Outcome Data Research Articles

Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Does pre-injury anticoagulation make chest tubes any less safe? A nationwide retrospective analysis

BackgroundOral anticoagulation is becoming more common with the aging population, which raises concern for the risk of invasive procedures that can cause bleeding, such as chest tube placement (thoracostomy). With the increase in CT imaging, more pneumothoraces and hemothoraces are being identified. The relative risk of thoracostomy in the presence of anticoagulation is not well-established. The objective of this study was to determine whether pre-injury anticoagulation affects the relative risk of tube thoracostomy following significant chest trauma. MethodsThis retrospective cohort study used data from the 2019 American College of Surgeons-Trauma Quality Program (ACS-TQP) database using R version 4.2.2. Data from the database was filtered based on inclusion and exclusion criteria. Outcomes were then assessed with the population of interest. Demographics, vitals, comorbidities, and injury parameters were also collected for each patient.This study included all adult patients (≥ 18 years) presenting with traumatic hemothorax, pneumothorax, or hemopneumothorax. Patients with missing data in demographics, vitals, comorbidities, injury parameters, or outcomes, as well as those with no signs of life upon arrival, were excluded from the study. Patients were stratified into groups based on whether they had pre-injury anticoagulation and whether they had a chest tube placed in the hospital. The primary outcome was mortality, and the secondary outcome was hospital length of stay (LOS). Logistic and standard regressions were used by a statistician to control for age, sex, and Injury Severity Score (ISS). ResultsOur study population included 72,385 patients (4250 with pre-injury anticoagulation and 68,135 without pre-injury anticoagulation). Pre-injury anticoagulation and thoracostomy were each independently associated with increased mortality and LOS. However, there was a non-significant interaction term between pre-injury anticoagulation and thoracostomy for both outcomes, indicating that their combined effects on mortality and LOS did not differ significantly from the sum of their individual effects. ConclusionThis study suggests that both pre-injury anticoagulation and thoracostomy are risk factors for mortality and increased LOS in adult patients presenting with hemothorax, pneumothorax, or hemopneumothorax, but they do not interact with each other. We recommend further study of this phenomenon to potentially improve clinical guidelines. Level of evidenceTherapeutic, Level III.

Early and late Results after Surgical Mitral Valve Repair: A High-Volume Center Experience.

Surgical mitral valve repair is the gold standard treatment of severe primary mitral valve regurgitation (MR). In the light of rapidly evolving percutaneous technologies, current surgical outcome data is essential to support heart team-based decision making. This retrospective, high-volume, single-center study analyzed in 1779 patients with primary MR early morbidity and mortality, postoperative valve function, and long-term survival after mitral valve repair. Surgeries were performed between 2009 and 2022. Surgical approaches included full sternotomy (FS) and right-sided mini-thoracotomy (MIC). Of the surgeries (mean age: 59.9 (SD:11.4) years; 71.5% males), 85.6% (n=1527) were mini-thoracotomies. Concomitant procedures were performed in 849 patients (47.7%), including tricuspid valve and/or atrial septal defect repair, cryoablation and atrial appendage closure. The majority of patients did not need erythrocyte concentrates. Mediastinitis and re-thoracotomy for bleeding rates were 0.1 and 4.3%, respectively. Reoperation before discharge for failed repair was necessary in 12 patients (0.7%). Freedom from more than moderate MR was >99%. Thirty-day mortality was 0.2% and did not differ significantly between groups (P=0.37). Median follow-up was 48.2 months with a completeness of 95.9%. Long term survival was similar between groups (P=0.21). In the FS and MIC groups, 1-year, 5-year and 10-year survival was 98.8 and 98.8%, 92.9 and 94.4%, and 87.4 and 83.1%, respectively. Mitral valve surgery, both minimally-invasive and via sternotomy, is associated with high repair rates, excellent perioperative outcomes, and long-term survival. Data underscore the effectiveness of surgical repair in managing MR, even in the era of advancing interventional techniques.

Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes.

While 'immuno-competence' is a well-known term, it lacks an operational definition. To address this omission, this study explored whether the temporal and structured data of the complete blood cell count (CBC) can rapidly estimate immuno-competence. To this end, one or more ratios that included data on all monocytes, lymphocytes and neutrophils were investigated. Longitudinal CBC data collected from 101 COVID-19 patients (291 observations) were analyzed. Dynamics were estimated with several approaches, which included non-structured (the classic CBC format) and structured data. Structured data were assessed as complex ratios that capture multicellular interactions among leukocytes. In comparing survivors with non-survivors, the hypothesis that immuno-competence may exhibit feedback-like (oscillatory or cyclic) responses was tested. While non-structured data did not distinguish survivors from non-survivors, structured data revealed immunological and statistical differences between outcomes: while survivors exhibited oscillatory data patterns, non-survivors did not. In survivors, many variables (including IL-6, hemoglobin and several complex indicators) showed values above or below the levels observed on day 1 of the hospitalization period, displaying L-shaped data distributions (positive kurtosis). In contrast, non-survivors did not exhibit kurtosis. Three immunologically defined data subsets included only survivors. Because information was based on visual patterns generated in real time, this method can, potentially, provide information rapidly. The hypothesis that immuno-competence expresses feedback-like loops when immunological data are structured was not rejected. This function seemed to be impaired in immuno-suppressed individuals. While this method rapidly informs, it is only a guide that, to be confirmed, requires additional tests. Despite this limitation, the fact that three protective (survival-associated) immunological data subsets were observed since day 1 supports many clinical decisions, including the early and personalized prognosis and identification of targets that immunomodulatory therapies could pursue. Because it extracts more information from the same data, structured data may replace the century-old format of the CBC.

Targeted Test and Treat at Point of Entry to Reduce Importation of Malaria Parasites: A Systematic Review.

As countries approach malaria elimination, imported cases of malaria make up a larger proportion of all cases and may drive malaria transmission. Targeted test and treat (TTaT) at points of entry (POEs) is a strategy that aims to reduce the number of imported infections in countries approaching elimination by testing and treating individuals at border crossings. No evidence has been systematically collected and evaluated to assess the impact and operational feasibility of this strategy. This systematic review gathered empirical evidence on the effectiveness of the intervention, contextual factors, and results of modeling studies that estimate its potential impact. Bibliographic searches were conducted in March 2021 and updated in April 2022, and a total of 1,569 articles were identified. All study designs were included, but none of them were intervention studies set up to measure the impact of TTaT at POEs. Seven nonrandomized observational studies were eligible for assessment of outcome data in terms of describing the extent of positive cases among people crossing borders. Also included in the review were three studies for assessment of acceptability and feasibility of the intervention and three for assessment of mathematical modeling. The positivity rates reported in the seven studies ranged between 0.0% and 70.0%, which may be attributable to the different settings and operational feasibility. Overall, there is limited evidence of the effect of TTaT at POEs on the prevalence of infection, and the certainty of the evidence was very low owing to critical risk of bias, serious inconsistency, and serious indirectness.

Mass Testing and Treatment to Accelerate Malaria Elimination: A Systematic Review and Meta-Analysis.

In regions where malaria transmission persists, the implementation of approaches aimed at eliminating parasites from the population can effectively decrease both burden of disease and transmission of infection. Thus, mass strategies that target symptomatic and asymptomatic infections at the same time may help countries to reduce transmission. This systematic review assessed the potential benefits and harms of mass testing and treatment (MTaT) to reduce malaria transmission. Searches were conducted in March 2021 and updated in April 2022 and included cluster-randomized controlled trials (cRCTs) as well as nonrandomized studies (NRSs) using malaria infection incidence, clinical malaria incidence, or prevalence as outcomes. The risk of bias was assessed with Cochrane's risk of bias (RoB2) tool and Risk of Bias Tool in Nonrandomized Studies - of Interventions (ROBINS-I), and the certainty of evidence (CoE) was graded for each outcome. Of 4,462 citations identified, seven studies (four cRCTs and three NRSs) contributed outcome data. The analysis revealed that MTaT did not reduce the incidence (risk ratio [RR]: 0.95, 95% CI: 0.87-1.04; 1,181 participants; moderate CoE) or prevalence (RR: 0.83, 95% CI: 0.67-1.01; 7,522 participants; moderate CoE) of malaria infection but resulted in a small reduction in clinical malaria (RR: 0.82; 95% CI: 0.70-0.95; 334,944 participants; moderate CoE). Three studies contributing data on contextual factors concluded that MTaT is an acceptable, feasible, and cost-effective intervention. Mathematical modeling analyses (n = 10) suggested that MTaT effectiveness depends on the baseline transmission level, diagnostic test performance, number of rounds, and other co-interventions. Based on the limited evidence available, MTaT has little to no impact on reducing malaria transmission.

Training experienced mental health practitioners to deliver foundational trauma education: The core curriculum on childhood trauma.

The majority of U.S. mental health practitioners receive little to no foundational trauma education, and instead rely on in-service or continuing education to fill this deficit. Consequently, it is essential to have experienced mental health practitioners capable of delivering trauma education. Since 2009; experienced mental health practitioners have been trained to use the Core Curriculum on Childhood Trauma (CCCT) to deliver trauma education to other mental health practitioners. Despite prior evidence that the CCCT increases the trauma skills of trainees, to date no evaluation has been conducted on developing facilitators' skills, a crucial element in ensuring effective education. Longitudinal, multiinstrument data were collected from 85 CCCT facilitators trained between October 2016-January 2020; along with learning outcome data from 1646 mental health practitioners trained by those facilitators through March 2021. High facilitator skill levels were seen across all instruments, including statistically significant change between preand posttraining measures for 7 core facilitator skills (effect sizes: .90 to 2.25). The data also identified challenges in facilitator development and retention. CCCT facilitator training effectively imparts skills needed to increase workforce trauma capacity; however, modifications to the facilitator development model are needed to maximize impact of scale-up efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

784 Effects of Optimal Versus Suboptimal Median Household Income on the Operative Traumatic Brain Injury Population: A Propensity Score-matched Analysis

INTRODUCTION: Median household income is a useful metric for healthcare disparity assessment. New England holds a highly diverse, densely populated metropolitan area with one of the highest living wages in the US. To our knowledge, there is no published data on the effects of optimal vs. suboptimal median household income on the operative traumatic brain injury (TBI) patients. METHODS: Demographic, clinical and outcome data of operative TBI patients between 2015 and 2021 were collected and stratified based on optimal (80 000$ or more) and suboptimal (less than 80 000$) median residential household income. 1:1 tight caliper (0.01) propensity score matching was performed to balance the groups for comparative analysis. RESULTS: From the initial 91 patients in the optimal and 102 patients in the suboptimal income groups, 62 patients were included in each group after propensity matching. There were significantly more ethnic minority patients in the suboptimal as compared to the optimal income group (66.1% and 35.7%, respectively; p=0.002). Optimal income group patients presented as transfers from other hospitals significantly more frequently than the suboptimal group (52.5% and 30.7%, respectively; p = 0.02). There were no significant differences in post-operative Glasgow coma scale scores (p = 0.15), modified Rankin scale scores at discharge (p = 0.92) and upon follow-up (p = 0.1), mortality (p > 0.999) or disposition destination distribution (p = 0.3). CONCLUSIONS: While the suboptimal income group is significantly more ethnically diverse, optimal versus suboptimal median household income does not seem to affect TBI outcomes and disposition. Optimal income group patients are more frequently presenting as transfers from other facilities indicating fair high-level care at a specialized high safety-net burden trauma center adapted to an ethnically diverse population.

Abstract 5072: Multi-omic, multi-scale characterisation of colorectal cancer defines spatiotemporal patterns of recurrence

Abstract Aim: Patients who undergo intended curative resection of colorectal cancer (CRC) have a 20-25% chance of metachronous recurrence, the site and timing of which are unpredictable and resistant to current treatment. The biological basis for such heterogeneous disease behavior remains to be elucidated. Bulk transcriptomic profiling and subsequently single-cell RNAseq have provided insight in the epithelial subtypes and immune microenvironment. Recently spatially resolved transcriptomic assessment allow molecular profiling of tissue while preserving tissue architecture. Utilizing ST technology we sought to perform deep characterization of a large cohort of patients with primary CRC with the intention to decipher the biological determinants of spatio-temporal patterns of recurrence. Methods: 750 patients who underwent resection of CRC with mature follow up were studied. Bulk transcriptomic, genomic and multiplex immune characterization was performed using a TMA format. Of these, 28 patients were assessed using single cell spatial transcriptomics (Nanostring CosMx Spatial Molecular Imager (SMI, 1000plex gene panel)), 120 tumors underwent regional whole transcriptome profiling of epithelium and TME (Nanostring GeoMx Digital Spatial Profiler using FFPE tissue). We used image analysis and bioinformatics to integrate these complex datasets in over 120000 single-cells in the context of their spatial tissue architecture and clinicopatholgical outcome and recurrence data. Results: Using the CosMx SMI we characterized cells with complete topographic detail and defined 2 unique epithelial cell states defined. Each epithelial state had distinct spatial properties including cell size and morphology, average distance to nearest lymphocyte, neighboring cell types and stromal neighborhood. This epithelial signature was integrated in GeoMx samples and were found to predict recurrence (p<0.05). The Epithelial, Fibroblast and Immune GeoMx transcriptomic compartments were expanded and grouped using unsupervised clustering. Each compartment demonstrated groups of patients where specific spatially derived signatures could predict site and time of recurrence (p<0.05). Conclusions: By maintaining the tissue structure, we have directly measured cellular interactions and captured cells commonly missed during dissociative studies whilst defining novel molecular subtypes of CRC with clinical relevance. Novel platforms such as CosMx allow deeper characterization of unique cell types and cellular interactions that may pave the way for novel therapeutics and precision medicine for patients with CRC. Citation Format: Colin Stuart Wood, Joao Da Silva Filho, Andrew Cameron, Assya Legrini, Holly Leslie, Tengyu Zhang, Yoana Doncheva, Claire Kennedy-Dietrich, Matthias Marti, Joanne Edwards, Paul Horgan, Campbell Roxburgh, Colin Steele, Nigel Jamieson. Multi-omic, multi-scale characterisation of colorectal cancer defines spatiotemporal patterns of recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5072.

Abstract 796: Exploring the impact of masculine beliefs on colorectal cancer screening participation among Hispanic/Latino men in Florida, New York, and Texas

Abstract Introduction: The existing literature on colorectal cancer-related inequities among Hispanic/Latino men may be poorly descried as most outcome data to date for this ethnic group are reported in aggregate. This study explored how masculine beliefs may influence colorectal cancer screening participation among ethnic subgroups of Hispanic/Latino men aged 45-75 years. Methods: Utilizing a consumer panel, self-identified Hispanic/Latino men that were age-eligible for colorectal cancer screening and fluent in either English or Spanish were recruited from Florida, New York, and Texas (February-March 2022). The Masculinity Barriers to Medical Care (MBMC) scale, comprising six theoretically derived subscales, was assessed masculinity. Multivariable logistic regression was employed to estimate the association between MBMC and colorectal cancer screening participation, adjusting for Hispanic/Latino subgroup, marital status, survey language, age, and health insurance status. Next, to explore differences by Hispanic/Latino subgroups (Mexican/Mexican American/Chicano; Puerto Rican; Cuban; Other Hispanic/Latino), results were stratified by subgroup and adjusted for confounding. Results: There were 611 male participants, with roughly 31% identifying as Puerto Rican, 30% a different Hispanic ethnic background (“Other Hispanic/Latino”), 26% Mexican, and 14% Cuban. More than half (63%) of whom had ever been screened for colorectal cancer. No variations in screening rates were observed across Hispanic/Latino subgroups. Stool-based tests were more commonly used for screening compared to exam-based tests (60% vs. 49%). After adjusting for confounding, masculinity barriers reduced the odds of the screening participation. Differences were observed by Hispanic/Latino subgroup for a few MBMC scale items. Specifically, Cuban men were most likely to report trust in healthcare professionals, but least likely to report receiving quality medical care. Latino men of other Hispanic ethnicity were more likely to report taking risks with their own health if it benefits their family. Among Puerto Rican men, higher scores on the restrictive emotionality subscale were associated with a lower likelihood of screening participation. Conversely, higher scores on the health-related self-reliance subscale were associated with a greater likelihood of screening participation among men of other Hispanic/Latino ethnicity. Conclusion: Differences in colorectal cancer screening participation by Hispanic/Latino ethnicity were not observed, suggesting barriers to screening may be similar among subgroups. Masculinity barriers to colorectal cancer screening may exist among Latino men, particularly among Puerto Rican men. Intervening on these masculinity-related barriers masculinity may improve colorectal cancer screening uptake among Latino men. Citation Format: Ami E. Sedani, Jessica Y. Islam, Derek M. Griffith, Kelly K. Rifelj, Cordero L. McCall, Omar García-Rodríguez, Marlene Camacho-Rivera, Charles R. Rogers. Exploring the impact of masculine beliefs on colorectal cancer screening participation among Hispanic/Latino men in Florida, New York, and Texas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 796.

Abstract 3519: Reconstructing a latent representation of gene expression from genomic alterations to improve clinical utility of real-world clinicogenomics data

Abstract Background: Molecularly and clinically well-annotated patient datasets are ideal for studying tumor biology and developing robust machine learning (ML) models for predicting outcome and treatment response. These data however rarely exist in real-world settings or in sufficient quantities within research contexts. Large publicly available datasets like The Cancer Genome Atlas (TCGA) which provid multi-omic profiles for diverse cancer types, have profoundly advanced cancer research and facilitated development of novel therapies and personalized medicines. However, the absence of patient outcome data tied to treatment limits the applicability of these data for understanding and modeling treatment response. Real-world clinicogenomics cohorts, such as the AACR Project GENIE, on the other hand are typically very rich in clinical annotations, including treatment regimens and outcomes measures. These data are however sparsely annotated for patient tumor molecular profiles, rarely exceeding ~100’s of genes profiled. We hypothesized that it would be possible to reconstruct latent tumor mRNA representations from limited genomic and clinical data available in real-world clinicogenomic cohorts, and that these reconstructed expression profiles would be useful for a variety of clinically meaningful downstream applications. Methods: We developed an ML model, called Mut2Ex, to reconstruct tumor gene expression profiles using genetic information available on commercial next generation sequencing panels using a Principle Label Space Transformation (PLST) we adapted to regression problem, along with embeddings from clinical information (OncoTree code, sex and stage) generated by a language model. Mut2Ex was trained on ~1200 cell lines from DepMap representing 26 cancer types, to generate ~2000 reconstructed mRNA gene profiles that were applied to a variety of clinical tasks. We used Mut2Ex to reconstruct mRNA profiles for ~10,000 tumors from TCGA and ~180,000 tumors from AACR Project GENIE. Results: Reconstructed mRNA expression by Mut2Ex was highly correlated with true expression in cell lines (rho = 0.926, [0.924-0.928 95% CI, N = 1184]). Compared to true expression, reconstructed profiles recapitulate sub-clusters within cancer types, PAM50 subtyping in breast tumors, survival signatures in colorectal tumors and multiple oncogenic signatures in a pan-cancer manner. Analysis of reconstructed expression for AACR Project GENIE tumors revealed expected enrichment of known driver genes within expression subtypes and enrichment of oncogenic signatures associated with distinct clinical outcomes in a cancer type specific manner. Conclusions: Our flexible analytic framework for reconstructing gene expression profiles from clinicogenomics data substantially augments the clinical utility and value of data acquired in real-world settings. Citation Format: Maayan Baron, Sunil Kumar, Felicia Kuperwaser, Dillon Tracy, Emily Vucic, Jeff Sherman. Reconstructing a latent representation of gene expression from genomic alterations to improve clinical utility of real-world clinicogenomics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3519.

The impact of adverse childhood events on service support and educational outcomes of children who are autistic: A theory-guided analysis using structural equation modeling.

Autistic children who have experienced adverse childhood experiences (ACEs) may have barriers to receiving special education or other developmental services-thus, impacting educational outcomes. Our objective was to model such a pathway using the 2016-2021 National Survey of Children's Health datasets. We extracted data for school outcomes, use of special education and autism-related specialty services and sociodemographic characteristics among autistic children within the data. Associations between sociodemographics and ACEs (categorized as 0, 1-3, and 4+) were tested using design-based X2 tests. We then used structural equation modeling to map the quasi-causal pathways. The sample for our analysis included 4717 autistic children-38.94% were aged 6-10 years, 35.73% of children aged 11-14 years, and 25.32% were between 15 and 17 years-with 88.70% living in metropolitan areas. The X2 showed significant relationships between ACEs and age, ethnoracial groups, and urbanicity among others. The SEM showed ACEs were directly associated with poorer school outcomes (β = -0.14 (0.04), p = 0.002) and through their inverse relationship with support services (β = -0.08 (0.04), p = 0.023)- when support services were increased, school outcomes improved (β = 0.62, p < 0.001). Findings suggested ACEs have a significant direct and indirect impact on school outcomes of autistic children, and 10.76% of children who are autistic have experienced four or more ACEs-which were more likely to occur with severe autism symptomatology and in rural areas. Results highlight the need for communities to recognize the potential long-term impact of ACEs on the academic outcomes of autistic children.

Scaphoid Fractures in Adults Aged 50 Years or Older: Epidemiology and Association With Osteopenia and Nonunion.

Scaphoid fractures are less commonly reported in adults older than 50 years. The association between bone density and outcomes following scaphoid fractures has not been explored in this patient population. The second metacarpal cortical percentage (2MCP) has been shown to predict low bone density. The purpose of this study is to describe the epidemiology and radiographic characteristics associated with scaphoid fractures in adults older than 50 years, determine the prevalence of osteopenia defined by 2MCP, and evaluate the characteristics associated with scaphoid nonunion in this population. We hypothesized that osteopenia defined by 2MCP would be common in this patient population and associated with scaphoid nonunion. Patients older than 50 years with an acute, closed scaphoid fracture were identified. Demographic data, radiographic characteristics, and outcome data were collected. The 2MCP was measured using standard hand radiographs. A total of 111 patients were identified. Most fractures were nondisplaced and occurred in women via low-energy mechanism. Fifty-six patients (50.5%) had osteopenia defined by a 2MCP less than 60%. Nondisplaced fractures achieved union faster than displaced fractures (P < .05). Displaced, unstable fractures were statistically associated with nonunion (P < .001). 2MCP did not correlate with nonunion. In adults older than 50 years, scaphoid fractures may represent a fragility fracture cohort given they occur more frequently in female patients via low-energy mechanisms and over half of the cohort had osteopenia defined by a 2MCP less than 60%. Displaced and unstable fractures were statistically more likely to go on to nonunion. Nonunion was not found to be associated with osteopenia.

Cryoballoon ablation for atrial fibrillation in South Africa: One-year outcome from the Cryo Global Registry

Background. Pulmonary vein isolation (PVI) with cryoballoon catheter ablation (CBA) is a well-established and widely adopted method for the treatment of patients with atrial fibrillation (AF) to prevent recurrences of AF. CBA adoption in South Africa (SA) and outcome data in SA patients are limited.Objectives. To evaluate real-world usage, safety and effectiveness of CBA in SA. Methods. In this sub-analysis of the Cryo Global Registry, 81 participants with paroxysmal AF (PAF) and persistent AF (PsAF) were enrolled between 2017 and 2021 across two private SA hospitals. Baseline characteristics, procedural characteristics, 12-month safety, effectiveness (atrial arrhythmia recurrence), healthcare utilisation (repeat ablation and all-cause hospitalisation), quality of life (QoL; measured by EQ-5D-3L) and predefined symptoms were reported on. Results. Participants in the SA cohort were a mean (standard deviation) of 60 (12) years old, 19 (23.5%) were female, and 48 (59.3%) presented with PAF. The overall presence of baseline comorbidities in the SA cohort was relatively low compared with the entire Cryo Global Registry cohort. The acute PVI success rate was high (98.8%). Two serious procedure-related adverse events occurred in 2 (2.5%) participants in the SA cohort. Freedom from arrhythmia recurrence was 97.4% (95% confidence interval (CI) 83.2 - 99.6%) in PAF and 78.4% (95% CI 58.1 - 89.7%) in persistent AF (p=0.035). Kaplan-Meier estimates for freedom from repeat ablations and all-cause hospitalisations were 97.0% (95% CI 88.4 - 99.2%) and 98.5% (95% CI 90.0 - 99.8%), respectively. Participants reported significant improvement in EQ-5D-3L index score and symptoms from baseline (0.90 (0.11)) - 12 months (0.97 (0.07), p&lt;0.001). Conclusion. CBA standard-of-care procedures in SA resulted in a high clinical freedom from arrhythmia recurrence, with a low risk of safety events within 12 months post ablation. In addition, participants experienced an improvement in QoL and high freedom from healthcare utilisation at 12 months. The obtained results will be important for guiding clinical decisions around CBA in SA.

Chromatin activation with H3K36me2 and compartment shift in metastatic castration-resistant prostate cancer

Epigenetic modifiers are upregulated during the process of prostate cancer, acquiring resistance to castration therapy and becoming lethal metastatic castration-resistant prostate cancer (CRPC). However, the relationship between regulation of histone modifications and chromatin structure in CRPC has yet not fully been validated. Here, we reanalyzed publicly available clinical transcriptome and clinical outcome data and identified NSD2, a histone methyltransferase that catalyzes H3K36me2, as an epigenetic modifier that was upregulated in CRPC and whose increased expression in prostate cancer correlated with higher recurrence rate. We performed ChIP-seq, RNA-seq, and Hi-C to conduct comprehensive epigenomic and transcriptomic analyses to identify epigenetic reprogramming in CRPC. In regions where H3K36me2 was increased, H3K27me3 was decreased, and the compartment was shifted from inactive to active. In these regions, 68 aberrantly activated genes were identified as candidate downstream genes of NSD2 in CRPC. Among these genes, we identified KIF18A as critical for CRPC growth. Under NSD2 upregulation in CRPC, epigenetic alteration with H3K36me2-gain and H3K27me3-loss occurs accompanying with an inactive-to-active compartment shift, suggesting that histone modification and chromatin structure cooperatively change prostate carcinogenesis.

Trend and Determinants of Neonatal Mortality at the Buea and Limbe Regional Hospitals, Southwest Region, Cameroon

Background: Over the years the rate of neonatal mortality in low-income settings has been on the increase and most cases of neonatal mortality can be associated with modifiable risk factors. However, the rate of neonatal mortality remains high in Cameroon with the Southwest Region having one of the highest rates of neonatal mortality. Objectives: We aimed to determine the trend and determinants of neonatal mortality in Buea and Limbe Regional Hospitals. Method and Materials: A hospital based retrospective study of files of neonates was conducted from the 1st of January 2017 to the 31st of December 2022. Socio-demographic, clinical and outcome data were obtained using a data extraction form and analyzed using Statistical Package for Social Science (SPSS) Version 27. Results: The trend of neonatal mortality was apparently constant (16.1% and 17.8%) between 2017 to 2022. Birth asphyxia 150(53.4%) was found to be the most common cause of neonatal mortality. Identified determinants were: acute fetal distress (AOR:2.6 [1.333-5.346]), no ANC visit (AOR:13.1 [3.849-44.284]), birth weight less than 2500g (AOR:2.050 [0.039-4.216]), birth weight greater than 4000 g (AOR:2 [1.002-3.43]), Apgar Score ˂ 3 (AOR:99.9 [87.036-100.000]) and Apgar score ˂ 6 (AOR=5.164 [1.768-15.082]). Conclusion: Neonatal mortality in our context is still below the expectations of SDG3 with perinatal asphyxia and its related modifiable factors influencing neonatal mortality the most. Therefore, more impactful community education and information sessions to build a positive mind set on pregnant women and their families to reduce neonatal mortality is required from all health sectors.

Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea

Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.

Does renal denervation require cardiovascular outcome-driven data?

Hypertension is a major driver of cardiovascular disease with a prevalence of 32-34% in adults worldwide. This poses a formidable unmet challenge for healthcare systems, highlighting the need for enhanced treatment strategies. Since 2017, eight major sham-controlled randomised controlled trials have examined the effectiveness and safety of renal denervation (RDN) as therapy for BP control. Although most trials demonstrated a reduction in systolic 24-hour/daytime ambulatory BP compared to control groups, open to discussion is whether major adverse cardiovascular events (MACE)-driven RDN trials are necessary or whether the proof of BP reduction as a surrogate for better cardiovascular outcomes is sufficient. We conducted an analysis of the statistical methods used in various trials to assess endpoint definitions and determine the necessity for MACE-driven outcome data. Such comprehensive analysis provides further evidence to confidently conclude that RDN significantly reduces blood pressure compared to sham controls. Importantly, this enables the interpolation of RDN trial endpoints with other studies that report on outcome data, such as pharmacological trials which demonstrate a significant reduction in MACE risk with a decrease in BP. Moreover, limitations associated with directly evaluating outcome data further support the use of BP as a surrogate endpoint. For example, conducting lengthier trials with larger numbers of participants to ensure robust statistical power presents a substantial challenge to evaluating outcome data. Thus, in light of the crucial need to tackle hypertension, there are notable advantages of considering BP as a surrogate for outcome data.

Improved Postoperative Pain Management Outcomes After Implementation of Enhanced Recovery After Surgery (ERAS) Protocol for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center. A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs). A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012). ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.

Disposable E-Cigarette Use and Subsequent Use Patterns in Adolescents and Young Adults.

Disposable electronic cigarettes (e-cigarettes) are widely used by adolescents and young adults (AYAs). Whether using disposable devices is associated with future e-cigarette use patterns is unknown but important for informing e-cigarette regulation. Prospective longitudinal study combining data from adolescent (14-17 years) and young adult (21-24 years) cohorts from Southern California surveyed at baseline and approximately 8-month follow-up during 2021 to 2022. The analyses included AYAs who used e-cigarettes in the past 30 days at baseline and had exposure and outcome data (N = 403; adolescent n = 124, young adult n = 279). In the pooled sample of AYAs who used e-cigarettes at baseline (57.2% cis-gender female, 56.2% Hispanic), 278 (69.0%) reported past 30-day disposable e-cigarette use, and 125 (31.0%) used only nondisposable e-cigarettes. Baseline use of disposable (versus only nondisposable) devices was associated with higher odds of continued e-cigarette use (adjusted odds ratio = 1.92; 95% confidence interval = 1.09-3.42) and a greater number of times used e-cigarettes per day at follow-up (adjusted incidence rate ratio = 1.29; 95% confidence interval = 1.02-1.63). In supplemental analyses, disposable e-cigarette use was associated with greater odds of no changes (versus reductions) in e-cigarette use frequency and puffs per episode from baseline to follow-up but was not associated with increases in use frequency and intensity. No differences in e-cigarette use outcomes were found between those with poly-device (disposable and nondisposable) versus only disposable device use. Use of disposable e-cigarette devices among AYAs may be associated with higher risks for persistent e-cigarette use patterns, which should be considered in tobacco product regulation designed to protect AYAs.