Concordance of Next-Generation Sequencing and Multiparametric Flow Cytometry Methods for Detecting Measurable Residual Disease in Adult Acute Lymphoblastic Leukemia: Optimizing Prediction of Clinical Outcomes From a Single-Center Study.

INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.

Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

BACKGROUND: Acetaminophen is a frequently used adjunct analgesic in pediatric patients undergoing tonsillectomy and adenoidectomy. We compared opioid administration following preoperative intravenous (IV) or oral acetaminophen in addition to a standard multimodal regimen to test the hypothesis that 1 loading dose approach would provide superior opioid sparing effects among pediatric surgical patients undergoing tonsillectomy and adenoidectomy. METHODS: This single-center, double-blind, double-dummy prospective randomized study was conducted in patients ages 3 to 15 years undergoing tonsillectomy and adenoidectomy with or without myringotomy and tube placement between September 2017 and July 2019. Subjects received 1 dose of either oral acetaminophen 30 mg/kg with IV placebo (oral group) or IV acetaminophen 15 mg/kg with oral placebo (IV group). Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen. Intraoperative opioid administration and postoperative analgesia were standardized. Standardized postoperative multimodal analgesia included opioid if needed to control pain assessed by standardized validated pediatric pain scales. The primary outcome measure was total opioid administration in the first 24 hours after surgery. Continuous data were not normally distributed and were analyzed using the Wilcoxon rank sum test and the Hodges-Lehman estimator of the median difference. Clinical significance was defined as a 100 µg/kg IV morphine equivalents per day difference. RESULTS: Sixty-six subjects were randomized into and completed the study (29 women, 37 men; age 5.9 ± 3.0 years; percentile weight for age 49.5 ± 30.2; no differences between groups). There was no opioid dose difference between oral (median 147.6; interquartile range [IQR], 119.6-193.0 µg/kg) and IV groups (median 125.4; IQR, 102.8-150.9 µg/kg; median difference 21.3; 95% confidence interval [CI] -2.5 to 44.2 µg/kg IV morphine equivalents; P = .13). No acetaminophen levels exceeded the predefined safety threshold (40 mg/L). No difference was found in the percentage of patients with severe pain: 50.0% oral group, 47.2% IV group; relative risk of severe pain in IV 0.94; 95% CI, 0.57-1.6; P = .82. Postoperative plasma acetaminophen levels were higher in oral (22; IQR, 16-28 mg/L) than IV (20; IQR, 17-22 mg/L) group (median difference 7.0; 4.0-8.0 mg/L; P = .0001). CONCLUSIONS: Opioid-sparing effects did not differ following an oral or standard IV acetaminophen loading dose with no identified acetaminophen toxicity in pediatric patients undergoing tonsillectomy and adenoidectomy who received standardized multimodal postoperative analgesia. An oral loading dose may provide more consistent serum acetaminophen levels at lower cost compared to a standard IV dose.

Simultaneous comparison of depth of sedation performance between SedLine and BIS during general anesthesia using custom passive interface hardware: study protocol for a prospective, non-blinded, non-randomized trial.

BACKGROUND: Intraoperative brain function monitoring with processed electroencephalogram (EEG) indices, such as the bispectral index (BIS) and patient state index (PSI), may improve characterization of the depth of sedation or anesthesia when compared to conventional physiologic monitors, such as heart rate and blood pressure. However, the clinical assessment of anesthetic depth may not always agree with available processed EEG indices. To concurrently compare the performance of BIS and SedLine monitors, we present a data collection system using shared individual generic sensors connected to a custom-built passive interface box. METHODS: This prospective, non-blinded, non-randomized study will enroll 100 adult American Society of Anesthesiologists (ASA) class I-III patients presenting for elective procedures requiring general anesthesia. BIS and SedLine electrodes will be placed preoperatively according to manufacturer recommendations and their respective indices tracked throughout anesthesia induction, maintenance and emergence. The concordance between processed EEG indices and clinical assessments of anesthesia depth will be analyzed with chi-square and kappa statistic. DISCUSSION: Prior studies comparing brain function monitoring devices have applied both sensors on the forehead of study subjects simultaneously. With limited space and common sensor locations between devices, it is not possible to place both commercial sensor arrays according to the manufacturer's recommendations, thus compromising the validity of these comparisons. This trial utilizes a custom interface allowing signals from sensors to be shared between BIS and SedLine monitors to provide an accurate comparison. Our results will also characterize the degree of agreement between processed EEG indices and clinical assessments of anesthetic depth as determined by the anesthesiologists' interpretations of acute changes in blood pressure and heart rate as well as the administration, or change to the continuous delivery, of medications at these timepoints. Patient factors (such as burst suppression state or low power EEG conditions from aging brain), surgical conditions (such as use of electrocautery), artifacts (such as electromyography), and anesthesia medications and doses (such as end-tidal concentration of volatile anesthetic or hypnotic infusion dose) that lead to lack of agreement will be explored as well. TRIAL REGISTRATION: Clinical Trials ( ClinicalTrials.gov ), NCT03865316 . Registered on 4 February 2019 - retrospectively registered. SPONSOR: Masimo Corporation.

Oncologic outcomes after surgery for locally aggressive basal cell carcinoma of the head and neck.

OBJECTIVE: Although basal cell carcinoma (BCC) is the most common skin cancer, locally aggressive BCC of the head and neck is rare and not well studied. STUDY DESIGN: Retrospective review of patients who underwent primary surgical resection of locally aggressive head and neck BCC at a single tertiary academic center. RESULTS: Eighty-seven patients with 98 tumors demonstrated a 5-year Kaplan-Meier estimated recurrence-free survival of 64.5%, overall survival of 83.3%, and disease-specific survival of 98.3%. Intraoperative positive frozen section margin was a strong independent predictor of local recurrence (hazard ratio 6.88, P = 0.038) and was more likely to occur in tumors previously treated with radiation (odds ratio 6.47 = 0.05). CONCLUSION: Locally aggressive BCCs of the head and neck have high rates of local recurrence but low disease-specific mortality when treated with primary surgery and selected use of adjuvant therapy. Intraoperative positive frozen section margin is a strong independent predictor of local recurrence and is more likely in tumors that were previously treated with radiation therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:115-119, 2020.

Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma.

The aim of this study was to determine the association of measures of skeletal muscle determined from 18F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

Late-onset en coup de sabre of the skull.

En coup de sabre is a rare subtype of linear scleroderma that characteristically affects the skin, underlying muscle, and bone of the frontoparietal region of the face and scalp. It typically presents in the first two decades of life, and may be associated with focal neurological deficits. We present a case of late-onset en coup de sabre of the frontal bone where the diagnosis was further complicated by a history of breast cancer, prior trauma to the region, and use of topical medication.