Challenges in Orthopedic Surgical Decision-Making for Multilevel Vertebrae Fractures.

Vertebral fractures commonly occur in postmenopausal women due to decreased bone density, a condition known as osteoporosis. They can occur after minimal trauma or even during routine activities. Vertebral fractures occur predominantly in individuals with a high fall risk. This case report explores the clinical complexities surrounding a 65-year-old female patient with a history of multilevel vertebrae fractures compounded by a history of chronic smoking, osteoporosis, multiple falls, and evident signs of osteopenia on X-ray. These risk factors complicate the decision to perform surgery and highlight the importance of constantly weighing the benefits and possible risks. This paper aims to emphasize the gender-specific challenges healthcare providers encounter when assessing surgical risks in the context of postmenopausal females with significant comorbidities. It underlines the need for tailored and comprehensive care strategies to manage orthopedic conditions in high-risk female individuals, further aligning with one of the World Health Organization's concerns on addressing gender-specific health considerations.

Banked Primary Progenitor Cells for Allogeneic Intervertebral Disc (IVD) Therapy: Preclinical Qualification and Functional Optimization within a Cell Spheroid Formulation Process.

Background/Objectives: Biological products are emerging as therapeutic management options for intervertebral disc (IVD) degenerative affections and lower back pain. Autologous and allogeneic cell therapy protocols have been clinically implemented for IVD repair. Therein, several manufacturing process design considerations were shown to significantly influence clinical outcomes. The primary objective of this study was to preclinically qualify (chondrogenic potential, safety, resistance to hypoxic and inflammatory stimuli) cryopreserved primary progenitor cells (clinical grade FE002-Disc cells) as a potential cell source in IVD repair/regeneration. The secondary objective of this study was to assess the cell source's delivery potential as cell spheroids (optimization of culture conditions, potential storage solutions). Methods/Results: Safety (soft agar transformation, ß-galactosidase, telomerase activity) and functionality-related assays (hypoxic and inflammatory challenge) confirmed that the investigated cellular active substance was highly sustainable in defined cell banking workflows, despite possessing a finite in vitro lifespan. Functionality-related assays confirmed that the retained manufacturing process yielded strong collagen II and glycosaminoglycan (GAG) synthesis in the spheroids in 3-week chondrogenic induction. Then, the impacts of various process parameters (induction medium composition, hypoxic incubation, terminal spheroid lyophilization) were studied to gain insights on their criticality. Finally, an optimal set of technical specifications (use of 10 nM dexamethasone for chondrogenic induction, 2% O2 incubation of spheroids) was set forth, based on specific fine tuning of finished product critical functional attributes. Conclusions: Generally, this study qualified the considered FE002-Disc progenitor cell source for further preclinical investigation based on safety, quality, and functionality datasets. The novelty and significance of this study resided in the establishment of defined processes for preparing fresh, off-the-freezer, or off-the-shelf IVD spheroids using a preclinically qualified allogeneic human cell source. Overall, this study underscored the importance of using robust product components and optimal manufacturing process variants for maximization of finished cell-based formulation quality attributes.

An Adhesive Hydrogel Technology for Enhanced Cartilage Repair: A Preliminary Proof of Concept.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels' adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

SPA Promotes Atherosclerosis Through Mediating Macrophage Foam Cell Formation-Brief Report.

BACKGROUND: Atherosclerosis is a progressive inflammatory disease in which macrophage foam cells play a central role in disease pathogenesis. SPA (surfactant protein A) is a lipid-associating protein involved with regulating macrophage function in various inflammatory diseases. However, the role of SPA in atherosclerosis and macrophage foam cell formation has not been investigated. METHODS: SPA expression was assessed in healthy and atherosclerotic human coronary arteries and the brachiocephalic arteries of wild-type or ApoE-deficient mice fed high-fat diets for 4 weeks. Hypercholesteremic wild-type and SPA-deficient mice fed a high-fat diet for 6 weeks were investigated for atherosclerotic lesions in vivo. In vitro experiments using RAW264.7 macrophages, primary resident peritoneal macrophages extracted from wild-type or SPA-deficient mice, and human monocyte-derived macrophages from the peripheral blood of healthy donors determined the functional effects of SPA in macrophage foam cell formation. RESULTS: SPA expression was increased in atherosclerotic lesions in humans and ApoE-deficient mice and in response to a proatherosclerotic stimulus in vitro. SPA deficiency reduced the lipid profiles induced by hypercholesterolemia, attenuated atherosclerosis, and reduced the number of lesion-associated macrophage foam cells. In vitro studies revealed that SPA deficiency reduced intracellular cholesterol accumulation and macrophage foam cell formation. Mechanistically, SPA deficiency dramatically downregulated the expression of scavenger receptor CD36 (cluster of differentiation antigen 36) cellular and lesional expression. Importantly, SPA also increased CD36 expression in human monocyte-derived macrophages. CONCLUSIONS: Our results elucidate that SPA is a novel factor promoting atherosclerosis development. SPA enhances macrophage foam cell formation and atherosclerosis by increasing scavenger receptor CD36 expression, leading to increasing cellular OxLDL influx.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Cartilage Repair: Promise of Adhesive Orthopedic Hydrogels.

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.

COVID-19 Mortality Disparities Among Socially Vulnerable Medicare Beneficiaries Associated With the Quality of Nurse Work Environments in U.S. Hospitals.

COVID-19 mortality disparities for socially vulnerable patients, including individuals facing higher levels of poverty, housing insecurity, and limited transportation, have been linked to the quality of hospitals where they received care. Few studies have examined the specific aspects of hospitals, such as nursing care quality, that may underlie disparate outcomes. Recent studies suggest that nursing resources in the pre-pandemic period were associated with mortality during the COVID-19 public health emergency. In this study, we examined the association between social vulnerability, the nurse work environment, and inpatient mortality among Medicare beneficiaries hospitalized with COVID-19. A cross-sectional analysis was conducted of linked survey data collected from nurses working in New York and Illinois, Medicare claims, American Hospital Association Annual Survey data, and the Social Vulnerability Index (SVI). Higher mortality rates were observed among patients in the highest quartile of social vulnerability compared to the lowest (6870 [25.8%] vs 5019 [19.1%]; P < .001). Using multivariable regression modeling, a statistically significant interaction was found between the highest SVI quartile and the nurse work environment (OR, 0.86; 95% CI, 0.76-0.98; P < .05), implying that the effect of a higher quality nurse work environment on mortality was decidedly greater for patients in the highest quartile (odds ratio = 0.86 × 0.94 = 0.80) compared to patients in the lowest quartile (OR, 0.94). Post-hoc analyses demonstrated that hundreds of COVID-19 related deaths among the most socially vulnerable patients may have been avoided if all hospitals had a high-quality nurse work environment. Strengthening the quality of nurse work environments may help to reduce health disparities and should be considered in public health emergency planning, specifically in hospitals serving socially vulnerable communities.

Handoff Education Interventions: A Scoping Review Focused on Sustaining Improvements.

Handoffs involve the transfer of patient information and responsibility for care between health care professionals. The purpose of the current scoping review was (1) to describe handoff studies with education as part of the intervention and (2) to explore the role of handoff educational interventions in sustaining handoff improvements. This scoping review utilized previously published systematic reviews and a structured, systematic search of 5 databases (January 2006-June 2020). Articles were identified, and data were extracted by pairs of trained, independent reviewers. The search identified 74 relevant articles, most published after 2015 (70%) and conducted in the United States (76%). Almost all of the studies (99%) utilized instruction, 66% utilized skills practice, 89% utilized a memory aid, and 43% utilized reinforcement. However, few studies reported using education theory or followed accepted tenets of curriculum development. There has been a substantial increase over time in reporting actual handoff behavior change (17%-68%) and a smaller but important increase in reporting patient outcomes (11%-18%). Thirty-five percent of studies (26/74) had follow-up for 6 months or more. Twelve studies met the criteria for sustained change, which were follow-up for 6 months or more and achieving statistically significant improvements in either handoff skills/processes or patient outcomes at the conclusion of the study. All 12 studies with sustained change used multi-modal educational interventions, and reinforcement was more likely to be used in these studies than all others (75%, 9/12) versus (37%, 23/62), P = 0.015. Future handoff intervention efforts that include education should use education theory to guide development and include needs assessment and goals and measurable objectives. Educational interventions should be multi-modal and include reinforcement. Future research studies should measure actual handoff behavior change (skills/process) and patient outcomes, include follow-up for more than 6 months, and use education reporting guidelines.

Reassessing Long-Term Cryopreservation Strategies for Improved Quality, Safety, and Clinical Use of Allogeneic Dermal Progenitor Cells.

In regenerative medicine, ongoing advancements in cell culture techniques, including isolation, expansion, banking, and transport, are crucial for clinical success. Cryopreservation ensures off-the-freezer availability of living cells, enabling long-term storage and transport. Customizing cryopreservation techniques and cryoprotective agents (CPAs) for specific cell types is crucial for cell source quality, sustainability, safety, and therapeutic intervention efficiency. As regenerative medicine progresses, it becomes imperative that the scientific community and industry provide a comprehensive, cell-specific landscape of available and effective cryopreservation techniques, preventing trial-and-error approaches and unlocking the full potential of cell-based therapies. Open-sharing data could lead to safer, more efficient cell therapies and treatments. Two decades of dermal progenitor cell use for burn wound treatment and Good Manufacturing Practice-compliant technology transfers have highlighted the need for further cryopreservation optimization in manufacturing workflows. In this paper, we present experimental data assessing 5 different cryopreservation formulae for long-term storage of clinical-grade FE002 primary progenitor fibroblasts, emphasizing the crucial difference between DMSO-based and DMSO-free CPAs. Our findings suggest that CryoOx, a DMSO-free CPA, is a promising alternative yielding cell viability similar to that of established commercial CPAs. This research highlights the importance of secure, robust, and efficient cryopreservation techniques in cell banking for maximizing quality, ensuring patient safety, and advancing regenerative medicine.

The Performance of Critical Congenital Heart Disease Screening in Rural Versus Urban Locations in the Northwest United States.

Objectives: Pulse oximetry screening of newborns detects critical congenital heart disease (CCHD). Rural birth location is known to affect timing and management of when infants with CHD undergo surgery, but its association with CCHD screening is unknown. We assess the relationship between rural location and postnatal CCHD diagnosis and describe lesion-specific modes of diagnosis. Study design: Data were abstracted from medical records at 2 cardiac surgery centers in Washington state. Infants with CCHD, defined as CHD requiring either cardiac intervention or resulting in death at <1 month of age, born between July 2015 and June 2020, were included and classified by method of identification. Patient home ZIP codes were used to determine rural location. Results: We included 561 newborns with CCHD; 35% were diagnosed postnatally. Predominant postnatal mechanisms of identification (n = 194) included symptomatic before CCHD screening period (56%), CCHD screening (22%), and symptomatic after false-negative screen (15%). Postnatal diagnosis rate increased with degree of ruralness (48% in small rural/isolated regions vs 32% in urban regions; P = .01) and incidence of undiagnosed CCHD at birth increased with lower nursery levels (5.5/10 000 live births in nursery level 1 vs 2.1/10 000 live births in level 4). Conclusions: CCHD screening identifies 22% of postnatally diagnosed CCHD and 7% of cases overall in our region. Postnatal diagnosis is more common in rural regions. The incidence of undiagnosed CCHD at birth increases with decreasing nursery levels. This study supports the value of CCHD screening in routine newborn care, especially in rural areas and hospitals with lower nursery levels.

Transgender and Gender Diverse Medical Education in Radiology: A Systematic Review.

RATIONALE AND OBJECTIVES: Physicians report a lack of Transgender and Gender Diverse (TGD) health competency for medical imaging. This knowledge gap contributes to negative medical imaging experiences, discrimination, stigma, and diagnostic errors for TGD individuals. Medical education plays an important role in improving this. However, the current landscape and gaps in TGD medical education in radiology is underexplored. We aimed to fill the knowledge gap on the current state of TGD medical education in radiology. MATERIALS AND METHODS: A PRISMA and SWiM guideline-compliant systematic review on TGD medical education in radiology was performed. Four databases were searched: Medline, Embase, Web of Science, and Scopus from inception to May 13, 2024. Article screening and extraction occurred independently and in duplicate. Narrative synthesis was performed on TGD medical education material in radiology, educational recommendations, barriers/enablers to education, and current guidelines. RESULTS: A total of 4360 records were identified with 76 articles included. Most articles (52, 68%) were from the United States. Most articles aimed to provide recommendations for TGD medical education in radiology (53, 69.7%). Some articles focused on developing medical education (7, 9.2%), evaluating medical education (7, 9.2%), evaluating guidelines (8, 10.5%), or developing guidelines (3, 4%). Identified TGD medical education in radiology is inconsistent, focusing on terminology guides, clinical scenarios, and cultural sensitivity workshops. Many current guidelines for TGD medical imaging were developed through extrapolation of guidance for cisgender patients, demonstrating limited relevance and meaningfulness for TGD patients. CONCLUSION: This systematic review identifies a need to develop consistent TGD medical educational material in radiology in partnership with TGD patients to cover patient perspectives and guidance for medical imaging considerations. Results can be used to identify TGD medical education resources in radiology which may be helpful, and guide development of future medical education.

Role of Source, Mineralogy, and Organic Complexation on Lability and Fe Isotopic Composition of Terrestrial Fe sources to the Gulf of Alaska.

Iron (Fe) is a key trace nutrient supporting marine primary production, and its deposition in the surface ocean can impact multiple biogeochemical cycles. Understanding Fe cycling in the subarctic is key for tracking the fate of particulate-bound sources of oceans in a changing climate. Recently, Fe isotope ratios have been proposed as a potential tool to trace sources of Fe to the marine environment. Here, we investigate the Fe isotopic composition of terrestrial sources of Fe including glacial sediment, loess, volcanic ash, and wildfire aerosols, all from Alaska. Results show that the δ56Fe values of glaciofluvial silt, glacial dissolved load, volcanic ash, and wildfire aerosols fall in a restricted range of δ56Fe values from -0.02 to +0.12‰, in contrast to the broader range of Fe isotopic compositions observed in loess, -0.50 to +0.13‰. The Fe isotopic composition of the dissolved load of glacial meltwater was consistently lighter compared to its particulate counterpart. The 'aging' (exposure to environmental conditions) of volcanic ash did not significantly fractionate the Fe isotopic composition. The Fe isotopic composition of wildfire aerosols collected during an active fire season in Alaska in the summer of 2019 was not significantly fractionated from those of the average upper continental crust composition. We find that the δ56Fe values of loess (<5 µm fraction) were more negative (-0.32 to +0.05‰) with respect to all samples measured here, had the highest proportion of easily reducible Fe (5.9-59.6%), and were correlated with the degree of chemical weathering and organic matter content. Transmission electron spectroscopy measurements indicate an accumulation of amorphous Fe phases in the loess. Our results indicate that Fe isotopes can be related to Fe lability when in the presence of organic matter and that higher organic matter content is associated with a distinctly more negative Fe isotope signature likely due to Fe-organic complexation.

Prognostic Factors for Multiligament Knee Injury Treated With Multiligament Reconstruction: Functional and Radiological Outcomes at 2 to 8 Years Postoperatively.

Background: Multiligament reconstruction (MLR) has become the standard surgical approach for treating multiligament knee injuries (MLKIs). Purpose: To identify prognostic factors for patient-reported outcome measures, return to work (RTW), return to sports, and radiographic osteoarthritis (OA) (Kellgren-Lawrence grade ≥2) after MLR for MLKI. Study Design: Case-control study; Level of evidence 3. Methods: Included were 52 consecutive patients (age, 35.5 ± 11 years; 75% men), with MLKI sustained between 2013 and 2019 and treated with MLR. At a mean follow-up of 3.8 ± 1.6 years, patient-reported outcome measure scores-including the International Knee Documentation Committee (IKDC), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI), and the 12-Item Short-Form Health Survey-RTW, return to sports, and weightbearing radiographs were obtained. A total of 20 determinants were hypothesized and tested by univariate logistic regression for binary variables or linear regression for continuous variables. Only factors identified as significant (P < .10) were entered into a multivariate logistic regression model. Results: The prevalence of injury severity according to the Schenck knee dislocation (KD) classification was as follows: KD I (44%), KD III (36%), KD IV (10%), and KD V (10%). Increased KD grades resulted in decreased IKDC (P = .002) and all 5 KOOS subscales (P≤ .007 for all) scores. Medial meniscectomy (23%) was associated with a worse ACL-RSI score (P = .007) and RTW failure (odds ratio [OR], 36.8; P = .035). Peroneal nerve palsy (6%) was associated with a worse ACL-RSI score (P≤ .001). Radiographic OA was observed in 38%, with distribution predominantly patellofemoral (80%) and medial tibiofemoral (45%). Traumatic cartilage damage (Outerbridge grade >2 [37%]) was associated with secondary patellofemoral (OR, 10; P = .012) and medial tibiofemoral (OR, 10; P = .019) OA. Anterior cruciate ligament reconstruction failure (7%) was a risk factor for medial tibiofemoral OA (OR, 25.8; P = .006). Conclusion: Increased Schenck KD grade, permanent peroneal nerve palsy, and irreparable medial meniscus lesions were prognostic factors for worse functional outcomes 3.8 years after MLKI was treated with MLR. Traumatic cartilage damage and anterior cruciate ligament failure were associated with the development of early OA.

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah-/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.

Sequences within and upstream of the mouse Ets1 gene drive high level expression in B cells, but are not sufficient for consistent expression in T cells.

The levels of transcription factor Ets1 are high in resting B and T cells, but are downregulated by signaling through antigen receptors and Toll-like receptors (TLRs). Loss of Ets1 in mice leads to excessive immune cell activation and development of an autoimmune syndrome and reduced Ets1 expression has been observed in human PBMCs in the context of autoimmune diseases. In B cells, Ets1 serves to prevent premature activation and differentiation to antibody-secreting cells. Given these important roles for Ets1 in the immune response, stringent control of Ets1 gene expression levels is required for homeostasis. However, the genetic regulatory elements that control expression of the Ets1 gene remain relatively unknown. Here we identify a topologically-associating domain (TAD) in the chromatin of B cells that includes the mouse Ets1 gene locus and describe an interaction hub that extends over 100 kb upstream and into the gene body. Additionally, we compile epigenetic datasets to find several putative regulatory elements within the interaction hub by identifying regions of high DNA accessibility and enrichment of active enhancer histone marks. Using reporter constructs, we determine that DNA sequences within this interaction hub are sufficient to direct reporter gene expression in lymphoid tissues of transgenic mice. Further analysis indicates that the reporter construct drives faithful expression of the reporter gene in mouse B cells, but variegated expression in T cells, suggesting the existence of T cell regulatory elements outside this region. To investigate how the downregulation of Ets1 transcription is associated with alterations in the epigenetic landscape of stimulated B cells, we performed ATAC-seq in resting and BCR-stimulated primary B cells and identified four regions within and upstream of the Ets1 locus that undergo changes in chromatin accessibility that correlate to Ets1 gene expression. Interestingly, functional analysis of several putative Ets1 regulatory elements using luciferase constructs suggested a high level of functional redundancy. Taken together our studies reveal a complex network of regulatory elements and transcription factors that coordinate the B cell-specific expression of Ets1.

Comparing barriers to early stage diagnosis of hepatocellular carcinoma between safety net hospitals and academic medical centers: An analysis from the United States Safety-Net Collaborative.

BACKGROUND AND OBJECTIVES: Early detection of hepatocellular carcinoma (HCC) is associated with improved survival. However, a greater proportion of patients treated at safety net hospitals (SNHs) present with late-stage disease compared to those at academic medical centers (AMCs). This study aims to identify barriers to diagnosis of HCC, highlighting differences between SNHs and AMCs. METHODS: The US Safety Net Collaborative-HCC database was queried. Patients were stratified by facility of diagnosis (SNH or AMC). Patient demographics and HCC screening rates were examined. The primary outcome was stage at diagnosis (AJCC I/II-"early"; AJCC III/IV-"late"). RESULTS: 1290 patients were included; 50.2% diagnosed at SNHs and 49.8% at AMCs. At SNHs, 44.4% of patients were diagnosed late, compared to 27.6% at AMCs. On multivariable regression, Black race was associated with late diagnosis in both facilities (SNH: odds ratio 1.96, p = 0.03; AMC: 2.27, <0.01). Screening was associated with decreased odds of late diagnosis (SNH: 0.46, p = 0.04; AMC: 0.37, p < 0.01). CONCLUSIONS: Black race was associated with late diagnosis of HCC, while screening was associated with early diagnosis across institutional types. These results suggest socially constructed racial bias in screening and diagnosis of HCC. Screening efforts targeting SNH patients and Black patients at all facilities are essential to reduce disparities.

"Smells like team spirit" the association between running club membership and performance in the London Marathon: An economic analysis.

This study examines the association between club membership and marathon performance using a dataset of 206,653 London Marathon runners. Our results show a statistically significant association between club membership and marathon performance for both males and females which sees club membership potentially mitigating pace decline with age and resulting in substantial improvements in finishing times of up to 40 minutes. We implement a production function framework and align with three principles of economic organisation. The findings have relevance for marathon participants, coaches, and athletic associations as well as implications beyond athletics to other sports or cooperative activities.