Within-episode relations among simultaneous alcohol and cannabis use and continued drinking: The role of momentary subjective responses, craving, and drinking context.

BACKGROUND: Simultaneous alcohol and cannabis use is associated with riskier daily drinking. However, little research has tested momentary mechanisms through which simultaneous use predicts continued drinking during acute drinking episodes. The current study tested whether simultaneous use moments predicted within-episode increases in subjective responses, craving, and continued drinking, and whether these relations were potentiated in social versus solitary settings. METHODS: Emerging adults who co-use alcohol and cannabis (N = 85) completed 21 days of ecological momentary assessment with event-contingent reports during drinking episodes. Three-level multilevel models tested whether simultaneous (vs. alcohol-only) use moments indirectly predicted subsequent, continued drinking through subjective responses (i.e., high-arousal positive/stimulant, high-arousal negative/aggression, low-arousal positive/relaxation, low-arousal negative/impairment) and alcohol craving, and whether relations differed by social versus solitary contexts. RESULTS: Within drinking episodes, simultaneous (vs. alcohol-only) use moments were associated with increased stimulation, which was indirectly associated with continued drinking through increased alcohol craving. Additionally, the relation between simultaneous (vs. alcohol-only) use and stimulating effects was potentiated during solitary drinking moments, whereas the relation between stimulating effects and craving was potentiated during social drinking moments. However, stimulating effects were higher in social contexts across all moments. Finally, simultaneous (vs. alcohol-only) use moments were associated with increased relaxation, which was indirectly associated with a lower likelihood of continued drinking through lesser craving. CONCLUSIONS: Simultaneous use predicted both continued within-episode drinking and cessation of drinking, with acute subjective effects and craving as mechanisms, dependent upon context. Just-in-time interventions should consider targeting affect, craving, and context in event-specific interventions.

Discovering what young adults want in electronic interventions aimed at reducing alcohol-related consequences.

BACKGROUND: Despite intervention efforts, negative alcohol-related consequences continue to impact young adults. Most alcohol interventions focus on reducing alcohol consumption; however, previous research indicates that focusing solely on alcohol use may not decrease consequences. Additionally, many alcohol interventions have diminishing engagement, and few are designed with young adults involved in the development process. Drawing on user-centered design, this study sought to understand young adult perceptions, preferences, and needs for electronic interventions specifically aimed at reducing alcohol consequences. METHODS: Using semi-structured qualitative interviews, 21 young adult drinkers (ages 18-24; 57.1% female) shared their opinions regarding the need for electronic interventions (i.e., mobile or web-delivered) to reduce alcohol consequences as well as their preferences for content, features, and ways to increase engagement. Interviews were coded and analyzed using a multi-step thematic analysis approach. RESULTS: As part of our discovery phase of intervention development, content coding revealed four main themes. Participants perceived several benefits of interventions focused on alcohol consequences, such as promoting mindful alcohol use and reducing alcohol-related harms. Participants also discussed perceived limitations of such programs, including believing consequences from drinking are unavoidable, necessary for learning, and associated with peer pressure. Preferences for features included real-time tracking, personalized feedback, and psychoeducation along with preferences for design including non-judgmental framing, interactive content, and a user-friendly platform. CONCLUSIONS: Engaging end users early in the development process is a valuable approach to increase intervention relevancy with the target population. This can also inform intervention content and design to maximize engagement and satisfaction (e.g., framing, features, and interactivity) while also reducing barriers identified early on (e.g., peer pressure).

Extended transcavernous posterior clinoidectomy in endoscopic endonasal surgery.

OBJECTIVE: Mastery of the posterior clinoidectomy technique is of utmost importance for neurosurgeons who specialize in endoscopic endonasal approaches, because the posterior clinoid process (PCP) is commonly involved in chondroid tumor resection. Three main techniques for posterior clinoidectomy have been developed: intradural, extradural, and transcavernous interdural. The authors introduce here a novel technical variant in which the transcavernous approach is extended to the dorsal clinoidal space after transection of the caroticoclinoid ligament, and they elaborate on its clinical application on the basis of anatomical dissections and radiological studies. METHODS: The authors reviewed CT angiography images and 3D reconstruction of the PCP in 50 adults to analyze the height and presence of ossified ligament attachments. In addition, endoscopic endonasal posterior clinoidectomy was performed in 20 lightly embalmed postmortem human heads. Three techniques, including extradural, transcavernous, and extended transcavernous posterior clinoidectomy, were performed sequentially, and anatomical landmarks and areas exposed with each technique were investigated and compared. RESULTS: Using radiological studies, the authors categorized the PCPs as 1 of 2 types: 1) normal, defined as less than or equal to 8 mm high with no ossified ligament attachments; or 2) complex, defined as greater than 8 mm high with or without an ossified ligament attachment. Compared with extradural (exposed PCP height 4.7 ± 0.5 mm) and transcavernous (exposed PCP height 7.3 ± 0.8 mm) posterior clinoidectomies, the extended transcavernous posterior clinoidectomy provided the maximally exposed PCP height (9.6 ± 0.4 mm; p < 0.0001). CONCLUSIONS: This report details the extended transcavernous posterior clinoidectomy as a novel technical variant for achieving maximal exposure of the PCP in endoscopic endonasal surgery. In addition, the positive results establish the importance of preoperative skull base imaging for surgical planning.

Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine.

BACKGROUND: Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube. METHODS: A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing. RESULTS: Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time. CONCLUSION: The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.

Prominent tissue hemophagocytic lymphohistiocytosis obscuring primary cutaneous gamma/delta (γδ) T-cell lymphoma.

Primary cutaneous gamma/delta (γδ) T-cell lymphoma (PCGDTCL) is a rare, aggressive malignant neoplasm of γδ T lymphocytes arising within the skin and subcutis. We present a challenging case of PCGDTCL diagnosed in a 35-year-old male soldier who presented with constitutional symptoms, pancytopenia, hemophagocytic lymphohistiocytosis (HLH), disseminated lymphadenopathy, and cutaneous lesions on his extremities and back following a deployment to Iraq and Syria. Histopathologic evaluation of an excisional biopsy showed that PCGDTCL can be focal, localized to the subcutaneous adipose tissue, and obscured by predominant HLH in the surrounding tissues. Pathologists should recognize that the diagnosis of PCGDTCL may be confounded by florid HLH and require multiple biopsies and a comprehensive immunohistochemical panel.

Lateral compartment of the cavernous sinus from the endoscopic endonasal approach: anatomical considerations and surgical relevance to adenoma surgery.

OBJECTIVE: The cavernous sinus (CS) has 4 compartments: superior, inferior, posterior, and lateral. Among these, the lateral compartment is the most common location for residual tumor, given the risk of neurovascular injury. The authors' study aimed to delineate the anatomical landmarks in this area and illustrate the technical nuances of the lateral transcavernous approach. METHODS: Twenty-two colored silicone-injected specimens were dissected via an endoscopic endonasal approach to the lateral compartment of the CS. The anatomical landmarks and the internal carotid artery (ICA) mobilization technique were investigated. Two illustrative cases are provided. RESULTS: The lateral compartment of the CS is bounded by the carotid-oculomotor membrane (COM) and optic strut as the roof and the petrolingual ligament and lingual process as the floor. It is divided into 2 asymmetrical subcompartments: the upper, larger subcompartment, located superior to the abducens nerve, accommodates the lateral parasellar ligament (LPL), inferolateral trunk (ILT), and branches of the tentorial artery; and the lower, smaller subcompartment, inferior to the abducens nerve, accommodates only the sympathetic nerve branches as they join the abducens nerve. The LPL is a well-defined ligamentous band and was identified in 38 (86%) hemispheres with 2 distinct configurations: 1) robust LPL (59%), with highly compacted ligamentous bands tightly adherent to the ICA; and 2) dispersed LPL (27%), with less compaction and adherence to ICA. The main attachment of the LPL to the cavernous ICA was most commonly observed at the horizontal ICA segment (55%), followed by the anterior (18%) and posterior (14%) genua. The ILT, as the main vessel in the lateral compartment, was identified in 41 (93%) hemispheres and originated from the horizontal ICA segment (80%) or the anterior genu (14%), from either the lateral (52%) or inferior (41%) aspect of the cross-section of the ICA. In 64% of hemispheres, the LPL wrapped the ILT, abducens nerve, and sympathetic nerve to form a broad and firm neurovascular-ligamental complex. Transection of the LPL, ILT, and COM enables medial ICA mobilization and enhances access to the lateral compartment of the CS, potentially increasing the exposure width by 6 ± 1 mm. CONCLUSIONS: This study provides valuable insights into the anatomical intricacies of the lateral compartment of the CS and underscores the potential benefits of the endoscopic endonasal lateral transcavernous approach. Further clinical applications are essential for validating these findings and optimizing surgical outcomes.

Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial.

BACKGROUND: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants. METHODS: In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination. FINDINGS: All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID50 groups, and YF-VAX group, respectively, remained seroprotected through D180. INTERPRETATION: vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development. FUNDING: Sanofi.

Examining whether young adults differ in their endorsement and subjective evaluation of alcohol consequences by age, drinking frequency, and current undergraduate status.

OBJECTIVE: There is considerable variability in how young adults (YAs) perceive drinking-related consequences, and some researcher-identified "negative" consequences are viewed by YAs as neutral or even somewhat positive. Little is known about individual difference factors that may influence subjective evaluations of alcohol consequences. METHOD: We tested whether endorsement and subjective evaluation ('extremely negative' to 'extremely positive') of 24 alcohol-related "negative" consequences differed by age (18-20, 21-27), past 3-month drinking frequency (3x/month or less, weekly or more), and current undergraduate status (4-year undergraduate, non-student). YAs were recruited for a longitudinal ecological momentary assessment study on cognitions and alcohol use. Participants in the analytic sample (N=640; 48.1% White non-Hispanic/Latinx, 50.0% female, mean age=22.2 years, SD=2.3) reported past 3-month drinking. Past 3-month drinking frequency, negative consequences (total and item-level), and subjective evaluations of consequences were assessed cross-sectionally. RESULTS: Compared to YAs 18-20, YAs 21+ experienced fewer total consequences, were significantly less likely to endorse experiencing physical/behavioral consequences, and rated these consequences more negatively if they were endorsed. YAs who drank weekly or more reported experiencing more consequences and were significantly more likely to experience all 24 consequences in comparison to YAs who drank 3x/month or less. Subjective evaluation ratings did not significantly differ by drinking frequency. There were few differences between 4-year undergraduate and non-undergraduates; non-undergraduates rated several health/responsibility-related consequences more negatively. CONCLUSIONS: Findings highlight the importance of identifying individual difference factors that contribute to subjective evaluation ratings, and may be useful for tailoring brief, personalized alcohol interventions for YAs.

Endoscopic Endonasal Approach to the Ventral Petroclival Fissure: Anatomical Findings and Surgical Techniques.

Objective The endoscopic endonasal approach has emerged as an excellent option for the treatment of lesions involving the petroclival fissure (PCF). Here, we investigate the surgical anatomy of the ventral PCF and its application in endoscopic endonasal surgery. Methods Sixteen head specimens were used to investigate the anatomical features of PCF and relevant technical nuances in translacerum, extreme medial, and contralateral transmaxillary (CTM) approaches. Two representative endoscopic endonasal surgeries involving the PCF were selected to illustrate the clinical application. Results From the endoscopic endonasal view, the ventral PCF is presented as a lazy L sign, which is divided into two distinct segments: (1) upper (or petrosphenoidal) segment, which extends vertically from the foramen lacerum inferiorly to the junction of the petrosal process of sphenoid bone and petrous apex superiorly, and (2) lower (or petroclival) segment, which extends inferolaterally from the foramen lacerum to the ventral jugular foramen. Approaching both segments of the ventral PCF first requires full exposure of the foramen lacerum, followed either by exposure of the anterior wall of cavernous sinus and paraclival internal carotid artery for upper segment access, or transection of pterygosphenoidal fissure and Eustachian tube mobilization for lower segment access. Combined with a CTM approach, the lateral extension of the surgical access can be improved for both upper and lower segment PCF approaches. Conclusion This study provides a detailed investigation of the microsurgical anatomy of the ventral part of PCF, relevant surgical approaches, and technical nuances that may facilitate its safe exposure intraoperatively.

Negative urgency as a state-level process.

OBJECTIVE: Test whether global self-reports of urgency moderated the within-person associations of affect and impulsive behaviors. BACKGROUND: Negative urgency is a personality trait that is a risk factor for a range of psychopathology. Although it is assumed that global self-reports of urgency measure individual tendencies to act more impulsively in the face of negative emotions, evidence from ecological momentary assessment studies is mixed. METHOD: In this Registered Report, we used ecological momentary assessment data from a large sample of young adults (n = 496, age 18-22, 5 surveys per day for 40 days). RESULTS: All forms of momentary impulsivity were impaired in moments when people reported more intense negative emotions, but global self-reports of urgency did not explain individual differences in this association. Moreover, averaged affective states, rather than specific dimensions, affective circumplex, or appraisals, best predicted impulsive states. CONCLUSIONS: Results suggest that face-valid interpretations of global self-report of urgency are inaccurate, and it may be important to understand how some people come to understand themselves as high on urgency rather than assuming that people's self-reports of their motivations are accurate. Momentary experiences of emotions globally impact multiple weakly to moderately associated impulsive behaviors, and future research should seek to understand both when and for whom these associations are strongest.

Simultaneous use of alcohol and cannabis and attenuated age-related declines in alcohol and cannabis use disorder symptoms across young adulthood.

Most young adults naturally mature out of high-risk substance use patterns, but it is important to identify factors that may impede normative declines. Use of alcohol and cannabis simultaneously (i.e., simultaneous alcohol and marijuana/cannabis [SAM]) is cross-sectionally associated with alcohol and cannabis concerns, and SAM use increases acute risks at the daily level. However, less is known about long-term risks of SAM use and, specifically, how SAM use relates to maturing out of alcohol and cannabis use. Using four consecutive years of survey data from young adults who reported SAM use (N=409; 1636 responses; aged 18-25 at baseline), we first estimated age-related changes in symptoms of alcohol and cannabis use disorder (AUD/CUD) using multilevel growth modeling. Findings supported a maturing out process, as both AUD and CUD symptom severity significantly declined across young adulthood, on average (4 % and 5 % per year respectively, with significant acceleration). Cross-level interactions tested whether participants' mean SAM use frequency across all four timepoints moderated age-related trajectories in AUD/CUD symptom severity. Significant interactions indicated that, relative to less-frequent SAM use, participants with more frequent SAM use showed less steep declines in AUD (1 % decrease per year vs. 6 % per year) and CUD symptoms (0 % decrease per year vs. 7 % per year); thus, SAM frequency was associated with slower/delayed maturing out of hazardous alcohol and cannabis use. Findings highlight that SAM use may be a correlate or risk-factor for prolonged high-risk substance use during young adulthood that relates to deviations from maturing out processes.

Randomized Feasibility Study Evaluating Multiple FDA-approved Microbubbles for CEUS Lymphography.

Prior studies on contrast-enhanced ultrasound (CEUS) lymphography for preoperative mapping before lymphaticovenous anastomosis surgery in patients with extremity lymphedema have been limited to using only Lumason and Sonazoid as microbubble contrast agents. The purpose of this study was to determine the feasibility of using two other Food & Drug Administration-approved microbubble agents, Optison and Definity, for imaging lymphatic vessels in the upper extremities. Nine female adults with unilateral upper extremity lymphedema anticipating lymphaticovenous anastomosis surgery underwent CEUS lymphography of the unaffected upper extremity randomized to either Lumason, Definity, or Optison. Lymphatic vessels were visualized in all but one case when undilated Definity was used. In the eight upper extremities where lymphatic vessels were visualized, an average of eight intradermal injections of microbubbles were performed in the extremity. Lymphatic vessels could be identified in 57% (36 of 63) of the injections. The effective dilution for each of the microbubble agents is provided. This was the first successful demonstration of lymphatic vessel visualization using either Definity or Optison. Broadening the range of available microbubble agents for CEUS lymphography could improve accessibility to the procedure and provide potentially safer alternatives.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Granuloma annulare and possible relation to purified protein derivative administration: a case report.

BACKGROUND: Granuloma annulare is a noninfectious inflammatory granulomatous skin disease characterized by an erythematous or skin colored annulare plaque. The diagnosis of granuloma annulare may be challenging owing to its diverse morphology. In such cases, a correlation between the clinical findings and histologic findings are necessary. CASE PRESENTATION: We report a case of granuloma annulare after purified protein derivative administration. A 56-year-old Caucasian female patient complained of mildly pruritic rashes which started on both arms and lower extremities, and eventually spread to both thighs, the left popliteal region, left upper back, and the right abdominal area. About 6 weeks prior to the eruption of the rashes, the patient had been given a purified protein derivative tuberculin skin test. Biopsy specimens revealed dermal histiocytes palisading around areas of mucin and degenerated collagen, confirming granuloma annulare. After treatment with 0.1% topical triamcinolone acetanide and 500 mg oral metronidazole, the patient's lesions resolved. DISCUSSION: Relatively little is known about granuloma annulare's exact etiology. Granuloma annulare has four variations presenting as either localized, generalized, subcutaneous, or perforating and patch granuloma annulare. The clinical prognosis for granuloma annulare varies according to clinical subtypes. Proposed causal mechanisms of subcutaneous granuloma annulare include physical trauma, infections, immunizations, insect bites, diabetes mellitus, and alterations in the cell-mediated immune responses. The disease likely has an inflammatory component. Clinically, granuloma annulare may be confused with many other skin diseases. CONCLUSION: This case of subcutaneous granuloma annulare was reported since it is a rare dermatologic pathological condition that can be confused with other skin rash disorders. Although it is a benign self-limited disease, definitive diagnosis is important to rule out other pathologies with similar clinical appearances, such as cancer or human immunodeficiency virus (HIV) infection. Diagnostic confirmation is best made through skin biopsy.

An Allergic Reaction in Contrast-enhanced Ultrasound Lymphography for Lymphovenous Bypass Surgery.

Lymphedema following oncologic intervention can cause significant lifelong morbidity for patients in whom conservative management fails. The associated swelling, discomfort, pain, and recurrent cellulitis greatly diminish quality of life. Surgical procedures, including suction-assisted lipectomy, lymphovenous anastomosis (LVA), and vascularized lymph node transfers, show effectiveness in both volume reduction in affected extremities and symptom relief. However, the success of procedures like LVA is dependent on effective preoperative lymphatic mapping to identify suitable vessels for anastomosis. Traditional superficial lymphatic mapping uses near infrared fluorescence indocyanine green (ICG) imaging. Moreover, recent advances in contrast-enhanced ultrasound (CEUS) lymphography increased lymphovenous bypass target identification for LVA in the extremities.7 CEUS lymphography uses microbubbles as a contrast-enhancing agent injected intradermally into the affected extremity with subsequent identification of superficial collecting lymphatic vessels using ultrasound. Although a recent report noted an uptick in severe and critical adverse drug reactions to an ultrasound contrast agent injected intravenously in stress echocardiography, adverse drug reactions associated with ultrasound contrast-enhancing agents in body ultrasound are rare. The safety profile and potential complications from CEUS lymphography in the lymphedema population have yet to be fully characterized. In this case report, the authors present the first cutaneous adverse drug event following a secondary exposure to the contrast used for CEUS imaging. Mechanisms and justifications for an immune-mediated process are explored, and a review of similar manifestations in other related contrast applications is discussed.

Estimating substance use disparities across intersectional social positions using machine learning: An application of group-lasso interaction network.

OBJECTIVE: An aim of quantitative intersectional research is to model the joint impact of multiple social positions on health risk behaviors. Although moderated multiple regression is frequently used to pursue intersectional research hypotheses, such parametric approaches may produce unreliable effect estimates due to data sparsity and high dimensionality. Machine learning provides viable alternatives, offering greater flexibility in evaluating many candidate interactions amid sparse data conditions, yet remains rarely employed. This study introduces group-lasso interaction network (glinternet), a novel machine learning approach involving hierarchical regularization, to assess intersectional differences in substance use prevalence. METHOD: Utilizing variable selection and parameter stabilization functionality for main and interaction effects, glinternet was employed to examine two-way interactions between three primary social positions (gender, sexual orientation, and race) predicting heavy episodic drinking, cannabis use, and cigarette use prevalence. Analyses were conducted using the All of Us Research Program (N = 283,403), a national sample with high representation from populations historically underrepresented in biomedical research. Results were replicated using holdout cross-validation and compared against logistic regression estimates. RESULTS: Glinternet prevalence estimates were more stable across discovery and replication samples relative to logistic regression, particularly among sparsely represented groups. Prevalence estimates for cigarette and cannabis use were elevated among sexual minority and White cisgender women compared to heterosexual and non-White women, respectively. CONCLUSIONS: Glinternet may improve upon traditional moderated multiple regression methods for pursuing intersectional hypotheses by improving model parsimony and parameter stability, providing novel means for quantifying health disparities among intersectional social positions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).