MRI, clinical, and radiomic models for differentiation of uterine leiomyosarcoma and leiomyoma.

PURPOSE: To assess the predictive ability of conventional MRI features and MRI texture features in differentiating uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS). METHODS: This single-center, IRB-approved, HIPAA-compliant retrospective study included 108 patients (69 LM, 39 LMS) who had pathology, preoperative MRI, and clinical data available at our tertiary academic institution. Two radiologists independently evaluated 14 features on preoperative MRI. Texture features based on 3D segmentation were extracted from T2W-weighted MRI (T2WI) using commercially available texture software (TexRAD™, Feedback Medical Ltd., Great Britain). MRI conventional features, and clinical and MRI texture features were compared between LM and LMS groups. Dataset was randomly divided into training (86 cases) and testing (22 cases) cohorts (8:2 ratio); training cohort was further subdivided into training and validation sets using ten-fold cross-validation. Optimal radiomics model was selected out of 90 different machine learning pipelines and five models containing different combinations of MRI, clinical, and radiomics variables. RESULTS: 12/14 MRI conventional features and 2/2 clinical features were significantly different between LM and LMS groups. MRI conventional features had moderate to excellent inter-reader agreement for all but two features. Models combining MRI conventional and clinical features (AUC 0.956) and MRI conventional, clinical, and radiomics features (AUC 0.989) had better performance compared to models containing MRI conventional features alone (AUC 0.846 and 0.890) or radiomics features alone (0.929). CONCLUSION: While multiple MRI and clinical features differed between LM and LMS groups, the model combining MRI, clinical, and radiomic features had the best predictive ability but was only marginally better than a model utilizing conventional MRI and clinical data alone.

Performance of VI-RADS in predicting muscle-invasive bladder cancer after transurethral resection: a single center retrospective analysis.

PURPOSE: To assess VIRADS performance and inter-reader agreement for detecting muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumor (TURBT). METHODS: An IRB-approved, HIPAA-compliant, retrospective study from 2016 to 2020 included patients with bladder urothelial carcinoma who underwent MRI after TURBT, and cystectomy within 3 months without post-MRI treatments. Three radiologists blinded to pathology results independently reviewed MR images and assigned a VI-RADS score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI-RADS were assessed for diagnosing MIBC using VI-RADS scores ≥ 3 and ≥ 4. Inter-reader agreement was assessed using Gwet's agreement coefficient (AC) and percent agreement. RESULTS: The cohort consisted of 70 patients (mean age, 68 years ± 11 [SD]; range 39-85; 58 men) and included 32/70 (46%) with MIBC at cystectomy. ROC analysis revealed an AUC ranging from 0.67 to 0.77 and no pairwise statistical difference between readers (p-values, 0.06, 0.08, 0.97). Percent sensitivity, specificity, PPV, NPV and accuracy for diagnosing MIBC for the three readers ranged from 81.3-93.8, 36.8-55.3, 55.6-60.5, 77.3-87.5, and 62.9-67.1 respectively for VI-RADS score ≥ 3, and 78.1-81.3, 47.4-68.4, 55.6-67.6, 72.0-78.8 and 61.4-72.9 respectively for VI-RADS score ≥ 4. Gwet's AC was 0.63 [95% confidence interval (CI): 0.49,0.78] for VI-RADS score ≥ 3 with 79% agreement [95% CI 72,87] and 0.54 [95%CI 0.38,0.70] for VI-RADS score ≥ 4 with 76% agreement [95% CI 69,84]. VIRADS performance was not statistically different among 31/70 (44%) patients who received treatments prior to MRI (p ≥ 0.16). CONCLUSION: VI-RADS had moderate sensitivity and accuracy but low specificity for detection of MIBC following TURBT, with moderate inter-reader agreement.

Interreader Agreement and Intermodality Concordance of O-RADS US and MRI for Assessing Large, Complex Ovarian-Adnexal Cysts.

Purpose To assess interreader agreement of the Ovarian-Adnexal Reporting and Data System (O-RADS) and intermodality concordance between US and MRI for characterizing complex adnexal cysts measuring 5 cm or larger. Materials and Methods This retrospective study included 58 "complex cysts" measuring at least 5 cm in size observed at both US and MRI in 54 women (median age, 37 years ± 12 [SD]; seven postmenopausal women) between July 2017 and June 2020, identified from an electronic US database. A separate set of two blinded radiologists independently reviewed the US or MR images to assign the O-RADS category, and an adjudicator resolved discrepancies (a total of six readers). Lesion outcome (49 benign, eight malignant, one lost to follow-up) was recorded. Interreader agreement of O-RADS US and O-RADS MRI and concordance between US and MRI were analyzed. Results Interreader agreement was fair for US (κ = 0.31), moderate for MRI (κ = 0.43), and moderate between US and MRI (κ = 0.58). A significant positive correlation was found between O-RADS US and MRI (τ = 0.72, P < .001). The O-RADS 4 threshold yielded the highest accuracy for both US and MRI (area under the receiver operating characteristic curve = 0.92 and 0.995, respectively). Considering O-RADS US 4 or 5 as potentially malignant and 1-3 as benign, eight lesions that were assessed as potentially malignant at US were correctly downgraded to benign by using findings at MRI. Using findings at MRI, one malignant lesion that was assessed as benign at US was upgraded to potentially malignant. Conclusion O-RADS US and MRI had excellent performance and positive correlation, but significant interobserver variability remains. Keywords: Ovary, MR Imaging, Ultrasonography © RSNA, 2022 See also the commentary by Baumgarten in this issue.

Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma.

The mutant IDH1 inhibitor ivosidenib improves outcomes for patients with IDH1-mutated cholangiocarcinoma, but resistance inevitably develops. Mechanisms of resistance and strategies to overcome resistance are poorly understood. Here we describe two patients with IDH1 R132C-mutated metastatic cholangiocarcinoma who developed acquired resistance to ivosidenib. After disease progression, one patient developed an oncogenic IDH2 mutation, and the second patient acquired a secondary IDH1 D279N mutation. To characterize the putative IDH1 resistance mutation, cells expressing the double-mutant were generated. In vitro, IDH1 R132H/D279N produces (R)-2HG less efficiently than IDH1 R132H. However, its binding to ivosidenib is impaired and it retains the ability to produce (R)-2HG and promote cellular transformation in the presence of ivosidenib. The irreversible mutant IDH1 inhibitor LY3410738 binds and blocks (R)-2HG production and cellular transformation by IDH1 R132H/D279N. These resistance mechanisms suggest that IDH1-mutated cholangiocarcinomas remain dependent on (R)-2HG even after prolonged ivosidenib treatment. Sequential mutant IDH inhibitor therapy should be explored as a strategy to overcome acquired resistance to mutant IDH inhibitors.

Perceptions of a virtual interview process for pharmacy residents during the COVID-19 pandemic: A multisite survey of residency candidates, preceptors, and residency program directors.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions. METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods. RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews. CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

Burnout Among Pharmacy Preceptors in Northern California.

Objective. The objectives of this study were to investigate the incidence of burnout syndrome among pharmacy preceptors and to identify predictors for the development of burnout in this population.Methods. This cross-sectional survey study examined burnout syndrome among pharmacy preceptors in Northern California. Preceptors were included if they self-identified as a preceptor to advanced pharmacy practice experience (APPE) students or to postgraduate pharmacy residents in their first year of residency. Burnout was assessed using the Maslach Burnout Inventory Human Services Survey, and preceptors were classified as having burnout syndrome if they scored high on emotional exhaustion and also either scored high on depersonalization or scored low on personal accomplishment. Additionally, respondents' demographics, workplace environment, workload, and day-to-day workflow were queried to help determine predictors of burnout syndrome among this population.Result. The study included 113 pharmacy preceptors. Of the preceptors, 22% reported scores consistent with burnout, with 57% of preceptors scoring positive for burnout in one of the three burnout criteria. On multivariate regression analysis, two independent risk factors for burnout syndrome were identified: preceptors who precepted many difficult or unmotivated learners per year and preceptors who did not feel their contributions as preceptors were appreciated by their institution.Conclusion. The rate of burnout among pharmacy preceptors is high, with preceptors exhibiting high emotional exhaustion and low levels of personal accomplishment. Predictors of burnout syndrome for this population appear to be precepting many difficult or unmotivated learners and not feeling that one's contributions as a preceptor are appreciated.

A measuring technique for intra-osseous pressure.

OBJECTIVE: Pulsatile intra-osseous pressures result in bone remodeling, and therefore may affect lesion growth and response to treatment. However, there is no known method used to measure intra-osseous pressures. The purpose of this study is to describe a novel image-guided technique for measuring intra-osseous pressures. MATERIALS AND METHODS: This study was IRB-approved and HIPAA compliant. Written informed consent was obtained. Intra-osseous pressure measurements were performed during a CT-guided bone marrow biopsy in eight patients (6 male, 2 female) with mean age 66 ± 13 years (median 72, range 45-87) and suspected or known bone marrow disease. Bone marrow pressure measurements were obtained connecting the biopsy needle to a dedicated monitor using a standard arterial line setup. Monitor data was collected at 5-s intervals in order to record continuous pressure measurements for 2 min. RESULTS: Pressure measurements were successfully performed in all 8 patients. The mean bone marrow pressures were 36.8 ± 7.2 mmHg (median 37.7, range 24.7-47.4). The peak and trough pressures varied by 11%, and the standard deviation of mean pressure measurement varied by 18%. Our findings for marrow pressure measures most closely approximate the pressure profile of the venous system. CONCLUSION: We describe a novel and minimally invasive technique able to provide functional data of bone marrow. This technique has the potential to provide insights into normal and diseased bone marrow and may be helpful to evaluate features of cystic and vascular tumors that may be amenable to percutaneous treatments.

High-fidelity simulation increases pharmacy resident perceived competence during medical emergencies.

INTRODUCTION: Our objective was to assess postgraduate year one (PGY1) pharmacy resident perceived competence during medical emergencies before and after implementation of a longitudinal simulation training curriculum. METHODS: At the University of California San Francisco (UCSF) Medical Center, PGY1 pharmacy residents serve as primary code team responders for code blue, code sepsis, and code stroke, among other medical emergencies. In 2015, the UCSF Residency Training Program implemented a longitudinal simulation curriculum for PGY1 pharmacy residents. Throughout the residency year, residents participated in four simulation lab sessions that addressed various medical emergencies. To assess the impact that the simulation curriculum had on resident perceived competence during medical emergencies, a 19-question survey (13 clinical questions and six control questions) was distributed to the residents at the end of the residency year. Resident responses from the 2015 to 2016 and 2016 to 2017 surveys were compared to a control residency class from 2014 to 2015 who did not undergo the simulation curriculum. RESULTS: Simulation-trained PGY1 pharmacy residents reported significantly greater perceived competence in five of the twelve medical emergency scenarios (acute coronary syndromes, symptomatic bradycardia, supraventricular tachycardia, ventricular tachycardia, and cardiac arrest) as compared to non-simulation-trained controls. In addition, the PGY1 pharmacy residents felt that their performance as a clinical pharmacist would significantly improve as a result of the simulation curriculum. CONCLUSIONS: Incorporation of a longitudinal simulation curriculum into PGY1 pharmacy resident training can positively impact resident self-reported competence when performing essential pharmacist functions during medical emergencies.

Vitamin C in surgical sepsis.

PURPOSE OF REVIEW: The current review discusses the supplemental use of vitamin C as an adjunct in the management of sepsis and septic shock. RECENT FINDINGS: The antioxidant properties of vitamin C are touted to be useful in modulating the inflammatory response, decreasing vasopressor requirements, and improving resuscitation. Current resuscitation practices are focused on addressing the hemodynamic instability and ensuring adequate oxygen delivery to tissues. The conceptual framework of the use of vitamin C during a resuscitation is to modulate in a beneficial fashion the inflammatory response to sepsis while concomitantly resuscitating and treating the infection. While there is promising animal and burn-related data on improved fluid resuscitation with the use of vitamin C as an adjunct, the most recent meta-analyses of the available data fail to show a survival benefit in sepsis, and concerns regarding nephrotoxicity remain. SUMMARY: Although there are large number of animal studies, only a few small prospective and retrospective studies in humans address the use of vitamin C to treat sepsis. Further research in a controlled and randomized fashion is needed to determine if vitamin C is effective in this role. While there is a promise of ascorbate's addition to the sepsis bundle as an adjunct to resuscitation, the evidence is not conclusive.

Clinical, radiological, and pathological features of extraskeletal osteosarcoma.

OBJECTIVE: To evaluate clinical and radiological features of pathology-proven extraskeletal osteosarcomas. METHODS: This retrospective study was IRB-approved and HIPAA-compliant. Our pathology database was queried for cases of extraskeletal osteosarcoma. Tumor location, size, imaging appearance, presence of metastases, and clinical outcome were documented. RESULTS: Nineteen patients met inclusion criteria (age 59 ± 15 (range 28-85) years; 15 male, 4 female). Tumors occurred in the lower extremities (12 out of 19, 63%), pelvis/gluteal region (3 out of 19, 16%), upper extremity (2 out of 19, 5%), thorax (1 out of 19, 5%), and neck (1 out of 19, 5%). Two out of 19 (11%) patients had undergone radiation to the tumor site previously. According to pathology, 16 out of 19 tumors were high-grade (84%). Tumors presented as soft-tissue masses measuring 9.5 ± 6.8 (2-29) cm. Tumor mineralization was present in 5 out of 19 cases (26%) and local invasion was found in 1 out of 19 cases (6%). On MRI, tumors typically appeared hyperintense on T2-weighted sequences with enhancement in 15 out of 15 (100%) contrast-enhanced studies, and with central necrosis in 10 out of 19 (53%) cases. Low-grade tumors were smaller (<4 cm; 3 out of 3, 100%) and lacked central necrosis (3 out of 3, 100%). 8 out of 19 patients (42%) had metastases, most commonly to the lung (7 out of 19, 37%) and bone (2 out of 19,11%). Two out of 8 patients (25%) with metastases and 8 out of 11 (73%) without metastases achieved recurrence-free survival (mean follow-up 3.8 ± 4.0 [0.2-14.2]) years. No metastases or deaths occurred in patients with low-grade histology. CONCLUSIONS: Extraskeletal osteosarcomas are rare, typically high-grade malignancies that commonly metastasize to lung and bones. Low-grade tumors and those without metastases have a good prognosis. MRI appearance is nonspecific, with T2 hyperintense signal and heterogeneous enhancement. Unlike conventional osteosarcoma, mineralization is rare.

Major publications in the critical care pharmacotherapy literature: January-December 2016.

PURPOSE: To summarize select critical care pharmacotherapy guidelines and studies published in 2016. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 31 journals monthly for relevant pharmacotherapy articles and selected 107 articles for review over the course of 2016. Of those included in the monthly CCPLU, three guidelines and seven primary literature studies are reviewed here. The guideline updates included are as follows: hospital-acquired pneumonia and ventilator-associated pneumonia management, sustained neuromuscular blocking agent use, and reversal of antithrombotics in intracranial hemorrhage (ICH). The primary literature summaries evaluate the following: dexmedetomidine for delirium prevention in post-cardiac surgery, dexmedetomidine for delirium management in mechanically ventilated patients, high-dose epoetin alfa after out-of-hospital cardiac arrest, ideal blood pressure targets in ICH, hydrocortisone in severe sepsis, procalcitonin-guided antibiotic de-escalation, and empiric micafungin therapy. CONCLUSION: The review provides a synopsis of select pharmacotherapy publications in 2016 applicable to clinical practice.

Demographic confounders in volumetric MRI analysis: is the posterior fossa really small in the adult Chiari 1 malformation?

OBJECTIVE: Measurement of posterior fossa volume has been proposed to have diagnostic utility and physiologic significance in the Chiari malformation type 1. This study evaluated the effects of demographics on posterior fossa volume and total intracranial volume in adult control subjects, adult patients with Chiari malformation type 1, and adult patients with idiopathic intracranial hypertension, who may share some imaging features of patients with Chiari malformation type 1. MATERIALS AND METHODS: Twenty-eight patients with Chiari malformation type 1, 21 patients with idiopathic intracranial hypertension, and 113 control subjects underwent brain MRI including contrast-enhanced 3D gradient-recalled echo (GRE) T1-weighted imaging. Linear measurements of the posterior fossa and intracranial space were obtained. Manual segmentation of the posterior fossa and intracranial space was performed to yield posterior fossa volume and total intracranial volume. Age, sex, race, and body mass index (weight in kilograms divided by the square of height in meters; BMI) were controlled for when comparing cohorts. RESULTS: Three of the 12 linear measurements significantly predicted total intracranial volume (accounting for 74% of variance), and four predicted posterior fossa volume (54% of variance). Age, race, sex, and BMI each statistically significantly influenced posterior fossa volume and total intracranial volume. No statistically significant differences in posterior fossa volume, total intracranial volume, or ratio of posterior fossa volume to total intracranial volume were seen between the Chiari malformation type 1 group and control group after controlling for demographics. Patients with idiopathic intracranial hypertension were more likely than control subjects to have smaller posterior fossa volumes (odds ratio [OR]=1.81; p=0.01) and larger total intracranial volumes (OR=1.24; p=0.06). CONCLUSION: Linear measurements of the posterior fossa are not strong predictors of posterior fossa volume. Age, race, sex, and BMI have statistically significant effects on intracranial measurements that must be considered, particularly with respect to posterior fossa volume in Chiari malformation type 1. Even when these demographic variables are appropriately accounted for, other similarly presenting diseases may show small posterior fossa volumes.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

OBJECTIVE: Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. MATERIALS AND METHODS: Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. RESULTS: Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). CONCLUSION: Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.