Citations

ABSTRACT 162 patients with relapsed secondary central nervous system lymphoma (R‐SCNSL) (median age, 65 years; male, 59.9%) including central nervous system (CNS)‐only ( n = 120) and concomitant CNS/systemic relapse ( n = 42) were retrospectively analyzed. Overall, 21.9% of patients were classified as high risk according to the CNS International Prognostic Index (CNS‐IPI). Several biological and clinical features were significantly associated with leptomeningeal involvement, including double‐ or triple‐hit (DHL/THL) status, MYC rearrangement, negative BCL6 expression by IHC, bone marrow involvement, and concomitant R‐SCNSL. Multivariable analysis showed that leptomeningeal involvement independently predicted inferior OS and was associated with a 98% increase in the hazard of death compared with parenchymal relapse (HR = 1.98, 95% CI: 1.20–3.26, p = 0.008). Based on anatomical localization, R‐SCNSL was classified into four subtypes: parenchymal‐only involvement (parenchymal‐CNS [P‐CNS], 68/42%) and parenchymal involvement plus systemic relapse (parenchymal‐concomitant [P‐concomitant], 17/10.5%); and leptomeningeal with or without parenchymal involvement (leptomeningeal‐CNS [LM‐CNS], 52/32.1%) and leptomeningeal with systemic relapse (leptomeningeal‐concomitant [LM‐concomitant], 25/15.4%). This anatomical classification significantly impacted OS and PFS ( p < 0.001). Two‐year OS and PFS were 58.2% and 29.1% for P‐CNS, 32.4% and 17.7% for P‐concomitant, 22% and 13.9% for LM‐CNS, and 7.1% and 0% for LM‐concomitant, respectively. ASCT showed a trend toward improved survival among patients with a response (CR/PR) in a 4‐month landmark analysis. These findings support the clinical application of the anatomical classification in the management of R‐SCNSL.

ABSTRACT Cohort studies are vulnerable to confounding and time‐related biases. Recent advances emphasize the importance of emulating a hypothetical target trial to minimize several of these biases. The target trial framework is a critical tool for designing cohort studies. It requires explicit specification of protocol components: eligibility criteria, treatment strategies, outcomes, timing of follow‐up (time zero), and the causal contrast to be estimated. Critical to this framework is defining “time zero” when treatment assignment takes place and follow‐up begins, which prevents prevalent user and immortal time bias and ensures proper temporal sequencing of confounders, exposure, and outcome. By guiding design, data collection, and analysis, the target trial framework helps align observational studies with the principles of randomized trials, improving the validity and interpretability of their findings. While it cannot eliminate unmeasured confounding, this approach promotes transparent, bias‐conscious cohort design, minimizes time‐related bias, and supports more robust causal inference with observational data.

ABSTRACT Background In pediatric kidney transplant recipients, native nephrectomy is sometimes performed to manage conditions such as polyuria, nephrotic syndrome, and recurrent infections. To minimize surgical morbidity, our center adopted a technique from the adult transplant program involving ligation of native ureters at the time of transplantation as an alternative to native nephrectomy in selected patients. Methods This retrospective study describes our center's experience with pediatric patients who underwent ureteral ligation at transplantation between December 2008 and December 2022. Patient selection was based on clinical judgment rather than predefined criteria. Results Sixteen patients underwent ureteral ligation, with polyuria (12/16) and proteinuria associated with focal segmental glomerulosclerosis (4/16) as the primary indications. Ligation was unilateral in 5 patients and bilateral in 11. The average follow‐up was 5.7 years. No operative complications directly attributable to ureteral ligation were observed, including native kidney pyelonephritis or need for reoperation. Although post‐transplant imaging often revealed hydronephrosis of the native kidneys, it had no clinical consequences. Late postoperative hypertension occurred in 31% of the ligation group compared to 47% of controls without ligation, while new‐onset hypertension was more common in the ligation group (18.8% vs. 5.1%). Pain scores postoperatively were comparable between groups. Conclusions This technical report suggests that native ureteral ligation at pediatric kidney transplantation is feasible in selected patients but represents an empirical, non‐standard‐of‐care approach. Prospective comparative studies are needed to refine patient selection and assess long‐term outcomes.

Abstract Aim Rectal prolapse is a full‐thickness intussusception of the rectum beyond the anal canal. It is often mistaken for other anorectal pathologies, leading to inaccurate referrals to colorectal surgeons and inappropriate management. However, the frequency of misdiagnosis is not well characterized. We aimed to assess the diagnostic accuracy of rectal prolapse referrals to three tertiary medical centres. Methods This is a retrospective study of patients referred for rectal prolapse to colorectal surgeons at the Mayo Clinic in Rochester, Jacksonville, and Phoenix from 2020 to 2024. The primary outcome is the accuracy of rectal prolapse diagnosis. The secondary outcomes are factors that correlate with diagnostic accuracy. Results Rectal prolapse was inaccurately diagnosed in 38.7% (186/480) of patients. Among misdiagnosed patients, the correct diagnosis was haemorrhoids (68.0%, n = 134), pelvic floor dysfunction (24.3%, n = 48) and rectocele (18.7%, n = 37). A diagnosis of rectal cancer was found in 3 patients (1.5%). The most common presenting symptoms were protrusion (66.3%, n = 345) and bleeding (33.6%, n = 175). Among the referring physicians, only 50.5% ( n = 227) performed an anorectal examination. Overall, there was significant variability in diagnostic accuracy across different specialties, with the highest accuracy from colorectal practices (84.0%) and the lowest from urologists (50.0%). Internal medicine physicians had a lower diagnostic accuracy with anorectal examination than without, though it did not reach statistical significance (44.0% vs. 59.5%, p = 0.2). Conclusion Over one‐third of rectal prolapse referrals were incorrectly diagnosed. This study highlights the opportunity for further training of referring providers on anorectal pathologies to improve diagnostic accuracy which could reduce treatment delays and optimize clinical outcomes.

ABSTRACT Introduction Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), initially developed for type 2 diabetes, have shown promise in improving renal outcomes in patients with and without diabetes. However, their effect on lithium‐associated kidney dysfunction remains unknown. Methods This historical cohort study included patients from Mayo Clinic (2001–2023) with mood disorders who received lithium for ≥ 6 months and later used SGLT2i for ≥ 1 month. Data on SGLT2i use and lithium treatment were extracted from electronic health records. Serum creatinine values were used to calculate estimated glomerular filtration rate (eGFR) trajectories. Linear mixed‐effects models with piecewise linear splines were used to estimate eGFR slopes before and after SGLT2i initiation, adjusted for age and sex. Results Fifty‐six patients (mean age 57.4 years, 46.4% female), predominantly with bipolar disorder (87.5%), were included. The mean eGFR, measured nearest to SGLT2i initiation, was 77.9 ± 26.0 mL/min/1.73 m 2 , and the mean duration of SGLT2i use was 19.5 ± 17.8 months. Before SGLT2i initiation, eGFR declined at a rate of −1.43 mL/min/1.73 m 2 per year ( p < 0.001). After initiation, eGFR increased by 0.69 mL/min/1.73 m 2 per year, reflecting a + 2.13 change ( p = 0.025). Sensitivity analyses, including only patients on lithium at SGLT2i initiation ( n = 22) or who had > 1 year of SGLT2i use ( n = 29) showed similar, though non‐significant, changes in slopes. Conclusion SGLT2i treatment was associated with a significant improvement in eGFR trajectory in patients with mood disorders who received long‐term lithium therapy. These findings suggest a potential role for SGLT2is in mitigating lithium‐associated kidney dysfunction and highlight the need for randomized controlled trials in this population.

Abstract Introduction: Laparoscopic salpingectomy is a commonly performed procedure and is often one of the first laparoscopic procedures performed by novice residents in Obstetrics and Gynecology (OB/GYN). Opportunities to practice before the operating room can be limited. Methods: We developed an animal tissue model and incorporated it into a laparoscopic salpingectomy simulation for OB/GYN residents in a single academic program. The simulation included a pre-simulation video describing the steps of laparoscopic salpingectomy, the laparoscopic salpingectomy simulation using an electrosurgical device, a post simulation survey, and debriefing with learner targeted feedback. Validity evidence for the simulation model was gathered using the Messick framework. Resident performance was assessed using the Objective Structured Assessment of Laparoscopic Salpingectomy (OSA-LS) and the Global Operative Assessment of Laparoscopic Skills (GOALS). Performance was correlated to the year of training with upper-level residents grouped for analysis. Results: Twenty-five simulations of laparoscopic salpingectomy were performed by 14 learners (first through fourth year). The tool was highly rated by participants. We found a significant correlation between the mean OSA-LS score and surgical experience. The mean GOALS score also increased with experience and was significantly different between 1st and 2nd years and between 1st and upper-level residents. A passing score of 12 was established for each assessment rubric. Discussion: This low-cost surgical model addresses a gap in simulation options for preoperative use of electrosurgical devices. This simulation can be used in OB GYN residency as a method to assess competency or provide feedback.

Abstract INTRODUCTION The tau positron emission tomography (PET) overlap index (OI) has shown promise in maximizing signal‐to‐noise for longitudinal tau PET imaging, particularly for early tau pathology, but requires validation against neuropathology. METHODS Fifty‐seven participants who underwent serial tau PET imaging (flortaucipir) and subsequent autopsy were included. Tau PET OI and standardized uptake value ratios (SUVRs) were compared across neuropathological diagnoses. RESULTS Tau PET OI showed greater concordance with neurofibrillary tangle (NFT) severity in the entorhinal cortex (a key region for Alzheimer's disease [AD] tauopathy) than SUVR, particularly in early Braak tangle stages (positivity: 52.2% for OI vs. 13.0% for SUVR). OI detected overlapping tau voxels that exhibited spatial correspondence with immunohistochemical and autoradiography measures of tau deposition across both AD and non‐AD tauopathies. DISCUSSION These findings demonstrate the enhanced capacity of OI in serial tau PET to robustly detect early and spatially localized tau pathology, supporting its application as a sensitive imaging metric in AD and select non‐AD tauopathies.

Abstract INTRODUCTION Hippocampal subfields are vulnerable to the transactive response DNA‐binding protein of 43 kDa (TDP‐43) and tau in primary age‐related tauopathy (PART). Geometry‐based morphometric analysis can improve the detection of structural changes in the hippocampus. METHODS Forty‐seven cases of autopsy‐confirmed PART without TDP‐43 and 19 cases of PART with TDP‐43 underwent antemortem magnetic resonance imaging (MRI) hippocampal segmentation and shape analysis. A separate cohort of 16 younger healthy individuals (YHIs) was included as a reference group. Hippocampal shape was analyzed in Python with non‐parametric cluster permutation testing. RESULTS PART(TDP+) group exhibited thinner left subiculum and CA1, with curvature deformations in left CA1 and CA2/3, relative to PART(TDP–). Both PART groups showed right‐sided predominance of thinning in presubiculum and subiculum, as well as curvature deformations in right presubiculum, subiculum, and CA1 when compared to YHIs. DISCUSSION Geometry‐based analysis showed different patterns of hippocampal thinning and curvature associated with PART(TDP+) compared to PART(TDP–).

ABSTRACT During normothermic regional perfusion (NRP), lactate is the most commonly used liver viability marker. Lactate production from pyruvate breakdown in erythrocytes is not suspended during pRBC storage. By transfusing blood at a variety of stored ages, variable amounts of lactate are added to the NRP circuit and may influence serial lactate measurements. Sixteen DCD donors undergoing NRP were enrolled in a prospective study. Samples were drawn from pRBC bags prior to use in the NRP circuit and were tested for lactate values. Lactate values of the NRP circuit perfusate were also assessed Q15 min. Lactate values of the pRBCs varied from 4.4 mmol/L to >20 mmol/L and were strongly correlated with the age of the stored blood ( r 2 = 0.74). Donors in which the pRBCs were > = 20‐days from expiration (Newer Blood group) had a significantly lower lactate at 60 min of NRP compared to donors in which pRBCs were <20 day from expiration (Older Blood group) (4.0±2.0 mg/dL vs. 6.3±2.3 mg/dL; p = 0.048). If the lactate is not decreasing as anticipated, transfusion of older pRBC should be entertained as one possible explanation. In cases where the liver seems acceptable for transplantation, additional lactate testing with longer time on NRP or sequential NRP/NMP should be considered in lieu of declining the liver outright.