Faculty Bibliography

BACKGROUND/UNASSIGNED:Bone metastases from breast cancer cause skeletal-related events (SREs), including pain, fractures, and the need for radiation or surgery. Denosumab and bisphosphonates (BP) reduce these complications, but their relative efficacy and safety remain unclear. METHODS/UNASSIGNED:PubMed, Scopus, Cochrane Library, and Google Scholar were searched through October 2025. Five publications (four unique studies: three randomized trials and one retrospective cohort) were included. Sensitivity analyses were limited to randomized trials when feasible. Outcomes included SRE incidence and skeletal endpoints, plus renal, metabolic, hematologic, musculoskeletal, gastrointestinal, infectious adverse events, osteonecrosis of the jaw (ONJ), and serious, grade ≥ 3, and treatment-related events. RESULTS/UNASSIGNED: = 0.04) were reduced. Other outcomes, including uNTx, ONJ, serious and grade ≥ 3 events, thrombocytopenia, infectious, gastrointestinal, and respiratory events, were comparable. Results were consistent in randomized-only analyses. CONCLUSION/UNASSIGNED:In breast cancer patients with bone metastases, denosumab may benefit those at higher risk of renal toxicity or skeletal complications, while treatment decisions should remain individualized. PROTOCOL REGISTRATION/UNASSIGNED:www.crd.york.ac.uk/PROSPERO identifier is CRD420251231881.

PURPOSE/UNASSIGNED:Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC) and is a spectrum autoimmune disease of the gastrointestinal tract. Large scale real-world evidence studies could provide valuable evidence about IBD for personalized healthcare recommendations. The Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) standardizes electronic health record (EHR) data, allowing for research that incorporates multiple data sources. We are interested in whether OMOP CDM data on IBD are fit-for-use. METHODS/UNASSIGNED:We selected IBD diagnosis codes to define the phenotype. We used a data quality checklist to evaluate 5 domains: conformance, completeness, concordance, plausibility, and temporality. We also did sensitivity analyses for CD and UC that consisted of at least 2 diagnosis codes that were at least 30 days apart. RESULTS/UNASSIGNED:All of the phenotype-defining ICD source codes mapped to SNOMED. Many concept prevalences were low. A total of 78 (30.1%) out of 253 concept correlations were above our strength threshold (⍴ > 0.5). The age distribution of concepts and relative frequency of IBD medications were plausible. The median time between diagnosis and biopsy for the cohort was 4.43 [-0.05, 104.29] weeks. For the subgroup of participants who had sufficient data for the timeline analysis, IBD diagnosis concepts tended to occur first. In our sensitivity analyses, the completeness percentages of many variables in the UC and CD subgroups were similar to IBD, except for disease specific workup and treatment concepts. CONCLUSION/UNASSIGNED:We have shown a novel implementation of our data quality framework on IBD cohorts.

PURPOSE/OBJECTIVE:Report turnaround time (R-TAT) is widely used as a radiology quality metric and is increasingly considered for national benchmarking. Beginning in 2026, the Centers for Medicare & Medicaid Services (CMS) will no longer accept continuous R-TAT reporting in the Merit-based Incentive Payment System (MIPS) and instead recommend threshold-based benchmarks. This study evaluates how radiology practices have used R-TAT in quality improvement and examines the evidence supporting implementation of national threshold-based R-TAT measures. METHODS:A systematic literature review was performed in accordance with PRISMA guidelines and included English-language studies published between 2000 and 2024 that reported radiology R-TAT defined as time from exam completion to report finalization. Two independent reviewers screened titles, abstracts, and full texts. Eligible studies were analyzed for practice setting and intervention type. Descriptive statistics were generated, and a narrative review discusses risks and feasibility of threshold-based benchmarking. RESULTS:Of 1,722 screened records, 13 studies met inclusion criteria. Most originated from U.S. academic practices (92%) and evaluated technology adoption (46%), targeted improvement projects (31%), or operational changes (23%). All studies relied on local pre- and post-intervention comparisons; none reported use of the American College of Radiology GRID TAT registry for benchmarking. Reported improvements in R-TAT were context-specific and heterogeneous. The narrative review identified important concerns regarding clinical risk, unintended consequences, and measurement validity associated with unadjusted threshold-based R-TAT metrics. CONCLUSION/CONCLUSIONS:R-TAT is a useful internal performance indicator for evaluating workflow and operational interventions. However, existing evidence does not support adoption of uniform national threshold-based R-TAT benchmarks without adjustment for case complexity, modality, practice setting, and workflow factors. Continuous R-TAT measures remain better suited for local quality improvement, and future policy implementation should incorporate balancing measures to ensure patient-centered, high-quality radiologic care.

Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

BACKGROUND:Solid organ transplant (SOT) patients undergoing total joint arthroplasty (TJA) may be at higher risk for complications due to complex medical and surgical histories, chronic immunosuppressive medications, and significant ongoing comorbidities. This study aimed to evaluate postoperative outcomes following primary, elective TJA in patients with a history of SOT. METHODS:We retrospectively reviewed 53,043 primary, elective TJA patients from 2011 to 2025. Patients were screened for SOT history prior to TJA. All SOT patients were taking some form of immunosuppressive medication following their transplantation. Demographics, SOT details, and surgical data were obtained. SOT patients (n = 70) underwent a nearest-neighbor 1:3 propensity-score matching to non-SOT (NSOT) controls (n = 210) based on age, sex, smoking, Charlson Comorbidity Index, body-mass index, and TJA indication. Kidney transplants were most common (61.4%), followed by liver (24.3%), and heart (8.6%). Differences in surgical outcomes and postoperative complications between the patients were investigated using Chi-squared tests, independent t-tests and effect size (ES) estimates. Baseline characteristics did not differ between the groups (P > 0.05). RESULTS:SOT patients had significantly longer hospital stays (92 vs. 51 h, P < 0.001, ES = 0.82), higher rates of discharge to skilled nursing facilities (SNF) (15.7% vs. 5.7%, P = 0.014, ES = 0.17) and all-cause 90 day readmissions (15.7% vs. 6.7%, P = 0.040, ES = 0.12), primarily driven by non-surgical reasons (14.3% vs. 4.3%, P = 0.010, ES = 0.16) compared to NSOT patients. All-cause revision rates were comparable between SOT and NSOT patients (4.3% vs. 3.8%, P = 0.999), including aseptic (2.9% vs. 1.9%, P = 0.642) and septic causes (1.4% vs. 1.9%, P = 0.999). CONCLUSIONS:Despite higher rates of SNF discharge and non-surgical 90 day readmissions, SOT patients achieved similar all-cause, septic, and aseptic revision rates, compared to NSOT patients. These findings suggest that compared to well-matched comorbid controls, SOT patients can safely undergo elective TJA with comparable revision risk. Enhanced perioperative care may help reduce readmission risks in this complex population.

BACKGROUND:Symptomatic postoperative fluid collections (POFCs) can result in significant morbidity and mortality after abdominal surgery requiring timely intervention. EUS-guided drainage is traditionally delayed up to four weeks to allow wall maturation and reduce perforation or peritonitis risk. However, some POFCs may be suitable for earlier intervention. This study compared the efficacy and safety of acute (≤ 15 days), early (16-30 days), and delayed (> 30 days) EUS-guided drainage. METHODS:A retrospective cohort of patients undergoing EUS-guided drainage for symptomatic POFCs between 2013 and 2023 at a single tertiary center was evaluated. Technical success was defined as accessing and draining a POFC by transmural stent placement on initial endoscopy. Clinical success was defined as radiographically or endosonographically confirmed symptomatic POFC improvement without further percutaneous or surgical intervention. RESULTS:Among 85 patients with POFCs, most (61%) had undergone distal pancreatectomy with splenectomy. 59% required drainage ≤ 30 days after surgery, with 28% managed acutely. Most (83%) received lumen-apposing metal stents. Overall technical and clinical success rates were 94% and 79%, respectively, after a median 2 endoscopies (IQR 2-3). Success did not differ by timing (technical: 92% vs. 96% vs. 94%; clinical: 83% vs. 85% vs. 71%; P = 0.86 and P = 0.37). Adverse event rates were similar across groups (P = 0.85). Transgastric access was associated with clinical success (P < 0.001) and fewer adverse events (P = 0.03). Transduodenal access predicted technical (P = .05) and clinical failure (P = 0.02). CONCLUSIONS:In this large single-center experience of symptomatic POFCS, acute and early EUS-guided drainage with lumen-apposing metal stents in carefully selected patients was found to be technically safe and clinically effective, potentially avoiding more morbid interventions such as ERCP, percutaneous drainage, or surgery. Further randomized, prospective studies are needed to define predictors of technical and clinical success as well as adverse events.

BACKGROUND:The illicit drug landscape in South America is going through a major shift. The appearance of Tusi (or "pink cocaine"), a mixture often containing ketamine and MDMA, along with the growing presence of synthetic opioids like fentanyl and nitazenes, signals a new chapter in the region's drug use, which has been traditionally dominated by alcohol, cannabis, and cocaine. MAIN BODY/METHODS:Drawing on data on seizures, forensic analyses, warning systems, and surveys from Brazil, Chile, and Colombia, this perspective highlights three movements of the drug supply: non-prescribed and synthetic opioids, ketamine, and Tusi. We also elaborate on their unique public health challenges. Brazil and Chile have seen an increase in non-prescribed opioid use, some of them diverted from healthcare, accompanied by seizures of illicit fentanyl and the discovery of nitazene production in Brazil in May 2025. Colombia, while historically experiencing low opioid use, has documented fentanyl analogs in ketamine and MDMA/Ecstasy samples, mixed with various other contaminants, thus increasing risks among people who use them. Concurrently, ketamine and Tusi use are expanding rapidly across all three countries, particularly among nightclub attendees and youth with criminal-legal involvement. Tusi's unpredictable composition poses heightened overdose risks, especially in settings lacking drug-checking and overdose-prevention education and programs. Furthermore, South America has minimal opioid agonist therapy coverage, limited naloxone access, and underdeveloped harm reduction systems. CONCLUSION/CONCLUSIONS:The emergence of synthetic opioids, ketamine, and Tusi signals a new synthetic drug phase in South America's supply. The convergence of traditional drugs with potent new substances poses important health-related harms. Strengthening regional surveillance, toxicological monitoring, and harm reduction services are urgently needed. Coordinated international research and public health responses will be essential to prevent a drug crisis.

The neocortex is a highly organized structure, with region-specific spatial patterns of cells and fibers constituting cyto- and myelo-architecture, respectively. These architectural features are modulated during neurodevelopment, aging, and disease. While invasive techniques have contributed significantly to our understanding of cortical patterning, the task remains challenging through non-invasive methods. Structural magnetic resonance imaging (MRI) has advanced to improve sensitivity in identifying cortical features, yet most methods focus on capturing macrostructural characteristics, often overlooking critical microscale components. Diffusion-weighted MRI (dMRI) offers an opportunity to extract quantitative information reflecting microstructural changes. Here we investigate how different dMRI modalities contribute to the detection of microstructural characteristics and whether per-bundle approaches can disentangle characteristics related to the orientational organization of the myelo- and cyto-architecture in an animal model of cortical dysplasia, a malformation of cortical development. We scanned 32 animals (n=16 experimental; n=16 control) at four different time points (30, 60, 120, and 150 post-natal days) using both structural and multi-shell dMRI. All dMRI metrics were sampled using a 2D curvilinear system of coordinates as a common anatomical descriptor across animals. Per-bundle metrics were labeled according to their orientation with respect to the cortical surface, and analyzed separately. Experimental animals showed diffusion abnormalities of the tangential and radial fiber components in deeper cortical areas, consistent with histological findings of neuronal and fiber disorganization. The ability of dMRI to detect abnormalities in an animal model of cortical dysplasia is indicative of the clinical potential of advanced dMRI methods to study cortical microstructure in neurological disorders.

Among the ways by which oncogenic KRAS upregulates glycolysis in cancer is direct interaction of KRAS4A with hexokinase 1 (HK1), but the mechanism is unknown. HK1 associates with the outer mitochondrial membrane (OMM) where its allosteric regulation depends on homodimerization. Using affinity capture, FRET, and blue native gels, we show that KRAS4A enhances oligomerization of HK1 on the OMM. Modeling the HK1/KRAS4A complex with AlphaFold3 predicts that the membrane association sequences of both HK1 and KRAS4A are oriented toward the OMM. Super-resolution microscopy showed colocalization of HK1 and KRAS4A on the OMM with HK1 enriched at discrete locations. Single-molecule tracking reveals HK1 diffusing freely along the OMM and dwelling at discrete regions where two molecules can be seen to colocalize transiently. KRAS4A expression decreased the diffusion coefficient of HK1 on the organelle. Thus, KRAS4A alters the dynamics of HK1 on the OMM and promotes oligomerization.