Wound healing is a complex process that often requires treatment with antibiotics. This article reports the initial development of a biodegradable polymeric nanofiber-based antibiotic delivery system. The functions of such a system would be (a) to serve as a biodegradable gauze, and (b) to serve as an antibiotic delivery system. The polymer used in this study was poly(lactide-co-glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the electrospinning process. The objective of this study was to determine the effect of fabrication parameters: orifice diameter (needle gauge), polymer solution concentration, and voltage per unit length, on the morphology and diameter of electrospun nanofibers. The needle gauges studied were 16 (1.19 mm), 18 (0.84 mm), and 20 (0.58 mm), and the range of polymer solution concentration studied was from 0.10 g/mL to 0.30 g/mL. The effect of voltage was determined by varying the voltage per unit electrospinning distance, and the range studied was from 0.375 kV/cm to 1.5 kV/cm. In addition, the mass per unit area of the electrospun nanofibers as a function of time was determined and the feasibility of antibiotic (cefazolin) loading into the nanofibers was also studied. The results indicate that the diameter of nanofibers decreased with an increase in needle gauge (decrease in orifice diameter), and increased with an increase in the concentration of the polymer solution. The voltage study demonstrated that the average diameter of the nanofibers decreased with an increase in voltage. However, the effect of voltage on fiber diameter was less pronounced as compared to polymer solution concentration. The results of the areal density study indicated that the mass per unit area of the electrospun nanofibers increased linearly with time. Feasibility of drug incorporation into the nanofibers was demonstrated with the use of cefazolin, a broad-spectrum antibiotic. Overall, these studies demonstrated that PLAGA nanofibers can be tailored to desired diameters through modifications in processing parameters, and that antibiotics such as cefazolin can be incorporated into these nanofibers. Therefore, PLAGA nanofibers show potential as antibiotic delivery systems for the treatment of wounds.

A better understanding of the pathophysiology and evolution of non-small cell lung cancer (NSCLC) has identified a number of molecular targets and spurred development of novel targeted therapeutic agents. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are implicated in tumor cell proliferation, migration, invasion, and angiogenesis in a broad spectrum of human cancers, including NSCLC. Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Implications for Practice: Identification of the role of the HGF-MET pathway in cancer, and specifically in non-small cell lung cancer (NSCLC) has led to the development of pharmaceutical agents targeting this pathway. In particular, MET's role in secondary resistance to EGFR-directed therapies has led to the investigation of combining MET-directed agents with erlotinib in patients with metastatic NSCLC. This article reviews the early development of MET-directed therapies as well as currently ongoing Phase III studies.We await the results of these studies, which will determine whether targeting MET in combination with EGFR is a valid clinical option in patients whose cancers progress following treatment with EGFR inhibitors.

Key Points Question Are cardiovascular risk factors assessed and appropriately managed in patients with prostate cancer initiating androgen deprivation therapy? Findings In this cross-sectional analysis of 90 494 US veterans with prostate cancer, 68.1% received comprehensive cardiovascular risk factor assessment and 54.1% had uncontrolled risk factors; of these, 29.6% were not receiving risk-reducing medication. Patients with known atherosclerotic cardiovascular disease had improved cardiovascular risk factor assessment, control, and treatment; however, androgen deprivation therapy initiation was not associated with meaningful differences in these outcomes. Meaning In this study, veterans with prostate cancer, including those initiating androgen deprivation therapy, appeared to have a high burden of underassessed and undertreated cardiovascular risk factors.

Lung cancer will be diagnosed in 230,000 patients in the U.S. in 2013. Adenocarcinoma will be the most common histology, and 10 % of lung cancers will be diagnosed in never or former light smokers. These patients will be those most likely to harbor targetable mutations, in particular, mutations in epidermal growth factor (EGFR). Preclinical work beginning in the 1980s led to the development of EGFR-targeted therapy in lung cancer patients. Analysis of the responders to gefitinib and erlotinib led to the discovery of activating mutations underlying sensitivity to EGFR-directed treatment. Although EGFR-mutant patients have higher response rates, better quality of life, and longer progression free survival, all patients eventually develop resistance. Mutations in the tyrosine kinase domain that render tumors resistant to erlotinib and gefitinib are the most common mechanism of resistance. A second generation of EGFR inhibitors are now making their way to the clinic, with hopes of thwarting these resistance mechanisms or providing more durable responses via irreversible inhibition, as well as targeting of additional HER receptors. Here we review the evolution of EGFR as a target in lung cancer, and the second generation of EGFR inhibitors in development.

Key Points Question Does androgen suppression improve clinical outcomes in hospitalized men with COVID-19? Findings In this randomized clinical trial including 96 men, androgen suppression with the addition of degarelix vs placebo plus standard care did not show reduction of the composite end point of mortality, ongoing hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Meaning This randomized clinical trial found that androgen suppression did not improve outcomes in men hospitalized for COVID-19.

IMPORTANCE Conservative management (ie, active surveillance or watchful waiting) is a guidelinebased strategy for men with low-risk and intermediate-risk prostate cancer. However, use of conservative management is controversial for African American patients, who have worse prostate cancer outcomes compared with White patients. OBJECTIVE To examine the association of African American race with the receipt and duration of conservative management in the Veterans Health Administration (VA), a large equal-access health system. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the VA Corporate Data Warehouse for 51 543 African American and non-Hispanic White veterans diagnosed with low-risk and intermediate-risk localized node-negative prostate cancer between January 1, 2004, and December 31, 2013. Men who did not receive continuous VA care were excluded. Data were analyzed from February 1 to June 30, 2020. EXPOSURES All patients received either definitive therapy (ie, prostatectomy, radiation, androgen deprivation therapy) or conservative management (ie, active surveillance or watchful waiting). MAIN OUTCOMES AND MEASURES Receipt of conservative management and (for patients receiving conservative management) time from diagnosis to definitive therapy. RESULTS The median (interquartile range) age of the 51 543 veterans in our cohort was 65 (61-70) years, and 14 830 veterans (28.8%) were African American individuals. Compared with White veterans, African American veterans were more likely to have intermediate-risk disease (18 988 [51.7%] vs 8526 [57.5%]), 3 or more comorbidities (15 438 [42.1%] vs 7614 [51.3%]), and high disability-related or income-related needs (9078 [24.7%] vs 4614 [31.1%]). Overall, 20 606 veterans (40.0%) received conservative management. African American veterans with low-risk disease (adjusted relative risk, 0.95; 95% CI, 0.92-0.98; P < .001) and intermediate-risk disease (adjusted relative risk, 0.92; 95% CI, 0.87-0.97; P = .002) were less likely to receive conservative management than White veterans. Compared with White veterans, African American veterans with low-risk disease (adjusted hazard ratio, 1.71; 95% CI, 1.50-1.95; P < .001) and intermediate-risk disease (adjusted hazard ratio, 1.46; 95% CI, 1.27-1.69; P < .001) who received conservative management were more likely to receive definitive therapy within 5 years of diagnosis (restricted mean survival time [SE] at 5 years, 1679 [5.3] days vs 1740 [2.4] days; P < .001). CONCLUSIONS AND RELEVANCE In this study, conservative management was less commonly used and less durable for African American veterans than for White veterans. Prospective trials should (continued) Key Points Question Are there racial differences in receipt and duration of conservative management (ie, active surveillance or watchful waiting) among veterans with low-risk and intermediate-risk prostate cancer? Findings In this cohort study of 51 543 veterans with low-risk and intermediaterisk prostate cancer, African American veterans were less likely than Whi...

Background Depression is common after a diagnosis of prostate cancer and may contribute to poor outcomes, particularly among African Americans. The authors assessed the incidence and management of depression and its impact on overall mortality among African American and White veterans with localized prostate cancer. Methods The authors used the Veterans Health Administration Corporate Data Warehouse to identify 40,412 African American and non‐Hispanic White men diagnosed with localized prostate cancer from 2001 to 2013. Patients were followed through 2019. Multivariable logistic regression was used to measure associations between race and incident depression, which were ascertained from administrative and depression screening data. Cox proportional hazards models were used to measure associations between incident depression and all‐cause mortality, with race‐by‐depression interactions used to assess disparities. Results Overall, 10,013 veterans (24.5%) were diagnosed with depression after a diagnosis of prostate cancer. Incident depression was associated with higher all‐cause mortality (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.23‐1.32). African American veterans were more likely than White veterans to be diagnosed with depression (29.3% vs 23.2%; adjusted odds ratio [aOR], 1.15; 95% CI, 1.09‐1.21). Among those with depression, African Americans were less likely to be prescribed an antidepressant (30.4% vs 31.7%; aOR, 0.85; 95% CI, 0.77‐0.93). The hazard of all‐cause mortality associated with depression was greater for African American veterans than White veterans (aHR, 1.32 [95% CI, 1.26‐1.38] vs 1.15 [95% CI, 1.07‐1.24]; race‐by‐depression interaction P < .001). Conclusions Incident depression is common among prostate cancer survivors and is associated with higher mortality, particularly among African American men. Patient‐centered strategies to manage incident depression may be critical to reducing disparities in prostate cancer outcomes.

The BZ reaction involves the continuous exchange of electrons, producing a dynamic shift from a reduced to oxidized state of a metallic atom. This active electron movement results in spatiotemporal patterns that provide a platform to study and understand nature. [3] A range of self-oscillating polymers are designed by incorporating metal catalysts to polymer matrices. [4] Different architectures are developed based on BZ reaction in past including porous microstructures, [5] microgels, [6,7] comb-type gels, [8] polyrotaxanes, [9] polymer brushes, [10] and micelles. [11] Furthermore, the force generated by the BZ reaction in the self-oscillating polymers have be used as propulsive system: [12] tubular-shaped gels; [13] ciliary motion in arrays of PMMA gels; [14] active surfaces transported microbodies; [15] and a cylinder-shaped gel self-walking structure. [16] Previous studies have confined the BZ reaction in different hydrogel systems fabricated using different approaches. Initial studies used flask-mediated polymerizations and microfluidics to produce a variety of hydrogels, [16,17] consisting of micelles Materials, [18] linear chains, [7,19] brushes, [20] etc. Microfluidics can fabricate 3D hydrogels with precise control, but their size is limited to the macro-and micro-length scale. [21] Other studies employed engineering techniques such as UV patterning [22] and microdispensing [23] to fabricate hydrogels; however, the Belousov-Zhabotinsky (BZ) reactions have been used to investigate periodic spatial patterns due to the oscillatory nature of the reaction. However, these systems have not been confined, nor controlled, in macro-scaled architectures, making it hard to translate observations to natural behavior. Here, a poly(electrolyte) complex is designed that can be ionically or covalently reinforced to construct 3D geometries with additive manufacturing techniques. Printed geometries varied in shape, size, and angle to investigate spatiotemporal pattern formation in 3D. Size variations correlated to trends in oscillating pattern frequencies, demonstrating a geometry effect on spatial alterations. Overall, the combination of 3D printing techniques with selfoscillating chemical reactions allows to model, study, and further understand macro-scale patterns observed in nature. The proposed approach can be used to design smart structure to replicate biological oscillators such as cardiac arrhythmias, neuron signaling, and camouflage skin patterns.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/admt.202100418.