Embolization of the Pancreas Using Microspheres: A Proof-of-Safety Study in a Porcine Model.

INTRODUCTION: Particle embolization of the pancreas with the intent of producing tissue ischemia has not been evaluated, but could have valuable application in the oncologic realm. A pig model was used to evaluate safety and impact on pancreatic function. METHODS: Embolization of the dorsal pancreatic artery using 100-300-micron particles was performed on fourteen Yorkshire pigs. Baseline and post-embolization glucose tolerance testing and serum amylase/lipase levels were obtained. Pigs were observed for two weeks to assess for behavioral signs of pain/distress, bowel changes, and changes to intake/output. After two weeks, euthanasia and necropsy with gross and histopathologic assessment of the pancreas was performed. RESULTS: Embolization was technically successful in all pigs. All animals survived the two-week follow up without evidence of pain/distress. There were significant increases in amylase and lipase at 24- and 48-hours (p < 0.001), which normalized by two weeks. There clinically significant change in glucose tolerance testing at 2 weeks. Bowel habits were unchanged without diarrhea. At necropsy, all examined pancreases had fibrosis in the distal body and tail, without gross evidence of ongoing inflammation. On histopathologic evaluation, all pancreases demonstrated fibrosis in the embolized portions without evidence of active inflammation in treated or adjacent pancreatic tissue. CONCLUSION: Particle embolization of the pancreas was feasible and tolerated by all tested pigs with transient amylasemia, lipasemia, and mildly impaired glucose tolerance, but without clinical or histopathologic evidence of acute pancreatitis and no evident impact on pancreatic endocrine or exocrine function.

Correlation of ablation volume with renal function loss after cryoablation in solitary functioning kidneys.

PURPOSE: The purpose of this study was to retrospectively analyze the degree of renal function deterioration after renal cryoablation in patients with a solitary functioning kidney based on ablation volume. MATERIALS AND METHODS: Over a 15-year period, 81 percutaneous cryoablations were performed in solitary functioning kidneys. After exclusion of patients with baseline end-stage renal disease(ESRD) and insufficient follow up, analysis was performed on 65 procedures in 52 patients (40 male, mean age 63.5 years). The post-cryoablation renal function was based on the lowest serum creatinine within 6 months post-procedure. Renal function change was defined as percentage glomerular filtration rate(GFR) change. Volumetric analysis was performed on the target lesion, renal parenchyma, and ablation zone. RESULTS: The median tumor diameter was 2.0cm (range 0.8-4.7cm). The median baseline GFR decreased from 56.4 mL/min/1.73m2 (range 17.5-89.7) to 46.9 (range 16.5-89.7) at median 95 days (p<0.001), equating to an -7.9% median renal function change (range -45.0 to +30.7). All patients had stage 2 or worse chronic kidney disease and baseline function did not correlate with renal function change. The median volume of ablated parenchyma was 19.7mL (range 2.4-87.3mL), equating to 8.1% (range 0.7-37.2%) of total parenchyma. The volume of parenchymal volume ablated correlated significantly with renal function loss, while age, hypertension, and diabetes mellitus did not. No patients developed ESRD within 1 year after cryoablation. CONCLUSION: Cryoablation in solitary functioning kidneys resulted in a modest reduction in renal function, even in patients with chronic kidney disease and ablations up to 20% of renal parenchymal volume.

ACR Appropriateness Criteria® Management of Uterine Fibroids: 2023 Update.

Uterine fibroids are the most common benign tumor in women of reproductive age and can present with symptoms including bleeding, bulk related symptoms, and infertility. Several treatment options are available for the management of uterine fibroids, including medical management, minimally invasive therapies such as uterine artery embolization and MR-guided focused ultrasound ablation, and surgical interventions ranging from laparoscopic myomectomy to open hysterectomy. Given this wide range of therapeutic interventions, it is important to understand the data supporting these interventions and to be able to apply it in different clinical settings. This document provides a summary of recent trials supporting various therapies for uterine fibroids, including recent evidence for MR-guided focused ultrasound ablation and a detailed discussion of fertility outcomes in myomectomy and uterine fibroid embolization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Long term impact of transjugular intrahepatic portosystemic shunt (TIPS) creation on hepatic morphology.

PURPOSE: The purpose of this study was to evaluate long-term morphologic changes occurring in the liver after TIPS creation with correlation with hepatic function to gain insight on the physiologic impact of TIPS on the liver. METHODS: This retrospective study included patients who underwent TIPS creation between 2005 and 2022 and had contrasted CT or MRI studies prior to and between 1 and 2 years post procedure. Strict exclusion criteria were applied to avoid confounding. Parenchymal volume and vessel measurements were assessed on the pre- and post-TIPS CT or MRI and MELD scores calculated. RESULTS: Of 580 patients undergoing TIPS creation, 65 patients (mean age, 55 years; 36 males) had pre-TIPS and post-TIPS imaging meeting inclusion criteria at median 16.5 months. After TIPS, the mean MELD score increased (12.9 to 15.4; p = 0.008) and total liver volume decreased (1730 to 1432 mL; p < 0.001). However, the magnitude of volume change did not correlate with MELD change. Neither portosystemic gradient nor TIPS laterality correlated with total or lobar hepatic volume changes or MELD changes. The main portal vein diameter increased (15.0 to 18.7 mm; p < 0.001). Thrombosis of the hepatic vein used for TIPS creation resulted in a mean increase in MELD of +4.1 compared to -2.1 in patients who had a patent and normal hepatic vein (p = 0.007). CONCLUSIONS: Given lack of correlation between portosystemic gradient, hepatic atrophy, hepatic function, and TIPS laterality, the alterations in portal flow dynamics after TIPS may not be impactful to hepatic function. However, hepatic vein patency after TIPS correlated with improved hepatic function.

Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals.

Background: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown. Methods: We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC. Results: During the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular. Conclusions: We found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC.

An End-to-End Platform for Digital Pathology Using Hyperspectral Autofluorescence Microscopy and Deep Learning-Based Virtual Histology.

Conventional histopathology involves expensive and labor-intensive processes that often consume tissue samples, rendering them unavailable for other analyses. We present a novel end-to-end workflow for pathology powered by hyperspectral microscopy and deep learning. First, we developed a custom hyperspectral microscope to nondestructively image the autofluorescence of unstained tissue sections. We then trained a deep learning model to use autofluorescence to generate virtual histologic stains, which avoids the cost and variability of chemical staining procedures and conserves tissue samples. We showed that the virtual images reproduce the histologic features present in the real-stained images using a randomized nonalcoholic steatohepatitis (NASH) scoring comparison study, where both real and virtual stains are scored by pathologists (D.T., A.D.B., R.K.P.). The test showed moderate-to-good concordance between pathologists' scoring on corresponding real and virtual stains. Finally, we developed deep learning-based models for automated NASH Clinical Research Network score prediction. We showed that the end-to-end automated pathology platform is comparable with an independent panel of pathologists for NASH Clinical Research Network scoring when evaluated against the expert pathologist consensus scores. This study provides proof of concept for this virtual staining strategy, which could improve cost, efficiency, and reliability in pathology and enable novel approaches to spatial biology research.

Vortex-assisted resin y90 delivery via 175 cm Truselect microcatheter: case factors for high residual despite double-flush protocol.

PURPOSE: To report efficiency of resin y90 delivery using SIROS via 175 cm TruSelect microcatheter with double-flush protocol (40 ml dextrose total). METHODS: IRB-approved retrospective review of all patients undergoing SIROS injection of y90 Sir-Spheres via TruSelect from 2019 through 2022 at one quaternary-care academic institution, including medical records. RESULTS: Included were 48 infusions in 25 patients across 11 cancer histologies. Mean planned, delivered, and residual activities were 28 ± 17, 27 ± 17, 1.1 ± 0.56 mCi respectively (mean residual 4.9% ± 2.8%) across flex-dosing precalibrations including 1-day, 2-day, and 3-day SIROS (4/51, 16/51, and 28/51). Mean liver treatment volume was 483 ± 306 ml with target dose mean of 128 ± 26 Gy in non-segmentectomy cases; Radiation segmentectomy was performed in 15/48 (31%). Arterial stasis was documented in 9/48 (19%) of cases. Use of a 3-day precalibrated SIROS dose, use of activity <10 mCi, treatment of smaller liver volumes (<200 ml) and documentation of stasis were associated with higher residual activity ( P  = 0.025, P  = 0.0007, P  = 0.0177, and P  = 0.049, respectively) were associated with higher residuals. CONCLUSION: Combining the new technologies of SIROS and the Truselect microcatheter with a double-flush protocol yielded <10% residual in 94% of y90 infusions. Future studies may clarify if the predictors of high residual dose seen here may warrant microcatheter-specific considerations for dosimetry or dose preparation at the Radiopharmacy level.

Mustn1 ablation in skeletal muscle results in functional alterations.

Mustn1, a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed Mustn1 expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear. This study sought to investigate the effects of Mustn1 in a conditional knockout (KO) mouse model in Pax7 positive skeletal muscle satellite cells. Specifically, we investigated the potential effects of Mustn1 on myogenic gene expression, grip strength, alterations in gait, ex vivo investigations of isolated skeletal muscle isometric contractions, and potential changes in the composition of muscle fiber types. Results indicate that Mustn1 KO mice did not present any substantial phenotypic changes or significant variations in genes related to myogenic differentiation and fusion. However, an approximately 10% decrease in overall grip strength was observed in the 2-month-old KO mice in comparison to the control wild type (WT), but this decrease was not significant when normalized by weight. KO mice also generated approximately 8% higher vertical force than WT at 4 months in the hindlimb. Ex vivo experiments revealed decreases in about 20 to 50% in skeletal muscle contractions and about 10%-20% fatigue in soleus of both 2- and 4-month-old KO mice, respectively. Lastly, immunofluorescent analyses showed a persistent increase of Type IIb fibers up to 15-fold in the KO mice while Type I fibers decreased about 20% and 30% at both 2 and 4 months, respectively. These findings suggest a potential adaptive or compensatory mechanism following Mustn1 loss, as well as hinting at an association between Mustn1 and muscle fiber typing. Collectively, Mustn1's complex roles in skeletal muscle physiology requires further research, particularly in terms of understanding the potential role of Mustn1 in muscle repair and regeneration, as well as with influence of exercise. Collectively, these will offer valuable insights into Mustn1's key biological functions and regulatory pathways.

Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection.

Background: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period. Methods: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection. Results: We identified three phenotypic clusters associated with PASC that could be characterized as remittent, persistent, or incident based on the 3-month change in symptom number compared to study entry: remittent (median; min, max: -4; -17, 3), persistent (-2; -14, 7), or incident (4.5; -5, 17) (p = 0.041 remittent vs. persistent, p < 0.001 remittent vs. incident, p < 0.001 persistent vs. incident). Despite younger age and lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, 24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, 4.36)]. Conclusion: An incident disease phenotype characterized by symptoms that were absent during acute illness and the observed association with high dose steroids during acute illness have potential critical implications for preventing PASC.

Multi-omic profiling reveals early immunological indicators for identifying COVID-19 Progressors.

We sought to better understand the immune response during the immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. In lymphocytes, the CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. These early stage observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. BACKGROUND: Much of the literature on immune response post-SARS-CoV-2 infection has been in the acute and post-acute phases of infection. TRANSLATIONAL SIGNIFICANCE: We found differences at early time points of infection in approximately 160 participants. We compared multi-omic signatures in immune cells between individuals progressing to needing more significant medical intervention and non-progressors. We observed widespread evidence of a state of increased inflammation associated with progression, supported by a range of epigenomic, transcriptomic, and proteomic signatures. The signatures we identified support other findings at later time points and serve as the basis for prognostic biomarker development or to inform interventional strategies.

Financial Impact of Imaging Examination Site of Service in the Medicare Population.

PURPOSE: The financial sustainability of the US healthcare system is a growing concern in an environment of declining reimbursement and rising costs. Variable Centers for Medicare and Medicaid (CMS) reimbursement and denial rates for specific imaging examinations exist across sites of service, adding complexity to financial planning for healthcare organizations. Understanding the financial implications of site of service in existing CMS reimbursement for imaging may be of strategic importance for organizations going forward. MATERIALS AND METHODS: Current Procedural Terminology (CPT) codes were obtained for common cross-sectional imaging examinations using the 2022 CMS Medicare Physician Fee Schedule. Using reimbursement rates with historical volumes and denial rates, a simulation was created to estimate the overall reimbursement of paired hospital outpatient departments (HOPD) and free-standing office (FSO) sites. A baseline simulation was performed with random allocation of imaging examinations between sites of service, and an optimized simulation was performed to estimate the maximum financial impact of targeted allocation between sites. These simulations were performed for paired CT and MR scanners separately. RESULTS: For CT, the baseline simulation estimated annual average reimbursement for combined HOPD and FSO was $3.25M. Reimbursement increased to $3.51M after optimized reallocation of studies between sites of service, resulting in an expected gain of $260,162 for a set of paired HOPD and FSO scanners. For MR, the same approach resulted in baseline reimbursement of $2.51M, increasing to $2.60M upon reallocation between sites for an expected gain of $87,532. Assuming a stable cost of service delivery, this approach would result in improved margins of 8% for CT and 3.5% for MR. There were 28 CT and 19 MRI daily patient imaging appointments at each respective HOPD and FSO scanners, unchanged between baseline and optimized cases. Differences in reimbursement rates between sites were the dominant driver of increased margins at low denial rates, although denial rates became dominant at values greater than 50%. CONCLUSION: Given CMS payment and denial rate variability, optimally allocating imaging studies between sites of service may improve reimbursement for the same services delivered. Although financial incentives exist for site allocation, such decisions should require physician input to assess safety and appropriate level of care. This work contributes to an understanding of financial incentives of existing reimbursement policy and may guide future policy design towards high value care.

Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation.

OBJECTIVES: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA). METHODS: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm. CONCLUSION: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.

Metastatic Adrenocortical Carcinoma With Chromothripsis: A Case Report and Literature Review.

Metastatic adrenocortical carcinoma (ACC) often has a poor outcome, with a five-year survival of less than 25%. We report a rare case of metastatic ACC with a myxoid variant with chromothripsis. We review the histologic variants of ACC, including myxoid type, molecular drivers, and current and investigational therapies for adrenocortical carcinoma. We also discuss the mechanism of chromothripsis, chromothripsis in ACC tumorigenesis, and propose potential therapies targeting chromothripsis.