Management Of Toxicity Research Articles

A Needs Assessment Exploring Radiation Oncology Nursing Confidence in Caring for Patients with Acute and Late Radiation Therapy Effects.

Registered Nurses (RN) have a critical and growing role in providing RO patient care. Moskalenko et al. published the first RO nursing needs assessment in the USA in 2021, reporting that RO nurses lacked standardized, structured education and certification programs for onboarding and continuing education. Herein, we report RN confidence in providing RO survivorship care. With permission from Moskalenko et al., an adapted version of their needs assessment survey was administered to RNs at a single academic medical center RO department in an IRB-exempt study. This survey used a Likert-type scale ranging from 1 (Not At All Confident) to 5 (Extremely Confident) to assess confidence across the following clinical domains: managing acute and late radiation effects, providing patient education regarding imaging, external beam radiation therapy (EBRT), high-dose rate brachytherapy (HDR), concurrent systemic therapy, anesthesia recovery, radiation safety, and general cancer knowledge. RNs in RO were surveyed with a 100% (n = 14) response rate. Respondents were 61.5% oncology-certified nurses (OCN). 84.6% attended schools without affiliated RO departments or RO clinical experiences. 69.2% reported ≥5 years of oncology experience, and 45% had ≥5 years of RO experience. All RNs reported performing patient education. RNs expressed a high degree of confidence in managing triage phone calls (median 4, IQR [4-5]). RNs had moderate confidence in their general understanding of radiation (3 [3-4]), RO care team responsibilities (3 [3-4]), radiation treatment planning (3 [2-4]) and set up (3 [2-4]). RNs expressed the lowest confidence in regulatory aspects of radiation safety (2.5 [2-3]). RN confidence with patient education included the following domains: CT (3 [3-4]), MRI (3 [3-4]), PET (3 [3-4]), simulation (3 [2-4]), EBRT (3 [3-4]), anesthesia recovery (3 [3-4]), HDR (2.5 [1-5]), medication side effect management (4 3-4]), hormone treatments (3 [2-4]), and concurrent chemoradiation (3 [3-4]). Regarding acute toxicity management, RNs reported highest confidence with prostate/genitourinary (4 [3-4]), lung (4 [3-4]), and sarcoma cancers (3.5 [2-4]); with lower scores across hematologic (2.5 [2-4]) and pediatric cancers (2 [1-4]). Regarding late side effect management, the highest scores were observed among prostate/genitourinary (3 [2-4]), sarcoma (3 [2-4]), and breast (3 [2-3]) cancers; with comparatively lower scores for skin (2 [2-4]), CNS (2 [2-3]), GI (2 [2-3]), hematologic (2 [2-3]), and pediatric cancers (2 [1-2]). While this single-site pilot project is limited by small sample size, it highlights the need for a formalized curriculum, scope of practice, and credentialing for RO nurses. These data can help to target education needs while guiding curriculum development.

Breast Cancer: Clinical-Epidemiological Profile and Toxicities of Women Receiving Treatment with Taxanes in the Amazon Region.

Breast cancer is the most common malignant disease and the leading cause of mortality among women worldwide. Antineoplastic chemotherapy is one of its primary treatments, typically based on the class of drugs known as taxanes. Despite their proven therapeutic efficacy, these drugs can induce severe toxicities, leading to dose limitations or even treatment discontinuation. The objective of this study was to describe the clinical-epidemiological profile, risk factors, and toxicities of taxane-based chemotherapy treatment in women with breast cancer in the Amazon region. This is a cross-sectional, quantitative, and descriptive study conducted with 300 women diagnosed with breast cancer undergoing taxane treatment. Most patients were in the 40-49 age range, of brown ethnicity, and had completed elementary school. The majority of patients had risk factors such as alcoholism and a sedentary lifestyles. Most women had their first pregnancy between the ages of 18 and 21, breastfed their children, had menarche between the ages of 12 and 13, and were pre-menopausal and with a family history of cancer. The most frequent histological type was non-special invasive carcinoma and the Luminal B subtype. Most participants in this study showed taxane toxicity, with neurotoxicity being the most frequent. These findings reveal the importance of early detection, comprehensive risk factors, and effective management of treatment toxicities to improve patient outcomes in breast cancer care in the Amazon region.

Lipid Emulsion for Spinal Anaesthesia Reversal - A Therapeutic Option

High spinal anaesthesia is also one of the commonly faced problems, with a low incidence of a complete spinal block; which is one of the life-threatening complications unless immediately identified and treated. Up to now, its management has relied mainly on intensive means such as respiratory and circulatory assistance. Intravenous lipid emulsions have an established position in the management of local anesthetic toxicity. After the success in this area, ILE has been used under clinical conditions for various kinds of overdose. At present, ILEs are expanding into a new field, that of reversing the effects of local anesthesia on peripheral nerves and neuraxial anesthesia. We report two cases of patients operated at our department, the first for genital prolapse under perimedullary anaesthesia, complicated by high spinal anaesthesia. The second case was a patient who underwent Caesarean section under spinal anaesthesia, intubated mid-operatively and presented with postoperative delayed awakening. Both complications were resolved by intralipid injection. We then reviewed the literature concerning similar cases and the different means used to resolve the problem.

Disparities in Acute Radiation-Related Pain and Dermatitis between Black and White Patients with Early-Stage Breast Cancer Receiving Adjuvant Radiation Following Breast Conserving Surgery

Historically, black patients with cancer experience poor clinical outcomes and low quality of life due to inadequate screening and management of cancer-related treatment toxicities. There are limited data documenting racial disparities in acute radiation-related toxicities (ARRTs) for patients with early-stage breast cancer. Therefore, we compared ARRTs between Black (B) and White (W) patients receiving adjuvant radiation following breast conserving surgery (BCS). This retrospective analysis included 317 patients with stage 0/1 breast cancer treated with adjuvant radiation between October 2019 and February 2022. 29% (N = 81) were B and 71% (N = 236) were W, with an average age of 65 (range: 32-88) for both. We abstracted weekly on-treatment-visit clinical notes (OTVs) completed by a nurse and radiation oncologist who utilized the Common Terminology Criteria for Adverse (CTCAE) v4.0 to evaluate each patient's pain score (scaled 0-10, 0 = no pain and 10 = worst), radiation dermatitis (RD; Grade 0-4), as well as non-CTCAE descriptors of pain and presence of hyperpigmentation or pruritus. We compared onset and severity of pain and rates of RD and pruritus between B and W patients. The proportion reporting pain was significantly lower among B vs. W patients (43.8% vs. 63.6%; P = 0.002). Of patients qualitatively reporting pain, B patients were significantly more likely to have their pain scored as 0 than W patients (24.3% vs. 11.7%; P = 0.024). B patients had significantly lower median pain scores than W patients (P = 0.010), with a median score of 3 (interquartile range [IQR]: 0-5.5) vs. 5 (IQR: 4-8). B patients had a significantly longer time to pain identification than W patients (P = 0.027), with median time to pain of 10th fraction (IQR: 4-13.5) vs. 8th fraction (IQR: 4-11). Radiation dermatitis was graded as 0 (50.6% vs 8.5%; P<0.001), 1 (44.4% vs 82.6%; P<0.001), 2 (14.8% vs 15.3%, P = NS), and 3 (3.7% vs 0.4%; P = 0.023), with no grade 4 RD, amongst B and W patients, respectively. Of note, B patients experiencing mild hyperpigmentation were graded as 0. We found no statistically significant differences in incidence of pruritus. Qualitative and quantitative analyses of ARRTs based on CTCAE v4.0 show discordance in pain scores and radiation dermatitis. The underscoring of pain amongst B patients suggests possible cultural hesitancy to report pain or implicit biases in evaluating pain suggesting the need for alternative ways to discuss and score pain in B patients. Our data suggests that CTCAE does not effectively assess radiation dermatitis in B patients. There are no descriptors of hyperpigmentation in grading of radiation dermatitis in CTCAE, which may lead to underreporting in dark-skinned individuals. Better assessment tools are needed to document ARRTs to ensure appropriate evaluation and treatment across all racial groups.

Sustainable antimony management via porphyrin ligand-based MOFs: From enrichment of antimony from water to the utilization in SbO2– based aqueous batteries

Antimony-based materials are rapidly developing towards industrialization, making it crucial to control potential toxicity and address sustainable antimony management. A strategy has been proposed to remove antimony from wastewater and sustainably convert the resulting antimony-enriched waste adsorbent into electrode materials. Herein, the porphyrin ligand-based zirconium metal-organic framework (PCN-222) was constructed for antimony adsorption. The antimony is initially adsorbed onto the Zr cluster nodes, spreads along the skeleton through hydrogen bonds, and finally terminates at the N-coordination fixed sites in the porphyrin ligand. Afterwards adsorption, the antimony-enriched waste adsorbent is converted to Sb nanoparticles embedded in N-doped porous carbon composite by one-step carbothermal reduction. The composite is applied into SbO2--based aqueous alkaline battery, which displays a high specific capacity with 122.5 mAh/g at 1 A/g and good cycling stability. The work provides valuable insights into the treatment of contaminated water and the management of antimony resources.

Three Cases of Local Anesthetic Systemic Toxicity following regional infiltration analgesia: The need for prompt recognition and treatment

Introduction: The diagnosis and management of systemic toxicity in patients following regional infiltration analgesia is of paramount importance. While the mechanism and risk factors have been elucidated in previous studies, we believe that due to the potentially life-threatening nature of this rare occurrence, a greater focus on diagnostic precision and management enhancements is warranted. Cases: Here, we describe three cases of LAST, the first in a 59 year old female following elective L4-L5 laminectomy and L5-S1 fusion, who suffered a cardiac arrest after receiving local Exparel and Marcaine at the time of closure; the second in a 69 year old woman following a rib block using local Exparel and Marcaine for the management of multiple rib fractures, who had a witnessed tonic-clonic seizure requiring intubation. The third patient is an 80-year-old male, who after an elective L4-L5 laminectomy and fusion, suffered a cardiac arrest after receiving local anesthetic (Exparel and Marcaine) at the time of closure. All patients were treated with intralipids and eventually recovered with no lasting deficits. Conclusion: LAST events most commonly occur in the first minutes after injection, and are characterized by CNS and cardiovascular toxicities, as seen in these patients. Delayed presentations up to several days post exposure have been described. These cases exposed the opportunity for education in early recognition and most important, the need to improve the availability of intralipids. Prompt recognition and access to intralipid is critical to the treatment of LAST, and education regarding this rare but life-threatening condition is needed in surgical and trauma centers.

The efficacy of trastuzumab-deruxtecan for the treatment of patients with advanced HER2-low breast cancer

ABSTRACT Introduction Until recently, the available human receptor epidermal growth factor 2 (HER2) targeted agents were ineffective for treating patients with HER2-low expressing breast cancer (defined as immunohistochemical expression of 1+ or 2+ without amplification). The development of novel and potent HER2-directed antibody-drug conjugates, affective at treating HER2-low expressing breast cancers, have changed the way we think about HER2-low expression and expanded the treatment options for many patients with advanced disease. Areas covered In this review, we summarize the current management of HER2-low breast cancer and commonly encountered challenges such as treatment sequencing and toxicity management. Expert opinion trastuzumab deruxtecan (T-DXd) is a treatment option for patients with advanced, HER2-low breast cancer, irrespective of the hormone receptor status. The current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer; however, other agents are available in this setting and risks and benefits for each should be considered in shared decision making. Up to 10–15% of patients receiving T-DXd develop interstitial lung disease. Patient and clinician education are key to safely implement T-DXd in clinical practice.

Definitive chemoradiation in vulvar squamous cell carcinoma: outcome and toxicity from an observational multicenter Italian study on vulvar cancer (OLDLADY 1.1)

BackgroundVulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT.MethodsThe primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale.ResultsRetrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010–November 2021). Median age at diagnosis was 72 years (range 32–89). With a median follow-up of 19 months (range 1–114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1–53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded.ConclusionIn the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.

Post-Transplant Cyclophosphamide for the Prevention of Graft-vs.-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Guide to Management for the Advanced Practitioner.

Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor cells as the donor source. Moreover, encouraging results in GVHD management have been shown with the use of PTCy alone or in combination with other immunosuppressives in the human leukocyte antigen-matched donor setting. The toxicity profile of cyclophosphamide varies extensively depending on dose, duration, overall drug exposure, and, potentially, pharmacogenetics. This review highlights the pharmacology, pharmacokinetics, and toxic effects of cyclophosphamide and offers practical guidance for clinical application in the post-transplant setting. We summarize data on the management of high-dose cyclophosphamide toxicities and provide insights into the pharmacogenetic implications on drug efficacy and safety data.

Evaluation of toxic and hazardous waste management in coal mining company heavy equipment workshop

Coal is a relatively abundant energy source, especially in East Kalimantan Province. PT X is one of the coal mining companies that has experienced increased demand to meet consumer needs. Coal mining activities use various heavy equipment that requires periodic maintenance workshops. Heavy equipment units produce Toxic and Hazardous Waste (THW). This study aims to evaluate the management of THW in workshop PT X based on applicable government regulations. THW management identifies the source, type, and generation of waste generated and activities for reduction, packaging, storage, collection/transportation, and utilization. The research results show that the number of heavy equipment used is 85 units. The THW produced during the 2021-2022 period is 13,847 tons/year of used batteries/batteries, 31,501 tons/year of used filters, 1,250 tons/year of used hoses, 30,420 tons/year of THW contaminated waste, 1,500 tons/year of used waste and oil lubricants 541,991 tons/year. Management of THW in the workshop as a whole has met the standards based on applicable regulations. Two things must be improved to improve THW management, namely labeling equipped with information about THW and THW storage areas which are classified based on the type of waste designated.

Se Ameliorates Cd Toxicity in Oilseed rape (Brassica napus L.) Seedlings by Inhibiting Cd Transporter Genes and Maintaining root Plasma Membrane Integrity.

Se (Selenium) has been reported to be an important protective agent to decreases Cd (Cadmium) induced toxic in plants. However, it remains unclear how Se mitigates the uptake of Cd and increased the resistance to Cd toxicity. Hydroponic experiments were arranged to investigate the changes of physiological properties, root cell membrane integrity and Cd-related transporter genes in rape seedlings. Comparison of the biomass between the addition of Se and the absence of Se under Cd exposure showed that the Cd-induced growth inhibition of rape seedlings was alleviated by Se. Cd decreased the photosynthetic rate (Pn), stomatal conductance (Gs) and photosynthetic pigment content including chlorophyll a, chlorophyll b and carotenoid. However, all these parameters were all significantly improved by Se addition. Moreover, exposure to Se resulted in a decrease in Cd concentration in both shoot and root, ranging from 4.28 to 27.2%. Notably, the application of Se at a concentration of 1 µmol L- 1 exhibited the best performance. Furthermore, Se enhanced cell membrane integrity and reduced superoxide anion levels, thereby contributing to the alleviation of cadmium toxicity in plants. More critically, Se decreased the expression levels of root Cd-related transporter genes BnIRT1, BnHMA2 and BnHMA4 under Cd stress, which are responsible for Cd transport and translocation. These results are important to increase crop growth and reduce Cd load in the food chain from metal toxicity management and agronomical point of view.

POSTER: AML-159 Case Report: Successful Management of Unusual Toxicity of Arsenic Trioxide (ATO) on Day 10 of Consolidation in Acute Promyelocytic Leukemia (APL)

POSTER: AML-159 Case Report: Successful Management of Unusual Toxicity of Arsenic Trioxide (ATO) on Day 10 of Consolidation in Acute Promyelocytic Leukemia (APL)

AML-159 Case Report: Successful Management of Unusual Toxicity of Arsenic Trioxide (ATO) on Day 10 of Consolidation in Acute Promyelocytic Leukemia (APL)

AML-159 Case Report: Successful Management of Unusual Toxicity of Arsenic Trioxide (ATO) on Day 10 of Consolidation in Acute Promyelocytic Leukemia (APL)

449 Carbon Fibre Versus Titanium Implant Construct in Separation Surgery with Post Adjuvant Stereotactic Ablative Radiotherapy for Spinal Oligometastatic Disease

Abstract Aim Radical treatment for Spinal Oligometastatic Disease (OMD) was often traditionally treated with morbid Tomita En Bloc Spondylectomy. Now, Stereotactic Ablative Radiosurgery (SABR) provides curative tumour ablation without open surgery, reduced cord toxicity and better pain management. SABR delivered postoperatively to Separation Surgery (SS) has shown excellent mortality rates, infection control, maximum local-control, and better pain management. This study is the first to compare clinical safety of carbon-fibre implantation (CFI) comparing to titanium implantation (TI). Method Retrospective review of OMD/OPD cases that underwent separation surgery with postoperative SABR investigating tumour histology, OMD type, instrumentation used for SS (CFI versus TI), mortality, local recurrence (LR), pain management, infection, complications, hospital length of stay, ICU length of stay and palliative outcomes at a quaternary level-1 spinal unit. Results 79 patients were in the OMD pathway, 36 patients underwent SS with/without SABR. 20 patients had SS with TI. 16 patients had SS with CFI. SS with TI±SABR: 30-day mortality-10%, 12-month mortality-15%. SS with TI+SABR: 30-day mortality-0% 12-month mortality-0%, 12-month LR-0% TI: Infection-4% SS with CFI±SABR: 30-day mortality-6%, 3-year mortality-12.5%. SS with CFI+SABR: 30-day mortality-0% 12-month mortality-0%, 12-month LR-0% CFI: Infection-0% Pain in both groups were associated with PD cases only. Conclusions SS with postoperative SABR regardless of construct material demonstrated excellent outcomes. CFI demonstrated to be superior to TI. When postoperative SABR was absent from treatment, patients had complications and was demoted to palliative decompression with neurological symptom management. This highlights the importance of SABR in conjunction to SS.

Diagnosis and practical management of digoxin toxicity: a narrative review and consensus.

There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus recommendations for management of digoxin toxicity in the clinical setting were developed through a modified Delphi approach. The recommendations highlight the importance of early recognition of signs of potentially life-threatening toxicity that requires immediate treatment with digoxin-specific antibodies. The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity. Supportive measures and management of specific signs of toxicity are also covered.

Sports fashion and sustainability: a perfect match?

PurposeSports fashion is marketed showing happiness, physical performance and self-care. Thus, sports fashion brands should see a good fit with sustainability: future orientation, self-care, care for others and going out for a physical experience, oftentimes in nature. On the other hand, sports fashion is regularly made of non-sustainable materials and produced under difficult work conditions. This paper aims to discuss the aforementioned issues.Design/methodology/approachThe paper at hand seeks to investigate sports brands' approach to sustainability by examining their product portfolio and their annual report data, analyzing their status quo and sustainability strategy. A content analysis is conducted employing the brands' annual reports and their online shops as data sources to assess their status quo in terms of sustainability as well as future plans.FindingsResults show that on the ecological side, brands unanimously focus on carbon reduction, organic cotton, recycled polyester, circularity-ready business model innovation and water and toxic waste management. The social aspect may be divided into the focal brand and the supply chain, including similar measures: equality and diversity, the promotion of ethnic and cultural minorities and increased safety and health for workers.Originality/valueThe paper derives development opportunities and pitfalls for sports fashion brands.

Diagnosis and management of toxicity associated with the recreational use of nitrous oxide.

Diagnosis and management of toxicity associated with the recreational use of nitrous oxide.

Management of plant nutrient dynamics under alkaline soils through graded application of pressmud and gypsum.

An incubation experiment was conducted to monitor the effect of different organic matter inputs with the graded application of gypsum at different time intervals on soil pH, sodium (Na) content and available plant nutrients like nitrogen (N) and sulphur (S) in alkaline soil. The experiment was formulated with nine treatments, i.e. control (T1), recommended dose of fertilizer (RDF) (T2), RDF+Gyp1 (T3), RDF+FYM5+Gyp2 (T4), RDF+FYM10+Gyp1 (T5), RDF+PM5+Gyp2 (T6), RDF+PM10+Gyp1 (T7), RDF+FYM2.5+PM2.5+Gyp2 (T8), RDF+FYM5+PM5+Gyp1 (T9) with three replications. Periodical soil samples were taken at six and twelve months intervals. Results showed that the addition of organic matter reduced the pH and Na content in the soil. More reduction was observed at one year period as compared to six months. The addition of farmyard manure (FYM) and pressmud (PM) at 10 t/ha with gypsum (1 t/ha) improved available N and available S content as compared to organic inputs (5 t/ha) with gypsum (2 t/ha) in soil. Pressmud application with FYM showed better availability of plant nutrients and a reduction of soil pH (8.39 to 7.79) and Na content from 626 to 391 mEq/L in the soil during the incubation period. During the study, the application of treatment T9 (FYM and PM in equal ratio with 1 t/ha gypsum) showed a better availability of available N (175 to 235 kg/ha) and S (15.44 to 23.24 kg/ha) and reduced the active ion concentration of Na. This study is very useful for the management of sodium toxicity, improving soil health and the mineralization rate of organic matter through the application of organic inputs for sustainable crop production.

Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins.

Copper is an essential mineral nutrient that provides the cofactors for some key enzymes. However, excess copper is paradoxically cytotoxic. Wilson's disease is an autosomal recessive hereditary disease characterized by pathological copper accumulation in many organs, with high mortality and disability. Nevertheless, many questions about the molecular mechanism in Wilson's disease remain unknown and there is an imperative need to address these questions to better exploit therapeutic strategy. In this study, we constructed the mouse model of Wilson's disease, ATP7A-/- immortalized lymphocyte cell line and ATP7B knockdown cells to explore whether copper could impair iron-sulfur cluster biogenesis in eukaryotic mitochondria. Through a series of cellular, molecular, and pharmacological analyses, we demonstrated that copper could suppress the assembly of Fe-S cluster, decrease the activity of the Fe-S enzyme and disorder the mitochondrial function both in vivo and in vitro. Mechanistically, we found that human ISCA1, ISCA2 and ISCU proteins have a strong copper-binding activity, which would hinder the process of iron-sulfur assembly. Of note, we proposed a novel mechanism of action to explain the toxicity of copper by providing evidence that iron-sulfur cluster biogenesis may be a primary target of copper toxicity both in cells and mouse models. In summary, the current work provides an in-depth study on the mechanism of copper intoxication and describes a framework for the further understanding of impaired Fe-S assembly in the pathological processes of Wilson's diseases, which helps to develop latent therapeutic strategies for the management of copper toxicity.

Asciminib in the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia: Focus on Patient Selection and Outcomes.

Tyrosine kinase inhibitors (TKIs) have significantly changed the treatment of chronic myeloid leukemia (CML) and improved outcomes for patients with CML in chronic phase (CML-CP) and accelerated phase (AP). Now armed with numerous effective therapeutic options, clinicians must consider various patient- and disease-specific factors when selecting the most appropriate TKI across lines of therapy. While most patients with CML expected to have a near-normal life expectancy due to the success of TKIs, emphasis has expanded beyond response and survival to include factors like quality of life, tolerability, and long-term toxicity management. Importantly, a subset of patients can achieve sustained deep molecular response and can attain treatment-free remission. Despite these successes, unmet needs remain related to CML treatment, including the persistent challenge of treatment resistance and intolerance, broadening treatment options for patients with resistance mutations or serious comorbidities, and focus on specific populations such as children and young adults. In particular, the only previously available treatments for patients with CML-CP with the T315I mutation were ponatinib, olverembatinib (exclusively approved for use in China at the time of this writing), omacetaxine, and hematopoietic stem cell transplantation. Asciminib has entered the CML treatment landscape as a new option for adult patients with CML-CP who have received ≥2 prior TKIs or those with the T315I mutation. Asciminib's unique mechanism of action, Specifically Targeting the ABL Myristoyl Pocket, sets it apart from traditional adenosine triphosphate-competitive TKIs. While asciminib may overcome unmet needs for patients with CML-CP and continues to be studied in other novel settings, guidance on how to integrate asciminib in treatment algorithms is needed. This review focuses on clinical data and how asciminib can overcome current unmet needs, discusses how to individualize patient selection, and highlights future directions to investigate asciminib in earlier lines of therapy and in children and adolescents.