Citations

Management of transplant renal artery stenosis has been a controversial issue. The authors have reviewed their experience with 31 such cases which represent 3.1% of a transplant population of 1015 patients. Evidence of chronic allograft rejection was noted in 14 of these patients. Ten patients were treated medically. The remaining patients were managed by either percutaneous transluminal angioplasty (8 cases) or surgery (13 cases). Three patients initially treated by percutaneous transluminal angioplasty later underwent surgical repair. Operative intervention resulted in a significant decrease in mean arterial pressure and the greatest degree of therapeutic success (defined as normal blood pressure without use of antihypertensive agents). In contrast to other reports, use of percutaneous transluminal angioplasty was not successful in a majority of patients. This divergence may reflect differences in criteria for success which, we believe, should be defined more rigorously. Our data indicate that decisions regarding definitive management strategies should be based on the specific characteristics of the lesion with identification of stenoses that may be amenable to surgical rather than angioplastic treatment.

Abstract Objectives There are an increasing number of centres performing research on high-resolution vessel wall magnetic resonance imaging (VW-MRI) in GCA. However, harmonized approaches to VW-MRI in GCA are lacking and are essential to performing multicentre studies. Using a data-driven, consensus-based approach, an international expert group developed a standardized MRI protocol and scoring system to advance multi-centred research in cranial GCA. Methods A targeted literature review of VW-MRI in cranial GCA was conducted. A working group comprised of radiologists, rheumatologists and ophthalmologists with expertise in VW-MRI and GCA reviewed the results of the literature search, presented relevant data and images from their respective centres, and then reached consensus on recommendations related to key MRI structures, MRI sequences, scoring system and other important considerations. Results A total of 21 relevant articles were identified and reviewed. Based on published literature, structures to be evaluated on MRI were categorized based on anatomic location (extradural cranial, intradural cranial and orbits) and prioritization (core vs elective). Essential and elective sequences to comprehensively image cranial and orbital structures while minimizing scan time were determined along with scoring systems to grade contrast enhancement. Conclusion This report describes a standardized approach to facilitate research of VW-MRI in cranial GCA that is the result of a multidisciplinary, international collaboration of experts in VW-MRI and/or GCA.

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