The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk-factors and outcomes are not well-understood due to a sparsity of cases spread across multiple centers. OBJECTIVES: The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplant-related risk factors and co-morbid critical care diagnoses associated with post-HCT DAH. STUDY DESIGN: Retrospective analysis was performed on a multi-center cohort of 6,995 patients ≤21 years old who underwent allogeneic HCT between 2008-2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox-proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox-regression with DAH as a time-varying covariate. RESULTS: DAH occurred in 81 patients at a median 54 days post-HCT (IQR 23-160 days), with a 1-year post-transplant cumulative incidence probability of 1.0% (95% CI 0.81-1.3%) and was noted in 7.6% of all PICU patients. Risk factors included transplant for non-malignant hematologic disease (Referent: malignant hematologic disease, HR=1.98, 95% CI 1.22-3.22, p=0.006), use of calcineurin inhibitor plus mycophenolate mofetil (CNI + MMF) as GvHD prophylaxis, (Referent: calcineurin inhibitor plus methotrexate, HR=1.89, 95% CI 1.07-3.34, p=0.029), and grade III-IV acute GvHD (HR=2.67, 95% CI 1.53-4.66, p<0.001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (p<0.05) than those without DAH. From the time of DAH, median survival was 2.2 months and one-year overall survival was 26% (95% CI 17-36%). Among all HCT patients, the development of DAH when considered was associated with a seven-fold increase in unadjusted all-cause post-HCT mortality (HR 6.96, 95% CI 5.42-8.94, p<0.001). In a landmark analysis of patients alive 2 months post-HCT, patients who developed DAH had a one-year overall survival of 33% (95% CI 18-49%) versus 82% (95% CI 81-83%) for patients without DAH (p<0.001). CONCLUSION: Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of non-malignant hematologic transplant indication, use of CNI + MMF as GvHD prophylaxis and severe acute GvHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

Prognostic significance of hemorrhage requiring embolization in the setting of previously treated head and neck squamous cell carcinoma: Systematic review and retrospective cohort.

BACKGROUND: The management of acute hemorrhage in patients with previously treated head and neck squamous cell carcinoma (HNSCC) is challenging due to the lack of substantial evidence to guide clinical decision making. METHODS: A systematic review and retrospective chart review were performed to identify patients with a history of HNSCC who underwent either primary or adjuvant radiation therapy (RT) and presented with hemorrhagic complications requiring embolization. Patient characteristics, history, presentation, and outcomes were reviewed. RESULTS: The systematic review included a total of 182 patients. Heterogeneity existed in outcomes reporting; 1-year overall survival approached 50%. From the retrospective chart review, 51 patients were included. Median survival time following hemorrhage was 2.2 months (range 1.2-11.4 months). Patients with malignancy at time of hemorrhage were identified as having worse survival. CONCLUSIONS: Acute hemorrhage in patients with a history of previously radiated HNSCC portends a high risk of mortality, with patients with active malignancy representing a worse prognostic group.

Pulmonary hypertension in the intensive care unit after pediatric allogeneic hematopoietic stem cell transplant: incidence, risk factors, and outcomes.

Objective: To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). Methods: This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Results: Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74-3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). Conclusions: PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement.

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice. Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice. Evidence Review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory. Prior to the meeting, attendees submitted key ethics and policy issues for psychedelic medicine. Responses were categorized into 6 broad topics: research ethics issues; managing expectations and informed consent; therapeutic ethics; training, education, and licensure of practitioners; equity and access; and appropriate role of gatekeeping. Attendees with relevant expertise presented on each topic, followed by group discussion. Meeting organizers (A.L.M., I.G.C., D.S.) drafted a summary of the discussion and recommendations, noting points of consensus and disagreement, which were discussed and revised as a group. Findings: This consensus statement reports 20 points of consensus across 5 ethical issues (reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping), with corresponding relevant actors who will be responsible for implementation. Areas for further research and deliberation are also identified. Conclusions and Relevance: This consensus statement focuses on the future of government-approved medical use of psychedelic medicines in the US and abroad. This is an incredibly exciting and hopeful moment, but it is critical that policymakers take seriously the challenges ahead.

Static posture weightbearing joint angle differences in patients with varus ankle osteoarthritis.

BACKGROUND: Advanced varus ankle osteoarthritis is a debilitating disease that can present with limited physical function, severe pain, and diminished quality of life. Weightbearing computed tomography enables submillimeter 3-dimensional visualization, computational analyses, and enhanced diagnoses in reporting complex degenerative changes more accurately. RESEARCH QUESTION: This study set to compare static posture weightbearing joint angle differences in healthy and varus ankle osteoarthritis patients (compensated and non-compensated). METHODS: Our retrospective assessment included 70 individuals, 44 of whom were diagnosed with advanced varus ankle osteoarthritis, and the remaining 26 were healthy participants to serve as controls. An automatic anatomic coordinate system was applied to each patient's 3-dimensional talus and calcaneus bone reconstructions from weightbearing computed tomography scans. Subtalar and midtarsal joint angles were calculated using Euler angles. RESULTS: We report statistical differences between the healthy group and both advanced varus osteoarthritis groups for midtarsal inversion/eversion. Specifically, both osteoarthritis groups' midtarsal joints were more inverted and plantarflexed as compared to healthy participants. Compensated and non-compensated subtalar joints were statistically different with respect to inversion/eversion. Non-compensated ankles exhibited a similar mean to healthy ankles who were both less inverted than compensated ankles. SIGNIFICANCE: Our study helps physicians to better understand underlying mechanisms of peritalar compensation in varus ankle osteoarthritis. Patients featuring hindfoot compensation on average had a greater subtalar joint angle indicating greater inversion than healthy and non-compensated patients.

Recommendation of minimal distal tibial length for long axis coordinate system definitions.

Accurate anatomical coordinate systems for the foot and ankle are critical for interpreting their complex biomechanics. The tibial superior-inferior axis is crucial for analyzing joint kinematics, influencing bone motion analysis during gait using CT imaging and biplane fluoroscopy. However, the lack of consensus on how to define the tibial axis has led to variability in research, hindering generalizability. Even as advanced imaging techniques evolve, including biplane fluoroscopy and weightbearing CT, there exist limitations to imaging the entire foot together with the full length of the tibia. These limitations highlight the need to refine axis definitions. This study investigated various superior-inferior axes using multiple distal tibia lengths to determine the minimal field of view for representing the full tibia long-axis. Twenty human cadaver tibias were imaged and segmented to generate 3D bone models. Axes were calculated based on coordinate definitions that required user manual input, and a gold standard mean superior-inferior axis was calculated based on the population's principal component analysis axis. Four manually calculated superior-inferior tibial axes groups were established based on landmarks and geometric fittings. Statistical analysis revealed that geometrically fitting a cylinder 1.5 times the mediolateral tibial width, starting 5 cm above the tibial plafond, yielded the smallest angular deviation from the gold standard. From these findings, we recommend a minimum field of view that includes 1.5 times the mediolateral tibial width, starting 5 cm above the tibial plafond for tibial long-axis definitions. Implementing these findings will help improve foot and ankle research generalizability and impact clinical decisions.

Are Psychedelic Experiences Transformative? Can We Consent to Them?

Psychedelic substances have great promise for the treatment of many conditions, and they are the subject of intensive research. As with other medical treatments, both research and clinical use of psychedelics depend on our ability to ensure informed consent by patients and research participants. However, some have argued that informed consent for psychedelic use may be impossible, because psychedelic experiences can be transformative in the sense articulated by L. A. Paul (2014). For Paul, transformative experiences involve either the acquisition of knowledge that cannot be obtained in any other way or changes in the self. Either of these characteristics may appear to undermine informed consent. This article argues, however, that there is limited evidence that psychedelic experiences are transformative in Paul's sense, and that they may not differ in their transformative features from other common medical experiences for which informed consent is clearly possible. Further, even if psychedelic experiences can be transformative, informed consent is still possible. Because psychedelic experiences are importantly different in several respects from other medical experiences, this article closes with recommendations for how these differences should be reflected in informed consent processes.

GPAW: An open Python package for electronic structure calculations.

We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.

ANGPTL7 and Its Role in IOP and Glaucoma.

Purpose: Loss-of-function variants in the ANGPTL7 gene are associated with protection from glaucoma and reduced intraocular pressure (IOP). We investigated the role of ANGPTL7 in IOP homeostasis and its potential as a target for glaucoma therapeutics. Methods: IOP, outflow facility, and outflow tissue morphology of Angptl7 knockout (KO) mice were assessed with and without dexamethasone (Dex). ANGPTL7 was quantified in conditioned media from human trabecular meshwork cells in response to Dex, in effluent from perfused human donor eyes, and in aqueous humor from human patients treated with steroids. Antibodies to ANGPTL7 were generated and tested in three-dimensional (3D) culture of outflow cells and perfused human donor eyes. Rabbits were injected intravitreally with a neutralizing antibody targeting ANGPTL7, and IOP was measured. Results: IOP was significantly elevated, but outflow facility and outflow tissue morphology were not different between Angptl7 KO mice and littermates. When challenged with Dex, IOP increased in wild-type but not Angptl7 KO mice. In human samples, increased ANGPTL7 was seen in the aqueous humor of patients treated with steroids, regardless of glaucoma status. Using 3D culture, recombinant ANGPTL7 decreased, and ANGPTL7-blocking antibodies increased hydraulic conductivity. Significantly, outflow facility increased in human eyes treated ex vivo with ANGPTL7-blocking antibodies, and IOP decreased for 21 days in rabbits after a single injection of blocking antibodies. Conclusions: Using multiple models, we have demonstrated that excess ANGPTL7 increases outflow resistance and IOP and that neutralizing ANGPTL7 has beneficial effects in both naïve and steroid-induced hypertensive eyes, thus motivating the development of ANGPTL7-targeting therapeutics for the treatment of glaucoma.

On the Thermodynamic Equivalence of Grand Canonical, Infinite-Size, and Capacitor-Based Models in First-Principle Electrochemistry.

First principles-based computational and theoretical methods are constantly evolving trying to overcome the many obstacles towards a comprehensive understanding of electrochemical processes on an atomistic level. One of the major challenges has been the determination of reaction energetics under a constant potential. Here, a theoretical framework was proposed applying standard electronic structure methods and extrapolating to the infinite-cell size limit where reactions do not alter the potential. Today, electronically grand canonical modifications to electronic structure methods, holding the potential constant by varying the number of electrons in a finite simulation cell, become increasingly popular. In this perspective, we show that these two schemes are thermodynamically equivalent. Further, we link these methods to capacitive models of the interface, in the limit that the capacitance of the charging components (whether continuum or atomistic) are equal and invariant along the reaction pathway. We benchmark the three approaches with an example of alkali cation adsorption on Pt(111) showing that all three approaches converge in the cases of Li, Na and K. For Cs, however, strong deviation from the ideal conditions leads to a spread in the respective results. We discuss the latter by highlighting the cases of broken equivalence and assumptions among the approaches.

Characterizing and Quantifying Material Fatigue of the Artificial Urinary Sphincter Pressure Regulating Balloon.

OBJECTIVE: To characterize and quantify changes in elastic properties and in vivo pressure characteristics of pressure regulating balloons (PRB) over time, we conducted an analysis of the mechanical characteristics of the PRB after removal from patients for revision surgery. METHODS: Pressure and elasticity characteristics of new and used 61-70 cm H2O PRBs were analyzed. Pressure-volume curves were generated using commercially available urodynamics equipment. PRB pressures were measured at a standard fill volume (23 cc). Elastance was calculated by the slope of the tangent line at the inflection point of the pressure-volume curve. Tests were repeated 5 times per PRB and intraclass correlations were used to gauge test-retest reliability. Regression models were used for continuous variables based on data distribution. RESULTS: Twenty-seven used PRBs were analyzed after excluding 3 for alternative pressure ratings and 2 for occult pinpoint leaks. Time from artificial urinary sphincter placement to removal ranged from 0.02-17.6 years (median 8.4, interquartile range (IQR) 5.7-10.0). The mean pressure of all extracted PRBs: 58.8 cm H=O (± 7.4), 17 (62.9%) below the standard operating range. Each year of use in-vivo was associated with 1.09 cm H2O pressure loss on linear regression (P <.01 CI -1.52 to -0.65). PRB pressures were not significantly different according to indication for removal (1-way analysis of variance (ANOVA) P = .11). Loss of elastance was non-linear, decreasing by 1.9% per year on Poisson regression (P <.01, CI -0.03 to -0.01). When accounting for PRB age, PRB pressure was independently associated with detrusor overactivity. CONCLUSION: In PRBs tested for pressure-volume characteristics, increasing PRB age was associated with decreased pressure and elasticity.

The interplay among a dental procedure, infective endocarditis, and an acute ischemic stroke.

BACKGROUND: This case report highlights the rare association among a dental procedure, infective endocarditis, and an acute ischemic stroke. CASE DESCRIPTION: A 54-year-old woman who experienced an acute ischemic stroke 5 weeks after a tooth extraction is described. The initial symptoms of this patient included mild to moderate word-finding difficulty and right facial droop. Computed tomographic angiography revealed a left M1 segment middle cerebral artery occlusion (thrombolysis in cerebral infarction scale, 0) with reconstitution of the distal middle cerebral branches through arterial collaterals. After initial administration of tissue plasminogen activator, endovascular thrombectomy was successfully performed with thrombolysis in cerebral infarction scale 3 (complete) recanalization. After the procedure, the patient showed improvement in language and neurologic deficits. Imaging showed multifocal, bilateral, cortical, and deep brain hemorrhages. Blood cultures grew Streptococcus mitis, ultimately leading to the diagnosis of endocarditis. Echocardiographic imaging revealed moderate to severe aortic insufficiency, a mitral valve vegetation, and mild mitral valve regurgitation. After evaluation by the cardiothoracic surgery team, the patient was discharged with intravenous antibiotics and short-term outpatient follow-up with the cardiothoracic surgery team. PRACTICAL IMPLICATIONS: Dental procedures, although generally safe, can introduce oral bacteria into the bloodstream, leading to bacterial seeding of cardiac valves and subsequent infective endocarditis. Recognizing infective endocarditis subsequent to a dental procedure, including a tooth extraction, as a potential cause of an acute ischemic stroke is vital so that prompt treatment can be initiated.

Long-Range Uniform Deposition of Ag Nanoseed on Cu Current Collector for High-Performance Lithium Metal Batteries.

Uniform lithium deposition is essential to hinder dendritic growth. Achieving this demands even seed material distribution across the electrode, posing challenges in correlating the electrode's surface structure with the uniformity of seed material distribution. In this study, the effect of periodic surface and facet orientation on seed distribution is investigated using a model system consisting of a wrinkled copper (Cu)/graphene structure with a [100] facet orientation. A new methodology is developed for uniformly distributed silver (Ag) nanoparticles over a large area by controlling the surface features of Cu substrates. The regularly arranged Ag nanoparticles, with a diameter of 26.4 nm, are fabricated by controlling the Cu surface condition as [100]-oriented wrinkled Cu. The wrinkled Cu guides a deposition site for spherical Ag nanoparticles, the [100] facet determines the Ag morphology, and the presence of graphene leads to spacings of Ag seeds. This patterned surface and high lithiophilicity, with homogeneously distributed Ag nanoparticles, lead to uniform Li+ flux and reduced nucleation energy barrier, resulting in excellent battery performance. The electrochemical measurements exhibit improved cyclic stability over 260 cycles at 0.5 mA cm-2 and 100 cycles at 1.0 mA cm-2 and enhanced kinetics even under a high current density of 5.0 mA cm-2.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.