Treatment Strategies Research Articles

Secondary Solid Cancers Among Patients with Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Multicenter Study.

We investigated the occurrence and characteristics of secondary solid cancers (SSC) in Philadelphia chromosome-negative myeloproliferative neoplasm (Ph- MPN) patients from Türkiye. We identified the potential risk factors for SSC development including the impact of cytoreductive therapies and assess the influence of SSC on patient survival. 1013 Ph- MPN patients diagnosed between 1995 and 2022 was retrospectively analyzed. Data related to demographics, clinical and laboratory parameters, SSC development, cytoreductive therapy exposure and survival outcomes were collected. Statistical analyses were performed using SPSS 26.0 software. Of the Ph- MPN patients, 6.6% developed SSC, with carcinoma being the most common type. Older age at Ph- MPN diagnosis and male gender were associated with SSC occurrence. Ph- MPN patients diagnosed with SSC and patients with no diagnosis of SSC showed no significant difference for complete blood count, spleen size, Ph- MPN diagnostic groups and driver mutation frequencies. However, SSC patients showed a higher frequency of arterial thrombosis and tendency towards increased rate for total thrombosis (p=0.030, p=0.069; respectively). In multivariate analysis, arterial thrombosis was the sole independent risk factor and interferon (IFN)-based therapy the sole protective factor for SSC development. Median overall survival (OS) did not differ between patients with and without SSC except for polycythemia vera (PV) patients with SSC, who had shorter OS (175±15 and 321±26 months, respectively; p = 0.005). Our study highlights the prevalence and characteristics of SSC in Turkish patients diagnosed with Ph- MPN. Arterial thrombosis was associated with increased SSC risk while IFN-based therapy offered potential protection from SSC. Screening for SSC in Ph- MPN patients with arterial thrombosis may be relevant. These findings emphasize the importance of malignancy screening in Ph- MPN patients, especially in high-risk subgroups and call for further research to elucidate the underlying mechanisms and optimize treatment strategies.

Seasonal Patterns of Injury Characteristics Among Farmers and Ranchers in the U.S. Central States

ABSTRACT Objective In high-risk agricultural environments, tasks, weather, and work conditions vary throughout the year. Also, injuries peak during certain periods. The primary objective of this study was to examine operator- and farm-level characteristics as risk factors for injuries within each of the four seasons. The secondary objective was to examine seasonal differences in the incident location and primary cause of these injuries. Method We analyzed data from the 2018 and 2020 Farm and Ranch Health and Safety Surveys (FRHSS), conducted in seven U.S. states by the Central States Center for Agricultural Safety and Health (CS-CASH), which were collected using a stratified random sampling approach to ensure representativeness. The survey data were merged with operation-level data from the Farm Market iD database. We employed Generalized Estimating Equations (GEE) to examine the association of seasonal injuries with individual and operation-level characteristics. The chi-square test of independence was used to assess the association between injury incident location and season, as well as injury cause and season. Pairwise Z-tests of proportions were conducted to evaluate the differences in the proportions of injuries due to specific combinations of injury location and cause across each pair of seasons. Results Surveys conducted in 2018 and 2020 yielded a combined response rate of 15.9%, with 5,428 responses and 7,915 unique operators. Of these, 903 operators reported at least one injury during the past 12 months. Seasonally, most injuries occurred in spring (34.2%), followed by summer (24.7%). Male operators had higher injury odds in the spring (adjusted OR = 1.42) and summer (aOR = 2.41). Those managing both a farm and a ranch reported increased injury risks in winter (aOR = 1.73) and spring (aOR = 1.48). Operators in cow-calf operations faced higher springtime injury risks (aOR = 1.45). High stress and exhaustion were consistent risk factors across all seasons. The highest proportion of injury incidents occurred in the farmyard (43.6%), and livestock were the most common cause of injury (24.9%). Conclusion Results highlight the need for season-specific prevention and intervention strategies, considering farmers’ and ranchers’ risk characteristics, injury locations, and causes. These findings can inform targeted measures for high-risk populations at optimal times and locations.

Dysfunction of the magnocellular subdivision of the visual thalamus in developmental dyslexia.

Developmental dyslexia (DD) is one of the most common learning disorders, affecting millions of children and adults worldwide. To date, scientific research has attempted to explain DD primarily based on pathophysiological alterations in the cerebral cortex. In contrast, several decades ago, pioneering research on five post-mortem human brains suggested that a core characteristic of DD might be morphological alterations in a specific subdivision of the visual thalamus - the magnocellular LGN (M-LGN). However, due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans, this finding was never confirmed in-vivo, and its relevance for DD pathology remained highly controversial. Here, we leveraged recent advances in high-resolution magnetic resonance imaging (MRI) at high field strength (7 Tesla) to investigate the M-LGN in DD in-vivo. Using a case-control design, we acquired data from a large sample of young adults with DD (n = 26; age 28 ± 7 years; 13 females) and matched control participants (n = 28; age 27 ± 6 years; 15 females). Each participant completed a comprehensive diagnostic behavioral test battery and participated in two MRI sessions, including three functional MRI experiments and one structural MRI acquisition. We measured blood-oxygen-level-dependent responses and longitudinal relaxation rates to compare both groups on LGN subdivision function and myelination. Based on previous research, we hypothesized that the M-LGN is altered in DD and that these alterations are associated with a key DD diagnostic score, i.e., rapid letter and number naming (RANln). The results showed aberrant responses of the M-LGN in DD compared to controls, which was reflected in a different functional lateralization of this subdivision between groups. These alterations were associated with RANln performance, specifically in male DD. We also found lateralization differences in the longitudinal relaxation rates of the M-LGN in DD relative to controls. Conversely, the other main subdivision of the LGN, the parvocellular LGN (P-LGN), showed comparable blood-oxygen-level-dependent responses and longitudinal relaxation rates between groups. The present study is the first to unequivocally show that M-LGN alterations are a hallmark of DD, affecting both the function and microstructure of this subdivision. It further provides a first functional interpretation of M-LGN alterations and a basis for a better understanding of sex-specific differences in DD with implications for prospective diagnostic and treatment strategies.

Circulating inflammatory cytokines and the risk of sepsis: a bidirectional mendelian randomization analysis

BackgroundSepsis is a life-threatening condition that is characterized by multiorgan dysfunction and caused by dysregulated cytokine networks, which are closely associated with sepsis progression and outcomes. However, currently available treatment strategies that target cytokines have failed. Thus, this study aimed to investigate the interplay between genetically predicted circulating concentrations of cytokines and the outcomes of sepsis and to identify potential targets for sepsis treatment.MethodsData related to 35 circulating cytokines in 31,112 individuals (including 11,643 patients with sepsis) were included in genome-wide association studies (GWASs) from the UK Biobank and FinnGen consortia. A bidirectional two-sample Mendelian randomization (MR) analysis was performed using single nucleotide polymorphisms (SNPs) to evaluate the causal effects of circulating cytokines on sepsis outcomes and other cytokines.ResultsA total of 35 inflammatory cytokine genes were identified in the GWASs, and 11 cytokines, including Interleukin-1 receptor antagonist (IL-1ra), macrophage inflammatory protein 1 (MIP1α), IL-16, et al., were associated with sepsis outcome pairs according to the selection criteria of the cis-pQTL instrument. Multiple MR methods verified that genetically predicted high circulating levels of IL-1ra or MIP1α were negatively correlated with genetic susceptibility to risk of sepsis, including sepsis (28-day mortality), septicaemia, streptococcal and pneumonia-derived septicaemia (P ≤ 0.01). Furthermore, genetic susceptibility of sepsis outcomes except sepsis (28-day mortality) markedly associated with the circulating levels of five cytokines, including active plasminogen activator inhibitor (PAI), interleukin 7 (IL-7), tumour necrosis factor alpha (TNF-α), beta nerve growth factor (NGF-β), hepatic growth factor (HGF) (P < 0.05). Finally, we observed that the causal interaction network between MIP1α or IL-1ra and other cytokines (P < 0.05).ConclusionsThis comprehensive MR analysis provides insights into the potential causal mechanisms that link key cytokines, particularly MIP1α, with risk of sepsis, and the findings suggest that targeting MIP1α may be a potential strategy for preventing sepsis.

Current Demography and Treatment Strategy of Vestibular Migraine in Neurotologic Perspective.

This study aims to describe the demographic features of vestibular migraine (VM) compared to other common peripheral vestibulopathies, and to assess the efficacy of trigger management as primary VM treatment. Retrospective study. Tertiary referral medical center. A retrospective chart review was performed of patients presenting with dizziness in a tertiary neurotology clinic. Among the newly diagnosed dizzy patients, those with a diagnosis of either VM, Ménière's disease, benign paroxysmal positional vertigo, or vestibular neuritis/labyrinthitis were selected for comparisons of the disease demographics. VM patients with multiple clinic visits in the study period were included for the treatment strategy analysis. A total of 1285 patients met the study inclusion criteria. In the newly diagnosed dizzy group comprising 814 patients, VM patients accounted for the largest (25%) and youngest (mean age 47 years) cohort, showing an obvious female preponderance of approximately 3.3:1. Furthermore, prevalence of VM declined significantly with advancing age, from 69%, to 34%, to 11%, in age groups of ≤30, 31 to 60, and >60 years, respectively. Trigger management, when employed as the primary VM first-year treatment, was effective for both sexes. Notably, it was more effective for women aged over than under 45 years. In our tertiary referral neurotologic center, VM was the most common diagnosis in newly diagnosed dizzy patients aged under 60 years, especially in women. For primary VM treatment, trigger management is an effective option deserving consideration.

Navigating uncharted waters: Assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: Challenges and innovations

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.

Alliin mitigates the acute kidney injury by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

Acute kidney injury (AKI) is a clinical syndrome that is characterized by a sudden loss of kidney function, leading to severe metabolic disorders, multiple organ failure, and even death. Recent studies have strengthened the evidence for ferroptosis in AKI development. Alliin, a sulfur-containing amino acid with multiple pharmacological functions, was claimed with promising antioxidant and anti-inflammation effects in protecting organ damages. Herein, Alliin's potential in AKI treatment was investigated by exploring its impact on ferroptosis, providing a new strategy for clinical AKI treatments. Cecal ligation and puncture (CLP) modeling was performed on rats, followed by treated with 7.5 and 15mg/kg/day of alliin for 6days. A declined survival rate, severe renal pathological changes, renal dysfunction, and enhanced inflammatory state were observed in CLP-treated rats, which were remarkably alleviated by alliin. Moreover, increased MDA levels, declined SOD activity, and downregulated Nrf2, GPX4, and xCT in CLP-treated rats were notably reversed by alliin. To explore potential mechanisms of alliin, NRK-52E cells were stimulated with 1μg/mL LPS for 24h, followed by culturing with 30 and 100μM of alliin for 24h. Reduced cell viability, enhanced apoptosis, increased ROS production, boosted MDA level, and declined SOD activity were observed in LPS-stimulated NRK-52E cells, accompanied by downregulated Nrf2, GPX4, and xCT, which were strikingly ameliorated by alliin. Additionally, the influence of alliin on cell viability, oxidative stress (OS), and ferroptosis in LPS-stimulated NRK-52E cells were markedly abolished by silencing Nrf2. Collectively, alliin mitigated AKI by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

MXene-Polydopamine-antiCEACAM1 Antibody Complex as a Strategy for Targeted Ablation of Melanoma.

Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.

Delayed-Onset Orbital Abscess After Orbital Blowout Fracture Repair Using Porous Polyethylene Implant.

This study aims at documenting a rare case of delayed-onset orbital abscess following the use of a nonabsorbable porous polyethylene implant in orbital fracture repair, highlighting the potential long-term risks associated with non-biodegradable orbital implants. A 44-year-old man presented with diplopia on down gaze, proptosis, and eyelid edema for 2 weeks. He had undergone repair of an inferior orbital wall fracture with a porous polyethylene implant 5 years ago. Computed tomography (CT) evaluation revealed a significant intraorbital abscess related to implant infection. Surgical interventions included abscess drainage and implant replacement, which led to patient recovery. Nonabsorbable implants, which are beneficial for orbital reconstruction, may pose a risk of occurrence of delayed infections several years following surgery. This report highlights the importance of long-term monitoring to mitigate the risks of potential late complications, which necessitate early diagnosis, appropriate intervention, and management strategies.

Characteristics of childhood cancer survivors attending a specialized survivorship clinic in the Deep South.

Childhood cancer survivors carry a high burden of late-occurring treatment-related morbidity. Long-term risk-based anticipatory surveillance allows for early detection and management of complications. We sought to examine demographic, clinical, and social characteristics associated with survivorship clinic attendance at the Taking on Life after Cancer (TLC) Clinic at the Children's Hospital of Alabama. The cohort included 1122 TLC-eligible patients diagnosed with cancer between 2000 and 2016. The outcome of interest was ≥1 TLC visit. Univariable logistic regression modeling assessed cancer type, treatment era, age, sex, race/ethnicity, payer type, rural/urban residency, and distance from clinic. Significant variables (P<0.1) were retained in multivariable modeling. The median age at diagnosis was 7 years old (0-19); 47% were female, 69% non-Hispanic White, 25% African American; 45% leukemia or lymphoma, 53% solid or CNS tumor, 3% other. We found that among 1122 survivors eligible to attend a survivorship clinic in the Deep South, only 52% attended. Odds of attendance were lower among survivors diagnosed at an older age, those with cancers other than leukemia/lymphoma, those lacking private insurance, and those living farther from the clinic. Race/ethnicity and rurality were not associated with clinic attendance. Just over half of eligible survivors attended survivorship clinic. Factors associated with non-attendance can be used to guide development of intervention strategies to ensure that childhood cancer survivors receive optimal long-term follow-up care. Measures of healthcare access (insurance status and distance to care) were identified as potential intervention targets to improve uptake of survivorship care.

Setting priorities in outpatient cardiovascular care to guarantee equitable access: the case of Tuscany region

Universal healthcare systems orient their actions towards promoting, restoring, and improving public health with a particular focus on the need to guarantee equitable access to care. Unwarranted variation in healthcare delivery poses significant challenges to health systems globally, impacting quality of care, financial sustainability, and equity of access. It is therefore important to assist healthcare management in measuring unwarranted variation in order to prioritise intervention strategies to ensure continuity of care and equity. Through an investigation of geographical variation in visit rates and waiting times, the study identifies vulnerable health districts which need priority interventions for patients with cardiovascular disease in the Tuscany region (Italy). Furthermore, a benchmarking-based method for identifying a quantitative estimate of the supply gap to be reduced is proposed. Results illustrate variation in visit rates and waiting times across local health districts in 2021, with some districts experiencing substantially lower rates and longer waiting times compared to the regional median. To address this gap, two targeted interventions aimed at increasing visit volumes and reduced waiting times through advanced training activities, technology integration, and multidisciplinary collaborations are presented. This study contributes to the topic of unwarranted variation by highlighting the necessity of tailored interventions to address diverse healthcare challenges across heterogeneous geographical areas. As healthcare systems globally navigate evolving complexities, the findings and tools presented here offer valuable guidance for policymakers and managers, aiming towards more equitable, efficient, and responsive healthcare services.

Enteric pathogen survival, food safety incidents, and potential mitigation strategies to address microbial contamination in wheat-based foods: a review.

Wheat-based foods has emerged as another potential vehicle for foodborne illness in humans. The recent occurrence of recalls involving wheat-based foods requires a full understanding of how these pathogens thrive in these food products and developing potential intervention strategies to address pathogen contamination. This manuscript is the second of a two-part review covering the status of the food safety of wheat-based products. In this manuscript, available information on the survival of enteric foodborne pathogens, food safety issues, and potential pathogen reduction steps on wheat-based foods were reviewed. Shiga toxin-producing E. coli and Salmonella are capable of surviving in wheat flours and grains for extended periods (≤ 2 years). Based on the food safety issues linked to wheat flour, the main enteric pathogens of concern are STEC (O157, O121, O26, and O103) and Salmonella. Diverse interventions such as tempering treatments, thermal treatments, and non-thermal technologies all effectively reduced the pathogenic loads of wheat grains and wheat flours (2 to 6 log CFU/g reduction). Addressing pathogen contamination of wheat-based foods is a major concern for the milling industry. Future studies could be focused on improving pathogen reduction performance and validating their effects against diverse product and process conditions.

Cervical Cancer Prevention in Individuals With Criminal Legal System Involvement.

Women with a history of criminal legal system involvement have cervical cancer rates that are 4-5 times higher than the general population-a disparity that has persisted for nearly 50 years. Our objective is to describe the intersection of mass incarceration in the United States and risk factors for cervical cancer to offer equitable prevention and treatment strategies for the field. A group was convened by American Society for Colposcopy and Cervical Pathology members and experts in the field to address a topic of importance relevant to cervical cancer elimination in underserved groups. This topic has received consistent attention from the American Society for Colposcopy and Cervical Pathology. After convening multiple times to discuss salient issues on the topic, the group proposed 12 specific recommendations related to vaccination, screening, treatment, practice, research, and policy to address the burden of cervical cancer among individuals with criminal legal system involvement. At least 10% of the incarcerated population is at risk for cervical cancer. Clinicians in all areas of practice will encounter patients with incarceration histories or current incarceration, regularly throughout their careers. Clinicians who provide preventive care for people at risk of cervical cancer can play a critical role in eliminating disparities for this vulnerable population, by drawing on these expert recommendations.

Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.

Combination therapy consisting of transarterial chemoembolization, lenvatinib, and programmed cell death protein 1 blockade for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case series study and literature review.

Patients with hepatocellular carcinoma (HCC) and inferior vena cava carcinoma tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors (TKIs) is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and one patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in one and three patients, respectively. Treatment-related adverse events of any grade occurred in of 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in one patient. The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Peritoneal dialysis-associated peritonitis caused by Tsukamurella inchonensis: a case report and literature review

BackgroundPeritoneal dialysis (PD)-associated peritonitis is a serious complication that can lead to PD discontinuation and mortality. Tsukamurella species are uncommon opportunistic pathogens that can cause peritonitis, often necessitating catheter removal.Case presentationA 46-year-old woman with a 1.5-year history of PD presented with fever and lower abdominal pain, along with cloudy peritoneal effluent showing an elevated cell count. Empiric antibiotic therapy with ciprofloxacin, cefazolin, and ceftazidime was started for PD-associated peritonitis. The peritoneal effluent culture yielded a gram-positive rod with weak acid-fast staining. A rebound in the cell count necessitated a switch of antibiotics to meropenem and vancomycin. This led to improvement, and the treatment was switched to oral levofloxacin on day 30 and the patient was discharged on day 35. Subsequently, 16S rRNA gene sequencing confirmed the isolate as Tsukamurella inchonensis.ConclusionThis case highlights the challenges in identifying and treating Tsukamurella peritonitis. Successful treatment without catheter removal in this case suggests that early detection and appropriate antibiotics may enable catheter salvage in this rare infection. However, further research is needed to establish optimal treatment strategies.

Resmetirom and Metabolic Dysfunction-Associated Steatohepatitis: Perspectives on Multidisciplinary Management from Global Healthcare Professionals.

The approval of resmetirom brings great hope to patients with metabolic dysfunction-associated steatohepatitis (MASH). The purpose of this review is to explore its impact on the global health environment. The implementation of multidisciplinary management MASH is proposed. Resmetirom has benefits in the treatment of MASH, and its safety and effectiveness have been studied. The adverse events (AEs) need to be noticed. To improve patient outcomes, a multimodal approach with medication such as resmetirom, combined with metabolic and bariatric surgery (MBS) and lifestyle interventions can be conducted. MASH, a liver disease linked with obesity, is a challenging global healthcare burden compounded by the absence of any approved pharmacotherapy. The recent conditional approval by the Food and Drug Administration(FDA) in the United States of resmetirom, an oral, liver-directed, thyroid hormone receptor beta-selective agonist, marks a significant milestone, offering a treatment option for adults with non-cirrhotic MASH and who have moderate to advanced liver fibrosis. This narrative review discusses the efficacy and safety of resmetirom and its role in the therapeutic landscape of MASH treatment. Despite the promising hepatoprotective effect of resmetirom on histological liver endpoints, its use need further research, particularly regarding ethnic differences, effectiveness and cost-effectiveness, production scalability, social acceptance and accessibility. In addition, integrating resmetirom with other multidisciplinary therapeutic approaches, including lifestyle changes and MBS, might further improve clinical liver-related and cardiometabolic outcomes of individuals with MASH. This review highlights the importance of a comprehensive treatment strategy, supporting continued innovation and collaborative research to refine treatment guidelines and consensus for managing MASH, thereby improving clinical patient outcomes in the growing global epidemic of MASH. Studies done to date have been relatively short and ongoing, the course of the disease is highly variable, the conditions of various patients vary, and given this complex clinical phenotype, it may take many years of clinical trials to show long-term benefits.

Exploring the Anticancer Potential of Furanpydone A: A Computational Study on its Inhibition of MTHFD2 Across Diverse Cancer Cell Lines.

Cancer poses a significant global health challenge due to its high mortality rate and complex treatment strategies. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), which is notably overexpressed in various malignancies, represents a promising target for anticancer drug development. Furanpydone A, a new 4-hydroxy-2-pyridone alkaloid isolated from the endophytic fungus Arthrinium sp. GZWMJZ-606, has shown potent inhibitory activity against several cancer cell lines. This study provides the first computational evaluation of furanpydone A, focusing on its potential inhibition of MTHFD2 through molecular docking and 200 ns molecular dynamics (MD) simulations. Molecular docking revealed a binding free energy of -8.08 kcal/mol for furanpydone A, comparable to the control compound DS44960156 (-8.13 kcal/mol), indicating stable interactions with the MTHFD2 active site. MD simulations confirmed the structural stability of the furanpydone A-MTHFD2 complex, with RMSD values ranging from 1.5 to 2.9 Å, RMSF values below 4 Å, and a radius of gyration (Rg) of 26.7 Å. Furanpydone A maintained approximately four consistent hydrogen bonds throughout the simulation. Analysis of furanpydone A binding pose orientations and interactions with the MTHFD2 enzyme at 0 ns, 40 ns, 80 ns, 120 ns, 160 ns, and 200 ns revealed consistent and stable binding. MM-PBSA analysis showed a binding free energy (ΔGbind) of -23.57 ± 0.13 kcal/mol, with electrostatic and van der Waals interactions contributing significantly, suggesting competitive binding affinity to the control compound (-25.32 ± 0.11 kcal/mol). The contribution of individual amino acid residues, including key residues such as ARG43, TYR84, ASN87, LYS88, GLN132, and PRO314, indicated strong interactions that support the stability of the furanpydone A-MTHFD2 complex. ADMET predictions indicated that furanpydone A met key drug-likeness criteria and demonstrated good oral bioavailability, suitable distribution profile, minimal risk of drug-drug interactions, efficient elimination, and low toxicity potential. These findings suggest that furanpydone A is a promising candidate for cancer treatment, warranting further in vitro and in vivo validation, and highlighting its potential impact on the development of new anticancer therapies.

EphA3 CAR T cells are effective against glioblastoma in preclinical models

BackgroundAdoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin...

Integrative radiomics clustering analysis to decipher breast cancer heterogeneity and prognostic indicators through multiparametric MRI

Breast cancer diagnosis and treatment have been revolutionized by multiparametric Magnetic Resonance Imaging (mpMRI), encompassing T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and Dynamic Contrast-Enhanced MRI (DCE-MRI). We conducted a retrospective analysis of mpMRI data from 194 breast cancer patients (September 2019 to October 2023). Using ‘pyradiomics’ for radiomics feature extraction and MOVICS for unsupervised clustering. Interestingly, we identified two distinct patient clusters associated with significant differences in molecular subtypes, particularly in Luminal A subtype distribution (p = 0.03), estrogen receptor (ER) (p = 0.01), progesterone receptor (PR) (p = 0.04), mean tumor size (p < 0.01), lymph node metastasis (LNM) (p = 0.01), and edema (p < 0.01). Our study emphasizes mpMRI’s potential in breast cancer by using radiomics-based cluster analysis to categorize tumors, uncovering heterogeneity, and aiding in personalized treatment strategies.