Citations

Objectives: We evaluated agreement between human papillomavirus (HPV) tests performed on self-collected vaginal and clinician-collected cervical specimens to advance HPV self-collection as a cervical cancer screening option in our health care system. Methods: This diagnostic accuracy study was conducted at an academic medical center. Participants were 25–65 years old with upcoming colposcopy appointments. One cohort (n = 79) self-collected a vaginal specimen in the clinic immediately before a clinician-collected cervical specimen. The second cohort (n = 115) self-collected a vaginal specimen at home, mailed it in, and had a clinician-collected cervical specimen in the clinic. Paired specimens were evaluated for total (TPA), positive (PPA), and negative (NPA) percentage agreement. Extreme temperature stability studies were also conducted. Results: Compared with clinician-collected cervical specimens, in-clinic self-collected vaginal specimens showed a TPA, PPA, and NPA of 98%, 100%, and 97% for HPV16; 99%, 100%, and 99% for HPV18; 86%, 94%, and 79% for high-risk other (HRO) HPV. The TPA, PPA, and NPA for at-home self-collected vaginal specimens compared with clinician-collected cervical specimens were 94%, 79%, and 96% for HPV16; 95%, 43%, and 98% for HPV18; 89%, 80%, and 93% for HRO. Vaginal specimens showed prolonged stability and were unaffected by extreme temperatures. Conclusions: In general, in-clinic and at-home self-collected vaginal HPV specimens for HPV screening demonstrate high agreement with clinician-collected cervical specimens, with the exception of low PPA in the at-home self-collected vaginal HPV18 subgroup. Our findings support the use of HPV self-collection as a practical option to expand access to cervical cancer screening.

Abstract The use of chimeric antigen receptor (CAR) T-cell therapy is increasing for adult B-cell acute lymphoblastic leukemia (B-ALL), with 3 CD19 CAR T-cell products commercially available. Several key clinical questions related to best practices for CAR T-cell administration in this population exist, and limited prospective randomized trials have been conducted to fill these knowledge gaps. Thus, to help guide clinical practice, we conducted a modified Delphi study to develop and validate consensus recommendations on the administration of commercially available CAR T-cell therapy for adults with B-ALL. Consensus panelists (n = 9) included principal investigators (PIs) from Real World Outcomes Collaborative of CAR T-Cell Therapy in Adult ALL (ROCCA) consortium sites and were selected based on expertise and CAR T-cell center volume. Final panel consensus recommendations were distributed for rating by the remaining PIs from ROCCA consortium sites, which served as the validation group (n = 27). Consensus topics included patient selection, bridging and pre–CAR T-cell leukemia staging, lymphodepletion, and CAR T-cell treatment setting, specific toxicity prevention and management, post–CAR T-cell response assessment and disease monitoring, and the role of consolidation and/or maintenance therapies after CAR T-cell therapy. Initially, 58 recommendation statements were evaluated for consensus. After 2 panel meetings, a total of 34 statements achieved consensus rating among the expert panel. After rating by the validation group, all but 1 recommendation statement continued to meet consensus, for a total of 33 consensus recommendation statements on the administration of CAR T-cell therapy in adult B-ALL.

Abstract Introduction Sedation is routinely administered to facilitate comfort and tolerance of life support for critically ill adults dependent on invasive mechanical ventilation. Isoflurane, a widely used anesthetic during surgery, has properties that may also benefit ICU patients requiring continuous sedation. However, efficacy as a sedative and safety in this population is not well established. Methods We conducted two identically designed multicenter randomized trials, INSPIRE ICU1 and INSPIRE ICU2, at hospitals across the US. Ventilator-dependent adults were randomly assigned in a 1.5:1 ratio to receive either inhaled isoflurane or intravenous propofol as the first-line sedative for up to 48 ± 6 hours, targeting a sedation depth between Richmond agitation-sedation scale (RASS) -1 (drowsy) to -4 (responsive only to physical stimuli). Isoflurane was administered via an anesthetic conserving device (Sedaconda ACD-S). In both arms, opioids were permitted at the lowest dose required to achieve freedom from pain. The primary outcome was the percentage of time at target sedation level, assessed as a noninferiority outcome with pre-specified margin of 15%. Secondary outcomes included opioid exposure, wake-up time after end of treatment, time to extubation, and proportion of time with spontaneous breathing effort. Results A total of 470 combined participants were included in the two trials. In each trial, 142 patients were randomly assigned to isoflurane and 93 to propofol. In INSPIRE ICU1, percentage of time within target sedation depth was 77.1 [53.2, 89.9] % with isoflurane and 80.9 [58.2, 96.4] % with propofol (difference -1.5 [-8.9, >99] %; p < 0.01 for noninferiority). In INSPIRE ICU2, percentage of time within target sedation depth was 72.6 [66.4, 78.9] % with isoflurane and 74.5 [67.5, 81.5] % with propofol (difference -1.9 [-9.4, >99] %; p < 0.01 for noninferiority). In both trials, patients assigned to isoflurane received significantly less opioid, measured as fentanyl equivalents, during the treatment period. In INSPIRE ICU2, participants receiving isoflurane were significantly likelier to exhibit spontaneous breathing efforts, but this finding was not replicated in INSPIRE ICU1. There were no significant differences in time to wake-up or time to extubation between groups in either trial. No episodes of malignant hyperthermia or propofol infusion syndrome were reported. Adverse events were comparable in type and frequency between groups. Conclusions In two US multicenter trials, isoflurane was noninferior to propofol for maintaining target sedation depth in adults undergoing invasive ventilation, and was associated with significantly lower opioid exposure. (NCT05327296, NCT05312385) This abstract is funded by: Sedana Medical

Objectives: Sexual minority women (SMW) have worse mental and physical health outcomes compared with heterosexual women. Limited research has explored menopause in SMW. This study compared menopause symptoms in cisgender SMW and heterosexual women. Methods: This cross-sectional analysis examined questionnaires from women 40-65 years, seen at women’s health clinics in Arizona, Florida, and Minnesota between December 2016 and February 2023. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS). An MRS score ≥ 12 indicates moderate or greater symptoms. Multivariable logistic regression was used to compare scores between cisgender SMW and heterosexual women, adjusting for factors that may impact menopause symptoms. Results: Data from 2,273 women were included, with 69 SMW. The mean age was 53.2 (SD: 6.1), body mass index 25.7 kg/m 2 , and a majority were White (91.9%). The median MRS score among all participants was 15 (interquartile range=10, 20); 67.3% reported MRS scores ≥ 12. The likelihood of being on hormone therapy or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors was comparable between groups. In both univariate (OR: 0.85, 95% CI: 0.52-1.40) and multivariable (OR: 0.83, 95% CI: 0.47-1.48) analyses, no significant associations between sexual orientation and MRS ≥ 12 were found. Conclusions: Menopause symptoms and likelihood of treatment were similar for cisgender SMW and heterosexual women presenting to tertiary care centers. Limited diversity in the cohort and the small number of SMW reduce the generalizability of the results. The lack of adverse social determinants of health may have contributed to the findings, but additional research in larger cohorts is needed.

Objective To evaluate the feasibility and potential efficacy of percutaneous spinal stimulation (epidural stimulation, ES) combined with task-specific training to reduce spasticity and improve gait and balance in individuals with progressive multiple sclerosis (MS). Methods Two men with progressive MS (EDSS 6.5) underwent ES lead implantation targeting the lower spinal cord, followed by one month of rehabilitation involving 12 ES-assisted training sessions. Assessments included instrumented gait analysis, Modified Ashworth Scale (MAS), pendulum test, and static balance testing performed at baseline, and at end of the study with ES-Off and ES-On conditions. Results Participant 1, with spastic hemiparetic gait, demonstrated improved lower extremity joint kinematics and muscle activation during gait, reduced knee extensor spasticity, and enhanced functional movement patterns with ES-On. Participant 2, with significant paraparesis and minimal spasticity, showed limited gait changes but experienced marked improvements in static balance, particularly under eyes-closed conditions. No adverse events were reported. Conclusion This pilot study demonstrates the feasibility and tolerability of ES paired with task-specific training in progressive MS. Participant-specific responses were observed, including improvements in gait kinematics, neuromuscular activation, spasticity, or balance; however, spatiotemporal gait parameters did not improve. These preliminary findings highlight response heterogeneity and the need for individualized ES parameter tuning. Trial registry name and URL: https://clinicaltrials.gov/study/NCT06019611

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

We previously reported initial results of the pivotal phase II trial of atezolizumab for patients with alveolar soft part sarcoma (ASPS; ClinicalTrials.gov identifier: NCT03141684 ). Here, we report on three additional years of observation. Fifty-three patients with ASPS received atezolizumab. Median duration of response increased to 37.0 months. Objective response rate (ORR) and median progression-free survival (mPFS) remained essentially as previously reported (35.8% [95% CI, 23.1 to 50.2] and 20.8 months [IQR, 7.6-not reached], respectively). ASPSCR1::TFE3 fusion type was determined for 47/53 patients; ORR and mPFS were higher among the 41 patients expressing type 1 (43.9% [95% CI, 28.5 to 60.2] and 28.3 months [IQR, 9.2-not reached], respectively) than the six patients expressing type 2 (0% [95% CI, 0 to 45.9] and 7.5 months [IQR, 3.9-not reached], respectively, PFS HR, 3.2 [95% CI, 1.01 to 10.2]). Eleven patients chose a per-protocol drug holiday (range, 3.5-26.4 months) after ≥2 years of treatment; two experienced disease progression during the holiday. Nine eligible patients elected to receive bevacizumab plus atezolizumab after progressing on monotherapy; ORR was 0% and mPFS was 18.5 months (IQR, 7.9-21.1) in this small cohort. Long-term results support using atezolizumab to treat ASPS, even for several years; a drug holiday with careful monitoring may be an option for some patients.

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

Epidural and dorsal root stimulation have emerged as promising therapies to restore function after spinal cord injury. However, how each modality uniquely or jointly engages spinal circuits remains unclear. To address this, we analyzed leg electromyography (EMG) responses to epidural stimulation (ES) and dorsal root ganglia stimulation (DRGS) delivered to the lumbosacral cord in the same individuals.