Citations

Background: The objective of this study was to describe thrombin generation in children undergoing cardiac surgery with cardiopulmonary bypass. Change in the endogenous thrombin potential (ETP) across three measurements before and after cardiopulmonary bypass (after protamine and at chest closure) was the primary outcome. Secondary analyses explored an association between thrombin generation and transfusion requirements and predictors of the thrombin generation decline. Methods: Blood samples of children (median age, 6.3 months; 68.5% weighed less than 10 kg) were collected intraoperatively three times: before administration of heparin (baseline), shortly after protamine, and at sternal closure. Platelet-poor plasma obtained after centrifugation of these samples was frozen at −80ºC. Thrombin generation and anti-Xa assays were performed in series on batches of thawed samples to evaluate thrombin generation parameters and functional activity of unfractionated heparin, which could have affected thrombin generation assay results. Results: Between August 2022 and May 2024, 162 plasma samples from 54 patients were collected and analyzed. Compared with baseline, mean ETP decreased by 1,911 nM (95% CI, 1,655 to 2,168) after administration of protamine and by 1,865 nM (95% CI, 1,609 to 2,122) at sternal closure (P < 0.001). Similar changes were observed in secondary thrombin generation parameters. Median unfractionated heparin activity was less than 0.1 U/ml at all three time points. Secondary analyses showed a strong negative correlation between ETP after protamine and volume of transfusion after bypass (ρ = −0.52, P < 0.001). Among five examined factors, only total heparin dose was independently associated with ETP decline, with a higher dose being predictive of greater ETP decline (P = 0.002). Conclusions: In children undergoing cardiac surgery, thrombin generation assay revealed significant and persistent decline in endogenous thrombin potential after cardiopulmonary bypass, despite hemostatic interventions. This reduced thrombin potential correlated with a higher volume of transfusions. Additionally, greater intraoperative heparin requirements could be linked to a more pronounced decline in thrombin generation.

Abstract Background We evaluated the Tecan Fluent Mix and Pierce Workstation as an automated platform to aliquot directly from whole blood collection tubes. The Fluent Mix and Pierce Workstation uses the Tube Rotator™, an on-deck rotisserie, to keep whole blood in suspension, and 8 Piercing Tips™ to cross the pierceable caps of collection tubes to aliquot samples. Methods We performed accuracy and precision testing by aliquoting residual whole blood specimens into an on-deck gravimetric scale. To test carryover, we aliquoted alternating blanks and high calibrators for several analytes and performed mass spectrometry on the blanks. We performed 168 runs over a 21-day period to test the robustness of the platform. We aliquoted and analyzed 2 batches of samples on both our clinical platform and the Mix and Pierce Workstation to check concordance. Results We observed that the Fluent Mix and Pierce Workstation can aliquot 200 µL with 0.5% inaccuracy and 0.9%CV and can aliquot 300 µL with 0.1% inaccuracy and 0.7%CV. We were unable to detect any analyte carryover using mass spectrometry. We observed no hardware failures during the instrument stress test. Clinical comparison runs indicated that the performance of aliquots made on the Fluent Mix and Pierce Workstation was equivalent to that of aliquots made by our current clinical method. Conclusions Overall, our evaluation showed that the Tecan Fluent Mix and Pierce Workstation is a viable platform for aliquoting whole blood for downstream work flows and can eliminate labor-intensive sample decapping and recapping in high-throughput settings.

Mitral regurgitation (MR) in lung transplant (LTx) recipients is a rare but complex cardiopulmonary phenomenon. The overlap between symptoms of MR and post-LTx complications, such as primary graft dysfunction, complicates its diagnosis and management. This systematic review aims to characterize the incidence, pathophysiology, presentation, and management of MR in LTx patients. We conducted a literature search in PubMed, Web of Science, Scopus, and Embase. The search yielded 133 studies, of which 11 were included. Data regarding MR development, clinical presentation, echocardiographic findings, and management strategies were extracted and analyzed. Perioperative MR, occurring during or immediately post-LTx, was frequently attributed to the systolic anterior motion of the mitral valve (MV) occurring in the setting of hypovolemia and/or inotrope usage. Later postoperative MR, on the other hand, was associated with reverse ventricular remodeling and mitral annular dilation, although some variability in the literature was present. Preexisting MR or ventricular dysfunction, elongated MV leaflets, and bilateral LTx procedure appeared to be risk factors for MR development. Management was dependent on the timing of MR and its pathophysiology, where systolic anterior motion–related MR was treated with medical therapy, whereas postoperative MR often required MV interventions. In conclusion, the diagnosis of MR in LTx patients is complicated by its symptomatic overlap with other post-LTx complications. Echocardiographic monitoring in patients with preexisting MR, regardless of severity, is essential for early identification and management. Further research is needed to better understand the underlying mechanisms and refine management strategies for MR in this population.

Abstract ZUMA-8 evaluated the safety of brexucabtagene autoleucel (brexu-cel), a CD19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapy, for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Patients with ≥2 prior lines of therapy (including a Bruton tyrosine kinase inhibitor) underwent leukapheresis, optional bridging therapy, and conditioning chemotherapy (fludarabine/cyclophosphamide) before infusion of 1 × 106 (cohort 1) or 2 × 106 (cohort 2) anti-CD19 CAR T cells per kg. Patients in cohort 3 (low tumor burden), and cohort 4A (postibrutinib) received 1 × 106 cells per kg. Fifteen patients, median age of 63 years (range, 52-79), were treated in cohorts 1 (n = 6), 2 (n = 3), 3 (n = 3), and 4A (n = 3). Median follow-up was 24.3 months. One dose-limiting toxicity was observed in cohort 3 (grade 4 cytokine release syndrome). Grade ≥3 neurologic events occurred in 3 patients (20%). Seven of 15 patients responded (overall response rate, 47%; complete response [CR], 7%), including all 3 patients in cohort 3 (1 with CR). CAR T-cell expansion occurred in 4 patients (27%), with an apparent weak inverse correlation with absolute lymphocyte count before apheresis. Brexu-cel had no new safety signals in R/R CLL. CAR T-cell expansion and responses occurred in patients with low tumor burden. This trial was registered at www.clinicaltrials.gov as #NCT03624036.

Abstract Rationale Stereotactic body radiation therapy (SBRT) represents an effective therapeutic strategy for early-stage non–small cell lung cancer (NSCLC); however, local and systemic recurrences represent ongoing challenges. Computed tomography (CT) radiomics-based risk models can potentially be used to predict the risk of local recurrence on pretreatment CT scans. Objective Development of a radiomics model to predict local recurrence after SBRT in patients with NSCLC. Methods This single-institution study includes a retrospective case-control training set (20 patients with local recurrence and 40 control subjects) and an independent validation set (198 consecutive cases) of patients with early-stage NSCLC treated with SBRT. Tumors were semiautomatically segmented, and 102 quantitative radiomic features, including texture, landscape, spatial, nodule shape, and nodule surface features, were extracted. These features were included in three separate multivariable models to predict the risk of recurrence on the basis of pre-SBRT, post-SBRT, and the difference between the pre-SBRT and post-SBRT scans (Delta model). The pre-SBRT model was subsequently validated in an independent validation set. Results Thirteen independent variables were selected for the models using the Boruta algorithm. The sensitivity, specificity, and area under the curve of the pre-SBRT, post-SBRT, and Delta models were 85%, 90%, and 0.91; 85%, 92.5%, and 0.92; and 85%, 92.5%, and 0.94, respectively. The pre-SBRT model was validated in the independent validation set (area under the curve, 0.89; confidence interval, 0.83–0.92), because this model was believed to be the most useful to assist in individualized treatment planning. Conclusions Radiomic analysis facilitated the development of three high-performing models predicting local recurrence using either pre-SBRT CT, post-SBRT CT, or the change between these two. We successfully validated the most clinically relevant model, the pre-SBRT model. Although this model needs further validation, it may facilitate individualized surveillance, treatment planning, and selection of adjuvant therapy.

Abstract Objective Noninvasive brain stimulation (NIBS) provides a treatment option for patients not eligible for surgical intervention or who seek low‐risk approaches and may be used in the hospital, clinic, and at home. Our objective is to summarize our single‐center experience with multiple NIBS approaches for the treatment of focal epilepsy. Methods A retrospective chart review identified drug‐resistant focal epilepsy patients who received NIBS as an epilepsy treatment at Mayo Clinic in Rochester, MN. Patients were typically treated as follows: (1) for TMS, 1 Hz stimulation was applied for five consecutive days in the neuromodulation clinic, (2) for outpatient tDCS, stimulation was applied for five consecutive days in the clinic, followed by optional treatment at home, and (3) for inpatient tDCS, stimulation was applied for three consecutive days. We analyzed continuous EEG data for the inpatient tDCS cohort and available HD‐EEG data for outpatient cohorts to quantify changes in interictal epileptiform discharges (IEDs) as a result of stimulation. Outcomes were assessed at 1 month for TMS and outpatient tDCS and 1 week for inpatient tDCS. Results Twenty‐four patients were treated with TMS ( n = 10) and tDCS ( n = 14, 9 as outpatients). The median age was 40 years (range 15–73). The median seizure reduction following stimulation was 50%. Fourteen patients (58%) were responders to treatment (TMS = 4/10, tDCS Outpatient = 7/9, tDCS Inpatient = 3/5). Five outpatient tDCS participants elected to continue treatment at home. Four TMS and four outpatient tDCS patients underwent high‐density EEG before and after 5 days of therapy. Following stimulation, IED rate was reduced in 4/5 inpatient tDCS patients, 4/4 outpatient tDCS patients, and 4/4 TMS patients. Two patients experienced an increase in seizure frequency (1 following TMS and 1 following outpatient tDCS), which returned to baseline 4–6 weeks after stimulation treatments were discontinued. Significance TMS and tDCS are potential treatment approaches for drug‐resistant focal epilepsy patients in the hospital, clinic, and home. They have a favorable safety profile and can lead to a reduction in IED rates and seizures. These results suggest further studies are needed to examine NIBS as a treatment for epilepsy. Plain Language Summary Noninvasive brain stimulation, such as transcranial magnetic stimulation and transcranial direct current stimulation, offers new treatment options for patients with focal seizures. This study reviewed the experience at Mayo Clinic using noninvasive brain stimulation in the hospital, clinic, and at‐home settings to treat seizures. The results showed an overall 50% median seizure reduction, and 58% of patients had at least a 50% reduction in seizures. Noninvasive brain stimulation is a promising treatment approach with a favorable safety profile.

Ewing sarcoma and osteosarcoma constitute 36% of all primary bone cancers. However, these 2 subtypes represent the most commonly diagnosed bone cancer types in the pediatric and adolescent population. Although still largely unknown, certain genetic mutations, rearrangements, and/or predisposition syndromes likely play a role in the pathogenesis of bone cancer. Osteosarcoma may also develop as a direct result of the long-term side effects of radiation therapy. With the implementation of a multimodality approach to treatment, including multiagent neoadjuvant and adjuvant chemotherapy regimens, targeted therapy options, surgery, and radiation, individuals with Ewing sarcoma and osteosarcoma are showing higher cure rates and improved overall survival. The NCCN Guidelines for Bone Cancer provide a consensus and evidence-based framework for the workup, management, and surveillance of local and recurrent/metastatic disease.

Poorly designed Electronic Health Records (EHRs) can lead to increased workloads, decreased efficiency, and medical errors. This cross-sectional study surveyed ICU providers’ perceptions of their EHR using the NASA-TLX and CSUQ surveys. We found that providers report increased temporal demand and effort when using the EHR, and that they are dissatisfied with the EHR’s interface quality.