Citations

Purpose: The purpose of this study is to characterize the clinical features, management strategies, and outcomes of endophthalmitis cases following pars plana vitrectomy using data from the American Academy of Ophthalmology (Academy) IRIS ® Registry (Intelligent Research in Sight). Methods: This is a retrospective cohort study of eyes that developed endophthalmitis following pars plana vitrectomy between 2013 and 2022. Data was collected from the Academy IRIS Registry. This study analyzed differences in visual acuity, intraocular pressure, rates of evisceration and enucleation, and rates of rhegmatogenous retinal detachment following endophthalmitis diagnosis. Results: A total of 1,223,777 unique eyes underwent a PPV during the study period, with 1,275 eyes meeting the inclusion criteria. The median time from pars plana vitrectomy to endophthalmitis diagnosis was 10 days. The majority of eyes (80.9%) were managed with intravitreal antibiotics alone, without a repeat pars plana vitrectomy. Long-term visual acuity, intraocular pressure, cup-to-disc ratio, and rate of evisceration or enucleation did not differ significantly between treatment groups. However, eyes that underwent the initial pars plana vitrectomy for retinal detachment repair had poorer long-term vision and higher rates of retinal detachment following endophthalmitis. Overall, 16.1% of eyes required evisceration or enucleation in this cohort. Conclusions: Despite its rarity, post-pars plana vitrectomy endophthalmitis can cause significant morbidity and even globe loss. There were no significant differences observed between eyes that were treated with intravitreal tap and inject versus repeat pars plana vitrectomy.

Importance Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative. Objective To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms. Design, Setting, and Participants This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October 28, 2020; chose ISDO or RRSO; and were followed up for 24 months. The analysis was performed on November 13, 2024. Interventions Participant-selected RRSO or ISDO. Main Outcomes and Measures Changes in sexual function and menopausal symptoms from baseline to 6, 12, and 24 months. Inverse probability weighting was applied to achieve covariate balance across groups. Results The analytic sample included 334 female participants (mean [95% CI] age at consent, 39.2 [38.7-.9.7] years) who underwent RRSO (n = 165) or ISDO (n = 169) and completed 6-month questionnaires. Significantly more participants experienced clinically meaningful worsening of sexual function at 6 months compared with baseline after RRSO vs ISDO (33.1% [39 of 118] vs 16.8% [17 of 101], respectively; odds ratio, 2.00 [95% CI, 1.20-3.35]) and at 12 months (39.2% [38 of 97] vs 18.3% [17 of 93], respectively; odds ratio, 1.69 [95% CI, 1.09-2.63]). This finding was no longer significant at 24 months. When restricted to the RRSO group who took hormone replacement therapy, there was no significant worsening of total sexual function scores or menopausal symptoms compared with baseline. No interval ovarian cancers were reported. Conclusions and Relevance This nonrandomized clinical trial comparing RRSO with ISDO found that ISDO was less likely to impair sexual function, which addresses an important barrier to surgical prevention in high-risk patients in premenopause. After RRSO, use of hormone replacement therapy mitigated menopausal symptoms and prevented decline in sexual function. More information is needed about the safety of ISDO. Trial Registration ClinicalTrials.gov Identifier: NCT02760849

Abstract Background The tumor, node, metastasis (TNM) classification at pathological evaluation determines prognosis following cancer treatment. For rectal cancer patients undergoing neoadjuvant therapy, whether ypTNM likely confers different prognosis than pTNM. We compared survival outcomes of patients classified by ypTNM vs pTNM staging. Methods Patients with resected locoregional rectal cancer from the National Cancer Database who underwent upfront surgery (pTNM) and had ≥5 years follow-up (2010-2017) were compared with those receiving neoadjuvant therapy followed by surgery (ypTNM). To address treatment selection bias, analyses were stratified by receipt of guideline-concordant care. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox regression analyses. Results Of 50 436 patients (median age = 60; 61.4% male), 11 732 (23.3%) underwent upfront surgery and 38 704 (76.7%) received neoadjuvant therapy; 78.8% of the upfront surgery group received guideline-concordant care. In analyses stratified by guideline-concordant care, overall survival was similar for stage 0-I (hazard ratio [HR] = 1.05; 95% CI = 0.96 to 1.15) but significantly worse for ypTNM vs pTNM in stage II (HR = 1.50; 95% CI = 1.27 to 1.77; 5-year OS = 75.6% vs 83.2%) and stage III (HR = 1.60; 95% CI = 1.46 to 1.75; 5-year OS = 67.0% vs 78.2%). Multivariable analysis confirmed ypTNM was associated with worse survival at each stage (stage 0-I: HR = 1.14, P = .004; stage II: HR = 1.49, P < .001; stage III: HR = 1.60, P < .001). Conclusion Stage for stage, ypTNM classification is associated with worse survival than pTNM classification, with increasing difference at higher stages. Future staging systems and management guidelines should account for these differences to optimize prognostication and stratification for clinical trials and surveillance strategies.

A structured approach for interpreting postoperative imaging of the anterolateral abdominal wall integrates anatomic knowledge with surgical techniques and their associated complication patterns.

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.

Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.

Abstract Background Lung cancer is the leading cause of cancer-related death, and the most common cancer diagnosed globally. Approximately 85% of lung cancer cases are non-small cell lung cancer (NSCLC). After initial surgical treatment, adjuvant therapy with conventional or targeted chemotherapy can help optimize survival. These treatments, however, must be tailored to each patients’ problematic situation, including cancer characteristics and goals of care. Shared decision making (SDM) is a method of care by which patients and clinicians work together to form plans of care that advance the patient’s problematic human situation. This method often requires evaluating alternative options, “trying them on” for fit given their practical demands and favorable and unfavorable effects. Tools used within the encounter can facilitate and support SDM conversations, yet none exist for considering care post-surgical treatment of NSCLC. Therefore, we aimed to evaluate the effectiveness of a novel encounter tool for SDM, NSCLC Choice, compared to usual care at improving SDM and reducing decisional conflict for patients with resected early-stage NSCLC considering adjuvant treatment. Methods We will conduct a parallel, patient-level randomized trial comparing NSCLC Choice with usual care. Patients will be eligible if they are adults with stage >1B NSCLC eligible for postsurgical adjuvant chemotherapy. Allocation will be central and post-consent. Patients will be blinded to our trial hypothesis, instead of being invited to evaluate an educational intervention. Our primary outcome is SDM quality, which we will assess using participant reported measures (patient SDM-Q-9) obtained immediately post-encounter and an observer measure estimated from video recording of trial encounters in both arms (OPTION12). With resources to conduct a 100-patient trial, we will have >80% power to detect a 12-point medium difference between arms in patient-reported SDM-Q-9. We will also assess the secondary outcomes of knowledge about the disease and the features of treatment options using an ad hoc questionnaire, decisional conflict using the Decisional Conflict Scale, and patient and clinician satisfaction using the metrics used in prior SDM intervention trials. We will also determine encounter length using video recordings. Discussion In testing NSCLC Choice, we seek to determine the extent to which this intervention can improve care for patients with NSCLC considering adjuvant therapy after surgery. In addition, we expect to determine whether this intervention is satisfactory to participants and feasible in practice. If successful, this study will result in an evidence-based tool for promoting patient-centered conversations around NSCLC and cancer care those fits. Trial Registration: NCT06122064 ClinicalTrials.gov

The tumor microenvironment (TME) plays a crucial role in tumor progression and therapeutic response. Monocytes and macrophages, depending on their phenotype, can either enhance anti-tumor immunity or promote tumor growth by regulating cytokines such as IL-6. Multiple myeloma (MM), a hematologic malignancy, expresses the IL-6 receptor CD126 on its surface. Chimeric antigen receptor (CAR)-T cells targeting CD126 have been developed and shown to effectively eliminate CD126-positive tumor cells. However, interactions between macrophages, myeloma cells, and CAR-T cells require further investigation to optimize treatment strategies and minimize adverse effects. In this study, THP-1-derived macrophages, CD126 CAR-T cells, and MM cells, especially RPMI 8226 cells, were used to explore these interactions. A reduced cell population and an increased apoptosis of RPMI 8226 cells were observed in the presence of M1 macrophages. Metformin, known to influence IL-6 production, reduced the viability of RPMI 8226 cells with decreased CD126 expression. However, the killing activity of CD126 CAR-T cells against RPMI 8226 cells decreased after co-culture with macrophages, likely due to interactions between the CAR-T cells and the macrophages. These findings highlight the significant role of macrophages and inflammatory responses in MM progression and in modulating the efficacy of CAR-T cell therapy, providing valuable insights for the optimization of immunotherapeutic strategies.