Are comorbidities associated with differences in healthcare charges among lung cancer patients in US hospitals? Focusing on variances by patient and socioeconomic factors.

OBJECTIVE: The clinical aspects of lung cancer patients are well-studied. However, healthcare charge patterns have yet to be explored through a large-scale representative population-based sample investigating differences by socioeconomic factors and comorbidities. AIM: To identify how comorbidities associated with healthcare charges among lung cancer patients. METHODS: We examined the characteristics of the patient sample and the association between comorbidity status (diabetes, hypertension, or both) and healthcare charge. Multivariate survey linear regression models were used to estimate the association. We also investigated sub-group association through various patient and socioeconomic factors. RESULTS: Of 212,745 lung cancer patients, 68.5% had diabetes and/or hypertension. Hospital charges were higher in the population with comorbidities. The results showed that lung cancer patients with comorbidities had 9.4%, 5.1%, and 12.0% (with diabetes, hypertension, and both, respectively) higher hospital charges than those without comorbidities. In sub-group analysis, Black patients also showed a similar trend across socioeconomic (i.e. household income and primary payer) and racial (i.e. White, Black, Hispanic, and Asian/Pacific Islander) factors. DISCUSSION: Black patients may be significantly financially burdened because of the prevalence of comorbidities and low-income status. More work is required to ensure healthcare equality and promote access to care for the uninsured, low-income, and minority populations because comorbidities common in these populations can create more significant financial barriers.

Does Opioid Use Disorder Matter for Health Care Utilization Among Lung Cancer Patients? Evidence from U.S. Hospitals During 2016-2020.

BACKGROUND AND OBJECTIVE: The number of hospitalizations due to opioid use disorders in the USA increased steadily from 62,010 in 1998-2000 to 136,240 in 2015-2016; however, no health care utilization of lung cancer patients with opioid use disorder has been reported. The purpose of this paper is to investigate health care utilization due to opioid use disorder among lung cancer patients and to investigate additional charge status due to this disorder. METHODS: The National Inpatient Sample of the USA was used to identify lung cancer patients (n = 11,418, weighted n = 557,090) from 2016 to 2020. The characteristics of patient samples, temporal trend of opioid use disorder, and its association with health care utilization measured by hospital charges were thoroughly examined by the multivariate survey linear regression model. RESULTS: Among 557,090 lung cancer patients, 2.4% had opioid use disorder. The proportion of opioid use disorder among lung cancer patients during the study periods had continuously grown. Hospital charges also continued to increase during the study period and were higher among lung cancer patients with opioid use disorder. Survey linear results showed that opioid use disorder was associated with 12.6% higher hospital charges. Analysis of subgroups revealed that this trend was similar across p < the majority of social groups; however, it was significantly higher among Caucasian individuals (0.001) and self-pay groups (p = 0.035) than among others. CONCLUSIONS: Research conducted has identified gaps in care in rural and suburban areas and a lack of equal care given to minority and low-income patients. These vulnerable groups access health care less often, are charged more for the care they receive, and often face multiple barriers to treatment. Unless these issues are addressed with a focus on socioeconomic factors, race, and region, the opioid epidemic will continue to negatively decimate these populations.

Health-Related Behaviors and Psychological Status of Adolescent Patients with Atopic Dermatitis: The 2019 Korea Youth Risk Behavior Web-Based Survey.

Objective: Atopic dermatitis (AD) is one of the common chronic diseases that occur in children and adolescents as a chronic relapsing pruritic inflammatory skin disease. This study investigated how AD is associated with stress and depressive symptoms in a large representative sample of adolescents in South Korea. Methods: The Korea Youth Risk Behavior Web-based Survey 2019 was used in this study (n = 57,069, weighted national estimates = 2,672,170). Multivariate logistic regression was used to determine significant associations between AD and mental health, measured by stress and depressive symptoms. Sub-group analysis was also conducted using various socio-economic variables. Results: Among the present sample, 6.5% of adolescents (n = 173,909) were diagnosed with AD in the past 12 months. After adjusting for other variables, AD diagnosis was associated with significantly higher odds of experiencing stress (OR = 1.43) and depressive symptoms (OR = 1.32) as compared to adolescents without AD. A similar trend is found in subgroup model analysis using socio-economic variables (ie, education levels, parent's income levels, and residence area). Specifically, female adolescents with AD, adolescents of low socio-economic status, those reporting smoking and drinking experience, and who do not participate in regular physical activity are more vulnerable to stress and depressive symptoms. Conclusion: This is a noteworthy finding because it denotes that AD may lead to negative outcomes, like depressive symptoms or stress, which could be prevented if suspected early.

Association between Physical Activity, Sedentary Behavior, Satisfaction with Sleep Fatigue Recovery and Smartphone Dependency among Korean Adolescents: An Age- and Gender-Matched Study.

The purpose of this study was to identify the association between physical activity (PA), sedentary behavior (SB), satisfaction with sleep fatigue recovery (SSFR), and smartphone dependency in South Korean adults. We analyzed data from the National Health and Nutrition Examination Survey 2020 data. We selected participants who answered Internet addiction-related questions as "Very much" (n = 241) and answered Internet addiction-related questions as "Not at all" (n = 241) in the questionnaire. The participants were matched by age and gender, then divided into two groups. Between the two groups, there were considerable differences in the number of days participating in moderate to vigorous PA (5 days or more, p = 0.01), the number of strength training days (1 day, p = 0.02), the number of light PA days for more than 60 min (every day for the last 7 days, p = 0.01), and the SSFR over the past 7 days (p < 0.05). Additionally, the mean smartphone usage time and mean sedentary behavior time between the two groups showed significant differences. The study demonstrated that there were significant associations between PA, SB, SSFR, and smartphone dependency among Korean adolescents matched by age and gender. Additionally, this study highlights the importance of increasing overall PA and number of days participating in MVPA, decreasing SB time and smartphone usage time could reduce the incidence of smartphone overdependence.

One-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics.

In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.

Hyperelastic, shape-memorable, and ultra-cell-adhesive degradable polycaprolactone-polyurethane copolymer for tissue regeneration.

Novel polycaprolactone-based polyurethane (PCL-PU) copolymers with hyperelasticity, shape-memory, and ultra-cell-adhesion properties are reported as clinically applicable tissue-regenerative biomaterials. New isosorbide derivatives (propoxylated or ethoxylated ones) were developed to improve mechanical properties by enhanced reactivity in copolymer synthesis compared to the original isosorbide. Optimized PCL-PU with propoxylated isosorbide exhibited notable mechanical performance (50 MPa tensile strength and 1150% elongation with hyperelasticity under cyclic load). The shape-memory effect was also revealed in different forms (film, thread, and 3D scaffold) with 40%-80% recovery in tension or compression mode after plastic deformation. The ultra-cell-adhesive property was proven in various cell types which were reasoned to involve the heat shock protein-mediated integrin (α5 and αV) activation, as analyzed by RNA sequencing and inhibition tests. After the tissue regenerative potential (muscle and bone) was confirmed by the myogenic and osteogenic responses in vitro, biodegradability, compatible in vivo tissue response, and healing capacity were investigated with in vivo shape-memorable behavior. The currently exploited PCL-PU, with its multifunctional (hyperelastic, shape-memorable, ultra-cell-adhesive, and degradable) nature and biocompatibility, is considered a potential tissue-regenerative biomaterial, especially for minimally invasive surgery that requires small incisions to approach large defects with excellent regeneration capacity.

Let's Live Healthier: The Relationship between Suicidal Behavior and Physical Activity in an Age-, Gender-, and Body Mass Index-Matched Adults.

The purpose of this study was to identify the association between physical activity (PA) and predictors of suicidal behaviors and to investigate whether the different PA measurements influence the association between PA and suicidal behaviors in South Korean adults. This study analyzed data from the National Health and Nutrition Examination Survey 2014-2015 data. The study selected participants who checked suicide-related questions as "Yes" (n = 99) and checked suicide-related questions as "No" (n = 99) in the questionnaire. The age, gender, and body mass index of participants between the two groups were matched. The moderate to vigorous PA (p = 0.000) and sedentary PA (p = 0.000), measured by accelerometers, were a significant risk factor for suicidal behaviors. Furthermore, the number of steps was a considerable difference between the two groups (healthy group: 61,495.76 steps; suicide group: 40,517.34 steps), and the accelerometer and questionnaire also showed significant differences. The study demonstrated that there were significant associations with physical activity and socioeconomic status and suicidal behaviors in anthropometry (i.e., age, gender, height, weight) matched groups. Additionally, this study highlights the importance of the assessment of PAs, and increasing PA levels could reduce the incidence of suicidal behaviors.

Hierarchical microchanneled scaffolds modulate multiple tissue-regenerative processes of immune-responses, angiogenesis, and stem cell homing.

Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured ('microchanneled') 3D printed scaffolds (named 'µCh'), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The µCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of µCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the µCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the µCh. Furthermore, the neo-blood vessel formation was more pronounced in the µCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the µCh. Further assays on the protein sequestration to the µCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the µCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the µCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the µCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the µCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms.

Angiogenesis in bone regeneration: tailored calcium release in hybrid fibrous scaffolds.

In bone regeneration, silicon-based calcium phosphate glasses (Bioglasses) have been widely used since the 1970s. However, they dissolve very slowly because of their high amount of Si (SiO2 > 45%). Recently, our group has found that calcium ions released by the degradation of glasses in which the job of silicon is done by just 5% of TiO2 are effective angiogenic promoters, because of their stimulation of a cell-membrane calcium sensing receptor (CaSR). Based on this, other focused tests on angiogenesis have found that Bioglasses also have the potential to be angiogenic promoters even with high contents of silicon (80%); however, their slow degradation is still a problem, as the levels of silicon cannot be decreased any lower than 45%. In this work, we propose a new generation of hybrid organically modified glasses, ormoglasses, that enable the levels of silicon to be reduced, therefore speeding up the degradation process. Using electrospinning as a faithful way to mimic the extracellular matrix (ECM), we successfully produced hybrid fibrous mats with three different contents of Si (40, 52, and 70%), and thus three different calcium ion release rates, using an ormoglass-polycaprolactone blend approach. These mats offered a good platform to evaluate different calcium release rates as osteogenic promoters in an in vivo subcutaneous environment. Complementary data were collected to complement Ca(2+) release analysis, such as stiffness evaluation by AFM, ζ-potential, morphology evaluation by FESEM, proliferation and differentiation analysis, as well as in vivo subcutaneous implantations. Material and biological characterization suggested that compositions of organic/inorganic hybrid materials with a Si content equivalent to 40%, which were also those that released more calcium, were osteogenic. They also showed a greater ability to form blood vessels. These results suggest that Si-based ormoglasses can be considered an efficient tool for calcium release modulation, which could play a key role in the angiogenic promoting process.

Biphasic nanofibrous constructs with seeded cell layers for osteochondral repair.

Biphasic scaffolds have gained increasing attention for the regeneration of osteochondral interfacial tissue because they are expected to effectively define the interfacial structure of tissue that comprises stratified cartilage with a degree of calcification. Here, we propose a biphasic nanofiber construct made of poly(lactide-co-caprolactone) (PLCL) and its mineralized form (mPLCL) populated with cells. Primary rat articular chondrocytes (ACs) and bone marrow-derived mesenchymal stem cells (MSCs) were cultured on the layers of bare PLCL and mPLCL nanofibers, respectively, for 7 days, and the biphasic cell-nanofiber construct was investigated at 4 weeks after implantation into nude mice. Before implantation, the ACs and MSCs grown on each layer of PLCL and mPLCL nanofibers exhibited phenotypes typical of chondrocytes and osteoblasts, respectively, under proper culture conditions, as analyzed by electron microscopy, histological staining, cell growth kinetics, and real-time polymerase chain reaction. The biphasic constructs also showed the development of a possible formation of cartilage and bone tissue in vivo. Results demonstrated that the cell-laden biphasic nanofiber constructs may be useful for the repair of osteochondral interfacial tissue structure.

Utilizing core-shell fibrous collagen-alginate hydrogel cell delivery system for bone tissue engineering.

Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ~700-1000 µm for the core and 200-500 µm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of ~22% at 7 days and ~43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core-shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core-shell fibrous carriers were implanted in a rat calvarium defect, the bone healing was significantly improved when the MSCs were encapsulated, and even more so after an osteogenic induction of MSCs before implantation. Based on these results, the newly designed core-shell collagen-alginate fibrous carrier is considered promising to enable the encapsulation of tissue cells and their delivery into damaged target tissues, including bone with defect-tunability for bone tissue engineering.

Gene delivery techniques for adult stem cell-based regenerative therapy.

Over the past decade, stem cells have been considered to be a promising resource to cure and regenerate damaged or diseased tissues with research extending from basic studies to clinical application. Furthermore, genetically modified stem cells have the potential to reduce tumorigenic risks and achieve safe tissue formation. Recent advances in genetic modification of stem cells have rendered these cells more accessible and stable. The successful genetic modification of stem cells relies heavily on designing vector systems, either viral or nonviral vectors, which can efficiently deliver therapeutic genes to the cells with minimum toxicity. Currently, viral vectors showing high transfection efficiencies still raise safety issues, whereas safer nonviral vectors exhibit extremely poor transfection in stem cells. Here, we attempt to review and discuss the main factors raising concern in previous reports, and devise strategies to solve the issues in gene delivery systems for successful stem cell-targeting regenerative therapy.

Mineralized poly(lactic acid) scaffolds loading vascular endothelial growth factor and the in vivo performance in rat subcutaneous model.

The functionalization of degradable polymeric scaffolds with therapeutic molecules such as vascular endothelial growth factor (VEGF) is a key strategy to gain better regenerative ability of damaged bone tissue by stimulating vascularization and tissue perfusion. Here, we combined VEGF with poly(lactic acid) (PLA) porous scaffold, after modifying the PLA surface with calcium phosphate (CaP) mineral. The mineralized PLA scaffold (mPLA) showed more effective loading capacity of VEGF than the PLA without mineralization as well as profiled sustainable release of VEGF for up to a couple of weeks. The VEGF-loaded mPLA scaffold presented significantly improved proliferation of primary endothelial cells for up to 7 days, with respect to the scaffold without the VEGF loading. The performance of the engineered scaffold was assessed after subcutaneous implantation in rats for 4 weeks. Histological results showed favorable tissue compatibility of both the mPLA scaffolds (with and without VEGF loading), as characterized by infiltration of inflammatory cells, formation of fibrous capsule, and ingrowth of fibroblasts into the matrices. Immunohistochemical staining of the von Willebrand Factor revealed significantly improved formation of neo-capillaries in the VEGF-loaded mPLA. Based on this study, the strategy of VEGF loading onto mineralized PLA scaffold is considered beneficial for gaining improved vascularization of the polymeric scaffolds, suggesting potential applications for bone tissue engineering.

Titanium phosphate glass microspheres for bone tissue engineering.

We have demonstrated the successful production of titanium phosphate glass microspheres in the size range of ∼10-200 µm using an inexpensive, efficient, easily scalable process and assessed their use in bone tissue engineering applications. Glasses of the following compositions were prepared by melt-quench techniques: 0.5P2O5-0.4CaO-(0.1-x)Na2O-xTiO2, where x=0.03, 0.05 and 0.07 mol fraction (denoted as Ti3, Ti5 and Ti7 respectively). Several characterization studies such as differential thermal analysis, degradation (performed using a novel time lapse imaging technique) and pH and ion release measurements revealed significant densification of the glass structure with increased incorporation of TiO2 in the glass from 3 to 5 mol.%, although further TiO2 incorporation up to 7 mol.% did not affect the glass structure to the same extent. Cell culture studies performed using MG63 cells over a 7-day period clearly showed the ability of the microspheres to provide a stable surface for cell attachment, growth and proliferation. Taken together, the results confirm that 5 mol.% TiO2 glass microspheres, on account of their relative ease of preparation and favourable biocompatibility, are worthy candidates for use as substrate materials in bone tissue engineering applications.

Performance of evacuated calcium phosphate microcarriers loaded with mesenchymal stem cells within a rat calvarium defect.

Tissue engineering of stem cells in concert with 3-dimensional (3D) scaffolds is a promising approach for regeneration of bone tissues. Bioactive ceramic microspheres are considered effective 3D stem cell carriers for bone tissue engineering. Here we used evacuated calcium phosphate (CaP) microspheres as the carrier of mesenchymal stem cells (MSCs) derived from rat bone marrow. The performance of the CaP-MSCs construct in bone formation within a rat calvarium defect was evaluated. MSCs were first cultured in combination with the evacuated microcarriers for 7 days in an osteogenic medium, which was then implanted in the 6 mm-diameter calvarium defect for 12 weeks. For comparison purposes, a control defect and cell-free CaP microspheres were also evaluated. The osteogenic differentiation of MSCs cultivated in the evacuated CaP microcarriers was confirmed by alkaline phosphatase staining and real time polymerase chain reaction. The in vivo results confirmed the highest bone formation was attained in the CaP microcarriers combined with MSCs, based on microcomputed tomography and histological assays. The results suggest that evacuated CaP microspheres have the potential to be useful as stem cell carriers for bone tissue engineering.

Direct deposited porous scaffolds of calcium phosphate cement with alginate for drug delivery and bone tissue engineering.

This study reports the preparation of novel porous scaffolds of calcium phosphate cement (CPC) combined with alginate, and their potential usefulness as a three-dimensional (3-D) matrix for drug delivery and tissue engineering of bone. An α-tricalcium phosphate-based powder was mixed with sodium alginate solution and then directly injected into a fibrous structure in a Ca-containing bath. A rapid hardening reaction of the alginate with Ca(2+) helps to shape the composite into a fibrous form with diameters of hundreds of micrometers, and subsequent pressing in a mold allows the formation of 3-D porous scaffolds with different porosity levels. After transformation of the CPC into a calcium-deficient hydroxyapatite phase in simulated biological fluid the scaffold was shown to retain its mechanical stability. During the process biological proteins, such as bovine serum albumin and lysozyme, used as model proteins, were observed to be effectively loaded onto and released from the scaffolds for up to more than a month, proving the efficacy of the scaffolds as a drug delivering matrix. Mesenchymal stem cells (MSCs) were isolated from rat bone marrow and then cultured on the CPC-alginate porous scaffolds to investigate the ability to support proliferation of cells and their subsequent differentiation along the osteogenic lineage. It was shown that MSCs increasingly actively populated and also permeated into the porous network with time of culture. In particular, cells cultured within a scaffold with a relatively high porosity level showed favorable proliferation and osteogenic differentiation. An in vivo pilot study of the CPC-alginate porous scaffolds after implantation into the rat calvarium for 6 weeks revealed the formation of new bone tissue within the scaffold, closing the defect almost completely. Based on these results, the newly developed CPC-alginate porous scaffolds could be potentially useful as a 3-D matrix for drug delivery and tissue engineering of bone.

Alginate combined calcium phosphate cements: mechanical properties and in vitro rat bone marrow stromal cell responses.

Here, we prepared self-setting calcium phosphate cements (CPCs) based on α-tricalcium phosphate with the incorporation of sodium alginate, and their mechanical properties and in vitro cellular responses were investigated. The addition of alginate enhanced the hardening reaction of CPCs showing shorter setting times within a range of powder-to-liquid ratios. When immersed in a body simulating fluid the alginate-CPCs fully induced a formation of an apatite crystalline phase similar to that of bare CPCs. The compressive and tensile strengths of the CPCs were found to greatly improve during immersion in the fluid, and this improvement was more pronounced in the alginate-CPCs. As a result, the alginate-CPCs retained significantly higher strength values than the bare CPCs after 3-7 days of immersion. The rat bone marrow derived stromal cells (rBMSCs) cultured on the alginate-CPCs initially adhered to and then spread well on the cements surface, showed an on-going increase in the population with culture time, and differentiated into osteoblasts expressing bone-associated genes (collagen type I, osteopontin and bone sialoprotein) and synthesizing alkaline phosphatase. However, the stimulated level of osteogenic differentiation was not confirmative with the incorporation of alginate into the CPC composition based on the results. One merit of the use of alginate was its usefulness in forming CPCs into a variety of scaffold shapes including microspheres and fibers, which is associated with the cross-link of alginate under the calcium-containing solution.