Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers.

BACKGROUND AND OBJECTIVE: Mitiperstat (AZD4831) is a novel irreversible oral myeloperoxidase inhibitor in clinical development for heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis and chronic obstructive pulmonary disease. This study evaluated the pharmacokinetics, safety and tolerability of multiple ascending doses of mitiperstat in healthy male Japanese and Chinese volunteers. METHODS: Three cohorts of eight Japanese participants were randomized to receive once-daily oral doses of mitiperstat 2.5, 5 or 10 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo, per cohort). One cohort of eight Chinese participants was randomized to receive mitiperstat 5 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo). RESULTS: Mitiperstat was rapidly absorbed, with a time to maximum plasma concentration of 1-2 h. Exposure was dose proportional over the investigated dose range, as assessed by area under the concentration-time curve and maximum and trough plasma concentrations. Steady state was reached within 10 days, and accumulation was observed, consistent with the observed long elimination half-life of mitiperstat (50.2-57.8 h). Except for a few events of maculopapular rash, mitiperstat up to 5 mg was well tolerated in participants of Japanese or Chinese origin. CONCLUSIONS: The pharmacokinetics of mitiperstat were similar among Japanese and Chinese participants. These characteristics were similar to those in a previous multiple ascending-dose study in healthy primarily white and Black/African American volunteers. Therefore, the pharmacokinetics of mitiperstat do not affect dosing regimens in these different populations. TRIAL REGISTRATION: NCT04232345 (03/01/2020).

The RAL Small G Proteins Are Clinically Relevant Targets in Triple Negative Breast Cancer.

Breast cancer (BC) is the most frequent cancer and second-leading cause of cancer deaths in women in the United States. While RAS mutations are infrequent in BC, triple-negative (TN) and HER2-positive (HER2+) BC both exhibit increased RAS activity. Here, we tested the RAS effectors RALA and RALB, which are overexpressed in BC, as tractable molecular targets in these subtypes. While analysis of the breast cancer patient sample data suggests that the RALs are associated with poor outcome in both TNBC and HER2+ BC, our in vivo and in vitro experimental findings revealed the RALs to be essential in only the TNBC cell lines. While testing the response of the BC cell lines to the RAL inhibitors RBC8 and BQU57, we observed no correlation between drug efficacy and cell line dependency on RAL expression for survival, suggesting that these compounds kill via off-target effects. Finally, we report the discovery of a new small molecule inhibitor, OSURALi, which exhibits strong RAL binding, effectively inhibits RAL activation, and is significantly more toxic to RAL-dependent TNBC cells than RAL-independent HER2+ and normal cell lines. These results support the RALs as viable molecular targets in TNBC and the further investigation of OSURALi as a therapeutic agent.

Utility of Common Bile Duct Identification on Biliary Ultrasound in Emergency Department Patients.

Background: Biliary ultrasound is often utilized in the evaluation of abdominal pain in the Emergency Department (ED). Common bile duct (CBD) identification is traditionally a standard component of the biliary ultrasound examination but can be challenging to perform for the novice sonographer. Previous work has demonstrated that CBD dilatation is rare in cases of cholecystitis with normal liver function tests (LFTs). We sought to assess the frequency of CBD dilatation in the subset of ED patients undergoing hepatobiliary ultrasound who have normal LFTs and an absence of gallstones or biliary sludge on ultrasound. We also performed an assessment of changes in CBD diameter by age and cholecystectomy status. Methods: This was a retrospective chart review at a single academic ED. Patients were enrolled in the study if they underwent a radiology performed (RP) hepatobiliary ultrasound within the 2 year study period. Records were reviewed for the presence of gallstones or sludge, CBD diameter, age, clinical indication for the ultrasound, and LFTs. Descriptive analyses were performed, and interobserver agreement among data abstractors was assessed by K analysis for the presence of CBD dilatation. The Mann-Whitney test was utilized to assess statistical significance in the comparison of differences between CBD diameters amongst age groups. Results: Of 1929 RP hepatobiliary ultrasounds performed in the study period, 312 were excluded and 1617 met inclusion criteria. Amongst these, there were 506 patients who had normal LFTs and an ultrasound with no stones or sludge. Ten patients within this group had a dilated CBD > 7 mm (1.98%, 95% CI of 1.08% to 3.6%). We also noted a statistically significant increase in CBD size in the older age cohort and in those individuals with a history of cholecystectomy. Conclusion: CBD dilation in ED patients who present with normal LFTs and an absence of gallstones and biliary sludge is rare. Physicians should be reassured that the routine identification of the CBD on ultrasound in this setting is of low yield and need not be pursued.

The common bile duct is often taught as part of the biliary point-of-care ultrasound examination. However, it is more challenging to identify than the gallbladder and thus may limit adoption of POCUS by ED physicians. Our study adds to the body of work demonstrating that omitting the common bile duct from an ultrasound evaluation is likely reasonable when both the gallbladder and liver function tests are normal. Our study also adds to the literature regarding the increase in common bile duct size with age and with post-cholecystectomy status.

Development and Evaluation of a Multi-Institutional Virtual Urology Course for Medical Students.

OBJECTIVE: Urological education has been declining in medical schools, leaving many students without adequate exposure to the fundamentals of the field. We aimed to create a virtual urology course for medical students preparing for subinternships. DESIGN: We created a 4-week curriculum of case-based urology modules with sections on hematuria, bladder cancer, kidney stones, vesicoureteral reflux, prostate cancer, urinary incontinence, and erectile dysfunction. Students completed precourse and postcourse surveys assessing confidence in content knowledge and 4 educational competencies. Faculty completed postcourse surveys. Confidence was scored on a 5-point Likert scale (0-4). SETTING: We offered the course in May 2022 and May 2023. The course was fully virtual and was offered at medical schools across the United States. PARTICIPANTS: The course included 157 medical students from 60 institutions and 44 faculty instructors from 30 institutions. All instructors were urologists representing a range of urological subspecialties. RESULTS: Surveys were completed by 61/157 students (39%) and 33/44 faculty (75%). Median student confidence in content knowledge increased across all disease processes: hematuria (3 vs. 2), bladder cancer (3 vs. 1), kidney stones (3 vs. 2), vesicoureteral reflux (3 vs. 1), prostate cancer (3 vs. 1), urinary incontinence (3 vs. 2), and erectile dysfunction (3 vs. 2) (all p < 0.001). Median confidence scores also increased across all 4 educational competencies: patient evaluation (3 vs. 2), pathophysiology (3 vs. 2), literature appraisal (3 vs. 2), and patient counseling (3 vs. 1) (all p < 0.001). Confidence increases in all areas were maintained at 7-month follow-up. Most students (85%) and faculty (91%) rated the course "excellent" or "very good." CONCLUSIONS: A multi-institutional virtual urology course for medical students led to a durable increase in confidence pertaining to content knowledge and various educational competencies.

Factors Associated With Tobacco Cessation Advice Recall and Quit Rates in Vascular Surgery Patients. A Single Center Study.

OBJECTIVES: Smoking is an important modifiable risk factor in all vascular diseases and verbal advice from providers has been shown to increase rates of tobacco cessation. We sought to identify factors that will improve tobacco cessation and recall of receiving verbal cessation advice in vascular surgery patients at a single institution. METHODS: The study is a retrospective cohort study. Patients seen in outpatient vascular surgery clinic who triggered a tobacco Best Practice Advisory (BPA) during their office visits over a 10-month period were contacted post-clinic and administered surveys detailing smoking status, cessation advice recall, and validated scales for nicotine dependence and willingness to quit smoking. This BPA is a "hard stop" that requires providers to document actions taken. Charts were reviewed for tobacco cessation documentation. Nine-digit zip-codes identified the area deprivation index, a measure of socioeconomic status. Univariate analysis was used to identify factors associated with cessation and advice recall. RESULTS: One hundred out of 318 (31.4%) patients responded to the survey. Epic Slicer Dicer found 97 BPA responses. To dismiss the BPA, 89 providers (91.8%) selected "advised tobacco cessation" and "Unable to Advise" otherwise. Of the 318 patients, 115 (36.1%) had cessation intervention documented in their provider notes and 151 (47.5%) received written tobacco cessation advice. Of survey respondents, 70 recalled receiving verbal advice, 27 recalled receiving written advice, 28 reported receiving offers of medication/therapy for cessation. 55 patients reported having tobacco cessation plans, and among those 17 reported having quit tobacco. Recall of receiving written advice (P < .001) and recall of receiving medication/therapy (P = .008) were associated with recall of receiving verbal cessation advice. CONCLUSIONS: Providing patients with tobacco cessation medication/therapy and written tobacco cessation education during office visits is associated with increased patients' recall of tobacco cessation advice. Vascular surgeons should continue to provide directed tobacco cessation advice.

Multidisciplinary Development and Implementation of a Trial of Void Algorithm to Standardize and Reduce Indwelling Urethral Catheter Use.

INTRODUCTION: Prolonged indwelling catheter use is a known risk factor for catheter-associated UTIs (CAUTIs). We sought to reduce catheter use by creating and implementing a trial of void (TOV) algorithm to standardize indwelling Foley catheter removal in surgical patients. METHODS: We partnered with the Departments of General Surgery and Nursing to develop an evidence-based TOV algorithm for a step-down unit at a large urban teaching hospital. Our cohort included patients treated with intra-abdominal, thoracic, vascular, urologic, and gynecologic surgeries. The primary outcome was mean cumulative indwelling urethral catheter patient-days. For example, if 2 patients had catheters for 3 and 7 days, respectively, then cumulative catheter days would be 10. We analyzed changes in catheter use 90 days before and after algorithm implementation. RESULTS: The mean number of hospitalized patient-days before and after algorithm introduction did not differ (32.2 vs 32.0, P = .60). After implementation, mean cumulative catheter patient-days decreased (14.8 vs 9.9, P < .01), as did mean daily number of patients with catheters on the unit (3.7 vs 3.1, P = .02). There was 1 CAUTI before and after algorithm implementation, the latter deemed associated with algorithm nonadherence. Catheter use in a surgical floor control group where the algorithm was not implemented did not differ for any outcome over the same time period (P > .05). CONCLUSIONS: A multidisciplinary approach to standardize catheter care with a TOV algorithm is feasible and effective in reducing catheter use. Further research is needed to determine its impact on CAUTI rate.

H-Wave® Device Stimulation for Chronic Neck Pain: A Patient-Reported Outcome Measures (PROMs) Study.

INTRODUCTION: Chronic neck pain (cNP) is one of the leading causes of disability worldwide, often being refractory to conventional forms of treatment. Various forms of electrical stimulation have been proposed to decrease pain and improve function. Patient-reported outcome measures (PROMs) for treatment of cNP have rarely been published. METHODS: An independent retrospective statistical analysis of PROMs data for users of H-Wave® device stimulation (HWDS), prospectively collected by the device manufacturer over a 4-year period, was conducted. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was further reduced to 1482 patients with cNP, sprain, or strain. RESULTS: Neck pain was reduced by 3.13 points (0-10 pain scale), with significant (≥ 20%) relief in 86.6%. Function/activities of daily living (ADL) improved in 96.19%, while improved work performance was reported in 84.76%. Medication use decreased or stopped in 65.42% and sleep improved in 60.39%. Over 95% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive benefit associations with longer duration of device use. CONCLUSION: Near-equivalent outcomes were self-reported by cNP HWDS patients as for (previously published) chronic low back pain (cLBP) patients. HWDS provided effective and safe cNP relief, improvements in function and ADL, along with additional benefits including decreased medication use, better sleep, and improved work performance.

Comparison of transvaginal ultrasound utilization between radiology and point of care ultrasound in first trimester pregnancy.

BACKGROUND: Transvaginal (TVUS) and transabdominal ultrasound (TAUS) are both utilized in the evaluation of early pregnancy patients. While many practitioners using point of care ultrasound (POCUS) will generally not pursue TVUS in cases where an intrauterine pregnancy (IUP) is visualized on TAUS, this may not be true in Radiology performed ultrasound. OBJECTIVES: To evaluate for differences in transvaginal ultrasound (TVUS) utilization between Radiology performed (RP) ultrasound and point of care ultrasound (POCUS) by Emergency Department (ED) physicians in early pregnancy patients. Secondarily, to assess length of stay (LOS) differences and the impact of specialized emergency ultrasound training on TVUS utilization. METHODS: This was a retrospective study at a single academic ED. Study population was all ED patients who underwent first trimester ultrasound during the one year period of March 1, 2021 to February 28, 2022. Variables evaluated were chief complaint, gestational age, LOS, TAUS and TVUS utilization, ultrasound findings, and ultrasound specialty training of the ED physician. RESULTS: There were 133 cases of POCUS ultrasound and 254 cases of RP ultrasound. All cases had TAUS imaging performed. Median LOS for patients when POCUS was utilized was 207 min (IQR 151-294) and 258 min (IQR 208-328) for those only using RP ultrasound, p ≤ 0.001. In the POCUS cohort, 38% (95% CI 30%-46%) received TVUS, while 94% received TVUS in the RP cohort (95% CI 90%-96%), p ≤ 0.001. Patients seen by ED faculty with ultrasound specialty training had TVUS 53% of the time (95% CI 41%-65%), while those seen by other ED faculty had TVUS 79% (95% CI 74%-83%) of the time, p = 0.035. CONCLUSION: POCUS in early pregnancy is associated with a significant reduction in TVUS usage. We suspect that POCUS users elect not to pursue TVUS after an IUP is identified on TAUS, while technicians perform protocol-based TVUS irrespective of TAUS findings. Patients seen by ultrasound trained ED physicians are less likely to receive TVUS.

Resident Remediation: A National Survey of Urology Program Directors.

OBJECTIVES: To describe formal remediation rates and processes in urology training programs nationally. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study by surveying program directors (PDs) through the Society of Academic Urologists. Formal remediation was defined as the process initiated when resident competency deficiencies were significant enough to necessitate documentation and notification of the Graduate Medical Education (GME) office. The primary outcome was the prevalence of urology programs that initiated formal remediation over the past 5 years. Secondary outcomes included reported competency deficiencies and formal remediation processes. RESULTS: Across 148 institutions, 73 (49%) PDs responded to the survey. The majority of PDs (67%, 49/73) stated that at least 1 resident underwent formal remediation over the last 5 years (median 1). "Professionalism" and "Interpersonal and Communication Skills" were the most common competency deficiencies that prompted formal remediation, whereas "Technical Skill" was the least common. While the majority of respondents notified the GME office of residents undergoing remediation, formal remediation plans varied from faculty coaching and mentorship (80%, 39/49) to simulation training (10%, 5/49). Absence of documented faculty feedback on poor performance was the most commonly cited barrier to formal remediation. The majority of PDs reported documentation in a resident's file (81%, 59/73); however, remediation processes differed with only half of PDs reporting that GME offices were routinely involved in creating and overseeing corrective action plans (56%, 41/73). Over the study period, 15% (11/73) of PDs did not promote a resident to the next year of training, and 23% (17/73) of PDs stated "Yes" to graduating a resident who they would not trust to care for a loved one. CONCLUSIONS: Formal remediation among urology residency programs is common, and processes vary across institutions. The most common competency areas prompting remediation were "Professionalism" and "Interpersonal and Communication Skills." Future research should address developing resources to facilitate resident remediation.

A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response.

Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was strongly attenuated. In contrast, poorly responsive patients were distinguished by persistent activation of IL-17-producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade-responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of >90% of IL-17-induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.

H-Wave® Device Stimulation for Chronic Low Back Pain: A Patient-Reported Outcome Measures (PROMs) Study.

INTRODUCTION: Chronic low back pain (cLBP) is a problem globally, creating a tremendous economic burden. Since conventional treatments often fail, various forms of electrical stimulation have been proposed to improve function and decrease pain. Patient-reported outcome measures (PROMs) have not been adequately reported in the electrical stimulation literature. METHODS: A retrospective independent statistical analysis was conducted on PROMs data for users of H-Wave® device stimulation (HWDS) collected by the device manufacturer over a period of 4 years. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was then reduced to 2711 patients with nonspecific cLBP, sprain, or strain. RESULTS: Reported pain was reduced by 3.12 points (0-10 pain scale), with significant (≥ 20%) relief in 85.28%. Function/activities of daily living (ADL) improved in 96.36%, while improved work performance was reported in 81.61%. Medication use decreased or stopped in 64.41% and sleep improved in 59.76%. Over 96% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive associations with longer duration of device use, home exercise participation, and working, whereas older age and longer pain chronicity resulted in reduced benefit. Similar analysis of the larger all-diagnoses cohort demonstrated near-equivalent positive outcomes. CONCLUSION: Treatment outcomes directly reported by cLBP HWDS patients demonstrated profound positive effects on function and ADL, robust improvement in pain perception, and additional benefits like decreased medication use, better sleep, and improved work performance, representing compelling new evidence of treatment efficacy.

Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.

Astrocyte activation is associated with neuropathology and the production of tissue inhibitor of metalloproteinase-1 (TIMP1). TIMP1 is a pleiotropic extracellular protein that functions both as a protease inhibitor and as a growth factor. Astrocytes that lack expression of Timp1 do not support rat oligodendrocyte progenitor cell (rOPC) differentiation, and adult global Timp1 knockout (Timp1KO) mice do not efficiently remyelinate following a demyelinating injury. Here, we performed an unbiased proteomic analysis and identified a fibronectin-derived peptide called Anastellin (Ana) that was unique to the Timp1KO astrocyte secretome. Ana was found to block rOPC differentiation in vitro and enhanced the inhibitory influence of fibronectin on rOPC differentiation. Ana is known to act upon the sphingosine-1-phosphate receptor 1, and we determined that Ana also blocked the pro-myelinating effect of FTY720 (or fingolimod) on rOPC differentiation in vitro. Administration of FTY720 to wild-type C57BL/6 mice during MOG35-55-experimental autoimmune encephalomyelitis ameliorated clinical disability while FTY720 administered to mice lacking expression of Timp1 (Timp1KO) had no effect. Analysis of Timp1 and fibronectin (FN1) transcripts from primary human astrocytes from healthy and multiple sclerosis (MS) donors revealed lower TIMP1 expression was coincident with elevated FN1 in MS astrocytes. Last, analyses of proteomic databases of MS samples identified Ana peptides to be more abundant in the cerebrospinal fluid (CSF) of human MS patients with high disease activity. A role for Ana in MS as a consequence of a lack of astrocytic TIMP-1 production could influence both the efficacy of fingolimod responses and innate remyelination potential in the MS brain.

Comparative Analyses and Ablation Efficiency of Thulium Fiber Laser by Stone Composition.

PURPOSE: There are limited data on ablation effects of thulium fiber laser (TFL) settings with varying stone composition. Similarly, little is known surrounding the photothermal effects of TFL lithotripsy regarding the chemical and structural changes after visible char formation. We aim to understand the TFL's ablative efficiency across various stone types and laser settings, while simultaneously investigating the photothermal effects of TFL lithotripsy. MATERIALS AND METHODS: Human specimens of calcium oxalate monohydrate, calcium oxalate dihydrate, uric acid, struvite, cystine, carbonate apatite, and brushite stones were ablated using 13 prespecified settings with the Coloplast TFL Drive. Pre- and postablation mass, ablation time, and total energy were recorded. Qualitative ablative observations were recorded at 1-minute intervals with photographs and gross description. Samples were analyzed with Fourier-transform infrared spectroscopy pre- and postablation and electron microscopy postablation to assess the photothermal effects of TFL. RESULTS: Across all settings and stone types, 0.05 J × 1000 Hz was the best numerically efficient ablation setting. When selected for more clinically relevant laser settings (ie, 10-20 W), 0.2 J × 100 Hz, short pulse was the most numerically efficient setting for calcium oxalate dihydrate, cystine, and struvite stones. Calcium oxalate monohydrate ablated with the best numerical efficiency at 0.4 J × 40 Hz, short pulse. Uric acid and carbonate apatite stones ablated with the best numerical efficiency at 0.3 J × 60 Hz, short pulse. Brushite stones ablated with the best numerical efficiency at 0.5 J × 30 Hz, short pulse. Pulse duration impacted ablation effectiveness greatly with 6/8 (75%) of inadequate ablations occurring in medium or long pulse settings. The average percent of mass lost during ablation was 57%; cystine stones averaged the highest percent mass lost at 71%. Charring was observed in 36/91 (40%) specimens. Charring was most often seen in uric acid, cystine, and brushite stones across all laser settings. Electron microscopy of char demonstrated a porous melting effect different to that of brittle fracture. Fourier-transform infrared spectroscopy of brushite char demonstrated a chemical composition change to amorphous calcium phosphate. CONCLUSIONS: We describe the optimal ablation settings based on stone composition, which may guide urologists towards more stone-specific care when using thulium laser for treating renal stones (lower energy settings would be safer for ureteral stones). For patients with unknown stone composition, lasers can be preset to target common stone types or adjusted based on visual cues. We recommend using short pulse for all TFL lithotripsy of calculi and altering the settings based on visual cues and efficiency to minimize the charring, an effect which can make the stone refractory to further dusting and fragmentation.

Cross-Referencing Self-Training Network for Sound Event Detection in Audio Mixtures.

Sound event detection is an important facet of audio tagging that aims to identify sounds of interest and define both the sound category and time boundaries for each sound event in a continuous recording. With advances in deep neural networks, there has been tremendous improvement in the performance of sound event detection systems, although at the expense of costly data collection and labeling efforts. In fact, current state-of-the-art methods employ supervised training methods that leverage large amounts of data samples and corresponding labels in order to facilitate identification of sound category and time stamps of events. As an alternative, the current study proposes a semi-supervised method for generating pseudo-labels from unsupervised data using a student-teacher scheme that balances self-training and cross-training. Additionally, this paper explores post-processing which extracts sound intervals from network prediction, for further improvement in sound event detection performance. The proposed approach is evaluated on sound event detection task for the DCASE2020 challenge. The results of these methods on both "validation" and "public evaluation" sets of DESED database show significant improvement compared to the state-of-the art systems in semi-supervised learning.

Antimicrobial Prophylaxis for Percutaneous Nephrolithotomy: Contemporary Practice Patterns.

Background: Updated in 2019, the American Urological Association's (AUA) Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis outlines prophylaxis for percutaneous nephrolithotomy (PCNL). Recent studies have challenged these recommendations. We hypothesized that endourologists do not routinely follow the AUA's statement on antibiotic use during PCNL and assessed their prescribing patterns. Methods: A 24-question survey was distributed to members of the Endourological Society. The primary outcome was adherence to the AUA's recommendations. Two multiple logistic regression analyses were performed with demographics and antibiotic preference as predictors of following the AUA. Results: A total of 51.4% of endourologists follow the AUA Best Practice Statement for antimicrobial prophylaxis of uncomplicated PCNL. No demographic data were predictive of following the AUA. 90.9% and 83.6% reported they have "never" used the first-line recommendation options of metronidazole and aztreonam, respectively. Preferred antibiotics were cephalosporins (uncomplicated 60%, complicated 52.6%), fluoroquinolones (13.3%, 7.2%), aminoglycosides (12.7%, 17.8%), penicillins (7.9%, 11.2%), carbapenems (0.6%, 0.7%), trimethoprim-sulfamethoxazole (2.4%, 5.9%), fosfomycin (0.6%, 0.7%), nitrofurantoin (2.4%, 2.6%), aztreonam (0%, 0.7%), and clindamycin (0%, 0.7%). For uncomplicated PCNL, 63.1% prescribe ≤24 hours of perioperative antibiotics. For complicated PCNL, 16.2% prescribe ≤24 hours of perioperative antibiotics, while 20.4% begin antibiotics 7 or more days prior. Conclusions: Nearly half of respondents do not follow the AUA's recommendations for antibiotic choice for PCNL. Few endourologists prescribe 7 days of preoperative antibiotics for complicated PCNL despite supporting data. Metronidazole and aztreonam are rarely used as a first-line antibiotic choice for PCNL and their roles needs to be further evaluated as first-line prophylaxis recommendations. Updates on antibiotic recommendations for PCNL are needed based on current literature, antimicrobial stewardship, and contemporary practice patterns.

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults.

Human respiratory syncytial virus (RSV) causes a substantial proportion of respiratory tract infections worldwide. Although RSV reinfections occur throughout life, older adults, particularly those with underlying comorbidities, are at risk for severe complications from RSV. There is no RSV vaccine available to date, and treatment of RSV in adults is largely supportive. A correlate of protection for RSV has not yet been established, but antibodies targeting the pre-fusion conformation of the RSV F glycoprotein play an important role in RSV neutralization. We previously reported a Phase 1 study of an mRNA-based vaccine (V171) expressing a pre-fusion-stabilized RSV F protein (mDS-Cav1) in healthy adults. Here, we evaluated an mRNA-based vaccine (V172) expressing a further stabilized RSV pre-fusion F protein (mVRC1). mVRC1 is a single chain version of RSV F with interprotomer disulfides in addition to the stabilizing mutations present in the mDS-Cav1 antigen. The immunogenicity of the two mRNA-based vaccines encoding mVRC1 (V172) or a sequence-optimized version of mDS-Cav1 to improve transcriptional fidelity (V171.2) were compared in RSV-naïve and RSV-experienced African green monkeys (AGMs). V172 induced higher neutralizing antibody titers than V171.2 and demonstrated protection in the AGM challenge model. We conducted a Phase 1, randomized, placebo-controlled, clinical trial of 25 µg, 100 µg, 200 µg, or 300 µg of V172 in healthy older adults (60-79 years old; N = 112) and 100 µg, 200 µg, or 300 µg of V172 in healthy younger adults (18-49 years old; N = 48). The primary clinical objectives were to evaluate the safety and tolerability of V172, and the secondary objective was to evaluate RSV serum neutralization titers. The most commonly reported solicited adverse events were injection-site pain, injection-site swelling, headache, and tiredness. V172 was generally well tolerated in older and younger adults and increased serum neutralizing antibody titers, pre-fusion F-specific competing antibody titers, and RSV F-specific T-cell responses.

The State of Urotrauma Education Among Residency Programs in the United States: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Management of urotrauma is a crucial part of a urologist's knowledge and training. We therefore sought to understand the state of urotrauma education in the United States. RECENT FINDINGS: Using themes of "Urotrauma" and "Education," we performed a systematic review and meta-analysis by searching for studies in MEDLINE, all Cochrane libraries, EMBASE, BIOSIS, Scopus, and Web of Science through May 2023. The primary outcome was the pooled rate of urology trainee and program director attitudes toward urotrauma education. Secondary outcomes involved a descriptive summary of existing urotrauma curricula and an assessment of factors affecting urotrauma exposure. Of 12,230 unique records, 11 studies met the final eligibility criteria, and we included 2 in the meta-analysis. The majority of trainees and program directors reported having level 1 trauma center rotations (range 88-89%) and considered urotrauma exposure as an important aspect of residency education (83%, 95% CI 76-88%). Despite possible increases in trainee exposure to Society of Genitourinary Reconstructive Surgeons (GURS) faculty over the preceding decade, nearly a third of trainees and program directors currently felt there remained inadequate exposure to urotrauma during training (32%, 95% CI 19-46%). Factors affecting urotrauma education include the limited exposure to GURS-trained faculty and clinical factors such as case infrequency and non-operative trauma management. Urology resident exposure to urotrauma is inadequate in many training programs, underscoring the potential value of developing a standardized curriculum to improve urotrauma education for trainees. Further investigation is needed to characterize this issue and to understand how it impacts trainee practice readiness.

Focused Ultrasonography in Cardiac Arrest.

Rapid diagnostic tools available to the emergency physician caring for cardiac arrest patients are limited. Focused ultrasound (US), and in particular, focused echocardiography, is a useful tool in the evaluation of patients in cardiac arrest. It can help identify possible causes of cardiac arrest like tamponade and pulmonary embolism, which can guide therapy. US can also yield prognostic information, with lack of cardiac activity being highly specific for failure to achieve return of spontaneous circulation. US may also be used to aid in procedural guidance. Recently, focused transesophageal echocardiography has been used in the emergency department setting.

POINT-OF-CARE ULTRASOUND FOR GUIDANCE OF CLOSED REDUCTION OF FIFTH METACARPAL NECK (BOXER'S) FRACTURE.

BACKGROUND: Ultrasound has been used previously in fracture identification, analgesia delivery, and fracture reduction for patients in the emergency department. It has not been previously described as a tool for the guidance of closed fracture reduction in fifth metacarpal neck fractures ("boxer's fractures"). CASE REPORT: A 28-year-old man presented with hand pain and swelling after punching a wall. Point-of-care ultrasound revealed a significantly angulated fifth metacarpal fracture, which was confirmed with a subsequent hand x-ray study. After an ultrasound-guided ulnar nerve block, closed reduction was performed. Ultrasound was used to assess reduction and ensure improvement in bony angulation during the closed reduction attempts. Post-reduction x-ray study confirmed improved angulation and adequate alignment. Why Should an Emergency Physician Be Aware of This? Point-of-care ultrasound has previously had efficacy in fracture diagnosis and anesthesia delivery for fifth metacarpal fractures. Ultrasound can also be used at the bedside to assist in the determination of adequate fracture reduction when performing closed reduction of a boxer's fracture.