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Treatment Delays and Survival in Patients with Hepatocellular Carcinoma: A Multicenter Cohort Study
No full textAlthough treatment delays have been reported for several cancers, fewer studies have described the prevalence, contributing factors, and impact on survival in patients with HCC. We aimed to evaluate these aspects in a multicenter cohort.
We conducted a retrospective cohort study of patients diagnosed with HCC from 2010 to 2018 across 4 U.S. health systems. Treatment delay was defined as the first treatment >90 days after HCC diagnosis. Univariable and multivariable logistic regression analyses were performed to identify factors associated with treatment delays. The association between treatment delay and overall survival was evaluated using multivariable Cox regression analysis.
Among 1,561 eligible patients (median age 61.7 years, 75.0% men, 65.5% BCLC stage 0/A), treatment delays occurred in 357 (22.9%) patients. Treatment delays were most frequent with BCLC stage 0 (31.1%), followed by stage A (24.3%), stage B (22.6%), and stage C (13.6%). Men (OR 0.68, 95%CI 0.51 - 0.91) and patients with BCLC stage C HCC (vs stage A: OR 0.40, 95%CI 0.25 - 0.63) were less likely to experience delays, whereas those with BCLC stage 0 (vs stage A: OR 1.56, 95%CI 1.06 - 2.29) were more likely to experience delays. In a 6-month landmark analysis, survival did not differ between delayed vs. timely treatment (HR 1.09, 95%CI 0.87 - 1.37). Median survival from the 6-month landmark was 12.1 months (IQR: 5.5 - 23.3) and 14.6 months (IQR: 5.1 - 30.0) for the treatment delay and timely treatment groups, respectively.
Treatment delays exceeding 90 days occurred in over one-fifth of patients but were not associated with significant differences in survival
Hematoma expansion in intracerebral hemorrhage retrospective chart review: Who are the super-expanders?
No full textHematoma expansion in intracerebral hemorrhage (ICH) is a predictor of poor outcome and remains an important therapeutic target. Little is known about the incidence and clinical characteristics of patients with severe hematoma expansion, who we hereafter label as super-expanders.
We retrospectively reviewed baseline clinical and radiological features in consecutive ICH patients admitted over a three-year period to a comprehensive stroke center. Hematoma expansion was defined conventionally as a > 33 % increase in hematoma volume or a > 6 ml increase in absolute hematoma volume between the baseline and 24-hour follow-up brain CT. Severe hematoma expansion was defined as a > 50 % increase in ICH volume associated with a decrease in the Glasgow Coma Scale of at least four points. We used Random Forest (RF) to generate importance plots searching for the determinants of super-expanders in ICH. In addition, a multivariable logistic regression model was done to examine independent factors associated with super-expanders.
We analyzed 417 cases. Hematoma expansion, defined conventionally, occurred in 97/417 (23 %) patients of which 15/417 (4 %) were super-expanders. In the univariate analysis, super-expanders were more likely to have a lobar hemorrhage, spot sign, and increased in-hospital mortality. Using the RF analysis, age, platelet count, and presence of a spot sign emerged as important determinants of super-expansion. In a multivariable model, only spot sign was an independent predictor for super-expansion [Age (OR = 1.43, 95 % CI=0.61–3.37), spot sign (OR = 6.25, 95 % CI=2.30–17.00), lobar location (OR = 4.63, 95 % CI= 0.92–23.42)].
We describe a low incidence of 4 % of severe hematoma expansion in ICH. There were no definitive clinical or radiological characteristics that differentiated super-expanders. Identifying such characteristics may allow for patient risk stratification. We encourage further investigations into the early identification of super-expanders, who arguably have the most to benefit from aggressive interventions.
•"Super-expander" hematomas comprised only 4 % (15/417) of intracranial hemorrhages, making them uncommon but clinically relevant.•CTA spot sign was the only independent predictor and potential early risk stratifier of super-expansion, with an odds ratio (OR) of 6.25•Super-expanders were more likely to have lobar hemorrhages, a spot sign, and higher in-hospital mortality.•Age, platelet count, and spot sign were important variables per Random Forest, but only spot sign was signficant per multivariable analysis
Atomistically informed partial dislocation dynamics of multi-principal element alloys
No full textMulti-principal element alloys (MPEAs) continue to attract considerable attention. However, one fundamental question regarding their plasticity remains far from well understood, namely, how the nanoscale heterogeneity and chemical short-range order (SRO) control dislocation motion and plasticity. Different from previous studies incorporating statistical variations of the energy landscape into full dislocation dynamics, the current work proposes an innovative atomistically informed partial dislocation dynamics (PDD) method, which directly considers the spatially-correlated non-uniform planar fault energy (PFE) at the atomic scale, and at the same time benefits from the larger temporal and spatial scales of the dislocation dynamics methods. Through systematic analysis, we find that the PFE field exhibits a negative correlation along the atomic slip direction, which reduces the critical stress required for dislocation motion in that direction. In contrast, the correlation characteristics along other directions can be approximated as uncorrelated noise, which also contributes to strengthening. In addition, it is found that SRO only slightly enhances the correlation strength along certain crystallographic directions, while it weakens the degree of negative correlation along the slip direction. Overall, the increase in the mean PFE induced by SRO significantly contributes to the strengthening of the dislocation depinning transition. The proposed model provides new opportunities for designing MPEAs with tailored macroscopic mechanical properties by manipulating their atomic distribution and spatial correlations.
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Validation of Lawrence and Botte classification of proximal fifth metatarsal fractures
No full textThe Lawrence and Botte (LB) classification of proximal fifth metatarsal fractures guides clinical management, yet its reliability has been sparsely evaluated. This study investigated intra- and inter-rater reliability of the LB system among trained observers.
A retrospective chart review identified patients with proximal fifth metatarsal fractures. Deidentified radiographs (AP, lateral, oblique) were reviewed by two orthopedic surgeons and one radiologist. Each observer classified fractures using the LB system in two surveys separated by at least two weeks. Identical radiographs were reordered between surveys to assess inter- and intra-rater reliability. Statistical analysis included Kruskal–Wallis, Friedman, weighted kappa, Cohen's kappa, and Fleiss' kappa.
200 patients were screened, and 85 radiographs included. Inter-rater reliability in Survey A showed no significant differences by Kruskal–Wallis; Friedman testing suggested minimal but significant variability. In Survey B, Kruskal–Wallis indicated significant differences in rankings. Weighted kappa coefficients for inter-rater reliability ranged 0.58–0.69 (moderate–substantial agreement). Intra-rater reliability ranged 0.61–0.82, with observer 2 highest (0.82). Cohen's kappa values were 0.58–0.71. Agreement between surveys (Fleiss' kappa) was 0.56, indicating moderate reliability.
The LB classification system demonstrates moderate inter-rater and substantial intra-rater reliability, though variability persists between raters and time points. While reasonably consistent, the findings highlight subjectivity in interpretation and suggest potential benefit in simplified schemes to improve agreement.
•Moderate inter-observer agreement using the Lawrence and Botte system•Substantial intra-observer agreement among experienced musculoskeletal specialists•Zone 2–3 fractures showed the greatest classification disagreement.•Dichotomized “tuberosity vs. non-tuberosity” model improved reliability
Habitat Type and Group Identity Influence Activity Budgets in White-Handed Gibbons (Hylobates lar) in Two Habitat Types in Western Thailand
No full textActivity patterns reveal important information about how primates cope with challenging ecological conditions. This study investigates behavioral variation in white-handed gibbons (Hylobates lar) living at the ecological extreme of their range in a heterogeneous landscape in western Thailand. We spent 13 months studying 4 groups at Khao Nang Rum Wildlife Research Station in Huai Kha Khaeng Wildlife Sanctuary, where gibbons are found living in both evergreen and savannah habitats, both of which we describe as poor-quality habitat. Given specific phenological properties (e.g., predominance of deciduous species) of the savannah habitat, we predicted that food resources would be less available in the savannah habitat compared to the evergreen habitat, making the savannah an even lower quality habitat for these frugivorous apes. The evergreen habitat produced more fruit and young leaves throughout all three seasons, and more flowers during the wet season, compared to the lower-quality savannah habitat. We furthermore predicted that habitat type would drive differences in activity budget. Gibbons in both habitats exhibited high rates of resting behavior (50.1% evergreen, 52.3% savannah), possibly in response to a particularly dry year. However, while activity budget differed between habitats, group identity was a better predictor of this variation. Specifically, compared to evergreen gibbons, savannah gibbons spent more time feeding (28.9% vs. 22.5%) and less time vocalizing (4.2% vs. 12.1%), but this varied between the two savannah groups with one group spending more time traveling (7.7% vs. 3.6%) and less time resting (50.0% vs. 58.4%) than the other group. We suggest that gibbons at this poor-quality site, and specifically in the even lower quality savannah habitat, are responding to the availability of specific key resources within their home ranges and that groups in the savannah habitat are employing unique strategies in response to the relative scarcity of fruit resources compared to the evergreen habitat
From Synthesis to Visualization: Lanthanide-Doped Carbon Dots as Emerging Tools in Bioimaging Research
No full textThe lanthanide (Ln) doped CDs have been identified as a useful candidate for dual mode imaging including fluorescence and magnetic resonance imaging (MRI). Their fluorescence and surface properties depend on the selection of the precursor and synthetic method. At present, most of the Ln-doped CDs are prepared by hydrothermal method and only few are made from microwave heating and other methods. In addition, most CDs possess a negative surface charge. Considering the diverse mode of preparation and properties, the development of Ln-CDs as a dual mode imaging agent is still in the early stage. In this work, we focus on (1) developing gadolinium doped CDs with a positive surface charge and compare the properties of CDs prepared from two synthetic methods: hydrothermal and microwave, (2) comparative study of Gd-CNDs produced from gadopentetic acid and gadolinium chloride as a Gd-source, and (3) study of Dysprosium doped CDs. The optical properties of CDs, cytotoxicity, and their applications in bioimaging were discussed. During the study, the Gd-CDs obtained from microwave (MW) method were found less toxic compared to those obtained from hydrothermal (HT) method. In addition, these CDs are less toxic to the non-cancer cells compared to the cancer ones. Furthermore, the magnetic resonance (MR) images produced from the CDs indicate that the Gd-MW CDs appeared much brighter than the images produced from Gd-HT CDs. The overall results and observations indicate that the microwave route of synthesis is preferable over hydrothermal, and the Gd-MW CDs could be a promising candidate for a multimodal theranostics agent due to their capability to image and target the tumor cells simultaneously. In other studies, the properties of Gd-CNDs prepared from two different gadolinium sources (gadopentetic acid and gadolinium chloride) were studied. In addition, Dysprosium doped CDs were presented as a future candidate for contrast agent in the high magnetic field MR imaging.</p
Body Talk: Correlates of Gut-Immune Dysregulation Phenotypes in People Living with HIV Who Use Methamphetamine
No full textMicrobial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors are interacting pathophysiologic processes linked to neuropsychiatric comorbidities and faster HIV disease progression. We examined correlates of distinct phenotypes of gut-immune dysregulation in people living with HIV (PWH) who use methamphetamine.
Participants were 122 PWH who had biochemically confirmed recent methamphetamine use, including non-injection use. Peripheral plasma markers reflected: intestinal permeability, microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors. Using latent profile analysis (i.e., clustering) of these markers, we identified gut-immune phenotypes and their clinical, demographic, and stigma-related correlates.
Three immune profiles emerged: (1) low gut-immune dysregulation with lower microbial translocation, macrophage activation, inflammation, and tryptophan catabolism; (2) moderate gut-immune dysregulation with all markers within average range; and (3) high gut-immune dysregulation with higher microbial translocation, immune activation, inflammation, and tryptophan catabolism. In adjusted analyses, higher viral load (one log10 copy/ml; AOR=1.97, 95% CI=1.02-3.82), injection of methamphetamine (AOR=3.60, 95% CI=1.23-10.50), and internalized stigma (AOR=1.78, 95% CI=1.01-3.15) were associated with having a moderate gut-immune dysregulation profile. Additionally, higher viral load (AOR=2.98, 95% CI=1.53-5.24) and injecting methamphetamine (AOR=5.45, 95% CI=1.34-17.78) were associated with having a high gut-immune dysregulation profile.
Distinct patterns of microbial translocation, immune activation, inflammation, and metabolism of amino acid precursors distinguished gut-immune phenotypes of PWH reporting injection methamphetamine use and greater internalized stigma. Interventions tailored to PWH who inject methamphetamine or struggle with internalized stigma could optimize HIV-related health outcomes
Association of hospital characteristics with outcomes for pediatric neurosurgical accidental trauma patients
No full textOBJECTIVE In the pediatric population, few studies have examined outcomes for neurosurgical accidental trauma care based on hospital characteristics. The purpose of this study was to explore the relationship between hospital ownership type and children's hospital designation with primary outcomes. METHODS This retrospective cohort study utilized data from the Healthcare Cost and Utilization Project 2006, 2009, and 2012 Kids’ Inpatient Database. Primary outcomes, including inpatient mortality, length of stay (LOS), and favorable discharge disposition, were assessed for all pediatric neurosurgery patients who underwent a neurosurgical procedure and were discharged with a primary diagnosis of accidental traumatic brain injury. RESULTS Private, not-for-profit hospitals (OR 2.08, p = 0.034) and freestanding children's hospitals (OR 2.88, p = 0.004) were predictors of favorable discharge disposition. Private, not-for-profit hospitals were also associated with reduced inpatient mortality (OR 0.34, p = 0.005). A children's unit in a general hospital was associated with a reduction in hospital LOS by almost 2 days (p = 0.004). CONCLUSIONS Management at freestanding children's hospitals correlated with more favorable discharge dispositions for pediatric patients with accidental trauma who underwent neurosurgical procedures. Management within a children's unit in a general hospital was also associated with reduced LOS. By hospital ownership type, private, not-for-profit hospitals were associated with decreased inpatient mortality and more favorable discharge dispositions
Urbanization and Livelihood Resilience in Mexican Small-Scale Fishing Communities
No full textDue to global trends in coastal development and population growth, more small-scale fishing (SSF) communities are living and working within urban environments. These urban transformations present SSF communities with unique opportunities and challenges. However, it is unclear how SSF communities and households are pursuing resilience in the face of these transformations. Policymakers can use the answer to this question to create policies that align with these resilience-building strategies and minimize the possibility that coastal development leads to the economic marginalization of SSF communities. In this dissertation, I aim to investigate this question through a case study of livelihood resilience, or the capacity of a livelihood to withstand shocks and stresses, in Mexican SSF communities. I divide this case study into three investigations detailed in Chapters Two, Three, and Four. Chapter Two is a systematic literature review that analyzes how opportunities and challenges for livelihood resilience differ between Mexico’s urban and rural SSF communities. Chapter Three is an ethnographic study that analyzes how fishers in Cancun perceive and pursue livelihood resilience in the face of rapid urbanization. Finally, Chapter Four is an econometric analysis that uses weighted logistic regression to estimate the relationship between the likelihood that fishing cooperatives have become inactive (defunct) and their distance to the nearest urban center. Together, these studies suggest that urban fishers in Mexico pursue livelihood resilience by adapting their strategies for self-organization (i.e., by favoring patron-client relationships or free fishing over cooperatives) or by exiting the fishing sector entirely. Policymakers interested in bolstering livelihood resilience in urban SSF communities must consider the opportunities and challenges for doing so that are inherent to the urban environment.</p