It is unclear how malignant neoplasms affect limb prognosis in patients with peripheral arterial disease (PAD). The purpose of this study was to clarify the association between malignant neoplasms and limb outcomes in patients with PAD complicated by chronic limb threatening ischaemia (CLTI).

Data for patients who underwent revascularisation between 2013 - 2015 were collected from the JAPAN Chronic Limb Threatening Ischaemia Database (JCLIMB), established as a part of the National Clinical Database. All patients included in this study had PAD with CLTI and were followed for two years. The prevalence of malignant neoplasms at the time of revascularisation was examined. Overall survival, cardiovascular death, primary patency, and major adverse limb events (MALE) were also investigated.

A total of 2 891 patients were included in the study. The patients underwent surgical revascularisation including hybrid treatment in 1 709 cases, and endovascular treatment in 1 182 cases. Overall, 62 patients (2.1%) had malignant neoplasms at revascularisation (malignancy bearing group). Primary patency and MALE free rates did not differ between patients with and without malignant neoplasms, regardless of treatment type. Overall survival was significantly poorer in the malignancy bearing than in malignancy free groups. Cardiovascular mortality was not significantly different between the malignancy bearing and malignancy free groups, regardless of treatment modality.

Approximately 2% of patients with PAD complicated by CLTI had a malignant neoplasm at the time of revascularisation. The presence of malignant neoplasms did not impact post-operative limb prognosis in patients with CLTI. Therefore, even if diagnosed with malignant neoplasms, there is no need to avoid performing optimal revascularisation for CLTI, including surgical revascularisation, provided the patient's condition and life prognosis are acceptable.

Chordomas are rare, locally aggressive primary neoplasms. Resection with negative margins is the primary recommended therapeutic approach, while adjuvant radiotherapy and chemotherapy can also play a role in their treatment in certain situations, including lesions with positive margins or those that are poorly differentiated or dedifferentiated. Cervical spine chordomas pose significant surgical challenges given their proximity to critical anatomical structures and the mechanical constraints of the cervical spine. In the current case series, authors aimed to explore the clinical and patient-reported outcomes (PROs) of the surgical treatment of cervical chordomas in a large multicenter cohort.

This multicenter case series analysis utilized data from the prospectively collected Primary Tumor Research and Outcomes Network (PTRON) registry, from its inception (May 16, 2016) to data extraction (February 29, 2024). The study population was restricted to patients with histologically confirmed cervical chordomas involving levels C0-7, who underwent surgical treatment at one of the participating centers, and for whom both the initially planned and postoperatively pathologically confirmed surgical margins were documented. Patient demographics, tumor characteristics, surgical and adjuvant treatments, local recurrence-free survival (LRFS), overall survival (OS), and perioperative adverse events were retrieved. PROs included the Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ2.0), EQ-5D, and SF-36 version 2.0 (SF-36v2).

Thirty-eight patients were identified, 12 of whom underwent true en bloc resection (EBR), 18 of whom underwent deliberate intralesional resection, and 8 of whom underwent EBR after intralesional surgery or in whom EBR failed. True EBR led to better LRFS (92% vs 83% vs 63%, respectively) and OS (83% vs 39% vs 50%, respectively). Surgical adverse events within 1 year were more frequent with true EBR (100% vs 39% vs 75%, respectively). EQ-5D, SOSGOQ2.0, and SF-36v2 showed improvement with true EBR, whereas the trends for PROs from the other groups were more variable.

This multicenter case series analysis provides critical insights into the clinical outcomes and PROs in the largest cohort of surgically treated cervical spine chordomas described to date. It underscores the importance and challenges of wide resection for oncological control. It establishes the associated morbidity and provides an overview of PROs following surgery. These findings contribute valuable evidence to inform shared decision-making and optimize patient care.

Breast cancer imposes a substantial disease burden on the Brazilian population. Furthermore, the potential unnecessary use of adjuvant chemotherapy exposes patients to risks and adverse effects without significant therapeutic benefits. The purpose of this study is to determine the extent to which genomic testing for treatment selection, particularly in early stages, is a cost-effective strategy for optimizing care, while minimizing costs and unnecessary interventions.

We estimated the economic impact of the Oncotype DX test to guide the decision about prescribing adjuvant chemotherapy. The model integrates a decision tree and a Markov model with transitions between the health states of recurrence-free survival, distant recurrence, acute myeloid leukemia, and death. The probabilities of distant recurrence were derived from the TAILORx and RxPONDER clinical trials, combined with local evidence regarding utility and overall survival estimates. The analysis was conducted from the perspective of the Brazilian private health care system, which covers about one quarter of the Brazilian population. Scenario and sensitivity analyses with Monte Carlo simulations were performed.

Compared with clinicopathologic risk assessment alone, use of the Oncotype DX test for both node-negative (N0) and node-positive (N1) leads to an increase in quality-adjusted life-years (QALYs) at lower costs (0.15 QALYs and $-3,975.59 US dollars [USD]). The main impact drivers were chemotherapy costs, chemotherapy prescription probabilities, and Oncotype DX test cost. Considering the Brazilian official cost-effectiveness thresholds ($8,000.00 USD to $24,000.00 USD per QALY), the probabilistic sensitivity analysis indicated a high probability of the test being cost-effective across all analyzed scenarios and indications.

Oncotype DX could be a cost-saving strategy in the Brazilian private health care perspective. Alternative scenarios and testing indications did not alter these conclusions.

Assessing therapeutic response in glioblastoma (GBM) is a major factor limiting the clinical development of effective therapies. The intracranial location limits serial biopsies and only provides an intermittent view of the tumor molecular profile from the initial resection. Liquid biopsy techniques, specifically small extracellular vesicle (sEV) analysis, have the potential to overcome these limitations by providing a window into the brain using peripheral blood. To address the need for monitoring tumor evolution and therapeutic resistance, we developed a GBM biomarker panel (ATPase subunit beta-2, excitatory amino acid transporter 2, CD24, CD44, CD133, and epidermal growth factor receptor) for multiplexed profiling of sEVs using an advanced GBM Extracellular Vesicle Monitoring Phenotypic Analyzer Chip. We successfully tracked patient response to treatment by monitoring changes in glioma stem cell markers on circulating sEVs. We propose that these results provide a strong rationale for using GBM sEVs as a serial monitoring tool in the future clinical management of patients with GBM.

NF2 (neurofibromatosis type 2)-related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas. While benign, these tumors can cause substantial morbidity, and effective pharmacological treatments remain limited. Here, we demonstrate that genetic ablation of focal adhesion kinase (Fak/Ptk2) impairs tumor formation and preserves hearing in a murine model of NF2. Mechanistically, we show that Fak deletion decreases macrophage infiltration, attenuates nucleotide-binding oligomerization domain-containing protein 2-, leucine rich repeats (LRR)- and pyrin domain-containing protein 3 inflammasome activation, and suppresses the hepatocyte growth factor-MET axis. Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.

In magnetic resonance imaging (MRI), direct dipole-dipole interactions between paramagnetic metal centers and water molecules govern the T₁ relaxation of contrast agents. Metal chelates featuring multiple unpaired electrons have long dominated MRI contrast agents. Despite theoretically offering more paramagnetic centers per probe, nanoparticle-based contrast agents have struggled because of the insufficient direct dipolar interactions with water, impeding their clinical adoption. Here, we present an electrophilicity-engineered magnetic sensor (EEMS), which leverages high-electronegativity metal atoms to enhance the electrophilicity of paramagnetic centers in nanosensors, enabling direct electrophilic catalytic dipolar interactions (ECD) with water for enhanced MRI. EEMS demonstrates robust T₁ contrast with a longitudinal relaxivity of 23.2 per millimolar per second at 9 tesla, visualizing tumor cell clusters as small as 68.5 micrometer in vivo. ECD-MRI allows detecting and precise resection of axillary lymph nodes containing dormant tumor cell clusters, achieving 100% survival in mice 100 days postsurgery. EEMS-enhanced ECD-MRI presents a transformative imaging principle for noninvasive visualization of previously undetectable biological entities.

Given the high recurrence rate of bladder cancer (BCa) and the significant adverse effects associated with conventional treatments, it is urgent to search for new clinical therapeutic targets and safer natural-derived compounds. Resveratrol (Res) has been demonstrated to exhibit cytotoxicity against various tumors. However, the signaling pathways and targets involved in inhibition of BCa cells still need further exploration. This study aims to investigate the mechanism of Res in Bca via suppression of the AURKA/STAT3 axis, providing important theoretical basis for subsequent further researches on Res for treating BCa.

Differentially expressed genes were identified through bioinformatics methods and the binding sites of resveratrol were also identified. The cell survival rate was detected by the CCK8 method to calculate the concentrations of Res for 30% inhibition and for 50% inhibition. Then, flow cytometry was used to detect the cell cycle and apoptosis after treatment with different concentrations of Res. Immunofluorescence staining was used to detect the effects of Res and MLN8237 on the expression of STAT3. Western blot and qPCR analyses were used to verify the reliability of the effects of Res and MLN8237 on target proteins.

AURKA was identified as the potential target of Res by computational analysis. Further validation through CCK8 assays and flow cytometry demonstrated that Res could inhibit BCa cells and their cell cycle in a time- and dose-dependent manner. Immunofluorescence staining revealed both Res and MLN8237 suppressed STAT3 expression in BCa cells. Additionally, western blot and qPCR analysis confirmed that Res and MLN8237 inhibited the expression of AURKA and known target genes (VEGF, Bcl-2, and Cyclin D1).

Our findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application.

The combination of Venetoclax (VEN), a BCL2 inhibitor, and Azacitidine (AZA), a hypomethylating agent, is the standard treatment for acute myelogenous leukemia (AML) in patients older than 65 years who are not eligible for intensive chemotherapy. While high response rates for this treatment have been noted, it has been also reported that the anti-apoptotic BCL2 family proteins BCL-XL and MCL1 may be involved in VEN resistance. However, no study has heretofore been conducted to investigate the effectiveness of treatment and the expression of BCL-XL or MCL1 in patients treated with VEN + AZA therapy. In this study, we analyzed blasts from patients with newly diagnosed AML treated with VEN + AZA therapy by qPCR, confirmed by siRNA in cultured cell lines, and evaluated the validity of the immunostaining method. We demonstrated that BCL-XL or MCL1 was highly expressed in leukemia cells of patients who did not respond to this treatment. In addition, leukemia cells from patients who had responded to VEN + AZA but relapsed during the course of treatment showed increased expression of BCL-XL or MCL1 compared to pre-treatment levels. Furthermore, downregulation of BCL-XL expression in a VEN-resistant AML cell line with siRNA increased sensitivity to VEN. On the other hand, the expression of BCL-XL and MCL1 in leukemia cells could be easily semi-quantified by immunostaining, with these results correlating with those obtained by qPCR. These results indicate that immunostaining for BCL-XL and MCL1 upon bone marrow examination at diagnosis not only can predict susceptibility to VEN + AZA therapy, but may also be useful for patient stratification for VEN + AZA treatment in the future.

BACKGROUND The most common vascular lesions of the liver are hepatic hemangiomas (HH), which are generally asymptomatic and do not require medical intervention. However, when the lesions are large or multiple, they can be a significant clinical problem. This report describes a unique case of an elderly patient with isolated hepatic hemangiomatosis associated with the onset of consumptive coagulopathy and hemolytic anemia, ultimately resulting in liver failure and death. CASE REPORT A 74-year-old man presented with jaundice, progressive weight loss, fatigue, lower-limb edema, and recurrent epistaxis. Laboratory findings revealed normocytic anemia, thrombocytopenia, hyperbilirubinemia, hypoalbuminemia, and elevated liver enzymes. Abdominal ultrasound (US) and computed tomography (CT) demonstrated hepatomegaly with multiple hypoechoic and hypodense focal lesions, initially raising suspicion of metastatic disease. Colonoscopy and upper gastrointestinal endoscopy showed no evidence of malignancy. A core-needle biopsy of the hepatic lesions, complemented by positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI), confirmed the benign nature of the lesions, consistent with isolated hepatic hemangiomatosis. The patient was managed symptomatically and discharged home with recommendations for continued outpatient monitoring and urgent consultation in the event of any clinical deterioration. Unfortunately, after 3 months of relative symptoms improvement, he developed gastrointestinal bleeding and acute liver failure, which ultimately resulted in his death. CONCLUSIONS Hepatic vascular lesions are diagnostically challenging; definitive diagnosis requires correlation of clinical, imaging, and histopathological findings, as well as multidisciplinary consultation. The clinical course of hepatic hemangiomatosis ranges from benign to life-threatening, with potential complications such as hepatic failure or coagulopathy.

IntroductionReuse of antineoplastic and supportive drugs can reduce costs by cutting down the amount of chemotherapy drug waste generated. Therefore, this study aims to analyze the disposal and reuse of preparations which contain these two pharmaceutical classes.MethodsThis is a prospective study conducted with pediatric and adult patients who did not undergo one or more chemotherapy session between July and November of 2024. The chemotherapy preparations were classified as reused or discarded and quantified. The reasons for drug disposal and patient's sociodemographic data were also analyzed.ResultsOne hundred and forty patients composed the studied population, all of them responsible for 188 missed chemotherapy sessions. The study's population is predominately adult, male, residing at Rio de Janeiro city and with less than 12 years of education. Almost half of the population (47.9%) had one or more comorbidity. The most prevalent tumors were those of the digestive system (40.1%). The drug disposal rate was 2.11%. The chemotherapy suspension rate was higher (66.3%) than non-attendance (32.6%). The patient's worsening clinical condition was the main reason (45.2%) that led to chemotherapy suspension, while miscommunication (37.1%) was the main reason attributed to non-attendance. Oxaliplatin was the most discarded drug whereas vincristine was the most reused drug.ConclusionsRate of chemotherapeutic drug disposal is higher than their reuse. Although session suspension and non-attendance are caused by different reasons, both can be reduced by implementation of an effective communication routine between patient and provider in the days prior to the scheduled session.