Citations

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P < 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P < 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P < 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P < 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P < 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

ImportancePatients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT.ObjectiveTo compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT.Design, Setting, and ParticipantsThis cohort study was a propensity score–matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score–matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score.ExposureLeft atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group).Main Outcomes and MeasuresThe primary outcome was time to first ischemic stroke.ResultsFour hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy.Conclusions and RelevanceIn patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Abstract Increased posterior tibial slope (PTS) is a risk factor for anterior cruciate ligament (ACL) tear and ACL reconstruction failure. Anterior closing‐wedge osteotomy (ACWO) decreases the PTS and the risk of reinjury after revision ACL reconstruction. ACWO techniques include supratubercular, transtubercular, or infratubercular. However, there are limitations to the amount of slope correction an ACWO can achieve in the context of a massively abnormal slope. If the necessary slope correction is greater than 20°, a supratubercular ACWO cannot achieve the required correction without high risk of brittle fixation, a transtubercular ACWO would introduce increased morbidity of a secondary osteotomy and change the biomechanics of the patellofemoral joint resulting in significant patella alta, and an infratubercular ACWO would require a major anterior tibial metaphysodiaphyseal resection. The tibial plateau leveling osteotomy (TPLO) is an alternative curved osteotomy commonly used in canines that avoids the adverse events associated with a large ACWO. Further benefits of TPLO for massive slope correction include improved maintenance of native soft‐tissue tension, avoidance of major recurvatum, and the ability to control the correct degree. We describe an open technique for a TPLO to decrease the PTS and the risk of recurrent ACL injury. Technique Video video See video under supplementary data.

Matrix metalloproteinases (MMPs) are significant drivers of many diseases, including cancer, and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous MMP inhibitors and are being pursued for the development of anti-MMP therapeutics. TIMPs possess many attractive properties for drug candidates, such as complete MMP inhibition, low toxicity, low immunogenicity, and high tissue permeability. However, a major challenge with TIMPs is their rapid clearance from the bloodstream due to their small size. This study explores a method for extending the plasma half-life of the N-terminal domain of TIMP2 (N-TIMP2) by appending it with a long, intrinsically unfolded tail containing Pro, Ala, and Thr (PATylation). We designed and produced two PATylated N-TIMP2 constructs with tail lengths of 100 and 200 amino acids (N-TIMP2-PAT100 and N-TIMP2-PAT200). Both constructs demonstrated higher apparent molecular weights and retained high inhibitory activity against MMP-9. N-TIMP2-PAT200 significantly increased plasma half-life in mice compared to the non-PATylated variant, enhancing its therapeutic potential. PATylation offers distinct advantages for half-life extension, such as fully genetic encoding, monodispersion, and biodegradability. It can be easily applied to N-TIMP2 variants engineered for high affinity and selectivity toward individual MMPs, creating promising candidates for drug development against MMP-related diseases.

Abstract Introduction Prostate cancer (CaP) significantly impacts Black men, who face higher morbidity despite lower overall mortality. The disease and its treatments profoundly affect sexuality, relationships, and quality of life (QoL), necessitating robust support systems. Healthcare, spousal support, community involvement, and interactions with other survivors are crucial for enhancing survivors' self-esteem and daily functioning. Virtual town halls offer a platform to share trusted information and foster community support, overcoming geographic and structural barriers. This town hall event will explore Black CaP survivors' experiences, focusing on sexuality post-diagnosis and related medical and psychological needs. MethodsOn June 13, 2024, The University of Oklahoma and Stephenson Cancer Center will host the 5th town hall event (via Microsoft Teams) to address Black CaP survivors' sexual health concerns. Previous town halls averaged 70 attendees and covered various aspects of the CaP journey. This event will include storytelling and panel discussions, with presentations from two CaP survivors and their spouses on personal experiences and coping strategies. A urologic oncologist will discuss treatment advancements and early detection, while a clinical health psychologist will address psychological and emotional aspects of survivorship. Simultaneous watch parties will be held in Milledgeville, Georgia, and Dallas, Texas. Interactive Q&A sessions will allow participant engagement. Attendees will complete a post-event survey to assess the session's impact and collect clinical and sociodemographic data. Quantitative data will be analyzed using SPSS v28, and audio-recorded sessions will be transcribed and thematically analyzed using Nvivo. Results will be available by the end of June and presented at the conference. Expected Results Participants will gain a deeper understanding of the intersection between CaP and sexuality in Black men's health. Discussions will highlight the psychological impact of a cancer diagnosis, challenges in maintaining sexual health during and after treatment, and the role of mental health support. The town hall aims to emphasize the importance of a strong support system, providing valuable coping skills through shared experiences and expert insights. Topics will include the emotional and psychological impact of sexual health challenges, partner support, and the necessity of open communication with healthcare providers. The event seeks to improve CaP survivors' QoL by emphasizing continuous education and integrating sexual health into overall survivorship care. Conclusion This town hall event aims to bridge gaps in understanding and addressing Black CaP survivors' sexual health concerns. By fostering open dialogue and providing expert insights, we hope to improve these men's QoL and survivorship care, emphasizing mental health support, spousal support, and continuous education. Citation Format: Motolani Ogunsanya, Ernie Kaninjing, Parisa Ghasemi, Skyler Danker, Daniel Morton, Kathleen Dwyer, Mary Ellen Young, Folakemi T. Odedina, Yaw Nyame, Amy Siston, Jordan Neil, Adam C Alexander, Perry Cole, Patrick Beckford, Donald Reese, Thomas Mitchell, Everett Montgomery, Roland Odeleye, Darla E. Kendzor. Beyond the diagnosis: A town hall event to explore black men’s journey with prostate cancer and sexuality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B028.

Highlights Spino-plastic surgery addresses complex spinal defects using a multidisciplinary approachThe plastic surgeon's role in spinal reconstructive surgery has evolved from reactive to proactive involvement in careVBGs reduce time to spinal fusion without significantly increasing operative time, monitoring, length of stay or transfusions.We discuss the VBGs within the reconstructive ladder, as well as the indications, anatomy and dissection of VBG types.

ObjectiveDe novo variants in cullin‐3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype–phenotype correlation, and investigate the underlying pathogenic mechanism.MethodsGenetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient‐derived T‐cells.ResultsWe assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss‐of‐function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin‐protein conjugates in vitro. Notably, we show that 4E‐BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient‐derived cells.InterpretationOur study further refines the clinical and mutational spectrum of CUL3‐associated NDDs, expands the spectrum of cullin RING E3 ligase‐associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2025;97:76–89

AbstractObjectivesAdolescents with functional abdominal pain (FAP) often experience pain and other gastrointestinal symptoms in the context of eating, which may place them at risk for eating disorders. This study compared disordered eating and its sequalae in adolescents with FAP to those with chronic headache.MethodsParticipants in this retrospective chart review study were 270 adolescents and young adults (mean age 15.9; standard deviation [SD] = 1.63; 60% female) attending an intensive, interdisciplinary pain treatment program, including 135 youth with FAP and an age‐ and gender‐matched control group with a primary pain diagnosis of chronic headache. Information was extracted related to eating‐ and weight‐related symptoms.ResultsIndependent t‐tests and χ2 analyses found that compared with adolescents with chronic headache, patients with FAP showed significantly more eating pathology as reflected by scores on the Eating Attitudes Test—26 (EAT‐26) (p < 0.001), endorsement of pain‐related restrictive eating (p < 0.01), eating disorder history (p < 0.001), and avoidant restrictive food intake disorder (ARFID) diagnoses (p < 0.001). Compared to those with chronic headache, significantly more patients with FAP had lost 10 pounds or more (p < 0.01) and a higher proportion were underweight (p < 0.001). Among all participants, a history of exclusion diets used to manage symptoms significantly increased the risk for ARFID (p < 0.001).ConclusionThe results of this study highlight the increased risk of eating‐related concerns among youth with FAP, as well as the judicious use of exclusion diets to manage symptoms in these patients.

OBJECTIVE The aim of this study was to compare the rate of achievement of the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) and satisfaction between cervical spondylotic myelopathy (CSM) patients with and without class III obesity who underwent surgery. METHODS The authors analyzed patients from the 14 highest-enrolling sites in the prospective Quality Outcomes Database CSM cohort. Patients were dichotomized based on whether or not they were obese (class III, BMI ≥ 35 kg/m 2 ). PROs including visual analog scale (VAS) neck and arm pain, Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), EQ-5D, and North American Spine Society patient satisfaction scores were collected at baseline and 24 months after cervical spine surgery. RESULTS Of the 1141 patients with CSM who underwent surgery, 230 (20.2%) were obese and 911 (79.8%) were not. The 24-month follow-up rate was 87.4% for PROs. Patients who were obese were younger (58.1 ± 12.1 years vs 61.2 ± 11.6 years, p = 0.001), more frequently female (57.4% vs 44.9%, p = 0.001), and African American (22.6% vs 13.4%, p = 0.002) and had a lower education level (high school or less: 49.1% vs 40.8%, p = 0.002) and a higher American Society of Anesthesiologists grade (2.7 ± 0.5 vs 2.5 ± 0.6, p < 0.001). Clinically at baseline, the obese group had worse neck pain (VAS score: 5.7 ± 3.2 vs 5.1 ± 3.3), arm pain (VAS score: 5.4 ± 3.5 vs 4.8 ± 3.5), disability (NDI score: 42.7 ± 20.4 vs 37.4 ± 20.7), quality of life (EQ-5D score: 0.54 ± 0.22 vs 0.56 ± 0.22), and function (mJOA score: 11.6 ± 2.8 vs 12.2 ± 2.8) (all p < 0.05). At the 24-month follow-up, however, there was no difference in the change in PROs between the two groups. Even after accounting for relevant covariates, no significant difference in achievement of MCID and satisfaction was observed between the two groups at 24 months. CONCLUSIONS Despite the class III obese group having worse baseline clinical presentations, the two cohorts achieved similar rates of satisfaction and MCID in PROs. Class III obesity should not preclude and/or delay surgical management for patients who would otherwise benefit from surgery for CSM.