Clinical Characteristics, Management, and Outcomes of Patients with Renal Medullary Carcinoma: A Single-center Retrospective Analysis of 135 Patients.

BACKGROUND AND OBJECTIVE: SMARCB1-deficient renal medullary carcinoma (RMC) is a rare kidney cancer associated with sickle cell hemoglobinopathies with poor outcomes described only in case reports and small series. We report disease and management characteristics as well as contemporary survival outcomes in a large cohort of patients with RMC. METHODS: Data were extracted retrospectively from all patients with RMC treated at MD Anderson Cancer Center between January 2003 and December 2023. Multivariable Cox regression was used to estimate overall survival (OS) by diagnosis period. KEY FINDINGS AND LIMITATIONS: Among 135 patients (median follow-up of 54.9 mo), only nine did not harbor a sickle hemoglobinopathy and were categorized as having renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP). Most patients (78%) presented with metastatic disease, predominantly to the retroperitoneal lymph nodes (81.7%), and hematuria was the most frequent presenting symptom (60%) in RMC associated with sickle hemoglobinopathy. Survival outcomes improved by diagnosis year (adjusted hazard ratio 0.70, 95% confidence interval 0.53-0.92, p = 0.01). RCCU-MP occurred in slightly older patients with median OS of 19.5 mo from diagnosis, did not show a predilection to the right kidney or male predominance, and afflicted mainly Caucasians (89%). The study is limited by its retrospective nature conducted at one center. CONCLUSIONS AND CLINICAL IMPLICATIONS: RMC frequently presents with hematuria and is highly likely to spread to the retroperitoneal lymph nodes. Survival outcomes are improving with contemporary management. RCCU-MP is very rare and may be slightly less aggressive. PATIENT SUMMARY: Renal medullary carcinoma (RMC) is a rare and aggressive subtype of kidney cancer afflicting primarily young men and women of African descent. There exist limited data regarding patient demographics and disease characteristics. We reported our institution's experience in treating patients with RMC. The first symptom most patients with RMC reported was blood in the urine, and the most common places where the cancer spread were the lymph nodes around the kidney. Patients with RMC are living longer with contemporary treatments.

Influence of Polymeric Microparticle Size and Loading Concentration on 3D Printing Accuracy and Degradation Behavior of Composite Scaffolds.

Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, machine precision, and degradation of 3D printed poly(ɛ-caprolactone)-based scaffolds. Using a main effects analysis, the sizes and loading concentrations of particle delivery vehicles investigated were found to have neither a beneficial nor disadvantageous influence on the metrics of printing quality such as material accuracy and machine precision. Meanwhile, particle loading concentration was determined to influence degradation rate, whereas printing temperature affected the trends in composite weight-average molecular weight. Neither of the two particle-related parameters (concentration nor diameter) was found to exhibit a significant effect on intra-fiber nor inter-fiber porosity. These findings evidence the capacity for controlled loading of particulate delivery vehicles in 3D printed scaffolds while preserving construct accuracy and precision, and with predictable dictation of composite degradation behavior for potential controlled release of encapsulated biomolecules.

Analysis of a Community Health Screening Program and the Factors Affecting Access to Care.

Introduction Free community health fairs and screening initiatives can be effective in broadening access to care and improving health outcomes in historically marginalized communities. UTHealthCares is a community health-focused organization developed at the University of Texas Health Science Center in Houston. At the beginning of 2023, UTHealthCares oversaw a free community health fair in the Eastex-Jensen Area - a medically underserved area in Northeast Houston. The health fair consisted of four stations - vitals and body mass index collection, vision screening, blood glucose screening, and dental screening. Participants also received coronavirus disease 2019 vaccinations, referrals, and health education. The purpose of this study is to evaluate the effectiveness of the UTHealthCares community health fair while assessing the factors that influence participants' access to medical care. Methods After completing the health fair, participants filled out an optional questionnaire. The questionnaire contained items that assessed satisfaction with the health fair, improvements in managing health, and access to resources. We calculated descriptive statistics, including mean response and 95% confidence intervals for rating scale questions. We used the chi-squared test to evaluate the independence of categorical variables and the Mann-Whitney U test to evaluate differences in means between distributions. Results A total of 111 people participated in the health fair, 91 of which completed a questionnaire. When participants rated their satisfaction with the health fair, the average response was 4.62 out of five. Participants also reported that they were more comfortable managing areas of health related to the stations offered at the fair. Many participants reported limited access to fresh food and long travel times to the physician. Participants that traveled further to reach one resource also tended to have significantly higher travel times for the other: X2 (4, N=78)=28.04, p<0.0001. However, 77.8% of respondents reported that the lack of insurance or cost was their greatest barrier to seeing a medical provider, while only 2.47% reported the lack of transportation as their greatest barrier. Participants who reported having health insurance also had a significantly higher probability of visiting a medical provider when they had a health issue: U=928.5, p=0.0006. Conclusion Overall, participants reported high satisfaction with the health fair. Participants also gave valuable feedback for improving future community health initiatives. Although many participants reported travel times greater than 30 minutes to reach community resources, very few participants indicated that transportation was their largest barrier to accessing medical care. Instead, the lack of insurance and high costs seem to be participants' most significant hindrances. Therefore, interventions in the Eastex-Jensen area focused on expanding access to care should also include components that improve access to insurance.

Effect of 3D Printing Temperature on Bioactivity of Bone Morphogenetic Protein-2 Released from Polymeric Constructs.

Growth factors such as bone morphogenetic protein-2 (BMP-2) are potent tools for tissue engineering. Three-dimensional (3D) printing offers a potential strategy for delivery of BMP-2 from polymeric constructs; however, these biomolecules are sensitive to inactivation by the elevated temperatures commonly employed during extrusion-based 3D printing. Therefore, we aimed to correlate printing temperature to the bioactivity of BMP-2 released from 3D printed constructs composed of a model polymer, poly(propylene fumarate). Following encapsulation of BMP-2 in poly(DL-lactic-co-glycolic acid) particles, growth factor-loaded fibers were fabricated at three different printing temperatures. Resulting constructs underwent 28 days of aqueous degradation for collection of released BMP-2. Supernatants were then assayed for the presence of bioactive BMP-2 using a cellular assay for alkaline phosphatase activity. Cumulative release profiles indicated that BMP-2 released from constructs that were 3D printed at physiologic and intermediate temperatures exhibited comparable total amounts of bioactive BMP-2 release as those encapsulated in non-printed particulate delivery vehicles. Meanwhile, the elevated printing temperature of 90 °C resulted in a decreased amount of total bioactive BMP-2 release from the fibers. These findings elucidate the effects of elevated printing temperatures on BMP-2 bioactivity during extrusion-based 3D printing, and enlighten polymeric material selection for 3D printing with growth factors.

Three-Dimensional Extrusion Printing of Porous Scaffolds Using Storable Ceramic Inks.

In this study, we describe the additive manufacturing of porous three-dimensionally (3D) printed ceramic scaffolds prepared with hydroxyapatite (HA), ß-tricalcium phosphate (ß-TCP), or the combination of both with an extrusion-based process. The scaffolds were printed using a novel ceramic-based ink with reproducible printability and storability properties. After sintering at 1200°C, the scaffolds were characterized in terms of structure, mechanical properties, and dissolution in aqueous medium. Microcomputed tomography and scanning electron microscopy analyses revealed that the structure of the scaffolds, and more specifically, pore size, porosity, and isotropic dimensions were not significantly affected by the sintering process, resulting in scaffolds that closely replicate the original dimensions of the 3D model design. The mechanical properties of the sintered scaffolds were in the range of human trabecular bone for all compositions. All ceramic bioinks showed consistent printability over a span of 14 days, demonstrating the short-term storability of the formulations. Finally, the mass loss did not vary among the evaluated compositions over a period of 28 days except in the case of ß-TCP scaffolds, in which the structural integrity was significantly affected after 28 days of incubation in phosphate-buffered saline. In conclusion, this study demonstrates the development of storable ceramic inks for the 3D printing of scaffolds of HA, ß-TCP, and mixtures thereof with high fidelity and low shrinkage following sintering that could potentially be used for bone tissue engineering in load-bearing applications.

Insect Bite-Associated Invasive Fungal Infections.

Insect bites are rarely reported to result in myocutaneous mycoses. We reviewed the literature and report 22 cases. Molds were the most common pathogens (15), especially Mucorales (9). Infections were typically misdiagnosed, and 68% had necrotizing features, often requiring amputation or extensive surgery. Both immunocompetent and immunosuppressed patients were affected.

Three-Dimensional Printing of Tissue Engineering Scaffolds with Horizontal Pore and Composition Gradients.

IMPACT STATEMENT: In this study, we report the development of a novel multimaterial segmented three-dimensional printing methodology to fabricate porous scaffolds containing discrete horizontal gradients of composition and porosity. This methodology is particularly beneficial to preparing porous scaffolds with intricate structures and graded compositions for the regeneration of complex tissues. The technique presented is compatible with many commercially available bioprinters commonly used in biofabrication, and can be adapted to better replicate the architectural and compositional requirements of individual tissues compared with traditional scaffold printing methods.

A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.

Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitable in vivo models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with Aspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized in vitro release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal-loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum-dependent manner. MPs were capable of releasing antifungals at concentrations above A. fumigatus Minimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction, p = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, p = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials-based therapies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867-1874, 2019.

Multimaterial Segmented Fiber Printing for Gradient Tissue Engineering.

IMPACT STATEMENT: This study introduces a segmented three-dimensional printing methodology to create multimaterial porous scaffolds with discrete gradients and controlled distribution of compositions. This methodology can be adapted for the preparation of complex, multimaterial scaffolds with hierarchical structures and mechanical integrity useful in tissue engineering.

Econazole-releasing porous space maintainers for fungal periprosthetic joint infection.

While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis, antifungal-eluting space maintainers are associated with greater limitations for treatment of fungal musculoskeletal infections including limited elution concentration and duration. In this study, we have designed a porous econazole-eluting space maintainer capable of greater inhibition of fungal growth than traditional solid space maintainers. The eluted econazole demonstrated bioactivity in a concentration-dependent manner against the most common species responsible for fungal periprosthetic joint infection as well as staphylococci. Lastly, these porous space maintainers retain compressive mechanical properties appropriate to maintain space before definitive repair of the joint or bony defect.