Citations

Abstract Introduction This is the first International Consultation on Sexual Medicine (ICSM) position paper on sexual health in older adults. Physical, cognitive, and psychosocial factors create a unique set of challenges related to sexuality in older adults. Objectives This study explores the impact of the physiological aspects of aging, state of health, psychological, relationship-related, and sociocultural factors, on sexual health in older adults. The goal of this review is to provide recommendations for the comprehensive evaluation and treatment of this population. Methods A narrative review was conducted under the auspices of the ICSM, as part of its ongoing efforts to develop expert, evidence-based guidance in the field of sexual health. A multidisciplinary panel of international experts composed of specialists in urology, gynecology, psychiatry, sexual medicine, social work, and sex therapy was convened. A comprehensive literature review was conducted based on a search of psychological sources (PsycInfo), medical databases (PubMed, Medline), and Google Scholar. All retrieved articles were reviewed and critically assessed. Recommendations were then formulated using a modified Delphi method. Results Although there is extensive literature on the prevalence and risk of sexual challenges of adults over the age of 65, there is limited evidence regarding the quality of treatment modalities. In particular, there is scant data on women in this age group. This population faces specific and multifactorial challenges, which point to the need for a comprehensive approach to their care. Conclusion Any approach to sexual health in older adults needs to take all the factors that affect sexual health into account, while endorsing the full spectrum of sexual expression in a non-judgmental way. Individuals in a relationship should be offered a couple-centered approach. Special attention is needed for individuals in cognitive decline. Healthcare providers must be aware of ageist biases, which may prevent them from providing appropriate care.

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, data on its efficacy in patients with sarcoidosis and HFrEF are limited. Methods Using the TriNetX network, we identified patients with sarcoidosis, heart failure with a left ventricular ejection fraction (LVEF) below 35%, and either left bundle branch block (LBBB) or prolonged QRS duration ( > 150 ms) between 2014 and 2019. Patients were categorized into two cohorts: (1) those who received CRT and (2) those who received an ICD‐only implant. Five‐year outcomes included all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%. Results Out of 245 eligible patients, we identified a cohort of 87 patients (mean age 62.6 ± 9.5 years) who received CRT and 87 patients (mean age 62.1 ± 11.1 years) who received ICD‐only implant, with similar propensity scores, and included them in a comparative analysis. At 5‐year follow‐up, the CRT group demonstrated outcomes comparable to the ICD‐only implant group for all‐cause mortality (14.9% vs. 20.7%; HR 0.63; 95% CI 0.31–1.28; p = 0.19), all‐cause hospitalization (83.9% vs. 77.0%; HR 1.24; 95% CI 0.89–1.73; p = 0.19), and heart failure exacerbation (28.7% vs. 28.7%; HR 0.90; 95% CI 0.52–1.57; p = 0.72). The proportion of patients with improvement in LVEF to greater than 40% and greater than 50% was also similar in both groups (LVEF > 40%, 43.7% vs. 33.3%; HR 1.30; 95% CI 0.80–2.10; p = 0.29; LVEF > 50%, 31.0% vs. 17.2%; HR 1.72; 95% CI 0.92–3.24; p = 0.09). Conclusion CRT implantation had similar long‐term outcomes compared to ICD‐only implantation in patients with sarcoidosis and HFrEF, particularly all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%.

ABSTRACT Central venous catheters (CVCs) are a cornerstone of hematopoietic stem cell transplantation (HSCT), facilitating the delivery of chemotherapy, parenteral nutrition, medications, and blood products. Despite CVCs’ essential role, prolonged use can lead to complications such as increased risk of infection, thrombosis, mechanical issues, and psychosocial burden. However, the timing of CVC removal remains highly variable across institutions. Additionally, there are no standardized guidelines to balance the benefits of extended access against the risks of prolonged use. This narrative review examines the existing literature on CVC management post‐HSCT, highlighting key factors influencing the removal timing, such as patient characteristics, disease‐specific considerations, and institutional practices. The review emphasizes the urgent need for multi‐institutional research and standardized protocols to improve outcomes, reduce complications, and enhance the quality of care for HSCT patients.

Purpose Hip arthroscopy is a minimally invasive procedure which has been increasingly used among athletes for several hip joint related pathologies as it allows for a faster recovery. However, objective return to sport criteria have not been described previously among this population. Objective To systematically review the literature to evaluate and describe the objective return-to-sport (RTS) criteria to release patients back to sport following hip arthroscopy. Methods We conducted a comprehensive literature search according to the PRISMA guidelines. Studies were included in the review if patients underwent a hip arthroscopy procedure and the study described criteria for their patients to RTS. Two independent reviewers selected studies for inclusion and extracted study characteristics and objective RTS criteria. Results Of the 306 that were a part of our original search, 6 studies fit our inclusion criteria. There were 250 athletes (average age: 26.1) and 263 hips which underwent hip arthroscopy surgery. Of these athletes, the cohort was on average 46.5% female and an average of 91.2% of athletes returned to sport about 6 months following surgery. The primary sports these athletes participated in were soccer, swimming, skiing/snowboarding, and hockey. The objective RTS measures that were generally described included sport specific tests, range-of-motion, hip strength, and performance-based criteria. Conclusion There are minimal studies who described objective RTS criteria to release patients back to sport following hip arthroscopy procedures. Sports specific tests, hip strength, and performance-based criteria were mentioned as objective criteria to release patients back to sport.

Introduction Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities. Methods and analysis The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness. Ethics and dissemination Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments. Trial registration number ACTRN12625001050448.

Abstract Description PBC is an archetypal autoimmune disease where the dominant autoantigen is mitochondrial PDC-E2. Hitherto, PBC treatment has been neither specific nor directed toward restoration of tolerance. CNP-104, a tolerogenic nanoparticle encapsulating PDC-E2, is hypothesized to restore tolerance to pathogenic T cells. We conducted a Phase 2a First-in-Human randomized controlled trial of CNP-104 in PBC patients unresponsive/intolerant to ursodeoxycholic acid. The 42 enrolled subjects were randomized 2:1 to receive two doses of CNP-104 or placebo (PBO) one week apart and were followed for 120 days to assess safety and treatment durability. CNP-104 was safe and well-tolerated. Compared to PBO, the CNP-104 group had a reduced percentage of antigen-specific Th17 T cells and increased antigen-specific tolerogenic CD8+ T cell counts (TIGIT, GARP). ALP, ALT, and total bilirubin were similar between groups. Clinically relevant effects on albumin levels, liver stiffness, and the rate of change in 5-year UK-PBC risk for liver outcomes were improved in the CNP-104 group compared to PBO. This trial is limited by small size and data variability. Induction of antigen-specific T cell tolerance, shown by reduced Th17 cells and increased TIGIT and GARP cells correlates with improved liver stiffness, albumin, and UK-PBC. These findings suggest the CNP-104 tolerogenic mechanism of action translates to clinical benefits. These data support future studies with this unique therapeutic platform to treat PBC. Topic Categories Therapeutic Approaches to Autoimmunity (THER)

Abstract Description Antigen receptor (CAR) T cells can be generated in vivo within the natural lymph node (LN) environment as the immune response to a virus infection unfolds. This in situ approach entails priming LNs with intradermal inoculations of replication defective adenoviruses encoding MHC class I and class II allo/xeno-antigens. Universal transplant antigens were devised for LN priming by introducing tryptophan into amino acid position 162 of the MHC HLA-A2:01 class I heavy chain and by using the mouse MHC class II beta chain to form chimeric class II antigens with endogenous class II alleles. The virus encoded mismatched MHC antigen presenting molecules are expressed functionally in the LN following intradermal inoculation provoking polyclonal T cells responses. Three days later CAR T cells are generated by directly injecting retroviruses encoding CARs of interest into the responding LN. Mouse CD19-specifc CAR T cells created in this manner in B6-DQ8 and DQ8/A2 mice effectively target endogenous B cells and are therapeutic in male and female Emu-myc lymphomas demonstrating the potential for the generating functional CAR T cells directly in vivo. While in situ CAR T cells are readily produced in B6, B6-IA0/DQ8, B6-IA0/DQ8/A2, and B6-IA0/DQ6 LNs, functional differences among the strains emerged in the periphery suggesting that properties of the autoimmune-associated HLA DQ8 class II allele is particularly reactive during the production of CAR T cells in vivo. Funding Sources MustangBio, Inc Mayo Clinic Center of Biomedical Research Mayo Clinic Department of Immunology Mayo Clinic Graduate School of Biomedical Science Fraternal Order of Eagles Mayo Clinic Ventures NIH R21 AI 097337 NIH R01 CA 178804 NIH T32 AI 07425 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Background Converging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD). Objective We investigated total intracranial volume (TIV), a neuroimaging marker of neurodevelopment, and years of education differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of FTD-causing genetic mutations. Methods This cross-sectional cohort study, facilitated through the FTD Prevention Initiative (FPI), included 902 adult pathogenic mutation carriers of GRN , MAPT , or C9orf72 , and 532 familial non-carriers. ANCOVAs were computed to compare TIV and education between groups per gene. Pearson's correlations were used to examine associations between TIV and education. Results Mutation carriers (mean ± SD age = 50.0 ± 13.2 years, sex = 55% female, n ( GRN ) = 298, n( MAPT ) = 187, n ( C9orf72 ) = 417) were compared to familial non-carriers (age = 48.0 ± 12.9 years, sex = 58% female, n ( GRN ) = 201, n( MAPT ) = 114), n ( C9orf72 ) = 217). Consistent with prior findings in young adults, GRN carriers showed larger TIV, on average by 20531 mm 3 , compared to familial non-carriers (95% CI [85.4, 40977], p = 0.049, η 2 p = 0.008). Larger TIV correlated with higher years of education in GRN carriers (95% CI [0.01, 0.24], r (295) = 0.12, p = 0.03) and GRN non-carriers (95% CI [0.08, 0.34], r(198) = 0.21, p = 0.002). MAPT carriers demonstrated smaller TIV than non-carriers, on average by 29896 mm 3 (95% CI [–58248, −1545], p = 0.039, η 2 p = 0.02). Models with C9orf72 and education as outcome variables did not reveal significant differences. Conclusions In support of the neurodevelopmental hypothesis of FTD, GRN and MAPT mutations are linked to structural neurodevelopmental changes in TIV. Further research is needed to identify mechanisms underlying neurodevelopmental influences of FTD mutations and ascertain their suitability as intervention targets.