Differences In Outcomes Research Articles

Belonging Interrupted: Toward an Understanding of How Virtual Learning Impedes Women Students’ Belonging in Engineering

AbstractAlthough the effects of COVID-19 were felt by all students, the pandemic exacerbated the barriers to belonging for women in engineering. Little work to date has investigated women’s experiences during the pandemic in disciplines that are hallmarked by masculinity. What scholarship has been completed on pandemic-necessitated virtual instruction has not examined how women’s experiences and sense of belonging differed by the college year in which this disruption in their learning environment occurred. Utilizing data from seven focus groups conducted in March 2022 with 22 students, this study investigates how pandemic-induced virtual instruction is related to sense of belonging for women within their engineering majors. We found not only that the disruption caused by the pandemic had differential outcomes for students, but that these differences were mainly related to the year in which pandemic-induced virtual instruction occurred. This study highlights the importance of focusing on belonging and related issues as women transition into their major. We offer implications and recommendations for practice and research based on the differential outcomes found.

Sex-Related Differences in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex. This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P=0.014). Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as &amp;gt;5mm erythema &amp; induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having &amp;gt; grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Racial capitalism and COVID-19

The aim of this article is to revisit the racial disparities in health outcomes from COVID-19 and to problematize the overly simplified attribution of these numbers to race. This article calls for a deeper understanding of society’s wider economic arrangements in which these racial disparities are produced. It considers why a proposed public-policy measure that targeted racism—though without substantively accounting for the underlying form of capitalism through which it materializes—in an effort to remediate the differential health outcomes from COVID-19 between whites and racialized others was problematic and incomplete. Such an approach neither sufficiently accounted for structural conditions that led vulnerable racial minorities to develop comorbidities at a much higher rate than the local white population nor did it explain the labor market dynamics that resulted in vulnerable racial minorities being more likely to be employed in low-paid, frontline work as compared to white workers, which made the most effective way by which to avoid contracting the virus (i.e., physical distancing) all but impossible. This article finds that should the unsettling numbers related to the racial health disparities that unfolded during the pandemic be analyzed from a critical perspective, it would show how race is a cog in the machinery of neoliberalism, which culminates in racial capitalism. Specifically, racial capitalism fosters the economic stratification necessary to yield the consequences it had in terms of disparities in health outcomes from COVID-19. This article uses COVID-19 to illuminate how racism and capitalism function symbiotically to organize society, and responding to the former is perfunctory without interrogating the latter.

Abstract PO3-08-09: Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer

Abstract Background: Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer (BC) is associated with lower survival and higher risk of disease recurrence. A new subtype of HER2-low BC which has been proposed from several studies demonstrates that HER2-low patients have distinct somatically genetic alterations and clinical outcomes. We have previously reported that HER2-low BC had distinct clinical and somatic mutational feature compared with HER2-zero and HER2-high tumors. We have therefore extended studies by comparing germline mutation expression among these HER2 subgroups. Methods: 530 Chinese women with BC were enrolled in a prospective protocol between May 2021 to March 2023 at Guangdong Provincial People's Hospital. Genomics data was generated from a gene panel that surveys 102 tumor mutations. Germline variants were classified into pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB) and benign (B) groups according to the ACMG/AMP Standards and Guidelines. The cohort was divided into three groups based on HER2 status as HER2-zero (n = 107), HER2-low (n = 259), and HER2-high (n = 127) according to immunohistochemistry and/or fluorescence in situ hybridization results. Results: The most common mutated genes were ATM, FANCD2, ATR, BRACA2, RECQL4 and APC. A total of 71 pathogenic or likely pathogenic (P/LP) mutations were identified in 25 cancer susceptibility genes from 64 patients (12.16%). The most frequent mutated P/LP genes are BRCA2, BRCA1, PALB2, PMS2, MUTYH and PTEN in the HER2-low group; BRCA2, BRCA1 and PALB2 in the HER2-zero cohort; Interestingly, among the nine HER2-high patients, we detected unique P/LP genes in each sample including MRE11, FANCM, ATM, FLCN, NTRK1, TP53, BRCA1, CHEKE2 and FANCA. In addition to P/LP mutations, 751 variants of uncertain significance (VUS) in 95 cancer susceptibility genes were also detected in 361 patients (68.11%). The most frequent mutated VUS mutations occurred genes are FANCD2, ATM, RECQL4, RAD54B and ATR in HER2-low group; ATM, FANCA, POLE, MSH2 and FANCD2 in HER2-zero cohort; and ATM, BRCA2, RECQL4, POLE, FANCI and FANCM for HER2-high patients. Most of mutated genes were homologous recombination repair (HRR) or DNA damage repair (DDR) pathway related genes. Several genes were differentially altered across HER2 subgroups, including the mutation frequency of the BMPR1A (p=0.0344), MSH2 (p=0.0103), and RAD51C (p=0.0336) genes that were significantly higher in HER2-zero group. It’s worth noting that RAD51C was only mutated in HER2-zero subgroup. BMPR1A and MSH2 were also mutated in HER2-low patients. Differentially mutated genes in specific HER2 subgroups may contribute to better research and choice of future therapeutic approaches. In 115 patients who received neoadjuvant therapy and 84 of them were evaluable for pathological response data, HER2-low patients had lower pathological complete response (pCR) rates than HER2-zero and HER2-high subgroups (p=0.0008). In particular, DDR pathway gene ERCC1 have significantly higher mutation frequency in pCR patients (p=0.0115). Conclusion: HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting. Keywords: breast cancer, germline mutations, human epidermal growth factor receptor 2 (HER2), HER2-low, targeted therapy, next-generation sequencing Table 1. List of most frequent mutated genes in HER2-zero, HER2-low and HER2-high groups Citation Format: Ning Liao, Weiqi Zhang, Liangqiu Liu, Wendy Wu, Siqi Wang, Li Cao, Jianguo Lai, Xueying Zhang, Airong Yang, Yulei Wang, Cheukfai Li, Guochun Zhang, Chongyang Ren, Lingzhu Wen. Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-09.

Cultural dynamics influencing decision-making during the COVID-19 pandemic: the Italian case.

The COVID-19 pandemic has brought about significant changes to the life of most individuals, worldwide. This study explores the cultural factors influencing decision-making during the pandemic, and is part of the CORNER Project, funded by the Research Council of Norway, aimed at understanding institutional response in the early phases of the Covid-19 emergency in Norway, Sweden, and Italy. Semi-structured interviews with key political-administrative leaders in Italy (N = 35) were conducted and content-analyzed, allowing the identification of the underlying cultural dynamics that played a role in these decisions. Thematic analysis was used to assess the influence of cultural factors on the crisis management and early reaction of institutions and citizens to the spread of Covid. In line with previous studies, and as expected, the individualism vs. collectivism dimension can explain differential health outcomes during the outbreak. In this paper we argue that individualism-collectivism cultural values can also play a pivotal role in public compliance with Covid-19 restrictions, and psychological responses during the pandemic.

Infection risk reduction with povidone-iodine rectal disinfection prior to transrectal prostate biopsy: an updated systematic review and meta-analysis

BackgroundTo prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection using povidone-iodine (PI) and antibiotic prophylaxis (AP).ObjectiveTo summarize available data and compare the efficacy of rectal disinfection using PI with non-PI methods prior to TRUS-PB.Evidence acquisitionThree databases were queried through November 2023 for randomized controlled trials (RCTs) analyzing patients who underwent TRUS-PB. We compared the effectiveness of rectal disinfection between PI groups and non-PI groups with or without AP. The primary outcomes of interest were the rates of overall infectious complications, fever, and sepsis. Subgroups analyses were conducted to assess the differential outcomes in patients using fluoroquinolone groups compared to those using other antibiotics groups.Evidence synthesisWe included ten RCTs in the meta-analyses. The overall rates of infectious complications were significantly lower when rectal disinfection with PI was performed (RR 0.56, 95% CI 0.42–0.74, p < 0.001). Compared to AP monotherapy, the combination of AP and PI was associated with significantly lower risk of infectious complications (RR 0.54, 95% CI 0.40–0.73, p < 0.001) and fever (RR 0.47, 95% CI 0.30–0.75, p = 0.001), but not with sepsis (RR 0.49, 95% CI 0.23–1.04, p = 0.06). The use of fluoroquinolone antibiotics was associated with a lower risk of infectious complications and fever compared to non-FQ antibiotics.ConclusionRectal disinfection with PI significantly reduces the rates of infectious complications and fever in patients undergoing TRUS-PB. However, this approach does not show a significant impact on reducing the rate of sepsis following the procedure.

Differential Adjustment Outcomes of International Students at U.S. Universities

We present a methodological example of an initial use of critical quantitative analysis (CritQuant) in international education research focused on international students to explore differences in social-emotional experiences intersectionally. Drawing on a sample of 558 international students attending 14 colleges and universities in the United States, we examined students' belonging, social support, academic stress and confidence, COVID-19 related stress, and social integration by students' gender, graduate level, and region of origin as well as by combinations of gender, graduate level, and region of origin. Key findings include that graduate and undergraduate female students as well as graduate male students reported better social-emotional experiences compared with undergraduate male students and that students' region of origin accounted for a range of differences in student outcomes. Findings are discussed in relation to the current literature and with respect to opportunities in the field of international student engagement and global student mobility.

Social Groups and Unequal Employment Opportunities in Skilled Occupations in India

Differential labour market outcomes are a major concern in the Indian labour market. This article looks into the caste and ethnicity-based employment gap in skilled jobs in India. The study has used data from two Periodic Labour Force Survey rounds, namely the 2021–2022 round and 2018–2019 round. The employment gap has been decomposed using the non-linear decomposition method. The results suggest that socially forward groups are more likely to participate in skilled jobs than socially backward classes. Moreover, a significant part of the employment gap remains unexplained by characteristic differences, including differences in endowments. However, both the employment gap and the contribution of discriminatory hiring practices are generally less in more skill-oriented jobs. The employment gap in high-skilled occupations is significantly explained by differences in productivity factors. The jobs requiring higher levels of skills are largely prevalent in the public sector that comes under the reservation policy. In the private sector as well, compared to low- or unskilled jobs, high-skilled occupations are more likely to be found in the form of formal jobs to which anti-discrimination laws may be applicable. Low-paying unskilled jobs are mainly dominated by socially backward-class workers in the Indian labour market.

CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival

Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type. In the context of pancreatic cancer, we have previously reported that CD200 is expressed in the pancreatic tumor microenvironment (TME), and that targeting CD200 in murine tumor models reduces tumor burden. We hypothesized that CD200 is overexpressed on tumor and stromal populations in the pancreatic TME and that circulating levels of soluble CD200 (sCD200) have prognostic value for overall survival. We discovered that CD200 was overexpressed on immune, stromal, and tumor populations in the pancreatic TME. Particularly, single-cell RNA-sequencing indicated that CD200 was upregulated on inflammatory cancer-associated fibroblasts. Cytometry by time of flight analysis of PBMCs indicated that CD200 was overexpressed on innate immune populations, including monocytes, dendritic cells, and monocytic myeloid-derived suppressor cells. High sCD200 levels in plasma correlated with significantly worse overall and progression-free survival. Additionally, sCD200 correlated with the ratio of circulating matrix metalloproteinase (MMP) 3: tissue inhibitor of metalloproteinase (TIMP) 3 and MMP11/TIMP3. This study highlights the importance of CD200 expression in pancreatic cancer and provides the rationale for designing novel therapeutic strategies that target this protein.

Early Outcomes in Patients With LVAD Undergoing Heart Transplant via Use of the SherpaPak Cardiac Transport System.

Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longer ischemic times, innovations in donor heart preservation may yield improved post-HT outcomes. The SherpaPak Cardiac Transport System is an organ preservation technology that maintains donor heart temperatures between 4 °C and 8 °C, which may minimize ischemic and cold-induced graft injuries. This analysis sought to identify whether the use of SherpaPak versus traditional cold storage was associated with differential outcomes among patients with durable LVAD undergoing HT. Global Utilization and Registry Database for Improved Heart Preservation-Heart (NCT04141605) is a multicenter registry assessing post-HT outcomes comparing 2 methods of donor heart preservation: SherpaPak versus traditional cold storage. A retrospective review of all patients with durable LVAD who underwent HT was performed. Outcomes assessed included rates of PGD, post-HT mechanical circulatory support use, and 30-day and 1-year survival. SherpaPak (n=149) and traditional cold storage (n=178) patients had similar baseline characteristics. SherpaPak use was associated with reduced PGD (adjusted odds ratio, 0.56 [95% CI, 0.32-0.99]; P=0.045) and severe PGD (adjusted odds ratio, 0.31 [95% CI, 0.13-0.75]; P=0.009), despite an increased total ischemic time in the SherpaPak group. Propensity matched analysis also noted a trend toward reduced intensive care unit (SherpaPak 7.5±6.4 days versus traditional cold storage 11.3±18.8 days; P=0.09) and hospital (SherpaPak 20.5±11.9 days versus traditional cold storage 28.7±37.0 days; P=0.06) lengths of stay. The 30-day and 1-year survival was similar between groups. SherpaPak use was associated with improved early post-HT outcomes among patients with LVAD undergoing HT. This innovation in preservation technology may be an option for HT candidates at increased risk for PGD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04141605.

Molecular patterns of resistance to immune checkpoint blockade in melanoma

Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways are observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions have a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and T cell receptor (TCR) clonality analyses. One anti-PD1 resistant lesion harbors a distinct immune cell niche, however, anti-PD1 resistant tumors are generally immune poor with non-expanded TCR clones. Such immune poor microenvironments are associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors have reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.

Dissecting the networks underlying diverse brain disorders after prenatal glucocorticoid overexposure.

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies.

Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents.

The objective of this study was to explore the longitudinal relationship between anxiety and depressive symptoms and migraine outcomes in children and adolescents. Children and adolescents with migraine experience more anxiety and depressive symptoms than their peers without migraine, but it is unknown if these symptoms are associated with differential migraine outcomes. In this prospective clinical cohort study, children and adolescents aged 8.0-18.0 years with migraine completed headache questionnaires and validated measures of anxiety and depressive symptoms (Patient-Reported Outcomes Measurement Information System) at an initial consultation and at their first follow-up visit with a neurologist. Changes in monthly headache frequency and changes in migraine-related disability (Pediatric Migraine Disability Assessment) were tracked at each time point. The relationships between these migraine outcomes and anxiety and depressive symptoms were estimated using models controlling for sex, age, headache frequency, and treatment type. There were 123 consenting participants. In models adjusted for age, sex, baseline disability score, and treatment type, baseline anxiety and depressive symptom levels were not significantly associated with change in headache frequency (for anxiety symptoms: β = -0.05, 95% confidence interval [CI] = -0.268 to 0.166, p = 0.639; for depressive symptoms: β = 0.14, 95% CI = -0.079 to 0.359, p = 0.209). Similarly, in models adjusted for age, sex, baseline headache frequency, and treatment type, the change in disability was not associated with baseline anxiety (β = -0.45, 95% CI = -1.69 to 0.78, p = 0.470), nor with baseline depressive symptom scores (β = 0.16, 95% CI = -1.07 to 1.40, p = 0.796). In post hoc exploratory analyses (N = 84 with anxiety and N = 82 with depressive symptom data at both visits), there were also no significant associations between change in mental health symptoms and change in headache frequency (for anxiety symptoms: β = -0.084, 95% CI = -0.246 to 0.078, p = 0.306; for depressive symptoms: β = -0.013, 95% CI = -0.164 to 0.138, p = 0.865). Similarly, the change in disability scores between visits was not related to the change in anxiety (β = 0.85, 95% CI = -0.095 to 1.78, p = 0.077) nor depressive symptom scores (β = 0.32, 95% CI = -0.51 to 1.15, p = 0.446). Baseline anxiety and depressive symptom levels were not associated with longitudinal migraine outcomes and neither were longitudinal changes in anxiety and depressive symptom levels; this contradicts popular clinical belief that mental health symptoms predict or consistently change in tandem with migraine outcomes.

Digital mental health interventions as stand-alone vs. augmented treatment as usual

BackgroundSmartphone-based digital mental health interventions (DMHI) have been described as a purported solution to meet growing healthcare demands and lack of providers, but studies often don’t account for whether patients are concurrently in another treatment modality.MethodsThis preregistered quasi-experimental intent-to-treat study with 354 patients enrolled in a therapist-supported DMHI examined the treatment effectiveness of the Meru Health Program (MHP) as a stand-alone treatment as compared to the MHP in combination with any other form of treatment, including (1) in-person therapy, (2) psychotropic medication use, and (3) in-person therapy and psychotropic medication use.ResultsPatients with higher baseline depressive and anxiety symptoms were more likely to self-select into multiple forms of treatment, an effect driven by patients in the MHP as adjunctive treatment to in-person therapy and psychotropic medication. Patients in combined treatments had significantly higher depressive and anxiety symptoms across treatment, but all treatment groups had similar decreasing depressive and anxiety symptom trajectories. Exploratory analyses revealed differential treatment outcomes across treatment combinations. Patients in the MHP in combination with another treatment had higher rates of major depressive episodes, psychiatric hospitalization, and attempted death by suicide at baseline.ConclusionsPatients with higher depressive and anxiety symptoms tend to self-select into using DMHI in addition to more traditional types of treatment, rather than as a stand-alone intervention, and have more severe clinical characteristics. The use the MHP alone was associated with improvement at a similar rate to those with higher baseline symptoms who are in traditional treatments and use MHP adjunctively.

Heterogeneity of primary and metastatic CAFs: From differential treatment outcomes to treatment opportunities (Review).

Compared with primary tumor sites, metastatic sites appear more resistant to treatments and respond differently to the treatment regimen. It may be due to the heterogeneity in the microenvironment between metastatic sites and primary tumors. Cancer‑associated fibroblasts (CAFs) are widely present in the tumor stroma as key components of the tumor microenvironment. Primary tumor CAFs (pCAFs) and metastatic CAFs (mCAFs) are heterogeneous in terms of source, activation mode, markers and functional phenotypes. They can shape the tumor microenvironment according to organ, showing heterogeneity between primary tumors and metastases, which may affect the sensitivity of these sites to treatment. It was hypothesized that understanding the heterogeneity between pCAFs and mCAFs can provide a glimpse into the difference in treatment outcomes, providing new ideas for improving the rate of metastasis control in various cancers.

Grand rounds in methodology: designing for integration in mixed methods research

Mixed methods research is a popular approach used to understand persistent and complex problems related to quality and safety, such as reasons why interventions are not implemented as intended or...

Prognostic and predictive impact of sex in locally advanced microsatellite instability high gastric or gastroesophageal junction cancer: An individual patient data pooled analysis of randomized clinical trials

BackgroundSurgery plus peri-operative/adjuvant chemotherapy is the standard of care for locally advanced GC/GEJC, though with unsatisfactory results. dMMR/MSI-high tumors have better prognosis and scant benefit from chemotherapy as compared to pMMR/MSS ones. The differential outcome of therapies in terms of safety and efficacy according to sex is still debated in GC/GEJC patients. MethodsWe previously performed an individual patient data pooled analysis of MAGIC, CLASSIC, ITACA-S, and ARTIST trials including GC/GEJC patients treated with surgery alone or surgery plus peri-operative/adjuvant chemotherapy to assess the value of MSI status. We performed a secondary analysis investigating the prognostic and predictive role of sex (female versus male) in the pooled analysis dataset in the overall population and patients stratified for MSI status (MSI-high versus MSS/MSI-low). Disease-free (DFS) and overall survival (OS) were calculated. ResultsPatients with MSI-high tumors had improved survival as compared to MSS/MSI-low ones irrespective of sex, whereas in those with MSS/MSI-low tumors, females had numerically longer OS and DFS (5-year OS was 63.2% versus 57.6%, HR 0.842; p = 0.058, and 5-year DFS was 55.8% versus 50.8%, HR 0.850; p = 0.0504 in female versus male patients). The numerical difference for the detrimental effect of chemotherapy in MSI-high GC was higher in females than males, while the significant benefit of chemotherapy over surgery alone was confirmed in MSS/MSI-low GC irrespective of sex. ConclusionsThis pooled analysis including four randomized trials highlights a relevant impact of sex in the prognosis and treatment efficacy of MSI-high and MSS/MSI-low non-metastatic GC/GEJC.

Sex differences in treatment effect in neuroprotectant trials for acute ischemic stroke: A systematic review

BackgroundPre-clinical data suggest sex differences in mechanisms of cerebral ischemic injury. This might result in differential outcomes of putative neuroprotectants by sex, though little systematic data is available to assess this. MethodsWe performed a systematic review of multicenter randomized controlled trials published from January 1980–June 2022 enrolling >100 subjects and testing neuroprotectants in acute ischemic stroke (AIS). For each trial, reported treatment effect by sex was extracted. When published results by sex were not available, we contacted individual authors to attempt to retrieve these data. ResultsWe identified 59 publications reporting 64 trials that met inclusion criteria. Of these, data on treatment effect by sex were published for 14/64 trials. Unpublished data for an additional 5 trials were obtained from trial investigators (19/64, or 29.7%). Two trials (one testing uric acid and one dexborneol) reported treatment benefit in women but not men. Pooled analysis of six trials of tirilazad reported worse treatment outcomes in women and no effect in men. No clear difference was apparent in the other trials. ConclusionsMost trials did not report treatment effect by sex. Of those that did, there was little evidence of systematic sex differences in treatment response.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.