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Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

Abstract Background Standardizing beam modeling in the treatment planning system is challenging due to machine‐specific configuration variations. Because of the proton therapy system (PTS) complexity and continuous development, there is no vendor's representative (“golden”) beam data like in LINACs at this stage. Purpose The primary goal of this study is to create a PTS‐specific repository of source model parameters and beam commissioning data for scanning proton therapy treatment planning systems and establish a set of reference values with associated bands of variations for this data. Methods We conducted a survey of 31 PTSs at 27 proton therapy centers to gather beam commissioning source model parameters used in their treatment planning system, ensuring a diverse selection of PTSs from major vendors: Hitachi, IBA, Varian, and Mevion. For each proton therapy center, we collected (i) beam meterset calibration in protons per MU, (ii) in‐air spot size at isocenter in terms of standard deviation in x‐ (crossline, σ x ) and y‐ (inline, σ y ) directions, (iii) in‐air angular spread at isocenter in x‐direction (θ x ) and y‐direction (θ y ) and (iv) distal falloff. For each PTS, we plotted each parameter as a function of nominal energy and performed polynomial regression analysis with optimal model selection based on Akaike Information Criterion. We calculated intraclass correlation coefficients (ICC) to quantify inter‐PTS variability and generated uncertainty bands representing standard deviations across PTSs for each parameter. Additionally, we computed percentage deviations of each individual PTS from the overall multi‐vendor mean to identify systematic vendor‐specific patterns and outliers across the 31 total PTSs analyzed. Results Multi‐vendor beam parameter analysis across 31 PTSs revealed systematic vendor‐specific patterns in inter‐PTS consistency and energy dependencies. Beam meterset calibration demonstrated excellent inter‐PTS consistency across most vendors (ICC: Varian ProBeam ≈ 0, IBA Proteus ONE = 0.006, Mevion S250i with HYPERSCAN = 0.015), with IBA Proteus PLUS systems showing moderate variation (ICC = 0.156 for the dedicated nozzle, ICC = 0.248, for the universal nozzle). Spot size and angular spread variability were highly vendor‐dependent, ranging from excellent consistency in IBA Proteus ONE to substantial variation in IBA Proteus PLUS with the universal nozzle (angular spread ICC = 0.566). Distal falloff maintained excellent consistency across all vendors (ICC < 0.023), indicating reliable energy spread characteristics. Uncertainty band analysis revealed characteristic energy‐dependent patterns, with most systems showing larger uncertainties at lower energies for spot size and angular spread, while IBA Proteus PLUS with the universal nozzle exhibited the largest uncertainty bands overall. Percentage deviation analysis demonstrated vendor‐specific clustering patterns, with some systems showing systematic positive or negative deviations from the multi‐vendor mean. Conclusions The reference data provided in this work will help to cross‐check the beam model during treatment planning system commissioning. Furthermore, this information is useful for Monte Carlo applications and research, where beam characteristics are required to set up phase space parameters, thereby avoiding the need to model the entire PTS. Finally, the results of this study will have indispensable educational value by providing valuable insights into the characteristics and capabilities of different PTSs.

Abstract Background 0.05% Chlorhexidine gluconate (CHG) is now commonly used as an antiseptic irrigation for inflatable penile prosthesis (IPP) surgery. Limited in vitro data suggest compatibility of 0.05% CHG with antibiotic impregnated IPP devices; however, very little clinical research exists to guide use of 0.05% CHG in this population. Aim Assess the relationship of 0.05% CHG and antibiotic impregnated IPP infection in a large multi-institutional cohort. Methods We retrospectively reviewed a multi-institutional cohort of patients who underwent antibiotic impregnated IPP implantation. We identified cases using intraoperative 0.05% CHG and an equal number of consecutive control cases without 0.05% CHG use from each center for comparison. The primary outcome was IPP infection requiring explantation. Patient demographics and surgical variables were analyzed using chi-square tests and multivariable logistic regression to identify variables associated with infection. Outcomes The primary outcome was IPP infection requiring device explanation. Results Among 14 participating institutions, 761 cases using an antibiotic impregnated IPP were analyzed. Of these, 348 (45.7%) had 0.05% CHG used during the case. Median follow-up was 4 months (interquartile range 1-12) for the 0.05% CHG group and 8 months (interquartile range 2-21) for the control group. Intraoperative 0.05% CHG utilization was not associated with antibiotic impregnated IPP infection rate (1.9% vs. 2.0%, P = .9). On multivariable analysis, prior IPP infection (OR 6.32, 95% CI 1.32-30.2, P = .021) and prior priapism (OR 10.01, 95% CI 1.18-89.7, P = .039) were associated with increased infection risk. Clinical implications The use of 0.05% CHG irrigation with antibiotic impregnated IPPs was associated with similar infection rates compared to antibiotic irrigation. Strengths and limitations Limitations include the use of a historical comparator cohort which may introduce unknown confounders, practice variation between multiple sites, shorter follow-up in the 0.05% CHG cohort, and the low incidence of IPP infection which may limit statistical power despite a large sample. The major strengths include the large, multi-institutional cohort, and the use of consecutive patients to minimize selection bias. Conclusion 0.05% CHG utilization was not associated with infection rates in antibiotic impregnated IPPs.

BACKGROUND Among antiretroviral therapy–suppressed (ART-suppressed) people with HIV (PWH), women have higher levels of some inflammatory markers than men, but the effect of sex on the inflammatory proteome, and whether age modifies these differences, remain unclear. METHODS Plasma inflammatory protein levels were assessed in ART-suppressed PWH from the Center for AIDS Research Network of Integrated Clinical Systems. The relationship between sex and plasma proteins — including 22 interferon-α response pathway proteins — was assessed, adjusting for confounders and assessing interactions by age. RESULTS Of 922 participants, 162 (18%) were female. The median age was 47, above which the majority of women had undetectable plasma anti-Müllerian hormone levels, a biomarker of ovarian reserve. Age modified the influence of sex on the inflammatory proteome. Older age (>47) was associated with greater increases among women than men in 194 proteins. Interferon-α response proteins were higher in men in those ≤ 47 but higher in women in those > 47 (interaction P < 0.001). Among the 131 proteins associated with mortality risk ( q < 0.05), only 5 differed by sex among those ≤ 47, while 79 differed by sex in those > 47, with nearly all being higher in women. Women had decreased mortality than men ≤ 47 ( P < 0.001) but had similar mortality > 47 ( P = 0.84). CONCLUSION The menopausal transition appears to increase systemic type I interferon responses and inflammation in women with HIV, which may contribute to a loss of female advantage in mortality. FUNDING NIH National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute of Allergy and Infectious Diseases.

Abstract Introduction Infection following inflatable penile prosthesis (IPP) placement is an uncommon yet serious complication, and its management poses significant clinical challenges. IPP infection management strategies continue to evolve, however, multicenter and robust studies evaluating and describing current practice patterns are lacking. Objective Using a large cohort from tertiary IPP referral centers in the United States to evaluate current infection management practice patterns and to identify factors that could predict the approach to managing IPP infections. Methods We queried a retrospective 14-center multi-institutional database for patients with IPP infections between April 2017 and January 1/2025. Patients were categorized by infection management strategy, which included device explant, malleable salvage, and 3-piece IPP salvage. Patient characteristics were compared using chi-square and independent t-tests. Multinomial analysis was performed to investigate patient and perioperative factors associated with management strategy at the time of infection. Results Among 2,934 cases, 85 (2.9%) patients developed IPP infection at a median of 40 (22-78) days after IPP implantation. Infections occurred after primary IPP surgery in 59 (69%), revision in 25 (29%), and after infection salvaged with IPP in 1 (1%). Infections were managed with device explant in 32 (38%), malleable salvage in 43 (51%), and IPP salvage in 10 (12%). A significantly higher proportion of non-White patients underwent salvage (either with malleable or IPP) compared to White patients (p=0.01). Multinomial regression showed no association between patient and perioperative characteristics and infection management (p&gt;0.05). Conclusions In this multi-institutional cohort of experienced implanters, infections were most commonly managed with malleable salvage. Patient and perioperative factors did not predict management approach, suggesting that the decision between explanation and salvage is primarily driven by individual surgeon preference. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston scientific

Abstract Introduction With the growing use of 0.05% Chlorhexidine Gluconate (CHG) as irrigation and dip for inflatable penile prosthesis (IPP) surgery, understanding the possible relationship between CHG use and non-infectious complications is imperative. Such information may guide provider decision-making during implant surgery. Objective We therefore sought to determine whether the use of 0.05% Chlorhexidine Gluconate (CHG) during inflatable penile prosthesis (IPP) surgery was associated with non-infectious wound complications. Methods We performed a multi-institutional retrospective cohort study of patients undergoing IPP surgery from January 2017 to March 2024. The primary outcome was wound complications (ex. rash, wound dehiscence, edema). Secondary outcomes included other non-infectious complications (Table 1). The primary exposure was whether patients received intraoperative CHG either as irrigation or dip. Descriptive comparisons were used to compare CHG and non-CHG cohorts. Univariable logistic regression was utilized to assess if CHG use was associated with any non-infectious complication. Multivariable logistic regression was subsequently performed to assess factors associated with certain non-infectious complications after IPP surgery – controlling for age, body mass index, race, diabetes, and hypertension as covariables. Results Across 2,933 patients, there were 1,573 non-CHG and 1,359 CHG patients. Non-infectious complications occurred in 83 (5%) non-CHG patients and in 65 (5%) CHG patients. Median follow-up was 22 months (IQR 7-59) for non-CHG patients and 8 months (IQR 3-16) for CHG patients. The incidence of wound complications was greater among CHG patients than non-CHG patients (1.0% vs. 0.1%, p&lt;0.01). On univariable logistic regression, CHG use was associated with increased odds of wound complications (OR 7.34, 95% CI 1.65-32.71) but was not associated with any other non-infectious complication (Table 2). On multivariable logistic regression, CHG use remained associated with an increased odds of wound complications (OR 13.86, 95% CI 1.80-106.44). Conclusions Among patients experiencing non-infectious complications after IPP, CHG use during IPP surgery appears to be associated with an increased odds of wound complications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Corporation and Boston Scientific

Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has gained popularity as an irrigant and dip for inflatable penile prosthesis (IPP) surgery. Prior in vitro data is conflicting on the impact of CHG use with hydrophilic coated devices. Objective We sought to identify possible associations between CHG use and hydrophilic IPP infection rate. Methods We conducted a retrospective cohort study of 2,933 patients undergoing IPP implantation across 14 referral centers. Data collection spanned from January 1, 2017 to March 1, 2024. Each surgeon contributed patients who underwent IPP implantation with CHG used as an irrigant and/or dip as well as an equal number of consecutive control patients without CHG use. The primary outcome was IPP explant for postoperative infection. Univariable analysis was used to compare patient demographics, and logistic regression analysis was performed to assess factors associated with infection. Results Hydrophilic devices were implanted in 2,150 patients. Median follow-up for non-CHG patients was 13 months (IQR 18) and four months (IQR 9) for CHG patients. The incidence of infection with intraoperative CHG use was significantly higher compared to those without CHG use (4.6%, 46/1,001 vs. 2.1%, 24/1,148, p&lt;0.001). On multivariable logistic regression analysis, intraoperative CHG use was associated with infection (OR 2.07, 95% CI 1.24-3.47, p=0.01). Additional variables associated with infection included immunosuppression, prior IPP infection, prior priapism, and revision surgery (p&lt;0.01, Table). On subgroup analyses, the increased infection risk of CHG was most clear when CHG was used as both irrigation and dip (OR 2.03, 95% CI 1.19-3.46, p=0.01) and when CHG was used during revision surgery (OR 3.36, 95% CI 1.15-9.82, p=0.03). Conclusions In a large multi-institutional cohort, intraoperative CHG use was associated with an elevated incidence of hydrophilic IPP infection. Providers may take these findings into consideration when performing IPP surgery with hydrophilic devices, especially during revision surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Corporation and Boston Scientific

Objectives: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists. Design: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as “advanced knowledge is essential,” “general, but not advanced, knowledge is essential,” or “knowledge is not essential.” Procedures were categorized as “intensivist performs routinely,” “intensivist only performs in an emergency,” or “intensivist knows” about the procedure. Setting: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors’ societies, were invited to participate. SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine. Interventions: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom’s polling feature. Measurements and Main Results: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as “intensivist performs.” Conclusions: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.

Background: Interstitial lung disease (ILD) involves numerous chronic pulmonary conditions that damage the lung parenchyma and alveolar interstitium. ILD has overlapping clinical and radiological features with other commonly seen cardiac and respiratory conditions. If not identified and treated in a timely manner, it may lead to irreversible fibrosis and a poor prognosis in the patient. The current diagnostic methods are either invasive or reliant on imaging or specialist interpretation, which can lead to diagnostic delay, increased radiation exposure, and healthcare costs. Lung crackles, often under-recognized as a non-specific feature of ILD, may serve as an important diagnostic clue in identifying not only the early stages of ILD but also its subtypes. This review explores the potential of analyzing the lung sounds in ILD through AI-based auscultation. Objective: To provide a comprehensive analysis of the pathophysiological stages of lung injury in ILD, the specific acoustic features, and the location associated with each ILD subtype and to evaluate the current state-of-the-art non-AI and AI methodologies that are used to diagnose ILD. This review aims to analyze the limitations associated with the current modalities and to envision AI-integrated auscultation as a powerful, cost-effective, non-invasive, radiation-free screening tool for early detection of ILD and its subtypes. Content Overview: The review begins with a detailed analysis of the lung sound pathophysiology, exploring the two-stage mechanism of alveolar epithelial injury and fibrosis formation. Existing hypotheses explaining the mechanism behind crackle production and the role of structural anatomy and surface tension in the generation of pathological lung sounds are examined. A tabulated summary of common ILD subtypes is provided, including their inciting events, pathogenesis, anatomical auscultation locations, and prognostic implications. Current diagnostic modalities for ILD, both non-AI and AI-based, are summarized along with their limitations, emphasizing the need for improved diagnostic tools. Discussion: Existing studies suggest that AI-based auscultation can match or exceed the current modalities in its sensitivity and specificity for detecting ILD-related crackles. Clinicians can identify the specific sound pattern and then correlate it with the ILD subtype and understand the prognosis in real time, thereby providing timely intervention to the patient. Additionally, AI-based auscultation can be used in resource-limited settings and can potentially reduce dependence on pulmonology expertise and radiation-based imaging for monitoring the condition. Conclusions: This literature review highlights the clinical potential of AI-based auscultation for early and accurate diagnoses of ILD. Understanding the associated pathological sounds, biomarkers, and genetic mutations linked to different subtypes opens avenues for future development of non-invasive diagnostic panels for ILD in clinical practice.

Abstract Background: Treatment of multiple myeloma (MM) has advanced dramatically over the past decade with median overall survival (OS) for newly diagnosed MM patients (pts) now exceeding 10 years. However, outcomes in pts with high-risk disease remain poor. While most pts with high-risk disease are identified through baseline cytogenetic risk stratification, presence of extramedullary disease, or R-ISS stage, there is also a population of pts who may or may not have these traditional high-risk factors who relapse earlier than expected and have similarly poor outcomes. These pts are often delineated as “functional high-risk,” but a standardized definition of this population in the era of modern myeloma therapy is lacking. Methods: Using the ASH Research Collaborative (ASH RC) Data Hub, we retrospectively searched 7,249 pts across 10 participating institutions for those with newly diagnosed multiple myeloma (NDMM) treated with a triplet or quadruplet induction regimen (with or without autologous stem cell transplant) who had response data available. We evaluated duration of response from first line therapy (PD1) on post-PD1 clinical outcomes such as: time to next treatment (TTNT), time to subsequent progression and/or death (PFS2), and OS. We also analyzed characteristics of those who did vs. did not progress at prespecified time points of interest (12-, 18-, 24-, and 36-months) from the start of induction. We utilized recursive partitioning analyses to iteratively explore all possible cutpoints and identify which one(s) provide the greatest differentiation in the risk of subsequent progression and/or death. Results: We identified 1,305 pts who met the eligibility criteria. Of these, 264 had PD1 data including 201 who had response follow-up (f/u) after PD1. Median f/u after PD1 in this population was 3.2 years, and median PFS2 f/u after PD1 (n=201) was 4.4 years. Months to PD1 was significantly associated with PFS2 (p=0.038). All prespecified time points examined showed inferior PFS2 compared to those with PD1 &gt;36 mos, although each subgroup was not statistically significant, likely due to limited numbers in each group: PD1 &lt;12 mos HR=1.44 (n=43; 95% CI: 0.90 – 2.30; p=0.126), PD1 12-24 mos HR=1.65 (n=30; 95% CI: 0.95 – 2.85; p=0.073), and PD1 24-36 mos HR=1.58 (n=52; 95% CI: 0.98 – 2.53; p=0.059). Similarly, timing of PD1 was also associated with OS post-PD1; pts with PD1 &lt;12 mos had significantly lower OS compared to those with PD1 &gt;36 mos (HR=2.35, 95% CI: 1.27 – 4.32; p=0.006). Our recursive partitioning analysis identified 30-months at the cutoff that produced the greatest differential in outcomes between those above vs. below the landmark. Approximately 23% of the pts analyzed had PD1 within 30 mos, and these pts had significantly lower OS compared to those with PD1 ≥30 mos (HR=1.99, 95% CI: 1.21 – 3.27; p=0.006). Similarly, pts who progressed within 30 mos of starting 1L therapy (n=98) had significantly shorter PFS2 (median=12.5 mos vs 22.8 mos; HR=1.55, 95% CI: 1.09 – 2.20; p=0.014) than those who did not (n=103). Those pts who progressed within 30 mos were more likely to have a higher R-ISS stage at diagnosis (p=0.048), but were not more likely to have high-risk cytogenetics (p=0.66) compared to pts with PD1 ≥30 mos. Interestingly, receiving SCT as part of 1L therapy was not significantly associated with improved PFS2 (HR=0.89, 95% CI: 0.62 – 1.29; 0.54) but was significantly associated with improved OS (HR=0.53, 95% CI: 0.31 – 0.90; 0.018) by univariate analysis. Conclusion: Our study is the first to use a large, multicenter, cohort to evaluate the definition of functional high-risk MM in the era of novel induction therapies. Our data suggest that pts who progress within 30 mos of induction on triplet or quadruplet regimens (irrespective of whether they underwent stem cell transplant) have poorer outcomes than those who progress at 30 mos or later, and that progression prior to 30 mos represents functional high-risk disease. These pts represent a clear unmet medical need, and additional focus should be taken to identify them early with the goal of designing trials to optimize their subsequent therapies.