Search Results (235)

Etoposide is a key component of many frontline and salvage chemotherapy regimens in pediatric oncology. However, its clinical use may be complicated by acute hypersensitivity reactions, which can disrupt treatment continuity and compromise therapeutic efficacy. Recent pediatric studies indicate that the incidence of etoposide-associated hypersensitivity is higher than historically reported and varies according to disease type and administration conditions. This narrative review provides a comprehensive overview of etoposide hypersensitivity in children, integrating clinical, immunological, and pharmaceutical perspectives. Current evidence suggests that true IgE-mediated type I hypersensitivity is uncommon in pediatric patients, whereas most reactions are consistent with non-IgE-mediated mechanisms, often related to formulation excipients such as polysorbate 80 and ethanol. We discuss the clinical features and differential diagnosis of acute reactions associated with etoposide administration, including hypersensitivity reactions and infusion-related reactions, such as ethanol-related toxicity. In addition, modifiable risk factors, preventive measures, and management strategies—such as infusion optimization, alternative formulations, and rapid desensitization protocols—are critically reviewed. A mechanism-based approach to etoposide hypersensitivity is essential to ensure patient safety while maintaining treatment intensity in pediatric cancer care. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Background/Objectives: After several decades of using titrated paclitaxel infusions, our institution adopted non-titrated infusions in April 2023 to streamline infusion workflows. We aimed to evaluate whether this alteration in infusion was associated with a higher incidence of HSRs. Methods: This was a retrospective cohort study of patients receiving paclitaxel with titration versus non-titration from April 2022 through November 2023. Patients diagnosed with gynecologic cancers who presented for their first or second paclitaxel lifetime infusions were included. Results: A total of 150 patients were included in this study, each with one or two infusions, for a total of 282 infusion visits. There were 176 infusions performed with titrated paclitaxel (62.4%), and 106 infusions performed with non-titrated paclitaxel dose (37.6%). HSRs occurred in 20.8% of the non-titrated paclitaxel infusions and in 11.9% of titrated paclitaxel infusions (RR 1.73 (95% CI 1.006–3.006), p = 0.047). Additionally, when stratifying by first- or second-visit infusions, the HSR rate increased significantly for non-titrated infusions to 22.4% during the second visit, while there was a decrease to 8.4% for titrated infusions (RR 2.66 (95% CI 1.105–6.413), p = 0.029). Non-titrated infusion reactions were associated with higher grades of reaction. Conclusions: HSRs occurred more frequently with non-titrated infusions, particularly during the second administration, suggesting that eliminating titration may increase hypersensitivity risk. These findings support a prospective evaluation of titration rates to further refine paclitaxel administration. Full article

Background: Cerliponase alfa is an intracerebroventricular (ICV) enzyme replacement therapy (ERT) and the only approved treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) disease. While generally well tolerated, infusion-associated reactions (IARs), including hypersensitivity events and anaphylaxis, remain a recognized safety consideration. Methods: This single-center, retrospective study describes the incidence and management of IARs in pediatric patients with CLN2 receiving long-term ICV cerliponase alfa at Great Ormond Street Hospital, London, United Kingdom. Results: Over a 10-year period (2014–2024), 31 patients received approximately 2705 ICV infusions. Eleven patients experienced at least one IAR. Most reactions were mild and transient, typically consisting of pyrexia, vomiting, or rash, and were managed conservatively with antipyretics and antihistamines. Four patients required steroid intervention following recurrent or more pronounced symptoms, which led to improved infusion tolerance. One patient experienced a single episode of anaphylaxis that required treatment with intramuscular adrenaline and intravenous hydrocortisone. Therapy was continued with a revised pre-medication regime, with no further severe reactions. Conclusions: These findings demonstrate that IARs to ICV cerliponase alfa are typically mild and readily manageable within a multidisciplinary framework. They highlight the importance of structured infusion protocols, vigilant monitoring strategies, and a coordinated management approach to ensure the long-term safety of ERT for children with CLN2 disease. Full article

Out-of-autoclave (OoA) processing has emerged as a promising route for manufacturing high-performance polymer composites while reducing energy consumption and production complexity. The authors investigate the effect of curing temperature on the thermo-mechanical performances of carbon fiber-reinforced composites produced via resin infusion. Five laminates composed of six carbon fiber plies were arranged in a [90/0/45/−45/0/90] lay-up and infused with an epoxy resin cured at 25, 40, 50, 60, and 70 °C. The influence of the processed temperatures of the mechanical properties was evaluated through tensile and three-point bending tests, whereas thermal performance was analyzed using Heat Deflection Temperature (HDT) measurements and differential scanning calorimetry (DSC). The results demonstrate an improvement in stiffness, strength, and HDT with increasing the curing temperature, with the 40–50 °C range yielding the most balanced enhancement in mechanical and thermal responses. DSC analyses confirm that higher curing temperatures promote a more complete crosslinking reaction, consistent with the improved laminate performance. Overall, the findings highlight the critical role of controlled thermal curing in optimizing OoA polymer composite systems and support their suitability for energy-efficient applications. Full article

Fabry disease (FD) is an X-linked systemic lysosomal storage disease caused by mutations in the galactosidase-α (GLA) gene, which encodes the α-galactosidase A (α-AGAL) enzyme. FD can lead to serious complications, including early death, if left untreated. For over 20 years, enzyme replacement therapy (ERT) based on the use of agalsidase-α and agalsidase-β has been the standard treatment for FD, alongside new molecules that have enriched the therapeutic armamentarium and others that are being tested to expand it further. Unfortunately, ERT can be associated with the formation of inhibiting antidrug antibodies (ADAs), which impact ERT clinical efficacy and have consequences affecting safety and therapeutic adherence. A group of FD specialists discussed the problem of immunogenicity in FD, analyzing the most recent literature and the strategies that are currently being used to address it. Once formed, fluctuating levels of ADAs persist and have an impact on the clinical picture and prognosis of the disease that is still the subject of lively scientific debate. The critical nature of ADAs is demonstrated by their ability to bind to the enzyme, increasing drug clearance while forming immune complexes that can build up in the tissues causing chronic inflammation that aggravates the progression of the disease and affects the onset of acute reactions after the infusion, impacting therapeutic adherence. Although similar in their therapeutic mechanism, agalsidase-α and agalsidase-β differ in their production process, with resulting differences from a pharmacokinetic and pharmacodynamic point of view and diverse immunological implications: despite showing rather overlapping efficacy outcomes, agalsidase-α demonstrates a better tolerability profile, with a lower frequency of ADAs, than agalsidase-β. Given the extreme variability of the clinical picture, it is crucial for optimal FD management that the most appropriate molecule is chosen by taking into account the unique immunological risk profile of each single patient, and particular attention should be paid to naïve subjects by periodic measurement of ADAs during therapy and cross-referencing data to correlate serological and clinical patterns. Full article

Background/Objectives: In Japan, cancer-related anemia (CRA) is common, and erythropoiesis-stimulating agents (ESAs) are not approved for chemotherapy-induced anemia. Modern intravenous (IV) iron formulations, such as ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), enable high-dose repletion; however, real-world evidence in ESA-free oncology settings remains limited. Methods: This single-center retrospective study included patients with CRA (N = 55) who received high-dose IV iron (FCM or FDI). Iron phenotypes were classified as absolute iron deficiency (ID), functional ID, or non-ID. The primary endpoint was hemoglobin (Hb) change from baseline to approximately 1 month (21–45 days) in the non-transfused patients. Secondary endpoints included responder rate (ΔHb ≥ 1.0 g/dL), transfusion avoidance rate, dosing adequacy relative to Ganzoni-calculated iron deficit, and safety, particularly hypophosphatemia. Results: Among the non-transfused patients, mean Hb increased from 8.76 ± 1.34 g/dL to 9.73 ± 1.75 g/dL (mean ΔHb +0.92 ± 1.44 g/dL; p < 0.001). The responder and transfusion avoidance rates were 48.9% and 81.8%, respectively. Functional ID was most prevalent (52.7%), with clinically meaningful Hb responses. A total of 38.2% achieved approximately 1000 mg dosing. The safety profile was excellent, and no infusion reactions or symptomatic hypophosphatemia was observed (median serum phosphate changed from 3.4 [3.0–3.9] to 3.2 [2.7–3.8] mg/dL). Conclusions: In this real-world Japanese oncology setting where ESAs were not available for chemotherapy-induced anemia, high-dose IV iron monotherapy (FCM or FDI) was well tolerated and was associated with modest short-term Hb increases and a high observed rate of transfusion avoidance within a 21–45-day assessment window. These findings suggest that a proactive, TSAT-guided IV iron therapy approach may be a pragmatic option for selected patients; however, durability beyond 1 month, optimal re-dosing, and generalizability require confirmation in larger, longer prospective studies. Full article

Volatile organic compounds (VOCs) play a central role in plant communication and ecology, acting as a chemical language that mediates interactions with other organisms and responses to environmental stimuli. Analyzing changes in the plant volatilome enables the effective differentiation between biotic and abiotic stresses. Consequently, monitoring VOC emissions offers valuable insights into plant signaling pathways and health status. These insights position this approach as a promising strategy for improving crop protection. Direct infusion (DI) online analytical techniques, such as proton transfer reaction mass spectrometry (PTR-MS) and adduct ionization mechanism mass spectrometry (AIM-MS), have been developed to detect and characterize VOCs in real time. Here, we evaluated the suitability of PTR-MS and AIM-MS for monitoring VOC emissions in pea plants (Pisum sativum L.). Comparative analysis revealed that AIM-MS, a recently developed technology, detected a higher number of distinct signals than PTR-MS. Annotation of detected and significant AIM-MS signals indicated a predominance toward those that were putative lipids-derived and amino acids-derived, whereas PTR-MS signals were primarily associated with putative phenolic compounds. These findings suggest that the newly developed AIM reactor offers a broader detection range and may enhance our ability to monitor plant VOC emissions. Consequently, AIM-MS emerges as a promising tool for the real-time assessment of pea plant health and stress responses. Further efforts are needed to improve the portability of DI-MS techniques and to integrate them with GC-MS techniques. Overall, these efforts will allow this technology to be exploited for plant protection in compromised environments. Full article

Developing effective CAR-T cell therapy for solid tumours remains challenging because of biological barriers such as antigen escape and an immunosuppressive microenvironment. The aim of this study is to develop a mathematical model of the spatio-temporal dynamics of tumour processes in order to assess key factors that limit treatment efficacy. We propose a reaction–diffusion model described by a system of partial differential equations for the densities of tumour cells and CAR-T cells, the concentration of immune inhibitors, and the degree of antigen escape. The methods of investigation include stability analysis and numerical solution of the model using a finite-difference scheme. The simulations show that antigen escape produces a resistant tumour core and relapse after an initial regression; increasing the escape rate from $\gamma =0.001$ to $0.1$ increases the final tumour volume at $t=100$ days from approximately 35.3 a.u. to 36.2 a.u. Parameter mapping further indicates that for $\gamma \le 0.01$ tumour control can be achieved at moderate killing rates ($k_{CT}\approx 1{\mathrm{day}}^{-1}$), whereas for $\gamma \ge 0.05$ comparable control requires $k_{CT}\approx 2$–$5{\mathrm{day}}^{-1}$. Repeated CAR-T administration improves durability: the residual normalised tumour volume at $t=100$ days decreases from approximately 4.5 after a single infusion to approximately 0.9 (double) and approximately 0.5 (triple), with a saturating benefit for further intensification. We conclude that the proposed model is a valuable tool for analysing and optimising CAR-T therapy protocols, and that our results highlight the need for combined strategies aimed at overcoming antigen escape. Full article

Titanium dioxide (TiO₂) and indium sulfide (In₂S₃) combined nanoarray films, fabricated via the hydrothermal and chemical bath deposition (CBD) methods, were employed as photoelectrocatalysts for water splitting applications through the photoelectrochemical (PEC) process. The resulting heterostructure nanoarray catalyst morphology, composition, and optical absorption have been analyzed. The photon illumination and its effect on the electrochemical impedance and photocurrent generation measurements exposed that the infusion of In₂S₃ on the TiO₂ films comprehensibly reduced the charge carrier transport resistance (700 Ohm·cm²) and enhanced the photocurrent (0.28 mA/cm²) with an increment of photo potential response (−1.02 V vs. Ag/AgCl). Further, the heterostructure films effectively degrade the organic molecules in the electrolyte under UV light illumination. The enhanced catalytic reaction is ascribed to the role of In₂S₃ deposition on the TiO₂, which effectively improves the charge carrier collection at the surface by In₂S₃ and promotes the dissociation of organic molecules at the interface. Full article

Vitamin B1 (thiamine) is a water-soluble B vitamin. As a cofactor of many enzymes, it is essential for the proper functioning of many body systems and organs, including metabolic and energy metabolism. In extreme cases, vitamin B1 deficiency causes neurodegenerative disorders, including beri-beri, or cognitive impairment resulting from encephalopathy. B1 avitaminosis may result from increased demand, dietary errors, malabsorption, or excessive loss. Thiamine supplementation is used in cases of vitamin B1 deficiency or for preventative measures in situations of increased demand. Vitamin B1 can be administered enterally or parenterally (intravenously, intramuscularly, subcutaneously). The route and dose depend on the individual patient’s clinical situation. Hypersensitivity to vitamin B1 is rare and appears to be primarily associated with rapid intravenous infusion of large doses of thiamine hydrochloride over a short period (intravenous bolus). Hypersensitivity to thiamine administered by routes other than intravenous or intramuscular injection appears to be an incidental phenomenon. Thiamine should also be considered as an occupational allergen. The mechanism of thiamine hypersensitivity has not been clearly elucidated. However, considering the clinical nature and dynamics of the reaction, the most likely reaction seems to be an immediate type of hypersensitivity reaction (immunoglobulin E (IgE)-dependent), in which thiamine (but not its metabolites) acts as a hapten. Diagnosing hypersensitivity to vitamin B1 is difficult due to the lack of validated tests for additional testing. In individuals requiring thiamine supplementation who have experienced hypersensitivity to intramuscular or intravenous administration of this vitamin, switching to oral administration may be considered (provided this does not reduce treatment efficacy). This form of supplementation is usually well tolerated by individuals allergic to parenteral thiamine. However, if enteral supplementation does not guarantee the maintenance of therapeutic potential, thiamine desensitization may be considered, which seems to be an effective therapeutic method in such a clinical situation. Full article

Tannins are key compounds determining the astringency of walnuts. Elucidating the structural characteristics of tannin cells in walnut inner seed coats and the accumulation patterns of esterified catechins (e.g., EGCG and ECG) is of significant importance for both quality regulation of walnuts and the high-value utilization of tannin resources. However, the enzymatic properties and biological functions of walnut tannases (JrTAs) have not been systematically investigated. Thus, the enzymatic characteristics of walnut tannase and its hydrolytic function on tannin-like substances were analyzed. It showed that tannin accumulation in the inner seed coat of ‘Nonghe 1’ walnut was closely associated with the development of tannin cells. During seed coats development, the total tannin content initially decreased and then increased, while the levels of monomeric phenolics related to tannin synthesis (GC, EGC and EC) continuously increased. Two walnut tannase genes, JrTA1 and JrTA2, were cloned and the recombinant proteins were purified. In vitro enzymatic activity tests confirmed that both enzymes effectively hydrolyzed ester-type catechins ECG and EGCG after 20 min of reaction at 40 °C and pH 7.0. Moreover, the transgenic Arabidopsis systems and green tea infusion study demonstrated that JrTA1 and JrTA2 retained their ability to specifically cleave the ester bonds of ester-type catechins in heterologous systems, achieving efficient tannin degradation. This study systematically elucidates the enzymatic functions of JrTAs, which provides a theoretical foundation for the further development and application of walnut tannases. Full article

Chemotherapy for breast cancer includes pertuzumab and trastuzumab regimens with docetaxel (PHD) or paclitaxel (PHP). Current approaches for using supportive care drugs to manage the side effects of PHD and PHP are unclear. Here, we investigated the occurrence of side effects before and after supportive care medications were modified by discontinuing antipyretic analgesics. We retrospectively analyzed adverse events that occurred within 24 h of treating 76 patients with PHD or PHP. The frequencies of adverse effects in the groups before and after modification did not differ significantly (45.5% [15/33] and 44.2% [19/43], respectively). Severity also did not significantly differ between the groups. Therefore, discontinuing antipyretic analgesics as supportive care drugs had little effect on the frequency of side effects. Symptoms of feeling hot, pyrexic, and flushed were frequent, and their severity increased in the group after the support drugs were modified. Discontinuation of supportive care medications, including antipyretic analgesics, might affect the severity of certain symptoms and lead to the development of side effects that require medical intervention. Overall, our findings indicate the need to consider premedication with antipyretic analgesics, including further analysis of the risk factors that can predict symptoms. Full article

Background/Objectives: Asparaginase (ASP)-based chemotherapy has substantially improved clinical outcomes in Epstein–Barr virus (EBV)-positive NK/T-cell lymphomas (NKTCL). However, as a bacterial-derived enzyme, ASP is frequently associated with immune-mediated adverse events, particularly hypersensitivity reactions (HSRs), which may compromise both treatment efficacy and patient safety. This report presents a case of an ASP-related HSR and reviews the incidence within our institutional cohort. Detailed Case Description: A 60-year-old female presented an immediate Grade 2 HSR during her second PEG-asparaginase infusion, with pruritus, vomiting, and presyncope. The infusion was discontinued, and she was subsequently transitioned to crisantaspase—an alternative formulation—which was well tolerated without further adverse events. She remains disease-free to date. A retrospective review of institutional records (2015–2025) identified six patients with NKTCL treated with ASP-containing chemotherapy. The incidence of HSRs in this cohort was 1 of 6 (16.7%). Conclusions: As in acute lymphoblastic leukemia, HSRs to asparaginase remains a major challenge in the management of NKTCL with potential implications for treatment safety and efficacy. The establishment of standardized, consensus-based criteria for the diagnosis, classification, and management of ASP-related HSRs is urgently needed to optimize patient outcomes. Full article

Introduction: Linezolid is a reserve antibiotic used to treat infections caused by Gram-positive bacteria with resistance genes. In critically ill patients, high intra- and interindividual variability has been observed, prompting the search for alternative methods to reduce this variability and achieve the pharmacokinetic/pharmacodynamic indices necessary for a favorable efficacy–safety balance. Aim of the study: We wished to compare the safety and effectiveness of a continuous infusion (CI) versus an intermittent infusion (II) of linezolid in patients requiring intensive care. Materials and Methods: This study, registered under the number NCT05801484), was a prospective, open-label, single-center, two-arm study. Data on hematologic safety and effectiveness were collected and compared between patients receiving CI and II, respectively, at the same daily dose of linezolid (1200 mg). Results: Twenty-nine patients from the intensive care unit were included, divided into two groups. No statistically significant difference was found in 30-day mortality between the groups, nor in the likelihood of post-treatment culture negativity. However, a significantly greater reduction in C-reactive protein levels was observed in the CI group compared to the II group. Regarding safety, at CrCl < 60 mL/min, the decrease in platelets was statistically significant in group II but not in group CI. Additionally, at the 30-day follow-up, recovery from thrombocytopenia was better in the CI group. Conclusions: Continuous infusion of linezolid proved to be non-inferior to intermittent infusion at the same daily dose in terms of effectiveness. Furthermore, a lower risk of adverse reactions was identified with continuous infusion. Full article