Functional assessment in patients with castration-resistant prostate cancer treated with darolutamide: results from the DaroAcT study.

BACKGROUND: Androgen receptor inhibitors (ARIs) are approved for the treatment of advanced prostate cancer; however, some patients may experience symptoms and side effects that hinder their physical functioning. The Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests are used to assess physical functioning in older adults and are recommended assessments for patients with prostate cancer, despite lacking validation in this setting. METHODS: DaroAct (NCT04157088) was an open-label, multicenter, phase 2b study designed to evaluate the effects of the ARI darolutamide (lead-in phase) and darolutamide vs enzalutamide (randomized phase) on physical functioning in men with castration-resistant prostate cancer (CRPC). Only the lead-in phase, in which participants received darolutamide 600 mg twice daily, was completed. The TUG and SPPB tests were used to assess physical functioning. RESULTS: The lead-in phase enrolled 30 participants. During 24 weeks of treatment, 8 (32.0%) of 25 evaluable participants exhibited clinically meaningful worsening in TUG from baseline (primary endpoint). At the week 24 visit, 5 (21.7%) of 23 participants had worsening in TUG time, and 8 (33.3%) of 24 participants had worsening in SPPB score. Because only 48% of participants had the same outcome on the TUG and SPPB tests, the study was terminated without initiating the randomized comparison. CONCLUSION: Most participants showed no clinically meaningful worsening in physical functioning after 24 weeks of darolutamide treatment, but poor agreement between tests was observed. Tools to accurately and consistently measure the impact of ARIs on physical functioning in patients with CRPC are needed.

Combining 5G New Radio, Wi-Fi, and LiFi for Industry 4.0: Performance Evaluation.

Fifth-generation mobile networks (5G) are designed to support enhanced Mobile Broadband, Ultra-Reliable Low-Latency Communications, and massive Machine-Type Communications. To meet these diverse needs, 5G uses technologies like network softwarization, network slicing, and artificial intelligence. Multi-connectivity is crucial for boosting mobile device performance by using different Wireless Access Technologies (WATs) simultaneously, enhancing throughput, reducing latency, and improving reliability. This paper presents a multi-connectivity testbed from the 5G-CLARITY project for performance evaluation. MultiPath TCP (MPTCP) was employed to enable mobile devices to send data through various WATs simultaneously. A new MPTCP scheduler was developed, allowing operators to better control traffic distribution across different technologies and maximize aggregated throughput. Our proposal mitigates the impact of limitations on one path affecting others, avoiding the Head-of-Line blocking problem. Performance was tested with real equipment using 5GNR, Wi-Fi, and LiFi -complementary WATs in the 5G-CLARITY project-in both static and dynamic scenarios. The results demonstrate that the proposed scheduler can manage the traffic distribution across different WATs and achieve the combined capacities of these technologies, approximately 1.4 Gbps in our tests, outperforming the other MPTCP schedulers. Recovery times after interruptions, such as coverage loss in one technology, were also measured, with values ranging from 400 to 500 ms.

Rotating particle pair produces hot complex plasma crystals.

Rotating quasipaired particles (torsions) are observed within a two-dimensional monolayer crystal suspended in an argon complex plasma for discharge powers of 1-10 W and pressures of 135-155 mTorr. The inclusion of a torsion in a crystal lattice fundamentally changes the overall lattice state to a "hot crystal." A torsion increases the particle motion and kinetic energy of other particles in the crystal, with the strongest effects on neighboring particles. The apparent effective range is to the third nearest neighbor, with the kinetic energy in the first three shells of particles increasing by at least 200% over baseline values for the crystal. However, the variance of the motion of all particles in the crystal increases by more than two times over the average background kinetic fluctuations for the whole crystal. The formation of a torsion perturbs the structure and symmetry of a plasma crystal. A single torsion causes the average interparticle spacing to increase by 11% compared to the same crystal without a torsion. Particles in the first two shells surrounding a torsion also display reduced hexagonal symmetry. The combination of the perturbed lattice structure and the larger range of motion for the microparticles contribute to a higher-energy-state crystal when torsions are present.

Revitalizing Urologists' Role in Transplantation as a Novel Strategy to Address Surgeon Shortage: Results from a Cross-Sectional Survey.

OBJECTIVES: Urologists represent functional alternatives for transplant surgeons, but their involvement is minimal. Evaluating urologists' interests in transplant and identifying associated factors may help to determine whether recruitment of more urological providers is a viable strategy to address transplant surgeon shortages in the United States. MATERIALS AND METHODS: We emailed a 10-question survey to individuals pursuing urology in the United States and collected demographic data, education and training backgrounds, and preferences for proposed integrated residency programs and abbreviated transplant fellowships. We stratified respondents based on transplant interest (yes/no); we made comparisons by using t-tests for continuous variables and Fisher exact tests for categorical variables. We used multivariable logistic regression to identify factors associated with interest in transplant surgery. RESULTS: Of 104 respondents, 98 were included in the final analysis, with 47% indicating a current or prior interest in transplantation. Male respondents were 3.7 times more likely than female respondents to be interested (odds ratio = 4.675; 95% CI, 1.411-15.495; P = .012). Participants aged <30 years were 93% less likely than older participants to be interested in transplantation (odds ratio = 0.071; 95% CI, 0.006-0.779; P = .03). International medical graduates reported higher enthusiasm for transplantation compared with US-trained counterparts (89% vs 42%), with a trend toward significance (P = .06). Nearly all (93%, 43/46) who expressed interest endorsed having an integrated training pathway. Only 70% (32/46) supported an abbreviated fellowship (<24 mo). Lifestyle concerns and insufficient exposure during residency were the most frequently cited reasons for lack of interest. CONCLUSIONS: Compared with male and older urology trainees, female and younger urology trainees were less inclined to pursue transplant surgery. Nonetheless, urologists represent an untapped pool of transplant surgeons. Proposing an integrated training program for urologists and increasing exposure to transplantation during urology residency represent potential strategies to decrease transplant surgeon shortages.

Bayesian inverse problem for a fractional diffusion model of cell migration.

In the present work, both direct and inverse problems are considered for a Fisher-type fractional diffusion equation, which is proposed to describe the phenomenon of cell migration. For the direct problem, a solution is given via the Fourier method and the Laplace transform. On the other hand, we solved the inverse problem from a Bayesian statistical framework using a set of data that are the result of a cell migration experiment on a wound closure assay. We estimated the parameters of the mathematical model via Markov Chain Monte Carlo methods.

Abdominal Transplant Surgeons: The Lack of Female Surgeons and People From Underrepresented Racial and Ethnic Minority Groups in Academic and Clinical Leadership.

OBJECTIVES: The demographic disparities among surgeons in academic leadership positions is well documented. We aimed to characterize the present demographic details of abdominal transplant surgeons who have achieved academic and clinical leadership positions. MATERIALS AND METHODS: We reviewed the 2022-2023 American Society of Transplant Surgeons membership registry to identify 1007 active abdominal transplant surgeons. Demographic details (academic and clinical titles) were collected and analyzed using the chi-square test, the Fisher exact test, and t tests. Multinomial logistic regressions were conducted. RESULTS: Female surgeons (P < .001) and surgeons from racial-ethnic minorities (P = .027) were more likely to be assistants or associates rather than full professors. White male surgeons were more likely to be full professors than were White female (P < .001), Asian female (P = .008), and Asian male surgeons (P = .005). There were no Black female surgeons who were full professors. The frequency of full professorship increased with surgeon age (P < .001). Male surgeons were more likely to hold no academic titles (P < .001). Female surgeons were less likely to be chief of transplant(P = .025), chief of livertransplant (P = .001), chief of pancreas transplant (P = .037), or chair of surgery (P = .087, significance at 10%). Chief of kidney transplant was the most common clinical position held by a surgeon from a racial or ethnic minority group. Female surgeons were more likely to hold no clinical titles (P = .001). CONCLUSIONS: The underrepresentation of women and people from racial and ethnic minority groups in academic and clinical leadership positions in the field of abdominal transplant surgery remains evident. White male physicians are more likely to obtain full professorship, and they comprise most of the clinical leadership positions overall. A continued push for representative leadership is needed.

Biodegradable Biocomposite of Starch Films Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Reinforced by Microfibrillated Cellulose.

Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

Elevated liver enzymes at the time of deceased donor organ donation do not affect recipient or pancreas allograft survival following pancreas transplantation.

BACKGROUND: There is a lack of data on the impact of donor liver function tests (LFTs) on pancreas transplantation outcomes. Understanding their contribution could expand the donor pool. METHODS: Using the UNOS database, data from January 2010-2022 was retrospectively analyzed. Multivariable cox regressions were performed to evaluate the association between LFTs (AST, ALT and total bilirubin levels), graft failure and mortality up to three years post-transplant. RESULTS: 9138 pancreas transplants were completed. Multivariate analysis showed no association between donor AST values > 500 U/L and increased rates of graft failure (p = 0.826) or mortality (p = 0.836). Similar findings were noted for donor ALT values > 500 U/L (p = 0.522 and p = 0.997, respectively). There was no correlation with graft failure (p = 0.322) or mortality (p = 0.423) for total bilirubin levels >3 mg/dL. CONCLUSION: LFTs in the deceased pancreas donor did not increase risk of graft failure or mortality following pancreas transplantation. Elevated LFTs should not serve as absolute contraindications to transplant.

Factors of poor prognosis in newborns with a prenatal diagnosis of gastroschisis in Bogota, Colombia.

OBJECTIVES: To identify factors associated with poor prognoses in newborns with a prenatal diagnosis of gastroschisis in eight hospitals in Bogota, Colombia, from 2011 to 2022. METHODS: A multi-center retrospective case-control study was conducted on newborns with gastroschisis in eight hospitals in Bogota, Colombia. Poor prognosis was defined as the presence of sepsis, intestinal complications, or death. RESULTS: The study included 101 patients. Preterm newborns under 32 weeks had a poor neonatal prognosis (OR 6.78 95 % CI 0.75-319). Oligohydramnios (OR 4.95 95 % CI 1.15-21.32) and staged closure with silo (OR 3.48; 95 % CI 1.10-10.96) were risk factors for neonatal death, and intra-abdominal bowel dilation of 20-25 mm was a factor for the development of intestinal complications (OR 3.22 95 % CI 1.26-8.23). CONCLUSIONS: Intra-abdominal bowel dilation between 20 and 25 mm was associated with intestinal complications, while oligohydramnios was associated with the risk of perinatal death, requiring increased antenatal surveillance of fetal wellbeing. Management with primary reduction when technically feasible is recommended in these infants, considering that the use of silos was associated with higher mortality.

Bacterial fluorescence imaging as a predictor of skin graft integration in burn wounds.

BACKGROUND: Split-thickness skin graft (STSG)1 integration rates are susceptible to improvement. Infection and/or biofilm should be appropriately addressed prior to grafting to improve the likelihood of graft-take. Incorporating technological aids such as fluorescence (FL)2 imaging (MolecuLight®), which accurately locates areas of bacterial loads above 104 CFU/gr, for graft site assessment and preparation could yield better outcomes. METHODS: This single-center, prospective observational study included adult burn patients with previously infected wounds that had been deemed clinically and microbiologically clean and were therefore candidates for grafting. Prior to grafting, a FL imaging assessment (blinded to the surgical team) localized areas positive for moderate-high bacterial loads (>104 CFU/gr). Intra-operatively, a standard swab sample from the recipient site was collected by the surgical team. Postoperatively, areas positive/negative for FL and areas of graft take and failure were overlapped and measured (cm2) over a 2D schematic. The performance and accuracy of FL imaging and swab sampling in relation to graft outcomes were assessed. RESULTS: 38 patients were enrolled in the study. The mean total body surface area (TBSA)3 involvement was 14.5 ± 12.4 % [range 0.8 - 40.2 %]. 25/38 of the subjects enrolled had complete graft take while 13 had partial graft losses. There were no total losses. FL-imaging was positive in 100 % of losses versus 31 % (4/13) of the swab microbiology. FL-imaging was found to have a sensitivity of 86 %, specificity of 98 %, PPV of 72 %, NPV of 99 %, and an accuracy of 94 % for predicting any type or range of graft loss in the entire cohort. Meanwhile, the sensitivity of microbiology from swab samples was 30 %, with a specificity of 76 %. CONCLUSIONS: FL imaging is an accurate method for assessing recipient sites and predicting the outcome of a skin graft among burn patients. These findings suggest that FL imaging can inform better decision-making surrounding grafts that may lead to better outcomes. LEVEL OF EVIDENCE: Level IIA, Therapeutic study.

A Comprehensive Analysis of Litigation in Organ Transplantation for Allegations of Insufficient Policy Coverage, Discrimination and Malpractice.

Introduction: Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design: The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results: One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion: Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.

Unintentional Injury Death Among Solid Organ Transplant Recipients: Trends and Risk Factors.

Unintentional injury death (UID) is a leading cause of mortality worldwide, and individuals with chronic diseases are at higher risk. Though organ transplant can improve the lives of those with chronic disease, these individuals remain in suboptimal physical and mental health after surgery that predisposes them to UID. To quantify the scale of UID among solid organ transplant recipients, we performed a retrospective analysis using United Network of Organ Sharing data from adults who underwent kidney, liver or pancreas transplant between 2000-2021. Our study aimed to identify risk factors for UID in this cohort by comparing basic patient, donor, and transplant characteristics of the groups (UID or all other cause death). The largest proportion of UID was seen in the kidney group (.8%), followed by liver (.7%) and then pancreas (.3%). Male sex was the most significant risk factor among kidney and liver recipients. Whites had a higher risk for UID relative to their non-White counterparts in the kidney and liver groups. In both groups, advancing age conferred a protective effect, whereas higher functional status was a risk factor. Our findings shed new light on a significant source of mortality within the transplant population.

Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis.

INTRODUCTION: IgA nephropathy (IgAN) can cause end-stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT). METHODS: Retrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival. RESULTS: Compared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90, p < .010, 95% CI [1.169-3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665, p = .044, 95% CI [.447-.989]), graft failure (HR .758, p = .002, 95% CI [.633-.907]), and death (HR .619, p < .001, 95% CI [.490-.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs. CONCLUSION: In patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality.

Equivalence in Color-coded Duplex Sonography Parameters before Complex Microsurgery.

Background: Color-coded duplex sonography (CCDS) is a widely proposed noninvasive diagnostic tool in microsurgery. CCDS has been applied to lower extremity salvage cases to define appropriate blood flow velocity criteria for achieving arterial success in diabetic foot and complex microsurgery cases. This study aimed to compare the success ratio of free flaps when using CCDS versus cases where CCDS was not used. Methods: We included complex microsurgery cases from 2019 to 2021. These cases were subsequently categorized into two groups: group A consisted of cases where CCDS parameters were applied, whereas group B comprised cases where CCDS was not performed at all. Results: The study encompassed 14 cases (11 men and three women). The age range varied from 23 to 62 years, with an average age of 42. Using CCDS analysis and planning demonstrated improved outcomes in comparison with cases where CCDS was not performed, albeit without statistical significance (P = 0.064). Conclusions: The application of CCDS proves to be beneficial in the realm of microsurgery. Although not achieving statistical significance, our data imply that CCDS utilization holds promise for enhancing microsurgical procedures.

Creating Value in Non-Profit Sports Organizations: An Analysis of the DART Model and Its Performance Implications.

This study aims to analyze the impact of value creation and cocreation, as measured by the dialogue, access, risk assessment, and transparency (DART) model, on the performance of non-profit sports organizations (NPSOs). To assess this impact, the authors analyzed data collected from sports and administration managers of NPSOs, specifically Colombian amateur soccer clubs. The study used partial-least-squares structural-equation modeling (PLS-SEM) with constructs of the reflexive-formative type. The results indicate that value creation has a positive impact on the performance of NPSOs through the mediating effect of value cocreation. Despite the limitations of this study, including the limited research on the relationship between value creation and cocreation and NPSO performance in Colombia, the findings contribute to the understanding of the mediating effect of cocreation. The authors found that cocreation mainly affects the sport, customers/members, communication and image, finance, and organization dimensions of NPSOs in developing countries. This study draws attention to the potential benefits of cocreation for NPSOs and emphasizes the importance of creating value in this context. The study concludes that further studies on the constructs proposed in this research would help to understand the phenomenon of innovation and its impact on NPSOs. Overall, this study provides valuable insights for managers and policymakers in NPSOs-especially in developing countries-on the importance of value cocreation in improving their performance.

Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern.

Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.