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Introduction Clonal hematopoiesis (CH) in solid organ transplant (SOT) recipients can lead to impaired tolerance to immunosuppressive therapy, increased risk for complications, and potentially compromise graft and patient outcomes. The impact of mutational profile in CH on risk for hematological transformation and patient/graft outcomes for kidney transplant (KT) recipients is largely unknown. Our aim was to assess the prevalence of CH and progression of CH in KT, evaluate the impact of CH on allograft function, assess patient outcomes and determine Clonal Hematopoietic Risk Score status. Methods We retrospectively reviewed the CH profile of patients 18+ years of age who received a kidney transplant at Mayo Clinic Enterprise between 01/01/1994-12-31/2022 and underwent bone marrow biopsy with aspirate pre- and/or post-transplant. Bone marrow biopsies were primarily performed post-transplant in the workup for cytopenias. Transplant database was used to collect our variables of interest including post-transplant malignancy and outcomes. CH was ascertained through next-generation sequencing (NGS) on bone marrow samples. A 47-gene panel was utilized in our study. CH was defined by presence of somatic mutation with a variant allele frequency of > 2.0%. CH in absence of cytopenias was classified as CHIP while CH in individuals with one or more cytopenias was classified as clonal cytopenias of undetermined significant (CCUS). The Clonal Hematopoiesis Risk Score (CHRS) was utilized for CHIP and CCUS risk stratification We excluded the patients who had a prior hematologic malignancy. Results 305 kidney transplant recipients met our study criteria. The median time to follow up, defined as time from transplant until first bone marrow biopsy with evidence of CH, was 46.1 months. The frequency of CH in kidney recipients was 27/305 (9.0%), of these 14/27 (52%) patients were found to have CCUS and 10/27 (37%) were found to have evidence of post-transplant myeloid malignancy. Of these cases, 5/10 (50%) developed acute myeloid leukemia while 5/10 (50%) developed myelodysplastic syndrome. Both CCUS and myeloid neoplasms were more common in female patients, accounting for 8/14 (57%) and 7/13 (54%) of each cohort, respectively. Amongst CCUS, the most frequent mutations were seen in ASXL1, DNMT3A and TET2. More than half of patients with CH, 14/27 (52%), exhibited mutations in 2 or more genes. Meanwhile, in cases of myeloid malignancy, the commonly mutated genes were ASXL1 and TP53, seen in 3/10 and 3/10 cases, respectively. The CCUS risk status was intermediate, with median score of 11.8 (range 9.5-14). One CCUS patient transformed to myelodysplastic syndrome. The time to progression from CCUS to myelodysplastic syndrome was 14.3 months and their respective CHRS status was determined to be high-risk. Infectious complications, including viral and opportunistic infections, were seen in 12/27 (44%) recipients with CH, with CMV viremia being the most common, followed by BK viremia. In this cohort, post-transplant cardiovascular events and venous thromboembolic events occurred in 2/27 (7.0%) and 7/27 (26%) patients, respectively. Allograft failure was seen in 17/27 (63%) recipients at a median of 93.4 months post-transplant. After a median of 122 months, there were 14/27 (52%) deaths at a median duration of 93.4 months post-transplant. Causes of mortality included myeloid malignancy, infection, cardiovascular complications, end-stage renal disease or were unknown. Conclusions Renal transplant recipients carry mutations in epigenetic regulators resulting in adverse outcomes. Similar to the general population, DNMT3A, TET2 and ASXL1 mutations were the most common mutations in post-transplant CCUS. Infections, cardiovascular events, and allograft failure were frequent. Prospective studies in a larger cohort are needed to evaluate the impact of CCUS in survival and myeloid malignancy transformation risk.

Introduction: Delirium is a common, severe neuropsychiatric syndrome in hospitalised older adults. We evaluated use of validated delirium assessment tools, adherence to national guidelines and prevalence and management of delirium across Scotland, identifying barriers to effective care. Methods: Secondary analysis of national survey data, collected by participating clinicians on World Delirium Awareness Day (15 March 2023). Results: Among 120 responses (3,257 patients), the 4AT was the most frequently used assessment tool (75%), while 14% of units reported using clinical judgement alone. The delirium assessment rate was 74%, with a prevalence of 22% at 8 am. Management protocols varied, with frequent routine non-pharmacological interventions including pain management (88%), hydration (87%) and open family visiting (80%). Barriers to delirium care included insufficient staffing and training. Conclusion: While many hospital settings follow national delirium guidelines, some still rely on clinical judgement for assessment, with variability in management protocols and practices. We have highlighted key barriers to effective delirium care in Scotland.

ABSTRACT Background Flat bone chondrosarcomas have worse outcomes than extremity tumors, but there is no data directly comparing the different flat bones. The aim of this study was to examine differences in recurrence and survival between pelvic and scapular chondrosarcoma. Methods One hundred and sixty‐nine (42 scapula, 127 pelvic) patients with chondrosarcoma who underwent surgical resection were reviewed. High‐grade tumors were defined as lesions that were Grade 3 or dedifferentiated on surgical pathology. Results Patients with low‐intermediate grade lesions of the scapula were more likely to have positive margins during definitive surgical management (14% vs. 3%, OR 5, 95% CI [1.15, 22.6], p = 0.02), however, this did not translate to differences in recurrence or survival ( p > 0.05). The presence of an associated soft tissue mass in low‐intermediate grade lesions was not associated with increased recurrence. Among high‐grade tumors, patients with scapular lesions had worse DSS (HR 2.99, 95% CI [1.05, 8.51], p = 0.04). One‐ and 2‐year DSS for high‐grade pelvic tumors was 75% and 57%, respectively, and 50% and 33% for scapular tumors. Conclusion Survival for high‐grade chondrosarcoma of the flat bones is poor, particularly for those of the scapula. Despite a higher rate of positive margins for low‐intermediate grade lesions of the scapula, there was no significant difference in survival compared to low‐intermediate grade lesions of the pelvis. Additional studies with larger sample sizes are needed to further elucidate differences between these locations.

Background: Right ventricular pacing (RVP) can have adverse cardiac effects and cause pacing induced cardiomyopathy (PiCM). His bundle pacing (HBP)&Left Bundle Branch area pacing (LBBAP) mimic physiologic conduction (PhysioP) and maintain biventricular synchrony. Hypothesis and Aims: Reduced left ventricular (LV) systolic function reserve in the presence of normal baseline LV ejection fraction (EF) could precede development of RV PiCM. Our aim was to compare the effects of RVP vs. PhysioP on bicycle exercise cardiopulmonary performance in patients with normal LVEF who required pacing for bradyarrhythmias. Methods: Patients with sinus rhythm and RVP or PhysioP&ventricular pacing burden of >70% who completed cardiopulmonary exercise test and simultaneous stress echocardiography (SE) were included. Pulmonary gas exchange was calculated using Ventilation/CO2 production at rest and during exercise. Changes in LV size, EF, longitudinal strain and diastolic function and gas exchange parameters were compared post and pre exercise in the 2 groups. Results: 25 of 29 patients completed the study [68 ± 23 yrs, 48% M; LVEF 56±5%, 11 RVP, 14 PhysioP]. There was no difference in baseline demographic&clinical variables, exercise duration, rest and peak heart rate and blood pressure between 2 groups. Pacing duration was 2.61±1.48 yrs in RVP vs. 0.84±0.67 yrs (p=0.003) in the Physio group. Resting echocardiographic parameters ( Table 1A) were comparable. Compared to RVP, reduction in LV end-diastolic volume (EDV) 3.4±14.1 ml vs. -23.1±18.1ml, p=0.006)&LV end-systolic volume (ESV -5.7±11.6 ml vs. -18.0±9.5ml, p=0.01) was more pronounced in the PhysioP group. Changes in LVEF, LV strain&diastolic function were not different between the 2 groups ( Table 1B ). There were no significant differences in changes in pulmonary gas exchange parameters in the 2 groups. Conclusions: In patients with normal LVEF and pacemaker dependent, RVP is associated with impaired but PhysioP with preserved LV systolic function reserve, which can be detected by exercise SE. SE may help identify patients at risk for RV PiCM. Benefit of PhysioP needs to be determined by larger studies with longer follow-up.

Abstract BACKGROUND Myxopapillary ependymomas (MPE) are slow-growing tumors of the spine typically involving the medullary conus and cauda equina. MPE is regularly managed with surgical resection with radiation therapy reserved for cases where gross total resection cannot be achieved. Management of inoperable cases represents a clinical challenge. No systemic therapy is approved for treatment of MPE. Addition of chemotherapy may improve outcomes for cases not amenable to resection. MATERIAL AND METHODS We report feasibility and preliminary efficacy of combination treatment with proton beam radiation therapy and temozolomide chemotherapy for a patient with large, unresectable MPE. RESULTS A 19-year-old female presented with one year of gradually worsening hip and back pain despite treatment with physical therapy. MRI Lumbar spine identified a destructive and expansile T2-heterogenous and hyperintense intraosseous mass (14 x 12 x 13 cm) with extraosseous expansion involving the sacrum, coccyx, and left SI joint with abnormal soft tissue enhancement extending along the posterior spine. No additional lesions were identified on neuro-axis imaging. Biopsy of the mass was consistent with a WHO grade 2 myxopapillary ependymoma. Standard treatment of care would include complete surgical resection. Unfortunately, this would require a morbid procedure in an en block fashion with immediate and permanent loss of bowel, bladder, sexual, and ambulatory function in a young patient whose primary symptom was pain and mild weakness. It was therefore elected to treat the patient in an unconventional approach and begin with proton beam radiation therapy (59.4 Gy in 33 fractions) with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide. Mild clinical improvement and significant radiographic response were achieved (size reduced to 8 x 7 x 11 cm). CONCLUSION This case suggests a potential role for use of proton radiation therapy with concurrent and adjuvant temozolomide for management of myxopapillary ependymoma not amenable to surgical resection.

AbstractWithin the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements.