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BackgroundCD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden of CAR-T. The recently developed CAR-HEMATOTOX (HT) score—composed of five pre-lymphodepletion variables (eg, absolute neutrophil count, platelet count, hemoglobin, C-reactive protein, ferritin)—enables risk stratification of hematological toxicity.MethodsIn this multicenter retrospective analysis, we characterized early infection events (days 0–90) and clinical outcomes in 248 patients receiving standard-of-care CD19 CAR-T for relapsed/refractory large B-cell lymphoma. This included a derivation cohort (cohort A, 179 patients) and a second independent validation cohort (cohort B, 69 patients). Cumulative incidence curves were calculated for all-grade, grade ≥3, and specific infection subtypes. Clinical outcomes were studied via Kaplan-Meier estimates.ResultsIn a multivariate analysis adjusted for other baseline features, the HT score identified patients at high risk for severe infections (adjusted HR 6.4, 95% CI 3.1 to 13.1). HThigh patients more frequently developed severe infections (40% vs 8%, p<0.0001)—particularly severe bacterial infections (27% vs 0.9%, p<0.0001). Additionally, multivariate analysis of post-CAR-T factors revealed that infection risk was increased by prolonged neutropenia (≥14 days) and corticosteroid use (≥9 days), and decreased with fluoroquinolone prophylaxis. Antibacterial prophylaxis significantly reduced the likelihood of severe bacterial infections in HThigh (16% vs 46%, p<0.001), but not HTlow patients (0% vs 2%, p=n.s.). Collectively, HThigh patients experienced worse median progression-free (3.4 vs 12.6 months) and overall survival (9.1 months vs not-reached), and were hospitalized longer (median 20 vs 16 days). Severe infections represented the most common cause of non-relapse mortality after CAR-T and were associated with poor survival outcomes. A trend toward increased non-relapse mortality in HThigh patients was observed (8.0% vs 3.7%, p=0.09).ConclusionsThese data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes prior to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse.

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive, extranodal lymphoma exclusively located in the central nervous system. High-dose methotrexate (HD-MTX)-based chemotherapy combination regimens are now the standard of care for the upfront treatment of PCNSL and are used in a salvage setting but are toxic and cumbersome to administer because of the need for inpatient supportive care. While the incidence of PCNSL is increasing in the aging population, a significant proportion of patients are unable to follow HD-MTX protocols owing to performance status and organ dysfunction. Consolidative autologous stem cell transplant or whole-brain radiation therapy improves progression-free survival at the cost of short- and long-term toxicities. Induction of low toxicity and consolidative and salvage therapeutic options are lacking. Due to its unique biology, PCNSL presents an exciting opportunity for the development of novel therapies with improved efficacy and toxicity. In this review, we focus on the biology of PCNSL and novel chemotherapeutics, including targeted and immunotherapeutic agents as well as cellular therapies. Expert Opinion summary: Given the lack of low-toxicity standard treatments for PCNSL, the outcomes for aging PCNSL patients remain suboptimal. Current research has focused on introducing targeted immunotherapies into the induction, salvage, and consolidation treatments of PCNSL.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has transformed the treatment landscape for hematological malignancies, showing high efficacy in patients with relapsed or refractory (R/R) disease and otherwise poor prognosis in the pre-CAR-T era. These therapies have been usually administered in the inpatient setting due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). However, there is a growing interest in the transition to outpatient administration due to multiple reasons. We review available evidence regarding safety and feasibility of outpatient administration of CD19 targeted and BCMA targeted CAR T-cell therapy with an emphasis on the implementation of outpatient CAR-T programs in community-based centers.

Protonated cyclic dipeptides undergo collision-induced dissociation, and this reaction mechanism strongly depends on the symmetry and the nature of the residues. We review the main dissociation mechanism for a series of cyclic dipeptides, obtained through chemical dynamics simulations. The systems range from the symmetrical cyclo-(glycyl-glycyl), with two possible symmetrical protonation sites located on the peptide ring, to cyclo-(tyrosyl-prolyl), where the symmetry of protonation sites on the peptide ring is broken by the dissimilar nature of the different residues. Finally, cyclo-(phenylalanyl-histidyl) shows a completely asymmetric situation, with the proton located on one of the dipeptide side chains, which explains the peculiar fragmentation mechanism induced by shuttling the proton, whose efficiency is strongly dependent on the relative chirality of the residues.

Analysis of the current state of nutrient stocks, flows, and balances of a territory is necessary to inform strategies that can transition the agri-food sector to a circular economy model. In this study, we quantified the nitrogen and phosphorus budgets for the Bolivian agri-food system at national and regional scales by way of agro-ecological zoning. We performed nutrient balances to calculate indicators for sufficiency (extent of nutrient deficit/surplus) and circularity (proportion of nutrients recirculated). We also evaluated the potential of renewable stocks (human excreta and livestock manure) to meet nutrient deficits in the system. Our results showed that there are apparent deficits of 32 kt N and 8 kt P in the system that cannot be accounted for using available data. We estimate the real deficits required to bring yields of 45 crops grown in Bolivia to parity with those of neighbouring countries to be 110 kt N and 33 kt P. About 44% of nitrogen and 74% of phosphorus is currently recirculated in the system, with the major nutrient inputs being biological nitrogen fixation, livestock manure, and crop residues. However, nutrient recycling is likely to decrease in the future because the national strategy to address nutrient deficits is to increase domestic production of synthetic fertilisers. Our analysis also shows that there is a sufficient stock of nutrients already available in human excreta (39 kt N and 5 kt P) to cover 100% of the nitrogen deficit and 64% of the phosphorus deficit. The low-altitude zone of Chiquitania-Pantanal alone accounts for 65% of cultivation and 80% of the nutrient demand in the country. Here, export-oriented crops like soybean and sorghum are grown, but less than 25% of the nitrogen is recirculated. In contrast, there are nutrient surpluses of 41 kt N and 34 kt P in agro-ecological zones like the Valleys and Altiplano where traditional agriculture is practiced, and the majority of food is grown for local consumption. Overall, we find that recycling of human excreta, combined with transfer of regional nutrient surpluses, could be an effective strategy to reduce the overall nutrient deficit in the system.

In the daily clinical practice of cattle, the use of locoregional anaesthesia is needed to provide analgesia during standing surgical procedures. It is important to ensure the success of the blockade before starting the surgery. One of the most used techniques is the paravertebral lumbar block. In this pilot study we evaluated the efficacy of thermography in assessing this block. For this matter, 12 cows from our university research and teaching farm, with similar characteristics, were included and in which an ultrasound-guided technique of lumbar paravertebral block (T13/L1) or (L1/L2) with lidocaine was performed. Thermal photographs were taken with a FLIR® One camera at 0, 15, 30 and 45 min and at the same time a test to evaluate the response to a painful stimulus was performed in each dermatome (T13, L1, L2 and L3). The data was collected in predesigned cards and placed in the Excel programme for further statistical analysis with the R programme. The analysis determined a correlation between the increase in skin temperature of the dermatomes that had been blocked and the increase in skin temperature and the negative response to the painful stimulus test. Although the pilot study has some limitations, this allows us to assess the use of thermography as an efficient method for assessing the success of lumbar paravertebral blockade in cattle.

Anaesthesia carries an inherent risk of morbidity and mortality in veterinary patients, yet the clinical impact of comprehensive pre-anaesthetic assessment (PAA) is insufficiently quantified. We retrospectively reviewed 350 PAAs including 267 dogs and 83 cats, performed at a small-animal teaching hospital in 2021. Signalment, history, physical examination findings, complementary diagnostics, initial ASA physical status (ASA-i), final ASA status after test review (ASA-f) and procedural outcomes were recorded. Complementary diagnostics—predominantly haematology, serum biochemistry, thoracic radiography, and electrocardiography—were requested in 82–86% of cases. ASA-f differed from ASA-i in 7.5% (11/306) of animals: +1 in 3.6%, +2 in 1.0%, −1 in 2.9%; no patient shifted by more than two classes. Fifty-seven planned procedures (16.2%) were cancelled following PAAs, chiefly abdominal (43.9%) and minor soft-tissue surgeries (31.6%). Internal-medicine abnormalities (47%) and cardiac findings (19%) were the leading causes; in 46% of cancellations, the trigger was an abnormal test result absent from the physical examination. Sixty-three percent of cancelled interventions were later completed after further evaluation or treatment. These data demonstrate that structured PAA substantially alters perioperative decision-making in small-animal practice and supports selective yet rigorous diagnostic test use to enhance patient safety and optimise theatre utilisation.

Type B lactic acidosis is a rare metabolic complication sometimes associated with hematologic malignancies. When present, this type of lactic acidosis is most commonly seen in patients with high-grade lymphomas or leukemias and is usually indicative of a dismal prognosis. We report a case of a 27-year man with acquired immunodeficiency syndrome (AIDS) that presented with bilateral lower extremity swelling, an abdominal mass, and weight loss. His lab values showed elevated anion gap with lactic acidosis and computed tomography (CT) of the abdomen showed a large soft-tissue mass arising from the left hepatic lobe. Biopsy of the abdominal mass demonstrated a high-grade diffuse large B-cell lymphoma. The patient’s lactic acidosis resolved after starting chemotherapy, and a complete response was evident on PET-CT after a third cycle of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOC-RR). Care-givers should be aware of the implications of lactic acidosis associated with malignancy and the need for prompt diagnosis and treatment.

The efficient separation of light hydrocarbons, particularly alkanes from their isomers (C5–C6), represents a significant and energy-intensive challenge for the petrochemical industry. Metal-Organic Frameworks (MOFs) offer promising solutions due to their exceptional porosity, surface area, and, crucially, their structural and chemical tunability. This study employs advanced computational methods, including Grand Canonical Monte Carlo (GCMC) simulations and Molecular Dynamics (MD), to systematically investigate the adsorption and separation of pentane isomers (n-pentane, isopentane, and neopentane) in the UiO-66 MOF family. Specifically, the impact of organic linker functionalization with -H (parent), -NH2, -CH3, and -COOH groups on adsorption isotherms, isosteric heats, and competitive behavior in mixtures is evaluated. The analysis provides a molecular-level view of host-guest and guest-guest interactions, elucidating the recognition and selectivity mechanisms governing the separation of these C5 isomers and the potential for engineering MOF materials for this application.

The ultrasound-guided cervical plexus plane (US-CPP) block has proven effective in humans; yet its application in dogs remains unexplored. This study aimed to describe a novel US-CPP approach in canines. A local sonoanatomy was mapped, the injection technique was tested, and a gross anatomical dissection (GAD) was performed on one cadaver. The bilateral injectate spread and nerve staining were then evaluated via a CT scan and GAD in the six cadavers. The transducer was aligned parallel to the cervical spine, caudal to the atlas. After identifying the cleidocervical and omotransversarius muscles and the C2-C3 interfascial plane, a spinal needle was inserted in-plane, and 0.15 mL/kg of a dye-contrast solution was injected. CT imaging showed the contrast reaching the C1, C2, and C3 vertebral bodies in 3 out of 12 (3/12), 11/12, and 12/12 injections, respectively, and the C4, C5, and C6 vertebrae in 8/12, 5/12, and 1/12 injections, respectively. No contrast was detected in the epidural space. The C1, C2, C3, C4, and C5 nerves were stained in 3/12, 10/12, 8/12, 2/12, and 0/12 injections, respectively. No significant differences were observed between the groups (p > 0.05). A single US-CPP injection successfully stained the C2 and C3 nerves, indicating the potential clinical applicability, although the injected volume rarely reached C4 and C5.