Thoracoscopic-assisted rib plating (TARP): initial single-center case series, including TARP in the super elderly, technical lessons learned, and proposed expanded indications

Objectives: The application of surgical stabilization of rib fractures (SSRF) remains inconsistent due to evolving indications and perceived associated morbidity. By implementing thoracoscopic-assisted rib plating (TARP), a minimally invasive SSRF approach, we expanded our SSRF application to patients who otherwise might not be offered fixation. This report presents our initial experience, including fixation in super elderly (aged ≥85 years), and technical lessons learned. Methods: This was a retrospective cohort study at a level 1 trauma center of admitted patients who underwent TARP between August 2019 and October 2020. Patient demographics, injury characteristics, surgical indications and outcomes are represented as mean±SD, median or percentage. Results: A total of 2134 patients with rib fractures were admitted. In this group, 39 SSRF procedures were performed, of which 54% (n=21) were TARP. Average age was 68.5±16 years. Patients had a median of 5 fractured ribs, with an average of 1 rib that was bicortically displaced, and 19% presented with \u27clicking\u27 on inspiration. Patient outcomes were a mean hospital length of stay (LOS) of 11±3.7 days, mean postoperative LOS of 8 days, and mean intensive care unit LOS of 6.6±2.9 days. Five patients were ≥85 years old with a mean age of 90.8±4.7 years. They presented with an average of 4 rib fractures, of which an average of 2.4 ribs were plated. The procedure was well tolerated in this age group with a hospital LOS of 9.4±2 days, and all five patients were discharged to a rehab facility with no in-hospital mortalities. Conclusion: Our experience incorporating TARP at our institution demonstrated feasibility of the technique and application across a broad range of patients. This approach and its application warrants further evaluation and potentially expands the application of SSRF.

A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device

Rearrangements of the MLL gene are significant in acute leukemia. Among the most frequent translocations are t(4;11)(q21;q23) and t(9;11)(p22;q23), which give rise to the MLL-AFF1 and MLL-MLLT3 fusion genes (alias MLL-AF4 and MLL-AF9) in acute lymphoblastic and acute myeloid leukemia, respectively. Current evidence suggests that determining the MLL status of acute leukemia, including precise identification of the partner gene, is important in defining appropriate treatment. This underscores the need for accurate detection methods. A novel molecular diagnostic device, the MLL FusionChip, has been successfully used to identify MLL fusion gene translocations in acute leukemia, including the precise breakpoint location. This study evaluated the performance of the MLL FusionChip within a routine clinical environment, comprising nine centers worldwide, in the analysis of 21 control and 136 patient samples. It was shown that the assay allowed accurate detection of the MLL fusion gene, regardless of the breakpoint location, and confirmed that this multiplex approach was robust in a global multicenter trial. The MLL FusionChip was shown to be superior to other detection methods. The type of molecular information provided by MLL FusionChip gave an indication of the appropriate primers to design for disease monitoring of MLL patients following treatment

γδ T-Cell Acute Lymphoblastic Leukemia/Lymphoma: Discussion of Two Pediatric Cases and Its Distinction from Other Mature γδ T-Cell Malignancies

Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL. She responded to the chemotherapy protocol poorly and had persistent diseases. Following an allogeneic bone marrow transplant, she went into remission. The second patient is an eleven-year-old boy with a normal white cell count, circulating blasts, and a normal karyotype, but without any immature cellular markers by flow cytometric analysis. He responded to the chemotherapy well and achieved a complete remission. These cases demonstrate the diverse phenotypic, cytogenetic, and molecular aspects of γδ T-ALL. Early T-precursor- (ETP-) ALL and their differential diagnosis from other mature γδ T-cell leukemia/lymphomas are also discussed

Outcomes of Protocol-Driven Venous Thromboembolic Chemo-Prophylaxis in Trauma Patients: A Trauma Quality Improvement Project Analysis

INTRODUCTION: Low molecular weight heparin (LMWH) is the standard for venous thromboembolic (VTE) chemo-prophylaxis in trauma patients; however, inconsistencies in the use of LMWH exist. The objective of this study was to assess VTE outcomes in response to a chemo-prophylaxis protocol guided by patient physiology (eg, creatinine clearance) and comorbidities. METHODS: ACS TQIP Benchmark Reports at a level 1 trauma center using a patient physiology and comorbidity directed VTE chemo-prophylaxis protocol were analyzed for Spring 2019 to Fall 2021. Patient demographics, VTE rates and pharmacologic VTE prophylaxis type were collected for All Patients and Elderly (TQIP: age ≥ 55 years) cohorts. RESULTS: Data was analyzed for 1919183 All Hospitals (AH) and 5843 patients single institution (SI) using the physiologic and comorbidity guided VTE chemo-prophylaxis protocol. Elderly subgroup had 701965 (AH) and 2939 (SI) patients. Use of non-LMWH chemo-prophylaxis was significantly higher at SI: All patients = 62.6% SI vs 22.1% ( \u3c .01); Elderly = 68.8% SI vs 28.1% AH ( \u3c .01). VTE, DVT, and PE rates for All Patients and Elderly subgroup were significantly reduced at SI, except Elderly PE which was statistically equivalent. CONCLUSIONS: Protocol-driven VTE chemo-prophylaxis was associated with significantly lower LMWH use accompanied by significant reductions in All VTE, DVT, PE, and Elderly VTE and DVT with no difference in Elderly PE rates. These results may imply that adherence to a physiologic and comorbidity directed chemo-prophylaxis protocol, rather than LMWH, reduces VTE events in trauma patients. Further investigation to elucidate best practice is warranted

Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

vaccine

Tests of Behavioral-Economic Assessments of Relative Reinforcer Efficacy II: Economic Complements

This experiment was conducted to test the predictions of two behavioral-economic approaches to quantifying relative reinforcer efficacy. The normalized demand analysis suggests that characteristics of averaged normalized demand curves may be used to predict progressive-ratio breakpoints and peak responding. By contrast, the demand analysis holds that traditional measures of relative reinforcer efficacy (breakpoint, peak response rate, and choice) correspond to specific characteristics of non-normalized demand curves. The accuracy of these predictions was evaluated in rats' responding for food or water: two reinforcers known to function as complements. Consistent with the first approach, predicted peak normalized response output values obtained under single-schedule conditions ordinally predicted progressive-ratio breakpoints and peak response rates obtained in a separate condition. Combining the minimum-needs hypothesis with the normalized demand analysis helped to interpret prior findings, but was less useful in predicting choice between food and water—two strongly complementary reinforcers. Predictions of the demand analysis had mixed success. Peak response outputs predicted from the non-normalized water demand curves were significantly correlated with obtained peak responding for water in a separate condition, but none of the remaining three predicted correlations was statistically significant. The demand analysis fared better in predicting choice—relative consumption of food and water under single schedules of reinforcement predicted preference under concurrent schedules significantly better than chance

Mapping transcriptomic vector fields of single cells

Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions