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Background Cancers persist despite expression of immunogenic neoantigens and ongoing antitumor immune responses. While some occult tumors likely are cleared by effective antitumor immune responses, the targeted antigens are not easily identifiable as those tumors spontaneously disappear. Methods We used mouse models with a defined antigenic protein mimicking tumor-specific neoantigens to address the nature of these spontaneous anti-tumor immune responses. Results BALB/c (H-2d ) mice challenged with BALB/c breast tumors expressing the rat-erbB2 oncoprotein succumb to their tumors despite ongoing immune responses targeting tumor-specific model antigens. Meanwhile, congenic BALB.B (H-2b ) and H-2d/H-2b F1 hybrid mice spontaneously eliminate genetically matched tumors in a major histocompatibility complex (MHC)-II dependent manner. Adoptive transfer and immune cell depletion strategies revealed CD4+ T cells and CD20+ B cells are crucial mediators of the protective response in H-2b mice. Furthermore, passive transfer of immune serum from mice rejecting their tumors confers resistance in tumor antigen-tolerant animals with an inversely proportional relationship between tumor outgrowth and the amount of rat-erbB2 specific antibody present in tumor-bearing mice. Introduction of the rat-erb2 ectodomain into other H-2b tumor models also promotes their spontaneous tumor rejection. Notably, the tumor microenvironments differ in rat-erbB2+ tumor-bearing BALB.B and BALB/c mice at the time of fate decision in the models reflecting the differences between effective and ineffective tumor immune responses. Conclusions We find that the effective antitumor immunity targeting neoantigens in these breast cancer models is determined by MHC-II-restricted presentation of optimal cancer-associated antigens. These responses are dependent on CD4+ T cells, B cells, and antigen-specific antibodies.

ImportanceDirect immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings.ObjectiveTo assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US.Design, Setting, and ParticipantsUsing modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution–based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024.Main Outcomes and MeasuresThe primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication.ResultsA total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys.Conclusions and RelevanceOverall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.

We describe the use of a videolaryngoscope in an unconventional manner, with the provider positioned in front of the patient during intubation. This is called a “face-to-face intubation” technique. During a deep brain stimulation surgery, with the head fixed in a Mayfield frame, the placement of the supraglottic airway was unsuccessful on the induction of general anesthesia due to inadequate formation of a seal. Due to these circumstances, we intubated the patient from the front using the face-to-face intubation technique. We believe that the ability to intubate a patient from the front adds to the anesthesiologist’s airway management skills.

OBJECTIVES: The goal of this scoping review was to review some of the challenges hospitals faced in dealing with the shortage of ventilators during the COVID-19 pandemic and the solutions they were able to implement or suggested. By highlighting these problems and solutions, we hope this review can catalyze further discussions about how to better prepare for future pandemics and medical supply shortages. DATA SOURCES: A comprehensive search strategy using identifying key words was applied to several different databases to procure relevant literature. STUDY SELECTION: Four thousand two hundred fifty-nine studies were found in the initial search. Inclusion and exclusion criteria were created and applied to screen studies. Included studies focused on the supply and distribution of ventilators during the COVID-19 pandemic. In the case where reviewers disagreed about whether a study should be included, a third reviewer acted as a tie-breaker. DATA EXTRACTION: Thirty-three studies were included for final data extraction. Two independent reviewers collected various data points from these studies, including the main challenges discussed by the authors, the level of ventilator shortage being addressed, whether ventilator sharing was discussed, and the limitations of the study. DATA SYNTHESIS: A third reviewer compared the collected data and decided on the results. CONCLUSIONS: Some of the common solutions for the ventilator shortage discussed included augmenting overall ventilator supply through increased production, transporting ventilators between hospitals, ventilator sharing, designing new ventilators, and repurposing other resources to help address shortages of supplies.

Abstract Studies have identified genetic and epidemiologic factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiologic factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiologic factors modulate relationships between genetic variants and MD. We conducted six separate genome-wide, gene–environment (GxE) interaction analyses, applying 2 degrees of freedom (df) and 1df interaction tests, for each of three MD phenotypes (percent density, dense area (DA), and nondense area (NDA)). The six epidemiologic factors considered were height, ever parous, parity, ever menopausal hormone therapy, ever breastfeeding, and months of breastfeeding. We included European ancestry participants from multiple studies within the Markers of Density consortium and the Breast Cancer Association Consortium (n = 4895-16 218 depending on specific analyses). We identified 11 loci with genome-wide significant (P < 5 × 10−8) interaction tests including two novel common genetic signals interacting with parity (8p21.2) and ever breastfeeding (19p13.2) for NDA. Our results suggest that epidemiologic risk factors might influence relationships between common genetic variants and MD phenotypes at particular genomic loci.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Introduction and Objectives: Urethral stricture disease is a challenging urologic problem with a high recurrence rate. Initial management is typically completed endoscopically (e.g., urethral dilation, direct visual internal urethrotomy); however, guidelines recommend against repeated endoscopic management. Currently, surgical urethroplasty or intermittent catheterization remains the only other option. We have demonstrated a minimally invasive approach to urethroplasty. In this video, we aim to demonstrate the techniques and early outcomes of transmeatal urethral surgery for short urethral strictures. Materials and Methods: We demonstrate the procedure in two different individuals with idiopathic bulbar urethral strictures less than 2 cm. The patient is prepped in dorsal lithotomy position. Under direct visualization via cystoscopy, the ventral place of the urethral stricture is first incised to a goal of 26 Fr lumen. Next, mucosal realignment is completed via LSI Solutions’ URTRAC sheath and the RD 180 endoscopic suturing device. Two sutures are placed on either side of the urethrotomy incision site, allowing the proximal and distal ends of the mucosa to be pulled perpendicular to the urethrotomy. After reapproximation, a titanium knot is introduced endoscopically to anchor each suture into place. An indwelling catheter is then left in place. Patients are then seen at four months postoperatively. Results: Out of four total patients, there is a 100% success rate cystoscopically at 4 months postoperatively. There have been no recorded intraoperative or postoperative complications. The average operating room time was 54 minutes, and the average estimated blood loss was 9 mL. Conclusions: Transmeatal urethral surgery for short strictures via incision and urethral reapproximation appears to be a safe and effective repair option for the management of short urethral strictures. All research procedures were carried out in accordance with ethical guidelines and institutional policies, reviewed by the IRB. Authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. The authors declare that there are no commercial associations or financial interests in any product or service discussed in this article that might create a conflict of interest. The authors have not engaged in any activities or relationships with commercial entities that would bias or influence the content of this study. Runtime of video: 5 mins 40 secs.

ImportanceUnderstanding the relationship between patients’ clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.ObjectiveTo quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.Design, Setting, and ParticipantsThis prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center between January 1, 2010, and July 31, 2022. Patients with advanced directives limiting critical care or who experienced cardiac arrest of traumatic or neurologic etiology were excluded. An international cohort of experts in post-arrest care based on clinical experience and academic productivity was identified. Experts reviewed the cases between August 24, 2022, and February 11, 2024.ExposurePatients who died after WLST.Main Outcome and MeasuresThree or more experts independently estimated recovery potential for each patient had life-sustaining treatment been continued, using a 7-point numerical ordinal scale. In the primary analysis, which involved the patient cases with death after WLST, a 1% or greater estimated recovery potential was considered to be clinically meaningful. In secondary analyses, thresholds of 5% and 10% estimated recovery probability were explored.ResultsA total of 2391 patients (median [IQR] age, 59 [48-69] years; 1455 men [60.9%]) were included, of whom 714 (29.9%) survived to discharge. Cases of uncertain outcome (1431 patients [59.8%]) in which WLST preceded death were reviewed by 38 experts who rendered 4381 estimates of recovery potential. In 518 cases (36.2%; 95% CI, 33.7%-38.7%), all experts believed that recovery potential was less than 1% if life-sustaining therapies had been continued. In the remaining 913 cases (63.8%; 95% CI, 61.3%-66.3%), at least 1 expert believed that recovery potential was at least 1%. In 227 cases (15.9%; 95% CI, 14.0%-17.9%), all experts agreed that recovery potential was at least 1%, and in 686 cases (47.9%; 95% CI, 45.3%-50.6%), expert estimates differed at this threshold.Conclusions and RelevanceIn this cohort study of comatose patients resuscitated from cardiac arrest, most who died after WLST were considered by experts to have had recovery potential. These findings suggest that novel solutions to avoiding deaths based on biased prognostication or incomplete information are needed.