Tag: pubmed

J Womens Health (Larchmt). 2023 Nov 1. doi: 10.1089/jwh.2023.0002. Online ahead of print.

ABSTRACT

Background: Social determinants of health are important contributors to maternal and child health outcomes. Limited existing research examines the relationship between housing instability during pregnancy and perinatal care utilization. Our objective was to evaluate whether antenatal housing instability is associated with differences in perinatal care utilization and outcomes. Materials and Methods: Participants who were surveyed during their postpartum hospitalization were considered to have experienced housing instability if they answered affirmatively to at least one of six screening items. The primary outcome was adequacy of prenatal care measured by the Adequacy of Prenatal Care Utilization index. Maternal, neonatal, and postpartum outcomes, including utilization and breastfeeding, were also collected as secondary outcomes. Multivariable logistic regression models were adjusted for sociodemographic and clinical covariates. Results: In this cohort (N = 490), 11.2% (N = 55) experienced housing instability during pregnancy. Participants with unstable housing were more likely to have inadequate prenatal care (17.3% vs. 3.9%; odds ratio [OR] 5.11, 95% confidence interval [CI] 2.15-12.14, p < 0.001), but findings were not significant after adjustment (aOR 1.72, 95% CI 0.55-5.41, p = 0.35). Similarly, postpartum visit attendance was lower for individuals with unstable housing (79.6% vs. 91.2%), but there was no difference in the odds of the postpartum visit attendance after adjustment (OR 0.69, 95% CI 0.29-1.66, p = 0.14). Conclusions: There were no statistically significant association with the maternal, neonatal, and other postpartum secondary outcomes. Housing instability appears to be a risk marker that is related to other social determinants of health. Given the range of housing instability experiences, future research must account for specific types and degrees of housing instability and their potential perinatal consequences.

PMID:37944106 | DOI:10.1089/jwh.2023.0002

JCO Glob Oncol. 2023 Sep;9:e2300294. doi: 10.1200/GO.23.00294.

ABSTRACT

Rapidly expanding systemic treatment options, combined with improved screening, diagnostic, surgical, and radiotherapy techniques, have led to improved survival outcomes for many cancers over time. However, these overall survival gains have disproportionately benefited patients in high-income countries, whereas patients in low- and middle-income countries (LMICs) continue to experience challenges in accessing timely and guideline concordant care. In September 2022, the Accelerating Anticancer Agent Development and Validation workshop was held, focusing on global cancer drug development. Panelists discussed key barriers such as the lack of diagnostic services and human resources, drug accessibility and affordability, lack of research infrastructure, and regulatory and authorization challenges, with a particular focus on Africa and Latin America. Potential opportunities to improve access and affordability were reviewed, such as the importance of prioritizing investments in diagnostics, investing health infrastructure and work force planning, coordinated drug procurement efforts and streamlined regulatory processing, incentivized pricing through regulatory change, and the importance of developing and promoting clinical trials that can answer relevant clinical questions for patients in LMICs. As a cancer community, we must continue to advocate for and work toward equitable access to high-quality interventions for patients, regardless of their geographical location.

PMID:37944089 | DOI:10.1200/GO.23.00294

J Clin Oncol. 2023 Nov 9:JCO2301193. doi: 10.1200/JCO.23.01193. Online ahead of print.

ABSTRACT

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs.

METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status.

RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001).

CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

PMID:37944079 | DOI:10.1200/JCO.23.01193

J Clin Oncol. 2023 Nov 9:JCO2202754. doi: 10.1200/JCO.22.02754. Online ahead of print.

ABSTRACT

PURPOSE: To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology.

METHODS: We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context.

RESULTS: Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods.

CONCLUSION: Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.

PMID:37944067 | DOI:10.1200/JCO.22.02754

J Neuropathol Exp Neurol. 2023 Nov 7:nlad086. doi: 10.1093/jnen/nlad086. Online ahead of print.

ABSTRACT

High-throughput digital pathology offers considerable advantages over traditional semiquantitative and manual methods of counting pathology. We used brain tissue from 5 clinical-pathologic cohort studies of aging; the Religious Orders Study, the Rush Memory and Aging Project, the Minority Aging Research Study, the African American Clinical Core, and the Latino Core to (1) develop a workflow management system for digital pathology processes, (2) optimize digital algorithms to quantify Alzheimer disease (AD) pathology, and (3) harmonize data statistically. Data from digital algorithms for the quantification of β-amyloid (Aβ, n = 413) whole slide images and tau-tangles (n = 639) were highly correlated with manual pathology data (r = 0.83 to 0.94). Measures were robust and reproducible across different magnifications and repeated scans. Digital measures for Aβ and tau-tangles across multiple brain regions reproduced established patterns of correlations, even when samples were stratified by clinical diagnosis. Finally, we harmonized newly generated digital measures with historical measures across multiple large autopsy-based studies. We describe a multidisciplinary approach to develop a digital pathology pipeline that reproducibly identifies AD neuropathologies, Aβ load, and tau-tangles. Digital pathology is a powerful tool that can overcome critical challenges associated with traditional microscopy methods.

PMID:37944065 | DOI:10.1093/jnen/nlad086

JCO Clin Cancer Inform. 2023 Sep;7:e2300056. doi: 10.1200/CCI.23.00056.

ABSTRACT

PURPOSE: Multidisciplinary tumor boards (MTBs) support high-quality cancer care. Little is known about the impact of information technology (IT) tools on the operational and technical aspects of MTBs. The National Comprehensive Cancer Network EHR Oncology Advisory Group formed a workgroup to investigate the impact of IT tools such as EHRs and virtual conferencing on MTBs.

METHODS: The workgroup created a cross-sectional survey for oncology clinicians (eg, pathology, medical, surgical, radiation, etc) participating in MTBs at 31 National Comprehensive Cancer Network member institutions. A standard invitation e-mail was shared with each EHR Advisory Group Member with a hyperlink to the survey, and each member distributed the survey to MTB participants at their institution or identified the appropriate person at their institution to do so. The survey was open from February 26, 2022, to April 26, 2022. Descriptive statistics were applied in the analysis of responses, and a qualitative thematic analysis of open-ended responses was completed.

RESULTS: Individuals from 27 institutions participated. Almost all respondents (99%, n = 764 of 767) indicated that their MTBs had participants attending virtually. Most indicated increased attendance (69%, n = 514 of 741) after virtualization with the same or improved quality of discussion (75%, n = 557 of 741) compared with in-person MTBs. Several gaps between the current and ideal state emerged regarding EHR integration: 57% (n = 433 of 758) of respondents noted the importance of adding patients for MTB presentation via the EHR, but only 40% (n = 302 of 747) reported being able to do so most of the time. Similarly, 87% (n = 661 of 760) indicated the importance of documenting recommendations in the EHR, but only 53% (n = 394 of 746) reported this occurring routinely.

CONCLUSION: Major gaps include the lack of EHR integration for MTBs. Clinical workflows and EHR functionalities could be improved to further optimize EHRs for MTB management and documentation.

PMID:37944060 | DOI:10.1200/CCI.23.00056

Bioinformatics. 2023 Nov 7:btad641. doi: 10.1093/bioinformatics/btad641. Online ahead of print.

ABSTRACT

MOTIVATION: The recent development of spatial resolved transcriptomics (SRT) technologies has facilitated research on gene expression in the spatial context. Annotating cell types is one crucial step for downstream analysis. However, many existing algorithms employ an unsupervised strategy to assign cell types for SRT data. They first conduct clustering analysis and then aggregate cluster-level expression based on the clustering results. This workflow fails to leverage the marker gene information efficiently. On the other hand, other cell annotation methods designed for single-cell RNA-seq (scRNA-seq) data utilize the cell-type marker genes information but fail to use spatial information in SRT data.

RESULTS: We introduce a statistical spatial transcriptomics cell assignment model, SPAN, to annotate clusters of cells or spots into known types in SRT data with prior knowledge of predefined marker genes and spatial information. The SPAN model annotates cells or spots from SRT data using predefined overexpressed marker genes and combines a mixture model with a hidden Markov random field to model the spatial dependency between neighboring spots. We demonstrate the effectiveness of SPAN against spatial and non-spatial clustering algorithms through extensive simulation and real data experiments.

AVAILABILITY: https://github.com/ChengZ352/SPAN.

PMID:37944045 | DOI:10.1093/bioinformatics/btad641

J Natl Cancer Inst. 2023 Nov 7:djad224. doi: 10.1093/jnci/djad224. Online ahead of print.

ABSTRACT

BACKGROUND: Males have 2-3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults.

METHODS: Using the Transplant Cancer Match (TCM) Study, we estimated the male-to-female incidence rate ratio in TCM (M: F IRRTransplant) for 15 cancer sites diagnosed between 1995-2017 using Poisson regression. M: F IRRs in the general population (M: F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race/ethnicity, and diagnosis year. M: F IRRs were compared using a chi-square test.

RESULTS: Among 343,802 solid organ transplants, 211,206 (61.4%) were among men and 132,596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M: F IRRTransplant: 1.81 vs M: F IRRGP: 3.96; P < 0.0001), stomach (1.51 vs 2.09; P = 0.002), colorectum (0.98 vs 1.43; P < 0.0001), liver (2.39 vs 3.44; P = 0.002), kidney (1.67 vs 2.24; P < 0.0001), bladder (2.02 vs 4.19; P < 0.0001), Kaposi sarcoma (1.79 vs 3.26; P = 0.0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P < 0.0001). The M: F IRRTransplant was not statistically different from the M: F IRRGP for other cancer sites.

CONCLUSIONS: Although male solid organ transplant recipients have higher cancer incidence than females, the attenuation in the M: F ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in females due to immunosuppression following transplantation.

PMID:37944040 | DOI:10.1093/jnci/djad224

Gerontologist. 2023 Nov 7:gnad152. doi: 10.1093/geront/gnad152. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Sleep disorders often predict or co-occur with cognitive decline. Yet, little is known how the relationship unfolds among older adults at risk for cognitive decline.To examine the associations of sleep disorders with cognitive decline in older adults with unimpaired cognition, or impaired cognition (mild cognitive impairment [MCI] and dementia).

RESEARCH DESIGN AND METHODS: 5,822 participants (Mage=70) of the National Alzheimer’s Coordinating Center database with unimpaired or impaired cognition were followed for three subsequent waves. Four types of clinician-diagnosed sleep disorders were reported: sleep apnea, hyposomnia/insomnia, REM sleep behavior disorder, or “other.” Cognition over time was measured by the Montreal Cognitive Assessment (MoCA) or an estimate of general cognitive ability (GCA) derived from scores based on 12 neuropsychological tests. Growth curve models were estimated adjusting for covariates.

RESULTS: In participants with impaired cognition, baseline sleep apnea was related to better baseline MoCA performance (b=0.65, 95%CI=[0.07, 1.23]) and less decline in GCA over time (b=0.06, 95%CI=[0.001, 0.12]). Baseline insomnia was related to better baseline MoCA (b=1.54, 95%CI=[0.88, 2.21]) and less decline in MoCA over time (b=0.56, 95%CI=[0.20, 0.92]). Furthermore, having more sleep disorders (across the four types) at baseline predicted better baseline MoCA and GCA, and less decline in MoCA and GCA over time. These results were only found in those with impaired cognition and generally consistent when using self-reported symptoms of sleep apnea or insomnia.

DISCUSSION AND IMPLICATIONS: Participants with sleep disorder diagnoses may have better access to healthcare, which may help maintain cognition through improved sleep.

PMID:37944004 | DOI:10.1093/geront/gnad152

BJU Int. 2023 Nov 9. doi: 10.1111/bju.16115. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the diagnostic performance and radiological staging impact of ⁶⁸ Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to ⁹⁹ Tc whole-body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa).

PATIENTS AND METHODS: A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as ‘negative’, ‘equivocal’, or ‘definite’ based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases).

RESULTS: There were 667 patients included. The median (interquartile range) prostate-specific antigen level was 9.2 (6.2-16) ng/mL and 60% of patients were high risk according to a modified D’Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high-risk (P = 0.030) and low-risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUV_max ) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUV_max of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively).

CONCLUSIONS: More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high-risk patients. The SUV_max of the primary tumour and metastases was associated with upstaging.

PMID:37943964 | DOI:10.1111/bju.16115