Analysis of treatment sequence and outcomes in patients with relapsed malignant peripheral nerve sheath tumors.

Background: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas originating from cellular components within the nerve sheath. The incidence of MPNST is highest in people with neurofibromatosis type 1 (NF1), and MPNST is the leading cause of death for these individuals. Complete surgical resection is the only curative therapeutic option, but is often unfeasible due to tumor location, size, or presence of metastases. Evidence-based choices of chemotherapy for recurrent/refractory MPNST remain elusive. To address this gap, we conducted a retrospective analysis of our institutional experience in treating patients with relapsed MPNST in order to describe patient outcomes related to salvage regimens. Methods: We conducted a retrospective electronic health record analysis of patients with MPNST who were treated at Johns Hopkins Hospital from January 2010 to June 2021. We calculated time to progression (TTP) based on salvage chemotherapy regimens. Results: Sixty-five patients were included in the analysis. Upfront therapy included single or combined modalities of surgery, chemotherapy, or radiotherapy. Forty-eight patients received at least 1 line of chemotherapy, which included 23 different regimens (excluding active clinical studies). Most patients (n = 42, 87.5%) received a combination of doxorubicin, ifosfamide, or etoposide as first-line chemotherapy. Salvage chemotherapy regimens and their TTP varied greatly, with irinotecan/temozolomide-based regimens having the longest average TTP (255.5 days, among 4 patients). Conclusions: Patients with advanced or metastatic MPNST often succumb to their disease despite multiple lines of therapy. These data may be used as comparative information in decision-making for future patients and clinical trials.

Impact of Donor Milk on Short- and Long-Term Growth of Very Low Birth Weight Infants.

Mother's own milk (MOM) reduces the risk of morbidities in very low birth weight (VLBW) infants. When MOM is unavailable, donor breastmilk (DM) is used, with unclear impact on short- and long-term growth. This retrospective analysis compared anthropometric data at six time points from birth to 20⁻24 months corrected age in VLBW infants who received MOM supplements of preterm formula (n = 160) versus fortified DM (n = 161) during neonatal intensive care unit (NICU) hospitalization. The cohort was 46% female; mean birth weight and gestational age (GA) were 998 g and 27.3 weeks. Multilevel linear growth models assessed changes in growth z-scores short-term (to NICU discharge) and long-term (post-discharge), controlling for amount of DM or formula received in first 28 days of life, NICU length of stay (LOS), birth GA, and sex. Z-scores for weight and length decreased during hospitalization but increased for all parameters including head circumference post-discharge. Short-term growth was positively associated with LOS and birth GA. A higher preterm formula proportion, but not DM proportion, was associated with slower rates of decline in short-term growth trajectories, but feeding type was unrelated to long-term growth. In conclusion, controlling for total human milk fed, DM did not affect short- or long-term growth.

Detection of femoroplasty on pre- and post-arthroscopic comparison radiographs following treatment of femoroacetabular impingement syndrome: multi-reader accuracy and agreement study.

OBJECTIVE: To assess diagnostic accuracy and agreement among radiologists in detecting femoroplasty on pre- and post-arthroscopic comparison frog lateral and anteroposterior (AP) pelvic radiographs after treatment of femoroacetabular impingement (FAI) syndrome. MATERIALS AND METHODS: In this retrospective, cross-sectional study, 86 patients underwent hip arthroscopy (52 with and 34 without femoroplasty) for treatment of FAI syndrome. Three radiologists blinded to clinical data and chronological order of the pre- and post-arthroscopic comparison radiographs independently examined AP pelvis and frog lateral radiographs to detect femoroplasty changes. Statistical analysis outputs included diagnostic accuracy parameters and inter- and intra-observer agreement. RESULTS: Identification of femoroplasty in the frog lateral projection has mean sensitivity 70%, specificity 82%, inter-observer agreement κ 0.74-0.76 and intra-observer agreement κ 0.72-0.85. Using the AP pelvis projection to detect femoroplasty has mean sensitivity 32%, specificity 71%, inter-observer agreement κ 0.47-0.65, and intra-observer agreement κ, 0.56-0.84. CONCLUSIONS: Radiologists are only moderately sensitive, though more specific, in femoroplasty detection in the frog lateral projection. The AP pelvis projection yields lower sensitivity and specificity. Both projections have moderate inter- and intra-observer agreement.

A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers.

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused into healthy randomized subjects. The mean ± SD 24-hour RBC recovery was 77.9% ± 3.3% and 72.7% ± 10.5% for Groups 1A and 2A, respectively. The mean ± SD RBC life span was 84.3 ± 8.3 days in Group 1A and 88.9 ± 6.2 days in Group 2A. The PK phase actual DSP loading doses (mean ± SEM) were 4.2 ± 0.27 mg and 16.9 ± 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be detected until 35 days after the single intravenous infusion in Group 2B. The mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to the 24-hour recovery of regulated RBC products intended for transfusion. There was a minimal but acceptable adverse impact on the survival of EDS-processed RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained dose of dexamethasone in vivo.

An Audio/Video Reporting Workflow to Supplement Standardized Radiology Reports.

Radiology studies are inherently visual and the information contained within is best conveyed by visual methodology. Advanced reporting software allows the incorporation of annotated key images into text reports, but such features may be less effective compared with in-person consultations. The use of web technology and screen capture software to create retrievable on-demand audio/visual reports has not yet been investigated. This approach may preempt potential curbside consultations while providing referring clinicians with a more engaged imaging service. In this work, we develop and evaluate a video reporting tool that utilizes modern screen capture software and web technology. We hypothesize that referring clinicians would find that recorded on-demand video reports add value to clinical practice, education, and that such technology would be welcome in future practice. A total of 45 case videos were prepared by radiologists for 14 attending and 15 trainee physicians from emergency and internal medicine specialties. Positive survey feedback from referring clinicians about the video reporting system was statistically significant in all areas measured, including video quality, clinical helpfulness, and willingness to use such technology in the future. Trainees unanimously found educational value in video reporting. These results suggest the potential for video technology to re-establish the radiologist's role as a pivotal member of patient care and integral clinical educator. Future work is needed to streamline these methods in order to minimize work redundancy with traditional text reporting. Additionally, integration with an existing PACS and dictation system will be essential to ensuring ease of use and widespread adoption.

The bioequivalence of frozen plasma prepared from whole blood held overnight at room temperature compared to fresh-frozen plasma prepared within eight hours of collection.

BACKGROUND: Overnight, room temperature hold of whole blood (WB) before leukoreduction and component processing offers significant logistic and cost advantages over WB processed within 8 hours. Plasma prepared from WB held at room temperature overnight (PF24RT24WB) may result in a degradation of plasma coagulation protein activities compared to plasma frozen within 8 hours of collection. In this study, we intended to evaluate the bioequivalence (BE) of PF24RT24WB prepared using a new WB collection, leukoreduction, and storage system compared to fresh-frozen plasma (FFP) after 12 months of frozen storage. STUDY DESIGN AND METHODS: We conducted a three-center, three-arm evaluation of the LEUKOSEP HWB-600-XL test system (Hemerus Medical LLC) compared to the RZ2000 control (Fenwal, Inc.). FFP was prepared from WB held at room temperature more than 6 hours and placed at less than -18 °C by 8 hours for control (n = 60) and test (n = 60) arms. PF24RT24WB (n = 60) was prepared with the test system from WB held at room temperature and then filtered and processed 20 to 24 hours postcollection. Frozen plasma was tested at 3, 6, and 12 months using a comprehensive panel of protein and coagulation factor assays. RESULTS: The test FFP was BE for all coagulation factors and tested proteins at 12 months. As expected, PF24RT24WB had a reduced Factor (F)VIII activity compared to control FFP (87.1%; 90% confidence interval, 79.4%-93.3%) with the lower confidence limit less than 80%. All other factors were within the BE region. CONCLUSION: Leukoreduced FFP and PF24RT24WB prepared using the LEUKOSEP HWB-600-XL system has been shown to be BE to control leukoreduced FFP with an expected decrease in FVIII activity after overnight hold.

Additive solution-7 reduces the red blood cell cold storage lesion.

BACKGROUND: Transfusion of long-stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC "storage lesion" is a major challenge in transfusion medicine. Additive solution-7 (AS-7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity. STUDY DESIGN AND METHODS: Storage quality in AS-7 was measured in a prospective, randomized, three-center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS-7 (n = 120) or for 42 days in the control solution AS-1 (n = 60). RESULTS: Hemolysis and shedding of protein-containing microvesicles were significantly reduced in RBCs stored in AS-7 for 42 and 56 days compared with RBCs stored in AS-1. Autologous in vivo recoveries of RBCs stored in AS-7 was 88 ± 5% at 42 days (n = 27) and 82 ± 3% at 56 days (n = 27), exceeding recoveries of RBCs stored in currently used solutions. CONCLUSION: Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS-7 ameliorates the long-term storage lesion resulting in significantly increased viability in vitro and in vivo.

Autopage and the use of computer scripts to automate microtasks.

Paging referring clinicians with imaging results is a frequently repeated "microtask" performed by practicing radiologists. Many institutions use online alpha-paging systems to provide this integral part of safe and efficient patient care. Although sending an alpha-page can often be accomplished within one minute, current tools may disrupt workflow by distracting users with a series of tedious mouse clicks. We describe the development, evaluation, and updates of a portable tool that sends alpha-pages to referring clinicians using two keystrokes. This software integrates study information obtained from the Picture Archiving and Communication System (PACS) with an existing hospital paging system.

A randomized controlled trial evaluating recovery and survival of 6% dimethyl sulfoxide-frozen autologous platelets in healthy volunteers.

BACKGROUND: Availability of platelets (PLTs) is severely limited by shelf life in some settings. Our objective was to determine and compare to Food and Drug Administration (FDA) criteria the PLT recovery and survival of autologous PLTs cryopreserved at -65°C or less in 6% dimethyl sulfoxide (DMSO) reconstituted with a no-wash method (cryopreserved PLTs [CPPs]) compared to autologous fresh PLTs. STUDY DESIGN AND METHODS: This was a randomized, Phase I study analyzing PLT viability and in vitro function in consenting healthy subjects. Apheresis PLTs (APs) were collected in plasma. APs were suspended in 6% DMSO, concentrated, and placed at not more than -65°C for 7 to 13 days. Frozen CPPs were thawed at 37°C and resuspended into 25 mL of 0.9% NaCl. Control PLTs (fresh autologous) and CPPs were labeled with (111) In or (51) Cr, and recovery and survival after reinfusion were determined using standard methods. A panel of in vitro assays was completed on APs and CPPs. RESULTS: After frozen storage, CPPs retained 82% of AP yield and showed increased PLT associated P-selectin and reduced responses to agonists. CPP 24-hour recovery (41.6 ± 9.7%) was lower than for fresh PLTs (68.4 ± 8.2%; p < 0.0001) and did not meet the current FDA criterion. CPPs had diminished survival compared to fresh PLTs (7.0 ± 2.1 days vs. 8.4 ± 1.2 days, respectively; p = 0.018), but did meet and exceed the FDA criterion for survival. CONCLUSION: While 24-hour recovery does not meet FDA criteria for liquid-stored PLTs, the CPP survival of circulating PLTs was surprisingly high and exceeded the FDA criteria. These data support proceeding with additional studies to evaluate the clinical effectiveness of CPPs.

Detection of exercise-induced ischemia by changes in B-type natriuretic peptides.

OBJECTIVES: The purpose of this study was to examine the effect of exercise-induced ischemia on levels of B-type natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-pro-BNP)and to determine whether measurement of these peptides can improve the diagnostic accuracy of exercise testing. BACKGROUND: The ability of exercise testing to detect coronary artery disease (CAD) is limited by modest sensitivity and specificity. B-type natriuretic peptides (NT-pro-BNP and BNP) are released by ventricular myocytes in response to wall stress. We hypothesized that exercise-induced ischemia results in increased wall stress and triggers release of NT-pro-BNP and BNP. METHODS: A total of 74 patients with known CAD, normal left ventricular function, and normal resting levels of NT-pro-BNP and BNP who were referred for exercise testing with radionuclide imaging, and 21 healthy volunteers, were enrolled. Blood was drawn before and after maximal exercise and analyzed for NT-pro-BNP and BNP. RESULTS: Of the patients with CAD, 40 had ischemia on perfusion images and 34 did not. Median post-exercise increases in NT-pro-BNP and BNP (DeltaNT-pro-BNP and DeltaBNP) were approximately four-fold higher in the ischemic group than in the nonischemic group (DeltaNT-pro-BNP 14.5 vs. 4 pg/ml, p < 0.0001; DeltaBNP 36.5 vs. 7.5 pg/ml, p < 0.0001). In volunteers, median DeltaNT-pro-BNP was almost identical to that of the nonischemic patient group. At equal specificity to the electrocardiogram (ECG) (58.8%), the sensitivities of DeltaNT-pro-BNP and DeltaBNP for detecting ischemia were 90% and 80%, respectively; in contrast, the sensitivity of the exercise ECG was 37.5%. CONCLUSIONS: Measurement of exercise-induced increases in BNPs more than doubles the sensitivity of the exercise test for detecting ischemia with no loss of specificity.

Does asymmetric basal ganglia or thalamic activation aid in seizure foci lateralization on ictal SPECT studies?

UNLABELLED: Basal ganglia or thalamic activation has been reported in ictal SPECT studies of patients with intractable epilepsy. We hypothesized that lateralization of activation of these subcortical structures may aid in the lateralization of seizure foci in patients in whom the cortical focus is subtle or equivocal. METHODS: This was a retrospective analysis of 72 ictal (99m)Tc-ethylcysteinate dimer SPECT studies in 43 patients with intractable epilepsy in whom seizure laterality could be eventually determined. All patients underwent video-electroencephalography (EEG) monitoring, MRI, and one or more ictal SPECT scans as well as an interictal SPECT scan. Intracranial electrode EEG monitoring and surgery were performed as clinically indicated. Ictal and interictal studies were coregistered with patients' MRI scans using automated software, and ictal minus interictal subtraction images were obtained. The presence of asymmetric basal ganglia or thalamic activation was determined by 2 experienced observers who were unaware of clinical information. The final seizure focus was determined by surgical cure in 37 patients. In patients in whom surgery was not indicated or initial surgery was performed at another institution (n = 6), a consistent focus detected by intracranial electrode monitoring or repeated stereotypical seizures all originating from the same site on video-surface EEG monitoring was considered to indicate the final seizure focus. RESULTS: Thirty-five patients had neocortical seizures and 8 had mesial temporal lobe seizures. Asymmetric basal ganglia activation was seen in 22 (30.6%) studies. This activation was ipsilateral to the final determined seizure focus in 17 of 22 of these studies (77.3%) and contralateral in 5 of 22 (21.7%). Asymmetric thalamic activation was seen in 15 studies (20.8%), of which 12 of 15 (80%) were ipsilateral to the final seizure focus, whereas 3 of 15 (20%) were contralateral. In 3 of 5 studies with contralateral basal ganglia activation and 1 of 3 studies with contralateral thalamic activation, the SPECT study as a whole was found to be falsely localizing. In another 2 cases of contralateral subcortical activation, the SPECT study as a whole was considered nonlocalizing. Worse outcome was not observed in patients with false ictal SPECT subcortical lateralization; however, the presence of asymmetric subcortical uptake, regardless of relationship to seizure focus, was associated with decreased incidence of seizures at 1 y after surgery. CONCLUSION: Although asymmetric basal ganglia or thalamic activation is common, it is rarely the sole indicator of seizure localization. However, it may be a useful confirmatory sign in subtle cases of cortical localization. In cases of false ictal SPECT subcortical lateralization, the basal ganglia appear to follow cortical activation pattern. Furthermore, there appears to be a correlation between lateralizing uptake in subcortical structures on ictal SPECT and postsurgical outcome in intractable epilepsy patients.