Healthcare disparities in access to surgical management and outcomes of patients with nonmetastatic primary liver cancer: A population based study from Louisiana tumor registry.

BACKGROUND: This study aims to identify factors associated with disparities in receipt and outcomes of surgical interventions in patients with primary nonmetastatic liver cancers. METHODS: Cases from 2010 to 2020 were identified using Louisiana Tumor Registry. Four surgical categories were utilized: none, ablation, resection, transplant. Bivariate relationships were assessed via Chi-square tests. Overall survival (OS) was visualized using Kaplan Meier plots, compared via log-rank test, and analyzed with Cox proportional hazards models. RESULTS: Only 24.5 â€‹% of patients underwent surgical interventions. Black race had decreased odds of undergoing transplant and decreased OS with transplant. Uninsured, Medicaid, and rural residence had decreased odds of receiving surgical intervention. Older age and no domestic partner had decreased odds of transplant. Older age, male sex, no domestic partner, and rural residence had decreased OS post-transplant. CONCLUSIONS: Identifying the population at risk for not receiving surgical intervention and allocating resources to access care is crucial to improve outcomes.

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Our proteome-wide analysis of older adults (mean age: 76) identified 13 WMH-associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis, two of which remained associated with late-life WMH volume when measured nearly 20 years earlier, during midlife. We replicated the relationship between 9 candidate proteins and WMH volume in one or more external cohorts; we found that 11 of the 13 proteins were associated with risk for future dementia; and we leveraged publicly available proteomic data from brain tissue to demonstrate that a subset of WMH-associated proteins was differentially expressed in the context of cerebral atherosclerosis, pathologically-defined Alzheimer's disease, and cognitive decline. Bidirectional two-sample Mendelian randomization analyses examined the causal relationships between candidate proteins and WMH volume, while pathway and network analyses identified discrete biological processes (lipid/cholesterol metabolism, NF-kB signaling, hemostasis) associated with distinct forms of SVD. Finally, we synthesized these findings to identify two plasma proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), as top candidate biomarkers for elevated WMH volume and its clinical manifestations.

Assessing the Dispersion Stability of Antimicrobial Fillers in Photosensitive Resin for Vat Polymerization 3D Printing.

Polymers are widely used in healthcare due to their biocompatibility and mechanical properties; however, the use of polymers in medical products can promote biofilm formation, which can be a source of hospital-acquired infections. Due to this, there is a rising demand for inherently antimicrobial polymers for devices in contact with patients. 3D printing as a manufacturing technology has increased exponentially in recent years. Surgical guides, orthotics, and prosthetics, among other medical devices, created by vat polymerization have been used in hospitals to treat patients. Biocompatible resins are available for these applications, but there is a lack of antimicrobial resins, which would further improve the technology for clinical use. The focus of this study was to assess settling of candidate antimicrobial metal and metal oxide fillers in vat polymerization resin to determine which fillers were compatible with the resin. Dispersion stability was assessed by measuring settling over the maximum print duration of the medium priced desktop 3D printers to evaluate printability of 17 potentially antimicrobial resins. Eight materials displayed settling behavior during the test period: molybdenum oxide, zirconium oxide nanopowder, scandium oxide, zirconium oxide, titanium oxide, tungsten oxide, lanthanum oxide, and magnesium oxide. No settling was observed for manganese oxide, magnesium oxide nanopowder, titanium oxide nanopowder, copper oxide, silver oxide, zinc oxide nanopowder, zinc oxide, silver nanopowder, and gold nanopowder during the test period. This method could be applied to assess settling of other fillers introduced into 3D printing resins before actual printing.

Validation of consumables used in the recovery of DNA evidence within Sexual Assault Referral Centres (SARCs).

This study assessed the fitness for purpose of consumables used for the recovery of body-fluids and biological material for subsequent DNA analysis in forensic medical examinations, specifically within Sexual Assault Referral Centres (SARCs). All 55 SARCs in England and Wales participated in this validation exercise by submitting unused critical DNA consumables from their local storage areas. Overall, 261 consumable items identified as forensic DNA grade were assessed for the presence of DNA contamination and 100 % passed testing, demonstrating that consumables purchased under the National Scenes of Crimes Consumables Contract remained fit for purpose, regarding detectable levels of DNA, up to the point of use within the SARCs. In addition, 14 non-forensic DNA grade items were analysed, of which over a third failed due to unsourced DNA contamination, highlighting why it is essential that only forensic DNA grade consumables are used for evidential recovery processes to minimise the risk of contamination.

Skin heating during simulated hemorrhage lowers arterial blood pressure but not tolerance following exercise in a cold environment.

Skin heating helps avoid hypothermia in trauma victims but may influence the systolic (SBP) and mean arterial blood pressures (MAP) helping to guide resuscitation. We examined the effect of skin heating on tolerance and arterial blood pressure during lower body negative pressure (LBNP) across four trials. Nine participants completed 15 exercise intervals [60 s 88% peak power output (PPO) and 60 s 10% PPO] in a cold environment (0°C, 70% RH) lowering mean skin temperature (Tsk) before undergoing LBNP to pre syncope where Tsk remained low (Cold Trial: 27.6 ± 1.1°C) or was increased via a water-perfused suit 60 s into LBNP to 32.3 ± 0.7°C (Normothermic Trial), 34.8 ± 0.4°C (Warm Trial), or 36.1 ± 0.8°C (Hot Trial). Tsk was different between trials (P = 0.001). Core temperature was not different between trials, increasing with exercise (36.9 ± 0.3°C to 37.9 ± 0.4°C) and remaining elevated during LBNP (37.7 ± 0.4°C). During LBNP, MAP was greatest in the Cold Trial (88 ± 7 mmHg) and relatively lowered in the Normothermic (83 ± 5 mmHg), Warm (82 ± 5 mmHg), and Hot Trials (79 ± 7 mmHg; all P ≤ 0.017 vs. Cold). SBP was greatest in the Cold (111 ± 9 mmHg) and Normothermic Trials (110 ± 10 mmHg) and relatively lowered in the Warm (105 ± 7 mmHg) and Hot Trials (103 ± 11 mmHg; both P ≤ 0.037). LBNP tolerance was not different between trials (P = 0.746). Following exercise in a cold environment, skin heating during simulated hemorrhage lowers arterial blood pressures and has implications for prehospital care of trauma victims.NEW & NOTEWORTHY Skin heating helps avoid hypothermia in trauma victims but may influence arterial blood pressures, thus helping to guide resuscitation depending on the type of injury. Following exercise in a cold environment, arterial blood pressure was elevated during LBNP with cold skin but lowered with skin heating without changing LBNP tolerance. These findings are important for understanding the effect of skin heating on arterial blood pressure control in the prehospital and combat casualty care of trauma victims.

Managing fruit rot diseases of Vaccinium corymbosum.

Blueberry is an important perennial fruit crop with expanding consumption and production worldwide. Consumer demand for blueberries has grown due to the desirable flavor and numerous health benefits, and fresh market production in the U.S. has risen in turn. U.S. imports have also increased to satisfy year-round consumer demand for fresh blueberries. Pre- and post-harvest fruit diseases such as anthracnose (caused by Colletotrichum spp.) and botrytis fruit rot (caused by Botrytis spp.) have a significant impact on fruit quality and consumer acceptance. These are also among the most difficult diseases to control in the blueberry cropping system. These latent pathogens can cause significant losses both in the field, and especially during transport and marketplace storage. Although both diseases result in rotted fruit, the biology and infection strategies of the causal pathogens are very different, and the management strategies differ. Innovations for management, such as improved molecular detection assays for fungicide resistance, postharvest imaging, breeding resistant cultivars, and biopesticides have been developed for improved fruit quality. Development and integration of new strategies is critical for the long-term success of the blueberry industry.

Psychosocial Health and the Association Between Cerebral Small Vessel Disease Markers With Dementia: The ARIC Study.

BACKGROUND: Associations between magnetic resonance imaging markers of cerebral small vessel disease (CSVD) and dementia risk in older adults have been established, but it remains unclear how lifestyle factors, including psychosocial health, may modify this association. METHODS: Social support and social isolation were assessed among participants of the community-based ARIC (Atherosclerosis Risk in Communities) Study, via self-reported questionnaires (1990-1992). Following categorization of both factors, participants were classified as having strong or poor mid-life social relationships. At visit 5 (2011-2013), participants underwent 3T brain magnetic resonance imaging quantifying CSVD measures: white matter hyperintensity volume, microbleeds (subcortical), infarcts (lacunar), and white matter integrity (diffusion tensor imaging). Incident dementia cases were identified from the time of imaging through December 31, 2020 with ongoing surveillance. Associations between CSVD magnetic resonance imaging markers and incident dementia were evaluated using Cox proportional-hazard regressions adjusted for demographic and additional risk factors (from visit 2). Effect modification by mid-life social relationships was evaluated. RESULTS: Of the 1977 participants with magnetic resonance imaging, 1617 participants (60.7% women; 26.5% Black participants; mean age at visit 2, 55.4 years) were examined. In this sample, mid-life social relationships significantly modified the association between white matter hyperintensity volume and dementia risk (P interaction=0.001). Greater white matter hyperintensity volume was significantly associated with risk of dementia in all participants, yet, more substantially in those with poor (hazard ratio, 1.84 [95% CI, 1.49-2.27]) versus strong (hazard ratio, 1.26 [95% CI, 1.08-1.47]) mid-life social relationships. Although not statistically significant, subcortical microbleeds in participants with poor mid-life social relationships were associated with a greater risk of dementia, relative to those with strong social relationships, in whom subcortical microbleeds were no longer associated with elevated dementia risk. CONCLUSIONS: The elevated risk of dementia associated with CSVD may be reduced in participants with strong mid-life social relationships. Future studies evaluating psychosocial health through the life course and the mechanisms by which they modify the relationship between CSVD and dementia are needed.

Neighborhood Socioeconomic Disadvantage Across the Life Course and Premature Mortality.

Importance: There are consistent data demonstrating that socioeconomic disadvantage is associated with risk of premature mortality, but research on the relationship between neighborhood socioeconomic factors and premature mortality is limited. Most studies evaluating the association between neighborhood socioeconomic status (SES) and mortality have used a single assessment of SES during middle to older adulthood, thereby not considering the contribution of early life neighborhood SES. Objective: To investigate the association of life course neighborhood SES and premature mortality. Design, Setting, and Participants: This cohort study included Black and White participants of the multicenter Atherosclerosis Risk in Communities Study, a multicenter study conducted in 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the northwestern suburbs of Minneapolis, Minnesota. Participants were followed up for a mean (SD) of 18.8 (5.7) years (1996-2020). Statistical analysis was performed from March 2023 through May 2024. Exposure: Participants' residential addresses during childhood, young adulthood, and middle adulthood were linked with US Census-based socioeconomic indicators to create summary neighborhood SES scores for each of these life epochs. Neighborhood SES scores were categorized into distribution-based tertiles. Main Outcomes and Measures: Premature death was defined as all-cause mortality occurring before age 75 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results: Among 12 610 study participants, the mean (SD) age at baseline was 62.6 (5.6) years; 3181 (25.2%) were Black and 9429 (74.8%) were White; and 7222 (57.3%) were women. The lowest, compared with the highest tertile, of neighborhood SES score in middle adulthood was associated with higher risk of premature mortality (HR, 1.28; 95% CI, 1.07-1.54). Similar associations were observed for neighborhood SES in young adulthood among women (HR, 1.25; 95% CI, 1.00-1.56) and neighborhood SES in childhood among White participants (HR, 1.25; 95% CI, 1.01-1.56). Participants whose neighborhood SES remained low from young to middle adulthood had an increased premature mortality risk compared with those whose neighborhood SES remained high (HR, 1.25; 95% CI, 1.05-1.49). Conclusions and Relevance: In this study, low neighborhood SES was associated with premature mortality. The risk of premature mortality was greatest among individuals experiencing persistently low neighborhood SES from young to middle adulthood. Place-based interventions that target neighborhood social determinants of health should be designed from a life course perspective that accounts for early-life socioeconomic inequality.

Effect of Hearing Intervention Versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE Study.

BACKGROUND: Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss. METHODS: Participants aged 70-84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; Washington County, Maryland) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle. RESULTS: Participants (n = 977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (ß = -0.12 [95% CI: -0.22, -0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS-fatigue score (ß = -0.32 [95% CI: -1.15, 0.51]). CONCLUSIONS: Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.

Initial surgery for spontaneous intestinal perforation in extremely low birth weight infants is not associated with mortality or in-hospital morbidities.

OBJECTIVE: Determine short-term outcomes following peritoneal drain (PD), laparotomy (LAP) after PD (PD-LAP), and LAP in extremely low birth weight (ELBW) infants with spontaneous intestinal perforation (SIP). STUDY DESIGN: ELBW infants with SIP were identified using the Children's Hospitals Neonatal Database. Mortality and length of stay (LOS) were compared among groups. RESULTS: Of 729 SIP infants from 6/2010-12/2016, 383(53%) received PD, 61(8%) PD-LAP, and 285(39%) LAP. PD infants had lower GA at birth, at SIP diagnosis and upon admission than PD-LAP or LAP; and higher sepsis rates than LAP. Bivariate analysis and Kaplan-Meier survival estimates suggested PD had increased mortality vs. PD-LAP and LAP (27%, 11.5%, and 15.8% respectively, p < 0.001). However, surgical approach was not significantly associated with mortality in multivariable analysis accounting for GA and illness severity. LOS did not differ by surgical approach. CONCLUSIONS: In ELBW infants with SIP, mortality, and LOS are independent of the initial surgical approach.

Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma.

PURPOSE: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. MATERIALS AND METHODS: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. RESULTS: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. CONCLUSIONS: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia.

Importance: Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. Objective: To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. Design, Setting, and Participants: In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013. Exposure: Plasma biomarkers of amyloid-ß 42 to amyloid-ß 40 (Aß42:Aß40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform. Main Outcomes and Measures: Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance. Results: Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aß42:Aß40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 (APOEε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aß42:Aß40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Conclusions and Relevance: Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers' association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.

Differences in [123I]Ioflupane Striatal Binding Between African American and White Patients.

Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore whether differences exist in [123I]ioflupane binding, which reflects dopamine transporter binding, between African American and White individuals. Methods: Medical charts were reviewed for patients who underwent [123I]ioflupane SPECT imaging as part of routine practice in a single academic medical center. All images were visually graded as showing normal or abnormal presynaptic dopaminergic function (normal or abnormal scan status). Quantitative [123I]ioflupane uptake as measured by the specific binding ratios in the right and left striata and their subregions (caudate nucleus and anterior and posterior putamen) and by bilateral putamen-to-caudate ratios were compared between African American and White patients using multiple linear regression adjusted for age, sex, and abnormal scan status. Additional models included an ethnicity-by-abnormal-scan-status interaction term to determine whether abnormal scan status was modulated by ethnicity effect. Results: The percentage of patients with abnormal scan status was comparable between African American and White patients. Compared with White patients (n = 173), African American patients (n = 82) had statistically significantly higher uptake as measured by specific binding ratios in the right and left striata and some of their subregions (right and left caudate nuclei and right posterior putamen). Ethnicity-by-abnormal-scan-status interactions were not statistically supported for any models. Conclusion: We observed differences in [123I]ioflupane binding between African American and White patients independent of presynaptic dopaminergic dysfunction status. Future studies are needed to examine whether and how ethnicity affects dopamine transporter binding activities and its clinical relevance.

Lung Function and Brain MRI Outcomes in the Atherosclerosis Risk in Communities Neurocognitive Study.

Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke. Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations. Methods: Lung function was measured at participants' midlife in 1990-1992 (mean age = 56±5 years) and later-life in 2011-2013 (mean age = 76±5 years), and brain MRI was performed in 2011-2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders. Results: In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, n = 1,223), higher forced-expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54-14.71) cm3 greater total brain volume per one-liter higher FEV1]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, n = 1,787), higher FVC levels were significantly associated with lower later-life brain volumes. Conclusions: Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers.

Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study.

INTRODUCTION: The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. METHODS: We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. RESULTS: Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). DISCUSSION: By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. HIGHLIGHTS: Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

Comprehensive Approach to the Management of Patients With Hypoplastic Left Heart Syndrome: Analysis of 100 Consecutive Neonates.

BACKGROUND: We report our comprehensive approach to the management of patients with hypoplastic left heart syndrome (HLHS) and describe our outcomes in 100 consecutive neonates. METHODS: We stratified 100 consecutive neonates (January 1, 2015 to September 1, 2023, inclusive) into 3 pathways. Pathway 1: 77 of 100 (77%) were standard risk and underwent an initial Norwood Stage 1. Pathway 2: 10 of 100 (10%) were high-risk with noncardiac risk factors and underwent an initial Hybrid Stage 1. Pathway 3: 13 of 100 (13%) were high-risk with cardiac risk factors: 10 underwent an initial Hybrid Stage 1 + Ventricular Assist Device insertion (HYBRID+VAD), and 3 were supported with prostaglandin as a planned bridge to primary cardiac transplantation. RESULTS: The overall 1-year mortality for the entire cohort of 100 patients was 9% (9 of 100). Pathway 1: Operative Mortality in Pathway 1 for the initial Norwood Stage 1 was 2.6% (2 of 77). Of the 75 survivors of Norwood Stage 1, 72 underwent successful Glenn, 2 underwent successful biventricular repair, and 1 underwent successful cardiac transplantation. Pathway 2: Operative Mortality in Pathway 2 for the initial Hybrid Stage 1 without VAD was 10% (1 of 10). Of 9 survivors of Hybrid Stage 1, 4 underwent successful cardiac transplantation, 1 died while awaiting cardiac transplantation, 3 underwent Comprehensive Stage 2 (with 1 Operative Mortality after Comprehensive Stage 2), and 1 underwent successful biventricular repair. Pathway 3: Of 10 patients supported with initial HYBRID+VAD in Pathway 3, 7 (70%) underwent successful cardiac transplantation and are alive today, and 3 (30%) died on VAD while awaiting transplantation. Median VAD support time was 134 days (range, 56-226 days). Of 3 patients who were bridged to transplant with prostaglandin, 2 underwent successful transplantation and 1 died while awaiting transplantation. CONCLUSIONS: A comprehensive approach to the management of patients with HLHS is associated with an Operative Mortality after Norwood of 2.6% (2 of 77) and an overall 1-year mortality of 9% (9 of 100). Ten patients (10%) were stabilized with HYBRID+VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged waiting times.

Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity.

Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown. Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity. Design, Setting, and Participants: Individual participant data from 6 US longitudinal cohorts (January 1, 1971, to December 31, 2019) were pooled. The analysis was performed from January 1, 2022, to January 2, 2024. The median follow-up was 21.6 (IQR, 13.6-31.8) years. Exposure: Time-dependent cumulative mean SBP. Main Outcomes and Measures: The primary outcome was time from baseline visit to first incident stroke. Secondary outcomes consisted of time to first incident IS, ICH, and SAH. Results: Among 40 016 participants, 38 167 who were 18 years or older at baseline with no history of stroke and at least 1 SBP measurement before the first incident stroke were included in the analysis. Of these, 54.0% were women; 25.0% were Black, 8.9% were Hispanic of any race, and 66.2% were White. The mean (SD) age at baseline was 53.4 (17.0) years and the mean (SD) SBP at baseline was 136.9 (20.4) mm Hg. A 10-mm Hg higher cumulative mean SBP was associated with a higher risk of overall stroke (hazard ratio [HR], 1.20 [95% CI, 1.18-1.23]), IS (HR, 1.20 [95% CI, 1.17-1.22]), and ICH (HR, 1.31 [95% CI, 1.25-1.38]) but not SAH (HR, 1.13 [95% CI, 0.99-1.29]; P = .06). Compared with White participants, Black participants had a higher risk of IS (HR, 1.20 [95% CI, 1.09-1.33]) and ICH (HR, 1.67 [95% CI, 1.30-2.13]) and Hispanic participants of any race had a higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]). There was no consistent evidence that race and ethnicity modified the association of cumulative mean SBP with first incident stroke and stroke type. Conclusions and Relevance: The findings of this cohort study suggest that cumulative mean SBP was associated with incident stroke type, but the associations did not differ by race and ethnicity. Culturally informed stroke prevention programs should address modifiable risk factors such as SBP along with social determinants of health and structural inequities in society.

Effects of post-curing duration on the mechanical properties of complex 3D printed geometrical parts.

This study aims to assess the efficacy of post-curing guidance supplied by 3D printing resin manufacturers. Current guidance applies generically to all geometries with the caveat that post-curing should be extended for 'large' or 'complex' geometries but specific guidance is not provided. Two vat-polymerisation 3D printers (Form3B, Figure 4 Standalone) were used to print test models in 6 biocompatible resins (Pro Black, Med White, Med Amber, Biomed Black, Biomed White, Biomed Amber). The test model is of a complex geometry whilst also housing ISO 527 test specimens in concentric layers. Two separate intervals of curing were applied (100%, 500% stated guidance) creating different curing treatments of the specimens throughout the model. Post processed test models were disassembled and pull testing performed on each of the specimens to assess the mechanical properties. The analysis showed that extending the curing duration had significant effects on the mechanical properties of some materials but not all. The layers of the model had a significant effect except for elongation at break for the Med Amber material. This research demonstrates that generic post-curing guidance regarding UV exposures is not sufficient to achieve homogenous material strength properties for complex geometries. Large variations in mechanical properties throughout the models suggest some material was not fully-cured. This raises a query if such materials as originally marketed as biocompatible are fully cured and therefore safe to use for medical applications involving complex geometries.

Emerging therapeutic approaches for peritoneal metastases from gastrointestinal cancers.

Peritoneal metastases from gastrointestinal malignancies present difficult management decisions, with options consisting primarily of systemic chemotherapy or major surgery with or without hyperthermic intraperitoneal chemotherapy. Current research is investigating expanding therapeutic modalities, and the aim of this review is to provide an overview of the existing and emerging therapies for the peritoneal metastases from gastrointestinal cancers, primarily through the recent literature (2015 and newer). These include the current data with systemic therapy and cytoreduction with hyperthermic intraperitoneal or pressurized intraperitoneal aerosol chemotherapy, as well as novel promising modalities under investigation, including dominating oncolytic viral therapy and adoptive cellular, biologic, and bacteria therapy, or nanotechnology. The novel diverse strategies, although preliminary and preclinical in murine models, individually and collectively contribute to the treatment of peritoneal metastases, offering hope for improved outcomes and quality of life. We foresee that these evolving treatment approaches will facilitate the transfer of knowledge and data among studies and advance discovery of new drugs and optimized treatments for patients with peritoneal metastases.

Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer.

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients.