancer patients with LCVC despite advancements in medical care and the implementation of BSI bundle. Several risk related studies have been published in cancer patients but did not include strict definition of CRBSI and relied on Central Line-Associated Blood Stream Infections (CLABSI) definitions in the setting of Mucosal Barrier Injuries (MBI) which might be emerging from the gut rather than the catheter. Our study aims at determining specific subgroups of cancer patients who are most susceptible for CRBSIs to determine the potential effectiveness of preventive interventions such as catheter locks. Independent predictors of CRBSI by multivariate logistic regression analysis Methods We retrospectively reviewed cancer patients with indwelling LCVC that remained in place for at least 3 weeks between 2018 and 2022. By simple random sampling, we compared 200 patients who developed a definite CRBSI to 400 patients who did not. A definite CRBSI was defined according to the stringent criteria by the Infectious Diseases Society of America. Results Among cancer patients with CRBSI, 82% had hematological malignancy. Over 50% of the catheters had 2 lumens. Patients with CRBSI were more likely to receive blood products through the catheter (81% vs 45%, p< 0.0001). The median time from catheter insertion to CRBSI was 51 days. Of the identified pathogens causing CRBSI, 62% were gram positive bacteria, 37% gram negative bacteria and 2% candida. By multivariate logistic regression analysis, the leading independent significant risk factors were the presence of multiple catheters in place, neutropenia, allogeneic transplants, followed by blood product administration, multiple catheters inserted within the past year, and basilic site insertion (table 1). Conclusion Cancer patients with LCVC are susceptible to CRBSI, particularly those who are neutropenic, had allogeneic transplants, have multiple catheters, received blood products, or had basilic site insertion. Effective preventive interventions such as antimicrobial locks and antimicrobial catheters with prolonged activity should be primarily implemented in these highest risk populations. Disclosures All Authors: No reported disclosures

Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation

BackgroundOsteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It is notorious for its high invasiveness, high disability rate, high mortality rate, and poor prognosis. In most primary and metastatic malignant tumors, bone destruction can promote cancer progression, which is closely related to osteoclast activation and the imbalance between osteoblasts and osteoclasts. A large number of studies confirmed that osteoclasts are an important part of OS, which play an active role in destroying bone homeostasis and promoting the progress of OS. Therefore, we conducted a detailed study of osteoclasts at the single cell level, aiming to find new OS therapeutic targets to prevent tumor progression and local spread.MethodsWe analyzed the single-cell sequencing data of OS patients and usedMonocle2, Cytotrace, and Slingshot software to analyze the pseudo-sequential trajectory during OS progression. CellChat was used to reveal the communication between cells. PySCENIC was used to identify active transcription factors in osteoclasts. Finally, we further demonstrated the results by RT-qPCR analysis, CCK-8 assay, wound healing assay, Transwell assay, etc.ResultsThrough the analysis of single-cell sequencing data in OS, we identified a highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP and the top 1 transcription factor PPARG in this subgroup played essential roles in osteoclast proliferation and differentiation. Given the pivotal role of osteoclasts in OS progression, we speculated that these signaling pathways and transcription factors could emerge as novel therapeutic targets, offering innovative strategies for OS treatment.ConclusionThis study enhanced our understanding of OS and osteoclasts through scRNA-seq. Furthermore, we discovered that PPARG amplifies osteoclast activation and proliferation, resulting in excessive bone resorption and degradation of the bone matrix, thereby creating a favorable environment for tumor cell proliferation and growth. By innovatively targeting PPARG, it affected osteoclast proliferation and thus affected tumor progression; this work offered new insights and directions for the clinical treatment of OS patients.

To Ask or Not to Ask: The Effects of Broadly and Narrowly Adopted Peer-Recognition Systems on Help Seeking

Many companies now use peer-recognition systems that allow employees to publicly recognize their peers for positive behaviors. Practitioners have touted the potential for these systems to increase helping among employees. However, the extent to which employees actually use these systems to recognize their peers varies across organizations; some are used broadly by many employees across all functional, specialty, geographic, and hierarchical subgroups of the organization, whereas others are only narrowly used by some, but not all, subgroups. Across three experiments, we examine how peer-recognition systems impact employees’ propensity to ask others for help (i.e., help seeking) based on whether the system is broadly used by all subgroups or only narrowly used by specific subgroups. We predict and find that a peer-recognition system broadly used by all subgroups strengthens employees’ perception of a help-seeking norm. This perception increases employees’ propensity to seek help directly through norm conformity and indirectly by reducing the perceived psychological costs of help seeking. We also predict and find that the effect of peer-recognition systems that are narrowly used by specific subgroups is moderated by whether employees belong to the subgroups using the system; whereas it increases help-seeking propensity for members of the subgroups using the system, it decreases help-seeking propensity for nonmembers relative to when there is no peer-recognition system. Our theory and results suggest that peer-recognition systems can increase help seeking, but these same systems could decrease help seeking for employees belonging to subgroups that do not use the system. This paper was accepted by Ranjani Krishnan, accounting. Funding: Supported by the University of Illinois at Urbana-Champaign; Indiana University. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.00318 .

Assessing Primary Prevention Programs for Intimate Partner Violence: A Review of Contemporary Approaches

A systematic review of primary prevention programs for intimate partner violence (IPV) was conducted. Inclusion criteria for studies included publication in a peer-reviewed journal, a representative, community, or clinical sample, written in English, and conducted in the United States. A total of 24 articles were included. All studies included some kind of intervention, such as knowledge and/or behavioral, to change outcomes in IPV perpetration and/or victimization. Of the 24 studies, 16 used experimental designs, with the majority focused on adolescent samples (n= 14). The majority of studies used a group modality. Several prevention programs were adapted for specific subgroups (i.e., refugees) with promising outcomes for preventing IPV. While the majority of research reviewed suggests some reduction in IPV, the field still yields mixed results. Research does point toward the importance of adapting or creating prevention programs specifically for marginalized or vulnerable subgroups. Comparisons to a prior review highlight developments in this body of research over the past 10 years. Recommendations for intervention and policy with future directions for IPV research are discussed.

Borderline Phyllodes Breast Tumors: A Comprehensive Review of Recurrence, Histopathological Characteristics, and Treatment Modalities

Phyllodes tumors account for 2–3% of all fibroepithelial breast tumors and less than 1% of all breast cancers. These tumors are categorized into benign, borderline, or malignant based on cellular atypia, mitotic activity, and stromal overgrowth. Surgical excision with clear margins, ideally greater than 1 cm, is the primary treatment for phyllodes tumors to ensure effective local control. Preoperative diagnosis is challenging due to the clinical and radiological similarities between phyllodes tumors and fibroadenomas. The efficacy and role of adjuvant treatments remain subjects of ongoing debate and investigation. Borderline phyllodes tumors exhibit biological characteristics that straddle the line between benign and malignant, presenting significant clinical and surgical management challenges. Given the rarity of this specific subgroup and the ambiguity of the risk of recurrence or progression to malignant phyllodes, this narrative review aims to provide a comprehensive overview of the recurrence risk associated with these tumors.

Survival disparities among Asian, Native Hawaiian and Pacific Islander (ANHPI) patients with non-Hodgkin lymphoma (NHL) in the United States.

Non-Hodgkin lymphoma (NHL) is the seventh most common cancer among Asian, Native Hawaiian and Pacific Islanders (ANHPIs), yet the risk of death in specific ANHPI subgroups in the US is unknown. We used Surveillance, Epidemiology, and End Results data to investigate relative survival and the risk of death among NHL patients in ANHPI subgroups. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI), comparing ANHPI subgroups to non-Hispanic White (NHW) NHL patients for all-cause death and NHL-specific death. Prognostic factors were further estimated within each ANHPI subgroup. We identified 4,513 East Asian, 4,034 Southeast Asian, 1,052 South Asian, 674 Native Hawaiian and Pacific Islander (NHPI), and 116,922 NHW patients with NHL. Compared to NHW patients, East Asian, Southeast Asian, and NHPI patients had a lower 5-year relative survival. The risk of 5-year all-cause death was 1.10-fold higher for East Asian patients (95% CI 1.04, 1.15), 1.34-fold higher for Southeast Asian patients (95% CI 1.27, 1.41), and 1.62-fold higher for NHPI patients (95% CI 1.43, 1.83) compared to NHW patients. Potential prognostic factors among ANHPI NHL patients included older age at cancer diagnosis, non-married status, advanced cancer stage, and a diagnosis of DLBCL or T-cell lymphoma. Our study revealed significant disparities in survival among ANHPI patients with NHL, particularly among East Asian, Southeast Asian, and NHPI patients. Addressing these disparities calls for the implementation of preventive strategies and interventions tailored specifically to ANHPI subgroups. Further studies are imperative to explore adverse health outcomes within these ANHPI subgroups.

Longitudinal analysis of in-hospital cardiac arrest: trends in the incidence, mortality, and long-term survival of a nationwide cohort

BackgroundIn-hospital cardiac arrest (IHCA) poses a considerable threat to hospitalized patients, leading to high mortality rates and severe neurological deficits among survivors. Despite the advancements in resuscitation practices, the prognosis of IHCA remains poor, and comprehensive studies exploring nationwide trends and long-term survival are scarce, particularly in the Asian populations.MethodsUtilizing data from the Taiwan National Health Insurance Research Database, we conducted a nationwide cohort study to analyze the IHCA events among adult patients between 2003 and 2020. The outcomes of interest in this study included the temporal trend in the IHCA incidence, in-hospital mortality, and median survival after discharge for overall hospitalizations.ResultsOver the 18-year period, the IHCA incidence in Taiwan declined by 70%, from an annual incidence of 7.1 per 1,000 admissions to a lower rate in 2020, accompanied by a 14% reduction in the in-hospital mortality rate, with an average of 86.5%. The overall long-term survival rate for discharged survivors was 63.9%. We observed a substantial 125% increase in the median survival duration of discharged survivors, rising from 1.56 years in 2003 to 3.51 years in 2015. Favorable in-hospital survival rates and extended life expectancy were notably seen in the patients with shockable rhythms, those with a cardiac primary diagnosis, women, and younger patients.ConclusionsOur study data revealed significant declines in the IHCA incidence and in-hospital mortality in Taiwan, along with improved long-term survival among survivors, particularly among specific subgroups. Women exhibited significantly better long-term survival as compared to men, underscoring the need to avoid sex-based treatment biases. Improvements in discharge survival rates and life expectancy were less pronounced in older survivors, indicating that age alone may not be sufficient to guide IHCA management decisions. Proactive resuscitation should be carefully considered for older patients, particularly those with mild frailty and potentially reversible conditions.Trial registration the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (Registration number: 202301625B0, Registered 7 November 2023)

Differential Risk Profiles of Incident Abdominal Aortic Aneurysms in Specific Subgroups: A Large Cohort-based Study.

The aim of this study is to explore the risk profiles associated with Abdominal aortic aneurysm (AAA) incidence in both the general population and diverse subpopulations. AAA is a life-threatening arterial disease, and there is limited understanding of its etiological spectrum across the age, sex, and genetic risk subgroups, making early prevention efforts more complicated. This study encompassed a sample size of 364399 participants from the UK. Utilizing the Cox proportional hazards model, we estimated the hazard ratios (HRs) and population attributable fraction (PAF) for 24 risk factors and 5 weighted risk scores associated with AAA incidence. Subsequently, this study investigated the relationships between AAA onset and various risk factors based on age, sex, and genetic susceptibility subgroups, and assessed the two- and three-way interactions. After a median follow-up of 12.62 years, 1684 participants developed AAA. Among the 24 risk factors from 5 different aspects, 12 exhibited significant associations with AAA development. Socio-demographic factors (age and sex) and genetic factors accounted for the majority of AAA cases in both the general population and diverse subpopulations. For lifestyle factors, AAA cases attributable to smoking are larger in the older group (PAF: 15.45% vs. 11.25%) and women (PAF: 23.79% vs. 16.75%). Similarly, physical inactivity had a greater effect on AAA risk in women (4.84% vs. 1.95%), but no age and genetic risk differences were observed. PAF of high C-reactive protein was the most prominent of all cardiometabolic factors across different age, sex, and genetic risk strata, with 18.92% (< 60 years) and 13.71% (≥ 60 years) in age groups, 18.18% (women) and 13.31% (men) in sex groups, and 17.64% (intermediate genetic risk) and 13.01% (high genetic risk) in genetic risk groups. Clinical comorbidities, such as cardiovascular diseases, dyslipidemia, and hypertension significantly associated with the risk of incident AAA, and these factors exerted a greater influence on AAA risk in younger group, women, and those with low genetic risk (P for interaction < 0.05). This study depicted specific risk profiles that influence AAA incidence among general population and diverse subpopulations, thereby aiding in the formulation of precise and effective strategies for AAA prevention.

Early Invasive versus Conservative Strategies in Cardiogenic Shock: A Meta-Analysis

Cardiogenic shock (CS) carries a high mortality rate. While early invasive strategies (EIS) like percutaneous coronary intervention (PCI) are often advocated, their superiority over conservative strategies (CS) remains debated. This meta-analysis compared the efficacy and safety of EIS versus CS in patients with CS. A systematic search of PubMed, Embase, and the Cochrane Library was conducted from January 2013 to December 2024. Randomized controlled trials (RCTs) and observational studies comparing EIS (early PCI, mechanical circulatory support) with CS (initial medical therapy) in adult CS patients were included. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included in-hospital mortality, stroke, major bleeding, and acute kidney injury. A random-effects model was used to pool data. Nine studies (n=4,875 patients) were included. EIS was associated with a significantly lower risk of 30-day mortality compared to CS (risk ratio [RR] 0.78; 95% confidence interval [CI] 0.65-0.93; p=0.006). Similarly, EIS reduced in-hospital mortality (RR 0.72; 95% CI 0.61-0.85; p=0.001). There was no significant difference in the incidence of stroke or major bleeding between the two groups. However, EIS was associated with a higher risk of acute kidney injury (RR 1.20; 95% CI 1.05-1.37; p=0.008). In conclusion, in patients with CS, EIS was associated with significantly lower 30-day and in-hospital mortality compared to CS. However, EIS may increase the risk of acute kidney injury. Further research is needed to identify specific patient subgroups that may benefit most from EIS.