Search Results (66)

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

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

Background/Objectives: Advanced hepatocellular carcinoma (HCC) presents limited treatment options; however, immunotherapy demonstrates encouraging outcomes and acceptable adverse reactions in advanced HCC. This study evaluates the efficacy and safety of combining serplulimab, the bevacizumab biosimilar HLX04, and hepatic arterial infusion chemotherapy (HAIC) as a first-line therapy. Methods: This prospective, observational, single-center phase II trial enrolled untreated HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C. All patients received serplulimab (4.5 mg/kg) and HLX04 (15.0 mg/kg) every 3 weeks, followed by the HAIC-FOLFOX regimen. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), and safety. Results: A total of 32 patients were enrolled. The best outcomes showed an ORR of 53.1%, including 17 partial responses (PR, 53.1%) and 12 stable diseases (SD, 37.5%), resulting in a DCR of 90.6%. Subgroup analysis showed a higher ORR in patients with a single lesion and those receiving ≥3 treatment cycles, with an ORR of 60.7% in the latter group. Additionally, five patients underwent successful hepatectomy after ≥3 treatment cycles, with postoperative pathology confirming extensive tumor necrosis. Kaplan–Meier analysis estimated PFS rates of 89.9% (95% CI: 79.5–100.0%) at 6 months and 70.8% (95% CI: 54.2–92.4%) at 12 months. No deaths related to adverse events (AEs) occurred; four (12.5%) patients experienced grade IV AEs and twelve (37.5%) patients experienced grade III AEs. Conclusions: Serplulimab, HLX04, and HAIC combined as a first-line treatment for advanced HCC have demonstrated promising efficacy, particularly in patients completing ≥3 cycles, with an acceptable safety profile. Further investigation in larger trials is required. Full article

Background/Objectives: Gaucher disease type 1 is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GBA1 gene. Although enzyme replacement therapy has improved patient outcomes, there is limited long-term real-world data on taliglucerase alfa. This study aimed to evaluate the long-term efficacy and safety of taliglucerase alfa in both treatment-naïve and previously treated patients with Gaucher disease type 1 over a 10-year period. Methods: This prospective, single-centre cohort study involved 29 patients (13 treatment-naïve and 16 previously treated with imiglucerase) who received taliglucerase alfa from 2015 to 2024. Clinical, hematological, visceral, skeletal, and biochemical parameters were assessed at baseline and at 12, 60, and 120 months. Biomarkers included chitotriosidase and glucosylsphingosine. Safety was evaluated through adverse event reporting and anti-drug antibody testing. Results: Hemoglobin and platelet counts improved or remained stable in all patients. By 60 months, liver volume had normalised in treatment-naïve patients (mean reduction: 23.1%), while spleen volume had decreased by up to 47.3%. Lyso-Gb1 levels decreased by 86.1% in patients who had not previously received treatment and by 59.5% overall, with a strong correlation to adherence. Bone mineral density improved in most cases. 137 adverse events were reported, 24% of which were mild infusion-related reactions. Anti-drug antibody developed in two patients, including one with a reduced therapeutic response. Conclusions: Taliglucerase alfa offers sustained long-term clinical, hematological and biochemical benefits in both treatment-naïve and previously treated Gaucher disease type 1 patients, with a favorable safety profile. Glucosylsphingosine proved to be a highly sensitive biomarker for monitoring therapeutic efficacy and detecting treatment response. Full article

Background: Periprosthetic joint infections (PJIs) remain among the most challenging complications in orthopedic surgery, often requiring prolonged antibiotic therapy and complex surgical interventions. Oritavancin, a long-acting semisynthetic lipoglycopeptide approved for acute bacterial skin and skin structure infections, has emerged as a potential off-label agent in PJI treatment due to its favorable pharmacokinetic properties, potent Gram-positive coverage, and documented antibiofilm activity. Objectives: This comprehensive review aims to assess the current clinical and preclinical data regarding the potential use of oritavancin in the management of PJIs. Methods: A comprehensive literature search was conducted in three major databases. Results: Six studies were included. In vitro data demonstrated strong activity of oritavancin against methicillin-resistant Staphylococcus aureus and S. epidermidis biofilms, particularly in synergy with rifampin. Clinical reports described successful outcomes in both acute and chronic PJI cases, including those with limited surgical options. Weekly or monthly dosing regimens were well-tolerated and effective in suppressive and curative contexts. Adverse events were infrequent but included infusion-related reactions. Conclusions: Oritavancin represents a promising adjunct or alternative to conventional antimicrobial regimens in PJIs, particularly for outpatient management or in patients with multidrug-resistant Gram-positive infections. Further prospective studies are needed to define its role, optimal dosing, and long-term efficacy in this complex clinical setting. Full article

Background: Intravenous vancomycin remains a key agent in the treatment of complex orthopedic infections, particularly those involving methicillin-resistant Staphylococcus aureus (MRSA). However, its use is associated with significant risks, most notably nephrotoxicity. Despite guideline recommendations, standardized dosing and monitoring protocols are often absent in orthopedic settings, leading to inconsistent therapeutic drug exposure and preventable adverse events. This study evaluated the clinical impact of implementing a structured standard operating procedure (SOP) for intravenous vancomycin therapy in orthopedic inpatients. Methods: We conducted a single-center, pre-post cohort study at a university orthopedic department. The intervention consisted of a standard operating procedure (SOP) for intravenous vancomycin therapy, which mandated weight-based loading doses, renal function-adjusted maintenance dosing, trough level monitoring, and defined dose adjustments. Patients treated before SOP implementation (n = 58) formed the control group; those treated under the SOP (n = 56) were prospectively included. The primary outcome was the incidence of vancomycin-associated acute kidney injury (VA-AKI) defined by KDIGO Stage 1 criteria. Secondary outcomes included therapeutic trough level attainment and infusion-related or ototoxic adverse events. Results: All patients in the post-SOP group received a loading dose (100% vs. 31% pre-SOP, p < 0.001). The range of measured vancomycin trough levels narrowed substantially after SOP implementation (7.1–36.2 mg/L vs. 4.0–80.0 mg/L). The proportion of patients reaching therapeutic trough levels increased, although this was not statistically significant. Most notably, VA-AKI occurred in 17.2% of patients in the control group, but in none of the patients after SOP implementation (0%, p = 0.0013). No cases of ototoxicity were observed in either group. Infusion-related reactions decreased after the implementation of the SOP, though not significantly. Conclusions: The introduction of a structured vancomycin protocol significantly reduced adverse drug events and improved dosing control in orthopedic inpatients. Incorporating such protocols into routine practice represents a feasible and effective strategy to strengthen antibiotic stewardship and clinical quality in surgical disciplines. Full article

This work introduces an original approach to the manufacturing of ionizing radiation-sensitive systems for radiotherapy applications—dosimetry. They are based on the Fricke dosimetric solution and the formation of macro-gels and capsules, and nano- and micro-gels. The reaction of ionic polymers, such as sodium alginate, with Fe and Ca metal ions is employed. Critical polymer concentration (c*) is taken as the criterion. Reaction of ionic polymers with metal ions leads to products related to c*. Well below c*, nano- and micro-gels may form. Above c*, macro-gels and capsules can be prepared. Nano- and micro-gels containing Fe in the composition can be used for infusion of a physical gel matrix to prepare 2D or 3D dosimeters. In turn, macro-gels can be formed with Fe ions crosslinking polymer chains to obtain radiation-sensitive hydrogels, so-called from wall-to-wall, serving as 3D dosimeters. The encapsulation process can lead to capsules with Fe ions serving as 1D dosimeters. This work presents the concept of manufacturing various gel structures, their main features and manufacturing challenges. It proposes new directions of research towards novel dosimeters. Full article

Background: Biosimilar versions of rituximab have similar safety and efficacy as the reference product across all indications based on the extrapolation principle. Our organization replaced intravenous (IV) rituximab (Mabthera) with IV rituximab (Truxima-Biosimilar) in 2021. Hence, our practice changed to providing first cycles of IV rituximab (Truxima-Biosimilar) instead of rituximab (Mabthera), and if the first cycle was completed without severe infusion-related reactions (IRRs), then subsequent cycles were given with subcutaneous (SC) rituximab as per institutional guidelines. However, the safety of this approach has not been evaluated. Methods: A retrospective study was conducted at the Princess Nourah Oncology Center in Saudi Arabia. The primary objective was to assess IRRs after using IV rituximab (Truxima-Biosimilar) in the first cycle followed by SC rituximab in subsequent cycles. Results: Of the 71 patients reviewed, 35 patients met the eligibility criteria. Only one (3%) patient developed an IRR. However, it was a Grade 1 IRR, as per CTCAE.V5, and the patient was able to complete the remaining IV infusion successfully. Hence, all patients transitioned from IV rituximab biosimilar to SC rituximab Mabthera. Conclusions: This real-world study demonstrates that transitioning from IV rituximab biosimilar to SC Mabthera is a well-tolerated and safe practice, confirming the extrapolation principle of biosimilars. Full article

Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies. Methods: This retrospective, single-center study examined pediatric IBD patients receiving anti-TNF-α therapy at the “Grigore Alexandrescu” Emergency Hospital for Children in Bucharest, Romania, from January 2015 to October 2024. AEs were categorized into non-infectious complications (acute infusion reactions, anti-drug antibody formation), dermatological effects (erythema nodosum, vasculitis), neurological effects (Guillain–Barré syndrome), and infections. AEs were analyzed in relation to the specific anti-TNF-α agent administered and comprehensively characterized. Results: Of 40 patients enrolled, 22 (55%) had Crohn’s disease (CD). The median (IQR) age at diagnosis was 14.8 years [10.8–15.9]. IFX was used in 34 (85%) patients while 6 (15%) patients received either ADA or IFX/ADA sequential therapy. Twenty-seven AEs were documented in 19 (47.5%) patients, the most prevalent being antidrug antibody formation (44.4%), infections (22.2%), and acute infusion reactions (22.2%). All ADA-exposed patients experienced at least one AE, compared to 41.2% (n = 14) patients treated with IFX, p = 0.01. Conclusions: AEs were observed in approximately half of the study cohort, with anti-drug antibody formation emerging as the most frequent complication. ADA therapy was associated with a significantly higher rate of AEs compared to IFX. These findings underscore the critical importance of vigilant monitoring for patients undergoing anti-TNF-α therapy in pediatric IBD management. Full article

Background: Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. A hallmark of the disease is the rapid remission of proteinuria following a high dose of steroids. Recurrent disease or steroid dependence are common, leading to a high steroid burden and the introduction of steroid sparing therapy. Anti-CD20 antibodies have been increasingly used with excellent results in complicated INS. Nevertheless, their use can be limited by the occurrence of infusion-related reactions (IRRs). Methods: This report discusses further treatment options for children who are intolerant to RTX and presents the first report of a successful switch to obinutuzumab (OBI) for a child with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS) and RTX intolerance who was unresponsive to a desensitization protocol. Results: A 12-year-old boy with SDNS since the age of 2, was treated with steroids, cyclophosphamide and cyclosporine A (CsA). Because of the prolonged use of calcineurin inhibitors, a course of rituximab (RTX) was planned. Unfortunately, during first infusion, the boy presented with IRR. A desensitization protocol following the first unsuccessful infusion also failed. Facing the risks of long-term cyclosporine therapy, a decision was made to switch to another type of anti-CD20 antibody. Obinutuzumab infusion with a modified premedication scheme was uneventful. Conclusions: Switching therapy to obinutuzumab may be considered an option in nephrotic children who are intolerant to RTX when alternative therapies have been exhausted. The addition of montelukast to premedication and employment of desensitization protocols may decrease the risk of infusion-related reactions to anti-CD20 agents. Full article

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients. Full article

Background: Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children’s quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments. Objective: This study aims to evaluate the long-term efficacy and safety of rituximab administration in children with SSNS, encompassing FRNS and SDNS, and SRNS over a two-year follow-up period, facilitating individualized management. Methods: We conducted an open-label, multicenter, randomized, and patient-oriented study (RICHNESS), involving children aged 3–18 with SRNS (18) and SSNS (11) undergoing 2 years continuous RTX therapy. The primary outcome was complete/partial remission (CR/PR), as defined by IPNA/KDIGO guidelines, at 6, 12, 18, and 24 months on RTX; secondary outcomes included adverse events. Key endpoints included the estimated glomerular filtration rate (eGFR), the albumin-to-creatinine ratio (ACR), CD20 levels, IgG levels, and the incidence of infections. Kidney biopsies were performed in 94% of SRNS patients. RTX was administered every 6–9 months, depending on CD20 levels, IgG levels, and the presence of infections. The eGFR and ACR were assessed every 6 months. Results: Some 31 children were selected for RTX treatment. Overall, 2 experienced severe allergic reactions, leading to their exclusion from the final analysis of 29 children. In the SSNS group, all children achieved and maintained complete remission within 2 years. Remission rates in the SRNS group ranged from 39% (RR 0.78; 95% CI: 16.4–61.4%, NNT 9) at the 6th month to 72% (RR 1.44; 95% CI: 51.5–92.9%) over the 2-year follow-up period due to continuous RTX therapy. The median duration of RTX use was 26.1 months, with a median cumulative dose of 1820 mg/m². Adverse reactions and complications were presented by mild infusion-related reactions in 3 children (10.3%), severe allergic reactions in 2 children (6.2%), hypogammaglobulinemia in 7 children (24%), infections in 3 children (10.3%), severe destructive pneumonia in 1 child, recurrent respiratory infections in 2 children, and neutropenia in 1 child (3.44%). Conclusions: RTX was tolerated well, and proved highly effective as a steroid-sparing agent, offering potential in terms of stopping relapses and minimizing steroid-related side effects. It also demonstrated efficacy in slowing progression in SRNS, indicating potential for use in ACR reduction and renal function restoration, but requires careful use given potential severe allergic reactions and infectious complications. Further studies should focus on long-term cost-effectiveness and deferred side effects. Full article