Metastatic malignant peripheral nerve sheath tumor of the uterus and cervix: Diagnostic Challenges, prognostic determinants and treatment.

•MPNST is an uncommon sarcoma of the nerve sheath that is rarely found in the female reproductive tract.•Preoperative uterine mass imaging should include pelvic MRI and thorough evaluation of imaging by an expert pelvic MRI radiologist.•Metastatic MPNST has a poor prognosis and systemic treatment options lack efficacy.

Healthcare Resource Utilization and Cost Associated with Allogeneic Hematopoietic Stem Cell Transplantation: A Scoping Review.

This scoping review summarizes the evidence regarding healthcare resource utilization (HRU) and costs associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study was conducted in accordance with the Joanne Briggs Institute methodology for scoping reviews. The PubMed, Embase, and Health Business Elite Electronic databases were searched, in addition to grey literature. The databases were searched from inception up to November 2022. Studies that reported HRU and/or costs associated with adult (≥18 years) allo-HSCT were eligible for inclusion. Two reviewers independently screened 20% of the sample at each of the 2 stages of screening (abstract and full text). Details of the HRU and costs extracted from the study data were summarized, based on the elements and timeframes reported. HRU measures and costs were combined across studies reporting results defined in a comparable manner. Monetary values were standardized to 2022 US Dollars (USD). We identified 43 studies that reported HRU, costs, or both for allo-HSCT. Of these studies, 93.0% reported on costs, 81.4% reported on HRU, and 74.4% reported on both. HRU measures and cost calculations, including the timeframe for which they were reported, were heterogeneous across the studies. Length of hospital stay was the most frequently reported HRU measure (76.7% of studies) and ranged from a median initial hospitalization of 10 days (reduced-intensity conditioning [RIC]) to 73 days (myeloablative conditioning). The total cost of an allo-HSCT ranged from $63,096 (RIC) to $782,190 (double umbilical cord blood transplantation) at 100 days and from $69,218 (RIC) to $637,193 at 1 year (not stratified). There is heterogeneity in the reporting of HRU and costs associated with allo-HSCT in the literature, making it difficult for clinicians, policymakers, and governments to draw definitive conclusions regarding the resources required for the delivery of these services. Nevertheless, to ensure that access to healthcare meets the necessary high cost and resource demands of allo-HSCT, it is imperative for clinicians, policymakers, and government officials to be aware of both the short- and long-term health resource requirements for this patient population. Further research is needed to understand the key determinants of HRU and costs associated with allo-HSCT to better inform the design and delivery of health care for HSCT recipients and ensure the quality, safety, and efficiency of care.

Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Use of Talimogene Laherparepvec to Treat Cutaneous Squamous Cell Carcinoma in a Renal Transplant Patient.

A 66-year-old female with a history of two renal transplants due to recurrent thrombotic thrombocytopenic purpura presented to clinic with multiple lesions identified to be non-metastatic cutaneous squamous cell carcinoma (CSCC). The patient previously underwent multiple Mohs procedures and radiation therapy treatment but continued to develop CSCC lesions with increasing frequency. After discussing multiple treatment options, it was elected to pursue treatment with Talimogene laherparepvec (T-VEC) given the systemic immune responses it can cause, with low theoretical risk of graft rejection. After starting intratumoral T-VEC injections, treated lesions began to decrease in size, and a reduction in the rate of new CSCC lesions was observed. Treatment was held due to unrelated renal complications during which time new CSCCs developed. Patient was restarted on T-VEC therapy with no recurrent renal issues. Upon reinitiating treatment, injected and non-injected lesions showed reduction in size, and the development of new lesions again ceased. One injected lesion was resected via Mohs micrographic surgery due to its size and discomfort. On sectioning, this demonstrated an exuberant lymphocytic perivascular infiltrate which was consistent with treatment response to T-VEC, with little active tumor. With high rates of non-melanoma skin cancer in renal transplant patients, their transplant status significantly limits treatment options, specifically with regards to anti-PD-1 therapy. This case suggests T-VEC can generate local and systemic immune responses in the setting of immunosuppression and that T-VEC may be a beneficial therapeutic option for transplant patients with CSCC.

Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents.

BACKGROUND: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia-reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. RESULTS: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. CONCLUSIONS: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

A Novel Approach to Delivering Evidence-based, High-quality Care in Psychiatry Through an Electronic Integrated Care Pathway (eICP) Pilot.

Integrated care pathways (ICPs) are evidence-based decision support tools intended to reduce variation and improve quality of care. Historically, adoption of ICPs has been difficult to measure, as the pathways were outside of the electronic health record (EHR), where care delivery documentation and orders were completed. This Technology Column describes the innovative development and implementation of a diagnosis specific electronic ICP that directly embeds pathway steps into an EHR to facilitate order sets, clinical decision-making, and usage tracking. The pathway was implemented at a seven-hospital academic medical center, and details the technology, team structure, early adoption results, and future directions. As such, the importance of investing and organizing resources to create an eICP (e.g., time, technology, and specialized teams) to provide a user-friendly experience to support early adoption is underscored. Preliminary findings show that the eICP had consistent use in the first year of implementation. This manuscript is intended to serve as a practical guide to build eICPs within behavioral health service areas across institutions.

ouR Space Commentary: Wellness Perspective From SABI's Early Career Committee.

ABSTRACT: Radiologists and members-in-training are experiencing higher (and escalating) rates of burnout, resulting in a profound impact on the health of physicians, patients, and the community. Lately, the radiology community has demonstrated a growing awareness of this phenomenon, which has led to emphasis on practicing and promoting wellness. With a myriad of factors contributing to burnout in radiology, a multifaceted approach is pivotal for counteracting burnout and fostering overall well-being, including efforts driven at both organizational and individual levels. This article discusses perspectives from the members of the Early Career Committee at the Society for Advanced Body Imaging (SABI); it explores their beliefs and practical strategies for maintaining personal well-being.

MR Imaging of the Ovaries: From Puberty to Menopause.

The ovary resides in the pelvic cavity and is a dynamic organ with physiologic changes from birth to menopause. The imaging features of the normal ovary depend on the physiologic changes through puberty, reproductive age, and menopause. It is important for radiologists to understand the imaging features of normal physiologic changes in the ovaries and differentiate them from disease states.

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit.

Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. The small population of surviving patients suffer extensive brain damage that results in substantial morbidity. Mitochondrial dysfunction in most organs after CA has been implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has shown promising results in the treatment for other diseases and is known to interact with the mitochondria. For the treatment of CA, prior studies have utilized metformin in a preconditioning manner such that animals are given metformin well before undergoing CA. As the timing of CA is quite difficult to predict, the present study, in a clinically relevant manner, sought to evaluate the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA (a) improves 72 h survival and neurologic function, (b) protects mitochondrial function with a reduction in apoptotic brain injury without activating AMPK, and (c) potentiates earlier normalization of brain electrophysiologic activity. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.

Comparison of Prostate Imaging and Reporting Data System V2.0 and V2.1 for Evaluation of Transition Zone Lesions: A 5-Reader 202-Patient Analysis.

OBJECTIVE: The aim of the study was to compare the distribution of Prostate Imaging and Reporting Data System (PI-RADS) scores, interreader agreement, and diagnostic performance of PI-RADS v2.0 and v2.1 for transition zone (TZ) lesions. METHODS: The study included 202 lesions in 202 patients who underwent 3T prostate magnetic resonance imaging showing a TZ lesion that was later biopsied with magnetic resonance imaging/ultrasound fusion. Five abdominal imaging faculty reviewed T2-weighted imaging and high b value/apparent diffusion coefficient images in 2 sessions. Cases were randomized using a crossover design whereby half in the first session were reviewed using v2.0 and the other half using v2.1, and vice versa for the 2nd session. Readers provided T2-weighted imaging and DWI scores, from which PI-RADS scores were derived. RESULTS: Interreader agreement for all PI-RADS scores had κ of 0.37 (v2.0) and 0.26 (v2.1). For 4 readers, the percentage of lesions retrospectively scored PI-RADS 1 increased greater than 5% and PI-RADS 2 score decreased greater than 5% from v2.0 to v2.1. For 2 readers, the percentage scored PI-RADS 3 decreased greater than 5% and, for 2 readers, increased greater than 5%. The percentage of PI-RADS 4 and 5 lesions changed less than 5% for all readers. For the 4 readers with increased frequency of PI-RADS 1 using v2.1, 4% to 16% were Gleason score ≥3 + 4 tumor. Frequency of Gleason score ≥3 + 4 in PI-RADS 3 lesions increased for 2 readers and decreased for 1 reader. Sensitivity of PI-RADS of 3 or greater for Gleason score ≥3 + 4 ranged 76% to 90% (v2.0) and 69% to 96% (v2.1). Specificity ranged 32% to 64% (v2.0) and 25% to 72% (v2.1). Positive predictive value ranged 43% to 55% (v2.0) and 41% to 58% (v2.1). Negative predictive value ranged 82% to 87% (v2.0) and 81% to 91% (v2.1). CONCLUSIONS: Poor interreader agreement and lack of improvement in diagnostic performance indicate an ongoing need to refine evaluation of TZ lesions.

Elucidation of Sequence-Function Relationships for an Improved Biobutanol In Vivo Biosensor in E. coli.

Transcription factor (TF)-promoter pairs have been repurposed from native hosts to provide tools to measure intracellular biochemical production titer and dynamically control gene expression. Most often, native TF-promoter systems require rigorous screening to obtain desirable characteristics optimized for biotechnological applications. High-throughput techniques may provide a rational and less labor-intensive strategy to engineer user-defined TF-promoter pairs using fluorescence-activated cell sorting and deep sequencing methods (sort-seq). Based on the designed promoter library's distribution characteristics, we elucidate sequence-function interactions between the TF and DNA. In this work, we use the sort-seq method to study the sequence-function relationship of a σ54-dependent, butanol-responsive TF-promoter pair, BmoR-PBMO derived from Thauera butanivorans, at the nucleotide level to improve biosensor characteristics, specifically an improved dynamic range. Activities of promoters from a mutagenized PBMO library were sorted based on gfp expression and subsequently deep sequenced to correlate site-specific sequences with changes in dynamic range. We identified site-specific mutations that increase the sensor output. Double mutant and a single mutant, CA(129,130)TC and G(205)A, in PBMO promoter increased dynamic ranges of 4-fold and 1.65-fold compared with the native system, respectively. In addition, sort-seq identified essential sites required for the proper function of the σ54-dependent promoter biosensor in the context of the host. This work can enable high-throughput screening methods for strain development.

Algorithmic Approach to the Splenic Lesion Based on Radiologic-Pathologic Correlation.

Splenic lesions are commonly discovered incidentally at imaging, without clinical signs or symptoms that may aid in diagnosis. As such, the differential diagnosis and subsequent management are based primarily on imaging characteristics. Much has been written about the myriad pathologic conditions that can occur in the spleen; however, there is little guidance on the approach to an incidental splenic mass. Applying an approach frequently used in imaging to the splenic mass-based on the number and consistency of lesions and refined by supplementary imaging features-allows formulation of a useful differential diagnosis. Solitary cystic masses include true cysts, pseudocysts, and parasitic cysts. When multiple cystic lesions are present, the differential diagnosis expands to include infectious lesions (abscess or microabscesses) and lymphangioma (a benign cystic neoplasm). Hemangioma is the most common solitary solid mass, although other vascular lesions (hamartoma, sclerosing angiomatoid nodular transformation) and nonvascular lesions (inflammatory pseudotumor, lymphoma) manifest as solitary and solid. When multiple solid masses are present, diffuse inflammatory disease (sarcoidosis), littoral cell angioma, and lymphoma should be considered. Malignancies, such as angiosarcoma or metastasis, can manifest as solitary or multiple and solid or cystic masses but are typically associated with symptoms or widespread primary malignancy. Careful assessment of the multimodality imaging characteristics of splenic lesions based on this approach aids the radiologist faced with the incidental splenic lesion. Online supplemental material is available for this article. Work of the U.S. Government published under an exclusive license with the RSNA.

The acceptability of a novel procedure service run by PAs and NPs.

BACKGROUND: Hospitalist physicians are performing fewer procedures because of multiple reasons, including expanded responsibilities beyond their patient panel. A procedure service that offloads hospitalists could expedite these necessary services. An opportunity exists for physician assistants (PAs) and NPs to fill this gap. OBJECTIVE: To describe the implementation of a PA- and NP-run procedure service at a large academic hospital. METHODS: This is a retrospective cohort study of procedures by the procedure service at one institution from 2015 to 2019. RESULTS: Over 5 years, 7,002 procedures were performed, with requests increasing over time. The most frequent procedures were venous access, lumbar puncture, paracentesis, and placement of nasogastric or nasojejunal tubes. Requesting services included hospitalists and residents from internal medicine, surgery, and neurology. CONCLUSIONS: A PA- and NP-run procedure service is well accepted at a large academic hospital despite the lack of involvement by attending physicians. Future directions are focused on augmenting coverage and procedures offered.

Increased plasma disequilibrium between pro- and anti-oxidants during the early phase resuscitation after cardiac arrest is associated with increased levels of oxidative stress end-products.

BACKGROUND: Cardiac arrest (CA) results in loss of blood circulation to all tissues leading to oxygen and metabolite dysfunction. Return of blood flow and oxygen during resuscitative efforts is the beginning of reperfusion injury and is marked by the generation of reactive oxygen species (ROS) that can directly damage tissues. The plasma serves as a reservoir and transportation medium for oxygen and metabolites critical for survival as well as ROS that are generated. However, the complicated interplay among various ROS species and antioxidant counterparts, particularly after CA, in the plasma have not been evaluated. In this study, we assessed the equilibrium between pro- and anti-oxidants within the plasma to assess the oxidative status of plasma post-CA. METHODS: In male Sprague-Dawley rats, 10 min asphyxial-CA was induced followed by cardiopulmonary resuscitation (CPR). Plasma was drawn immediately after achieving return of spontaneous circulation (ROSC) and after 2 h post-ROSC. Plasma was isolated and analyzed for prooxidant capacity (Amplex Red and dihydroethidium oxidation, total nitrate and nitrite concentration, xanthine oxidase activity, and iron concentration) and antioxidant capacity (catalase and superoxide dismutase activities, Total Antioxidant Capacity, and Iron Reducing Antioxidant Power Assay). The consequent oxidative products, such as 4-Hydroxyl-2-noneal, malondialdehyde, protein carbonyl, and nitrotyrosine were evaluated to determine the degree of oxidative damage. RESULTS: After CA and resuscitation, two trends were observed: (1) plasma prooxidant capacity was lower during ischemia, but rapidly increased post-ROSC as compared to control, and (2) plasma antioxidant capacity was increased during ischemia, but either decreased or did not increase substantially post-ROSC as compared to control. Consequently, oxidation products were increased post-ROSC. CONCLUSION: Our study evaluated the disbalance of pro- and anti-oxidants after CA in the plasma during the early phase after resuscitation. This disequilibrium favors the prooxidants and is associated with increased levels of downstream oxidative stress-induced end-products, which the body's antioxidant capacity is unable to directly mitigate. Here, we suggest that circulating plasma is a major contributor to oxidative stress post-CA and its management requires substantial early intervention for favorable outcomes.

Racial disparities in the SOFA score among patients hospitalized with COVID-19.

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic. RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients? STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first admission with COVID-19, if they did not have SOFA score recorded within 24 hours of admission, if race and ethnicity data were not Non-Hispanic Black, Non-Hispanic White, or Hispanic, or if they had other missing data. The primary outcome was SOFA score, with peak score within 24 hours of admission dichotomized as <6 or ≥6. RESULTS: Of 2982 patients admitted with COVID-19, 2320 met inclusion criteria and were analyzed, of whom 1058 (45.6%) were Non-Hispanic White, 645 (27.8%) were Hispanic, and 617 (26.6%) were Non-Hispanic Black. Median age was 65.0 and 1226 (52.8%) were female. In univariate logistic screen and in full multivariate model, Non-Hispanic Black patients but not Hispanic patients had greater odds of an elevated SOFA score ≥6 when compared to Non-Hispanic White patients (OR 1.49, 95%CI 1.11-1.99). INTERPRETATION: Given current unequal patterns in social determinants of health, US crisis standards of care utilizing the SOFA score to allocate medical resources would be more likely to deny these resources to Non-Hispanic Black patients.

The potential impact of triage protocols on racial disparities in clinical outcomes among COVID-positive patients in a large academic healthcare system.

BACKGROUND: The COVID-19 pandemic has had a devastating impact in the United States, particularly for Black populations, and has heavily burdened the healthcare system. Hospitals have created protocols to allocate limited resources, but there is concern that these protocols will exacerbate disparities. The sequential organ failure assessment (SOFA) score is a tool often used in triage protocols. In these protocols, patients with higher SOFA scores are denied resources based on the assumption that they have worse clinical outcomes. The purpose of this study was to assess whether using SOFA score as a triage tool among COVID-positive patients would exacerbate racial disparities in clinical outcomes. METHODS: We analyzed data from a retrospective cohort of hospitalized COVID-positive patients in the Yale-New Haven Health System. We examined associations between race/ethnicity and peak overall/24-hour SOFA score, in-hospital mortality, and ICU admission. Other predictors of interest were age, sex, primary language, and insurance status. We used one-way ANOVA and chi-square tests to assess differences in SOFA score across racial/ethnic groups and linear and logistic regression to assess differences in clinical outcomes by sociodemographic characteristics. RESULTS: Our final sample included 2,554 patients. Black patients had higher SOFA scores compared to patients of other races. However, Black patients did not have significantly greater in-hospital mortality or ICU admission compared to patients of other races. CONCLUSION: While Black patients in this sample of hospitalized COVID-positive patients had higher SOFA scores compared to patients of other races, this did not translate to higher in-hospital mortality or ICU admission. Results demonstrate that if SOFA score had been used to allocate care, Black COVID patients would have been denied care despite having similar clinical outcomes to white patients. Therefore, using SOFA score to allocate resources has the potential to exacerbate racial inequities by disproportionately denying care to Black patients and should not be used to determine access to care. Healthcare systems must develop and use COVID-19 triage protocols that prioritize equity.

Understanding physiologic phospholipid maintenance in the context of brain mitochondrial phospholipid alterations after cardiac arrest.

Cardiac arrest (CA) induces whole-body ischemia resulting in mitochondrial dysfunction. We used isolated mitochondria to examine phospholipid alterations in the brain, heart, kidney, and liver post-CA. Our data shows that ischemia/reperfusion most significantly alters brain mitochondria phospholipids, predominately after resuscitation. Furthermore, the alterations do not appear to be a function of dysregulated importation of phospholipids, but caused by impaired intra-mitochondrial synthesis and/or remodeling of phospholipids. Our data demonstrates only brain mitochondria undergo significant alterations in phospholipids, providing a rationale for the high vulnerability of the brain to ischemia/reperfusion. Furthermore, analyzing this pathophysiologic state provides insight into physiologic mitochondrial phospholipid metabolism.