Platelet Endothelial Cell Adhesion Molecule (PECAM/CD31) Blockade Modulates Neutrophil Recruitment Patterns and Reduces Infarct Size in Experimental Ischemic Stroke.

The infiltration of polymorphonuclear leukocytes (PMNs) in ischemia-reperfusion injury (I/RI) has been implicated as a critical component of inflammatory damage following ischemic stroke. However, successful blockade of PMN transendothelial migration (TEM) in preclinical studies has not translated to meaningful clinical outcomes. To investigate this further, leukocyte infiltration patterns were quantified, and these patterns were modulated by blocking platelet endothelial cell adhesion molecule-1 (PECAM), a key regulator of TEM. LysM-eGFP mice and microscopy were used to visualize all myeloid leukocyte recruitment following ischemia/reperfusion. Visual examination showed heterogeneous leukocyte distribution across the infarct at both 24 and 72 hours after I/RI. A semiautomated process was designed to precisely map PMN position across brain sections. Treatment with PECAM function-blocking antibodies did not significantly affect total leukocyte recruitment but did alter their distribution, with more observed at the cortex at both early and later time points (24 hours: 89% PECAM blocked vs. 72% control; 72 hours: 69% PECAM blocked vs. 51% control). This correlated with a decrease in infarct volume. These findings suggest that TEM, in the setting of I/RI in the cerebrovasculature, occurs primarily at the cortical surface. The reduction of stroke size with PECAM blockade suggests that infiltrating PMNs may exacerbate I/RI and indicate the potential therapeutic benefit of regulating the timing and pattern of leukocyte infiltration after stroke.

Burnout: A Call to Action From the AUA Workforce Workgroup.

PURPOSE: We hypothesize burnout has failed to improve and certain demographics may be disproportionately affected. MATERIALS AND METHODS: The AUA Workforce Workgroup examined work from the annual AUA Census over the past several years. Particular to this study, relevant burnout-related data were examined from the past 5 years. RESULTS: In 2021, 36.7% of urologists reported burnout compared to 36.2% in 2016. Burnout in men decreased from 36.3% to 35.2%, but increased in women from 35.3% to 49.2%. When examined by age, the largest increases in burnout were seen in those <45 years old, increasing from 37.9% to 44.8%, followed by 45-54 years old, increasing from 43.4% to 44.6%. When asked about the effect of COVID-19 on burnout, 54% of urologists didn't feel COVID-19 impacted burnout. Beyond burnout, only 25.0% of men and 4.6% of women reported no conflict between work and personal responsibilities, while 25.7% of men and 44.7% of women resolved these conflicts in favor of work or were unable to resolve them. Of respondents, 22.5% of men and 37.1% of women were "dissatisfied" with work-life balance. Similarly, 33.6% of men reported their work schedule does not leave enough time for personal/family life, compared to 57.5% of women. CONCLUSIONS: Overall, urologists have higher burnout now when compared to 2016. The gender discrepancy has vastly widened with women experiencing burnout at an increased rate of 14% compared to 2016, while burnout in men decreased by 1%. Burnout has increased the most in those <45 years old. Further action is needed to substantiate the causes of burnout.

Inhibition of PECAM-1 Significantly Delays Leukocyte Extravasation into the Subcortex Post-Stroke.

BACKGROUND AND PURPOSE: Current therapies for ischemic stroke focus on reperfusion but do not address the acute inflammatory response that results in significant reperfusion injury. To advance future therapies, a thorough understanding of the precise spatiotemporal underpinnings of leukocyte extravasation and infiltration is necessary. We describe the evolution of the inflammatory response in a mouse transient middle cerebral artery occlusion (tMCAO) stroke model at several time points after reperfusion and the modulation of this response with PECAM blockade. METHODS: The transient Middle Cerebral Artery Occlusion model (90 minutes of ischemia followed by reperfusion) was used to simulate large vessel occlusion stroke and recanalization. We used wide field and confocal immunofluorescence microscopy to examine the exact distribution of neutrophils with close examination of the leukocyte position with regard to the brain vasculature and the perivascular space. Flow cytometry of single cell suspensions was used to confirm cell identity at different time points post-stroke. RESULTS: Large ischemic strokes involving both the subcortex and cortex (over 20% of the ischemic hemisphere) were induced in mice. At 12 and 24 hours, leukocyte recruitment and extravasation was primarily localized to the cortical surface. This contrasts with other organs where there is considerable migration of neutrophils deep into the inflamed tissue by 24 hours. Flow cytometry showed at 24 hours a majority of leukocytes were neutrophils. Over 48 to 72 hours, leukocytes were increasingly found deeper into the subcortex. Throughout the infarct (determined with triphenyl tetrazolium chloride staining), leukocyte recruitment was not uniform but rather organized in clusters. Disrupting leukocyte diapedesis with PECAM function-blocking monoclonal antibody restricted leukocytes to within 500 microns of the surface when compared to control; and this was still evident at 72 hours (n=3 mice per group, p<0.01, Control 46% ± 4.0 %; PECAM-1 Ab 62% ± 5.0%). High-resolution wide-field microscopy confirmed inhibition of TEM by PECAM-1 blockade at 24 hours. Flow cytometry showed approximately equal numbers of monocytes and neutrophils at 72 hours. CONCLUSIONS: Our findings demonstrate that leukocyte infiltration into a stroke evolves over several days following reperfusion. The use of PECAM blockade modulates the natural progression of leukocytes into the infarcted stroke bed. A better understanding of leukocyte spatiotemporal infiltration and its regulators could help inform the next generation of therapeutic interventions.

Impact of the COVID-19 Pandemic on Urological Care Delivery in the United States.

PURPOSE: We examined changes in urological care delivery due to COVID-19 in the U.S. based on patient, practice, and local/regional demographic and pandemic response features. MATERIALS AND METHODS: We analyzed real-world data from the American Urological Association Quality (AQUA) Registry collected from electronic health record systems. Data represented 157 outpatient urological practices and 3,165 providers across 48 U.S. states and territories, including 3,297,721 unique patients, 12,488,831 total outpatient visits and 2,194,456 procedures. The primary outcome measure was the number of outpatient visits and procedures performed (inpatient or outpatient) per practice per week, measured from January 2019 to February 2021. RESULTS: We found large (>50%) declines in outpatient visits from March 2020 to April 2020 across patient demographic groups and states, regardless of timing of state stay-at-home orders. Nonurgent outpatient visits decreased more across various nonurgent procedures (49%-59%) than for procedures performed for potentially urgent diagnoses (38%-52%); surgical procedures for nonurgent conditions also decreased more (43%-79%) than those for potentially urgent conditions (43%-53%). African American patients had similar decreases in outpatient visits compared with Asians and Caucasians, but also slower recoveries back to baseline. Medicare-insured patients had the steepest declines (55%), while those on Medicaid and government insurance had the lowest percentage of recovery to baseline (73% and 69%, respectively). CONCLUSIONS: This study provides real-world evidence on the decline in urological care across demographic groups and practice settings, and demonstrates a differential impact on the utilization of urological health services by demographics and procedure type.

Automatic detection of graticule isocenter and scale from kV and MV images.

PURPOSE: To automate the detection of isocenter and scale of the mechanical graticule on kilo-voltage (kV) or mega-voltage (MV) films or electronic portal imaging device (EPID) images. METHODS: We developed a robust image processing approach to automatically detect isocenter and scale of mechanical graticule from digitized kV or MV films and EPID images. After a series of preprocessing steps applied to the digital images, a combination of Hough transform and Radon transform was performed to detect the graticule axes and isocenter. The magnification of the graticule was automatically detected by solving an optimization problem using golden section search and parabolic interpolation algorithm. Tick marks of the graticule were then determined by extending from isocenter along the graticule axes with multiples of the magnification value. This approach was validated using 23 kV films, 26 MV films, and 91 EPID images in different anatomical sites (head-and-neck, thorax, and pelvis). Accuracy was measured by comparing computer detected results with manually selected results. RESULTS: The proposed approach was robust for kV and MV films of varying image quality. The isocenter was detected within 1 mm for 98% of the images. The exceptions were three kV films where the graticule was not actually visible. Of all images with correct isocenter detection, 99% had a magnification detection error less than 1% and tick mark detection error less than 1 mm, with the exception of 1 kV film (magnification error: 3.17%; tick mark error: 1.29 mm) and 1 MV film (magnification error: 0.45%; tick mark error: 1.11 mm). CONCLUSION: We developed an approach to robustly and automatically detect graticule isocenter and scale from two-dimensionla (2D) kV and MV films. This is a first step toward automated treatment planning based on 2D x-ray images.

Retrospective Analysis of Long-Term Outcomes After Combat Injury: A Hidden Cost of War.

BACKGROUND: During the conflicts in Iraq and Afghanistan, 52,087 service members have been wounded in combat. The long-term sequelae of these injuries have not been carefully examined. We sought to determine the relation between markers of injury severity and the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. METHODS AND RESULTS: Retrospective cohort study of critically injured US military personnel wounded in Iraq or Afghanistan from February 1, 2002 to February 1, 2011. Patients were then followed until January 18, 2013. Chronic disease outcomes were assessed by International Classification of Diseases, 9th edition codes and causes of death were confirmed by autopsy. From 6011 admissions, records were excluded because of missing data or if they were for an individual's second admission. Patients with a disease diagnosis of interest before the injury date were also excluded, yielding a cohort of 3846 subjects for analysis. After adjustment for other factors, each 5-point increment in the injury severity score was associated with a 6%, 13%, 13%, and 15% increase in incidence rates of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease, respectively. Acute kidney injury was associated with a 66% increase in rates of hypertension and nearly 5-fold increase in rates of chronic kidney disease. CONCLUSIONS: In Iraq and Afghanistan veterans, the severity of combat injury was associated with the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease.

Cell cycle inhibition reduces inflammatory responses, neuronal loss, and cognitive deficits induced by hypobaria exposure following traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) patients in military settings can be exposed to prolonged periods of hypobaria (HB) during aeromedical evacuation. Hypobaric exposure, even with supplemental oxygen to prevent hypoxia, worsens outcome after experimental TBI, in part by increasing neuroinflammation. Cell cycle activation (CCA) after TBI has been implicated as a mechanism contributing to both post-traumatic cell death and neuroinflammation. Here, we examined whether hypobaric exposure in rats subjected to TBI increases CCA and microglial activation in the brain, as compared to TBI alone, and to evaluate the ability of a cyclin-dependent kinase (CDK) inhibitor (CR8) to reduce such changes and improve behavioral outcomes. METHODS: Adult male Sprague Dawley rats were subjected to fluid percussion-induced injury, and HB exposure was performed at 6 h after TBI. Western blot and immunohistochemistry (IHC) were used to assess cell cycle-related protein expression and inflammation at 1 and 30 days after injury. CR8 was administered intraperitoneally at 3 h post-injury; chronic functional recovery and histological changes were assessed. RESULTS: Post-traumatic hypobaric exposure increased upregulation of cell cycle-related proteins (cyclin D1, proliferating cell nuclear antigen, and CDK4) and microglial/macrophage activation in the ipsilateral cortex at day 1 post-injury as compared to TBI alone. Increased immunoreactivity of cell cycle proteins, as well as numbers of Iba-1+ and GFAP+ cells in both the ipsilateral cortex and hippocampus were found at day 30 post-injury. TBI/HB significantly increased the numbers of NADPH oxidase 2 (gp91phox) enzyme-expressing cells that were co-localized with Iba-1+. Each of these changes was significantly reduced by the administration of CR8. Unbiased stereological assessment showed significantly decreased numbers of microglia displaying the highly activated phenotype in the ipsilateral cortex of TBI/HB/CR8 rats compared with TBI/HB/Veh rats. Moreover, treatment with this CDK inhibitor also significantly improved spatial and retention memory and reduced lesion volume and hippocampal neuronal cell loss. CONCLUSIONS: HB exposure following TBI increases CCA, neuroinflammation, and associated neuronal cell loss. These changes and post-traumatic cognitive deficits are reduced by CDK inhibition; such drugs may therefore serve to protect TBI patients requiring aeromedical evacuation.

Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase.

Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A, and PDCD4 knockout mice have a high penetrance for B-cell lymphomas. Here, we show that on B-cell receptor (BCR)-mediated p70s6K activation, PDCD4 is degraded, and eIF4A activity is greatly enhanced. We identified a subset of genes involved in BCR signaling, including CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives. Expression of these known oncogenic proteins is enhanced on BCR activation and is attenuated by the eIF4A inhibitor Silvestrol. Antigen-experienced immunoglobulin (Ig)G(+) splenic B cells, from which most DLBCLs are derived, have higher levels of eIF4A cap-binding activity and protein translation than IgM(+) B cells. Our results suggest that eIF4A-mediated enhancement of oncogene translation may be a critical component for lymphoma progression, and specific targeting of eIF4A may be an attractive therapeutic approach in the management of human B-cell lymphomas.

Trends of Hemoglobin Oximetry: Do They Help Predict Blood Transfusion During Trauma Patient Resuscitation?

BACKGROUND: A noninvasive decision support tool for emergency transfusion would benefit triage and resuscitation. We tested whether 15 minutes of continuous pulse oximetry-derived hemoglobin measurements (SpHb) predict emergency blood transfusion better than conventional oximetry, vital signs, and invasive point-of-admission (POA) laboratory testing. We hypothesized that the trends in noninvasive SpHb features monitored for 15 minutes predict emergency transfusion better than pulse oximetry, shock index (SI = heart rate/systolic blood pressure), or routine POA laboratory measures. METHODS: We enrolled direct trauma patient admissions ≥18 years with prehospital SI ≥0.62, collected vital signs (continuous SpHb and conventional pulse oximetry, heart rate, and blood pressure) for 15 minutes after admission, and recorded transfusion (packed red blood cells [pRBCs]) within 1 to 3, 1 to 6, and 1 to 12 hours of admission. One blood sample was drawn during the first 15 minutes. The laboratory Hb was compared with its corresponding SpHb reading for numerical, clinical, and prediction difference. Ten prediction models for transfusion, including combinations of prehospital vital signs, SpHb, conventional oximetry, and routine POA, were selected by stepwise logistic regression. Predictions were compared via area under the receiver operating characteristic curve by the DeLong method. RESULTS: A total of 677 trauma patients were enrolled in the study. The prediction performance of the models, including POA laboratory values and SI (and the need for blood pressure), was better than those without POA values or SI. In predicting pRBC 1- to 3-hour transfusion, adding SpHb features (receiver operating characteristic curve [ROC] = 0.65; 95% confidence interval [CI], 0.53-0.77) does not improve ROC from the base model (ROC = 0.64; 95% CI, 0.52-0.76) with P = 0.48. Adding POA laboratory Hb features (ROC = 0.72; 95% CI, 0.60-0.84) also does not improve prediction performance (P = 0.18). Other POA laboratory testing predicted emergency blood use with ROC of 0.88 (95% CI, 0.81-0.96), significantly better than the use of SpHb (P = 0.00084) and laboratory Hb (P = 0.0068). CONCLUSIONS: SpHb added no benefit over conventional oximetry to predict urgent pRBC transfusion for trauma patients. Both models containing POA laboratory test features performed better at predicting pRBC use than prehospital SI, the current best noninvasive vital signs transfusion predictor.

Computer Modelling Using Prehospital Vitals Predicts Transfusion and Mortality.

OBJECTIVE: Test computer-assisted modeling techniques using prehospital vital signs of injured patients to predict emergency transfusion requirements, number of intensive care days, and mortality, compared to vital signs alone. METHODS: This single-center retrospective analysis of 17,988 trauma patients used vital signs data collected between 2006 and 2012 to predict which patients would receive transfusion, require 3 or more days of intensive care, or die. Standard transmitted prehospital vital signs (heart rate, blood pressure, shock index, and respiratory rate) were used to create a regression model (PH-VS) that was internally validated and evaluated using area under the receiver operating curve (AUROC). Transfusion records were matched with blood bank records. Documentation of death and duration of intensive care were obtained from the trauma registry. RESULTS: During the course of their hospital stay, 720 of the 17,988 patients in the study population died (4%), 2,266 (12.6%) required at least a 3-day stay in the intensive care unit (ICU), 1,171 (6.5%) required transfusions, and 210 (1.2%) received massive transfusions. The PH-VS model significantly outperformed any individual vital sign across all outcomes (average AUROC = 0.82), The PH-VS model correctly predicted that 512 of 777 (65.9%) and 580 of 931 (62.3%) patients in the study population would receive transfusions within the first 2 and 6 hours of admission, respectively. CONCLUSIONS: The predictive ability of individual vital signs to predict outcomes is significantly enhanced with the model. This could support prehospital triage by enhancing decision makers' ability to match critically injured patients with appropriate resources with minimal delays.

Predictive value of hyperthermia and intracranial hypertension on neurological outcomes in patients with severe traumatic brain injury.

BACKGROUND: Intracranial hypertension (ICH) and hyperthermia are common after traumatic brain injury (TBI) and associated with worse neurological outcomes. This study sets out to determine the combined power of temperature and intracranial pressure (ICP) for predicting neurologic outcomes and prolonged length of stay (LOS) following severe TBI. METHODS: High resolution (every 6 seconds) temperature and ICP data were collected in adults with severe TBI from 2008-2010. Temperatures were plotted against concurrent ICP and divided based on breakpoints (Temperature: <36, 36-38.5 or >38.5 °C, ICP: <20, 20-30 or >30 mmHg). The percentage of time spent in each section, as well as several pooled unfavourable conditions (hyperthermia ± ICH), were then evaluated for predictive value for ICU-LOS > 7 days and short-term (<6 months) vs. long-term (>6 months) dichotomized neurologic outcomes. RESULTS: Fifty patients were included for analysis with severe TBI. Evaluation of the area under the operating receiver curve (AUC) showed significant periods of fever and high ICP (<30 mmHg) had a strong association with poor long-term neurological outcomes (Day 3, AUC = 0.71, p = 0.04) and were higher than either condition alone. ICU-LOS > 7 days was increased when hyperthermia and/or ICH remained uncontrolled by Day 5 (AUC = 0.82, p = 0.02). SUMMARY: Hyperthermia combined with ICH were shown to be significant prognostic indicators of future poor neurologic outcomes in patients with severe traumatic brain injury.

Topical hemostatic agents and dressings in the prehospital setting.

PURPOSE OF REVIEW: Death from exsanguinating hemorrhage remains a priority in the management of combat casualties and civilian trauma patients with truncal and junctional injuries. Appropriate use of hemostatic agents and dressings in the prehospital setting may allow for earlier control and an improved survival rate. RECENT FINDINGS: Third-generation chitosan-based hemostatic agents and dressings appear to be equally efficacious to the dressing currently deployed by the US military forces in the management of hemorrhage not amenable to tourniquet placement. Unfortunately, a lack of clinical trials places a heavy reliance on anecdotal reports and laboratory studies in agent selection and application. SUMMARY: Efficacy of currently available hemostatic agents and dressings appears to have plateaued in recent years although new agents and delivery mechanisms under development may improve control in cases of severe hemorrhage.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive 'mild' blast-related traumatic brain injury.

Blast-related traumatic brain injury (TBI) has been one of the "signature injuries" of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive 'mild' blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI served as a validation dataset. The second independent cohort underwent an initial scan within 30days post-injury. 75% of the scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in the participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p=0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required.

Detection of blast-related traumatic brain injury in U.S. military personnel.

BACKGROUND: Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS: We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS: Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS: DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).

Hyperventilation During Manual Ventilation Can Be Reduced Using a Novel Ventilator but Not With Education Interventions.

INTRODUCTION: Traumatic brain injury (TBI) is the leading cause of combat casualties in modern war with an estimated 20% of casualties experiencing head injury. Since the release of the Brain Trauma Foundation's Guidelines for the Management of Severe Traumatic Brain Injury in 1995, recommendations for management of TBI have included the avoidance of routine hyperventilation. However, both published and anecdotal data suggest that many patients with TBI are inappropriately ventilated during transport, thereby increasing the risk of morbidity and mortality from secondary brain injury. MATERIALS AND METHODS: Enlisted Air Force personnel with prior emergency medical technician training completing a 3-week trauma course were evaluated on their ability to provide manual ventilation. Participants provided manual ventilation using either an in-situ endotracheal tube (ETT) or standard face mask on a standardized simulated patient manikin with TBI on the first and last days of the course. Manual ventilation was provided via a standard manual ventilator and a novel manual ventilator designed to limit tidal volume (VT) and respiratory rate (RR). Participants were given didactic and hands-on training on the third day of the course. Half of the participants were given simulator feedback during the hands-on training. All students provided 2 minutes of manual ventilation with each respirator. Data were collected on the breath-to-breath RR, VT, and peak airway pressures generated by the participant for each trial and were averaged for each trial. A minute ventilation (MV) was then derived from the calculated RR and VT. RESULTS: One hundred fifty-six personnel in the trauma course were evaluated in this study. Significant differences were found in the participant's performance with manual ventilation with the novel compared to the traditional ventilator. Before training, MV with the novel ventilator was less than with the traditional ventilator by 2.1 ± 0.4 L/min (P = .0003) and 1.6 ± 0.5 L/min (P = .0489) via ETT and face mask, respectively. This effect persisted after training with a difference between the devices of 1.8 ± 0.4 L/min (P = .0069) via ETT. Both traditional education interventions (didactics with hands-on training) and simulator-based feedback did not make a significant difference in participant's performance in delivering MV. CONCLUSIONS: The use of a novel ventilator that limits RR and VT may be useful in preventing hyperventilation in TBI patients. Didactic education and simulator-based feedback training may not have significant impact on improving ventilation practices in prehospital providers.

Factors Influencing Medication Selection for Management of Overactive Bladder: Trends and Insights From AUA Quality Registry.

OBJECTIVE: To determine how a patient's demographics, including insurance type, race/ethnicity, gender, and age, may impact the choice of medication prescribed for overactive bladder (OAB). METHODS: We queried the AUA Quality Registry for adults between 2014 and 2020 with a diagnosis of OAB for >1year, excluding neurogenic causes. Variables included age, race/ethnicity, gender, insurance type, medication first prescribed, year of prescription, provider metropolitan status, and provider practice type. Primary outcome was which factors were associated with increased odds of beta-3 prescription as first medication choice. RESULTS: We found 1,453,566 patients with OAB, 641,122 (44.1%) with complete data. Of these, 112,021 (17.5%) were prescribed medication. On multivariate analysis, patients with Medicaid, Medicare, and other/self-pay insurance were less likely to receive a beta-3 vs an anticholinergic compared to private or military insurance. Compared to white patients, Asian, Black, and other races were less likely to receive a beta-3, as were patients outside of metropolitan areas. Age >50, prescriptions after 2014, and nonacademic settings were associated with increased odds of beta-3 prescription. There was no difference between genders. CONCLUSION: Many nonclinical factors, including insurance type and race, may affect which medication is first prescribed for OAB. This is useful for practicing urologists and may help lower barriers to beta-3 prescription through policy change and advocacy.

Multiscale imaging of corneal endothelium damage and Rho-kinase inhibitor application in mouse models of acute ocular hypertension.

We developed a multiscale optical imaging workflow, integrating and correlating visible-light optical coherence tomography, confocal laser scanning microscopy, and single-molecule localization microscopy to investigate mouse cornea damage from the in-vivo tissue level to the nanoscopic single-molecule level. We used electron microscopy to validate the imaged nanoscopic structures. We imaged wild-type mice and mice with acute ocular hypertension and examined the effects of Rho-kinase inhibitor application. We defined four types of intercellular tight junction structures as healthy, compact, partially-distorted, and fully-distorted types by labeling the zonula occludens-1 protein in the corneal endothelial cell layer. We correlated the statistics of the four types of tight junction structures with cornea thickness and intraocular pressure. We found that the population of fully-distorted tight junctions correlated well with the level of corneal edema, and applying Rho-kinase inhibitor reduced the population of fully-distorted tight junctions under acute ocular hypertension. Together, these data point to the utility of multiscale optical imaging in revealing fundamental biology relevant to disease and therapeutics.

Freeform robotic optical coherence tomography beyond the optical field-of-view limit.

Imaging complex, non-planar anatomies with optical coherence tomography (OCT) is limited by the optical field of view (FOV) in a single volumetric acquisition. Combining linear mechanical translation with OCT extends the FOV but suffers from inflexibility in imaging non-planar anatomies. We report the freeform robotic OCT to fill this gap. To address challenges in volumetric reconstruction associated with the robotic movement accuracy being two orders of magnitudes worse than OCT imaging resolution, we developed a volumetric registration algorithm based on simultaneous localization and mapping (SLAM) to overcome this limitation. We imaged the entire aqueous humor outflow pathway, whose imaging has the potential to customize glaucoma surgeries but is typically constrained by the FOV, circumferentially in mice as a test. We acquired volumetric OCT data at different robotic poses and reconstructed the entire anterior segment of the eye. The reconstructed volumes showed heterogeneous Schlemm's canal (SC) morphology in the reconstructed anterior segment and revealed a segmental nature in the circumferential distribution of collector channels (CC) with spatial features as small as a few micrometers.

An Analysis of American Urological Association Census Trends: Earlier Planned Retirement and Practice Pattern Changes May Exacerbate the Urology Workforce Shortage.

OBJECTIVE: To explore how changes in planned retirement age, practice setting, and physician productivity may impact the workforce shortage in urology. METHODS: We compared data between the 2015 and 2022 American Urological Association census, a specialty-wide annual survey which collects data on demographics, practice patterns, and procedures from a representative sample of U.S. urologists. Workforce productivity was measured by the self-reported number of hours worked per week and patients seen per week. A novel formula was developed to demonstrate how planned retirement age and productivity impact the workforce's production capacity. RESULTS: The total number of practicing urologists increased during the period from 2015 to 2022 (11,990 to 13,976), while the mean age of practicing urologists decreased slightly (55.0 to 54.5years; P < .002). During this period, the mean planned age of retirement for all urologists decreased from 68.9years to 67.7 (P < .001). Urologists in solo practice had a significantly higher planned age of retirement at 71.9years (P < .001) as compared to all other practice models. The number of patients seen per week for all urologists decreased from 78.7 to 72.9 (P < .001). The amount of hours worked per week remained relatively constant between the study periods. The maximum possible number of patients seen by the workforce prior to retirement increased by only 2.4% during the study interval. CONCLUSION: Though the U.S. urology workforce is growing and the mean age is decreasing, decreases in planned retirement age and productivity may offset these gains and intensify the physician shortage for U.S. urologists.