Treatment Options Research Articles

Malignant pleural mesothelioma: The disdained member of thoracic oncology!

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure. The ban on asbestos has helped to lower the incidence, but in developing countries like India, it is expected to rise. It has an extended latency period usually progressing over decades and presents with nonspecific symptoms. It has a median survival ranging between 10-22 months. The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT, with the last two predicting the resectability of the tumor better than CT alone. A pleural biopsy along with an array of immunohistochemical markers, such as p16, BRCA1 associated protein 1, and claudin-4, are required for a definitive diagnosis. Several genetic alterations have prognostic significance as well. The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored. The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. However, the latter continues to be a robust treatment option for patients with the epithelioid subtype. Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant, adjuvant, and palliative settings along with systemic treatment. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc ) that have led to significant developments in recent years with clinically meaningful results.

EMERGENCY ESOPHAGECTOMY FOR ESOPHAGEAL PERFORATION FOLLOWING BALLOON DILATION DUE TO STENOSIS POST-ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL CANCER: A CASE REPORT

Introduction and importance: Esophageal perforation from endoscopic dilation is rare (0.53% to 0.6% incidence) but serious, with mortality rates of 12.5% to 20%. Optimal treatment is debated and depends on the medical facility’s capabilities, patient’s symptoms, extent of perforation, and severity of associated lesions. Treatment options include medical management (fasting, antibiotics), esophageal stenting, surgical closure, or emergency esophagectomy. Early diagnosis and treatment are crucial to reduce mortality and hospital stay. Case presentation: A 49-year-old male with lower third esophageal cancer (stage cT1aN0M0) underwent endoscopic submucosal dissection (ESD) and developed esophageal stenosis. Dilation attempts led to esophageal perforation, necessitating emergency esophagectomy with gastric conduit reconstruction. The patient improved and was discharged on day 10 post-operation without complications. Clinical discussion: Managing esophageal perforation post-endoscopic dilation is complex. This case highlights the importance of rapid recognition and intervention. Esophageal dilation, while effective for stenosis, carries a perforation risk. Treatment decisions must be tailored to individual patients, considering perforation severity, patient’s health, and facility resources. Here, severe perforation and clinical condition warranted emergency esophagectomy. The successful outcome underscores the efficacy of this surgical intervention when performed timely at specialized centers. Conclusion: Emergency esophagectomy with gastric conduit reconstruction for treating esophageal perforation due to stenosis post endoscopic submucosal dissection for esophageal cancer is considered a safe procedure and can be performed at an experienced esophageal surgery center.

Overall Survival and Cancer-Specific Mortality in Patients with Prostate Cancer Undergoing Definitive Therapies: A Narrative Review

The overall survival (OS) of patients with prostate cancer (PCa) who receive locally definitive therapy is generally better than that of patients who do not receive definitive therapy. There is no difference in the incidence of local recurrence or distant metastasis between treatment modalities. Because the prognosis of PCa is relatively good, many studies have focused on quality of life after treatment as an endpoint. However, a limited number of patients develop biochemical recurrence after definitive treatment for PCa and subsequently develop distant metastasis or die from PCa. Therefore, we believe that preventing local recurrence and distant metastasis and prolonging the OS should be emphasized when selecting a treatment modality for PCa. In this review, the significance and usefulness of radical prostatectomy and radiation therapy as the main modalities of definitive therapies for local PCa and locally advanced PCa were evaluated, as well as the outcomes of OS and PCa-specific mortality and the treatment options after biochemical recurrence to improve the oncological outcomes.

Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease

AbstractNeurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are prominently life‐threatening examples of neurodegenerative diseases. The complexity of the pathophysiology in neurodegenerative diseases causes difficulties in diagnosing. Although the drugs temporarily help to correct specific symptoms including memory loss and degeneration, a complete treatment has not been found yet. New therapeutic approaches have been developed to understand and treat the underlying pathogenesis of neurodegenerative diseases. With this purpose, clustered‐regularly interspaced short palindromic repeats/CRISPR‐associated protein (CRISPR/Cas) technology has recently suggested a new treatment option. Editing of the genome is carried out by insertion and deletion processes on DNA. Safe delivery of the CRISPR/Cas system to the targeted cells without affecting surrounding cells is frequently investigated. Extracellular vesicles (EVs), that is exosomes, have recently been used in CRISPR/Cas studies. In this review, CRISPR/Cas and EV approaches used for diagnosis and/or treatment in AD, PD, ALS, and HD are reviewed. CRISPR/Cas and EV technologies, which stand out as new therapeutic approaches, may offer a definitive treatment option in neurodegenerative diseases.

An in vitro assessment of ionizing radiation impact on the efficacy of radiotherapy for breast cancer

Abstract Objectives Ionizing radiation is still one of the most effective treatment options for various cancers. It is possible to reduce the side effects of this effective treatment method and increase the chance of success by elucidating the responses it creates at the molecular level in the cell. This study aims to investigate of the molecular effects of therapeutic ionizing radiation on breast cancer, which is the most prevalent cancer type. Methods MDA-MB-231 and MCF7 cell lines were irradiated with 4 and 8 Gy ionizing radiation and monitored for up to 7 days. RNA was collected at 48 and 96 h, when cellular molecular mechanisms became most evident, and quantitative expression levels of microRNAs (miR-208a, miR-124, miR-145), for which cancer-radiation associations have been determined from existing literature and databases, were evaluated. Results Exposure to ionizing radiation resulted in a dose-dependent reduction in cell viability in both MCF7 and MDA-MB-231 breast cancer cell lines. Furthermore, microRNA expression analysis revealed notable changes at all levels. The research demonstrates that miR-208a, miR-145, and miR-124 are crucial in the biological response to ionizing radiation. Conclusions Therapeutic ionizing radiation profoundly affects cell viability and microRNA expression in breast cancer cell lines, showing dose and time-dependent effects. The observed microRNA expression patterns suggest potential biomarkers for radiation response and therapeutic targets to improve radiotherapy efficacy. Further in vivo validation and exploration of these microRNAs’ roles in modulating cellular response to ionizing radiation are needed.

Ferroptosis Inhibition: A Key Opportunity for the Treatment of Ischemia/Reperfusion Injury in Liver Transplantation.

The outcome after liver transplantation has improved in recent years, which can be attributed to superior storage and transportation conditions of the organs, as well as better peri- and postoperative management and advancements in surgical techniques. Nevertheless, there is an increasing discrepancy between the need for organs and their availability. Consequently, the mortality rate on the waiting list is high and continues to rise. One way of counteracting this trend is to increase the use of "expanded criteria donors." This means that more and more donors will be included, especially those who are older and having additional comorbidities (eg, steatosis). A major complication of any transplantation is the occurrence of ischemia/reperfusion injury (IRI), which often leads to liver dysfunction and failure. However, there have been various promising approaches to minimize IRI in recent years, but an effective and clinically applicable method to achieve a better outcome for patients after liver transplantation is still missing. Thereby, the so-called marginal organs are predominantly affected by IRI; thus, it is crucial to develop suitable and effective treatment options for patients. Recently, regulated cell death mechanisms, particularly ferroptosis, have been implicated to play a major role in IRI, including the liver. Therefore, inhibiting this kind of cell death modality presents a promising therapeutic approach for the management of this yet untreatable condition. Thus, this review provides an overview of the role of ferroptosis in liver IRI and transplantation and discusses possible therapeutic solutions based on ferroptosis inhibition to restrain IRI in marginal organs (especially steatosis and donation after circulatory death organs).

Serial OCT Imaging of Spontaneous Closure of a Pediatric Traumatic Macular Hole

Purpose: To describe a case of spontaneous closure of a pediatric traumatic macular hole (MH) using serial optical coherence tomography (OCT) imaging. Methods: A single case was evaluated. Results: An 8-year-old girl developed a full-thickness MH in the right eye after sustaining blunt trauma from a bungee cord. She was observed monthly. By 3 months, the MH spontaneously closed, at which time an epiretinal membrane (ERM) developed. Spontaneous release of the posterior hyaloid and ERM at 5 months resulted in a relatively normal foveal contour. At the patient’s last follow-up, the visual acuity in the right eye had improved from 20/80 to 20/30. Conclusions: Observation of a pediatric traumatic MH is a viable initial treatment option. Serial OCT imaging was useful in observing the natural history and mechanism behind spontaneous closure of a traumatic MH.

A comprehensive review of AAV-mediated strategies targeting microglia for therapeutic intervention of neurodegenerative diseases

AbstractNeurodegenerative diseases pose a significant health burden globally, with limited treatment options available. Among the various cell types involved in the pathogenesis of these disorders, microglia, the resident immune cells of the central nervous system, play a pivotal role. Dysregulated microglial activation contributes to neuroinflammation and neuronal damage, making them an attractive target for therapeutic intervention. Adeno-associated virus (AAV) vectors have emerged as powerful tools for delivering therapeutic genes to specific cell types in the central nervous system with remarkable precision and safety. In the current review, we discuss the strategies employed to achieve selective transduction of microglia, including the use of cell-specific promoters, engineered capsids, and microRNA (miRNA) strategies. Additionally, we address the challenges and future directions in the development of AAV-based therapies targeting microglia. Overall, AAV-mediated targeting of microglia holds promise as a novel therapeutic approach for neurodegenerative diseases, offering the potential to modify disease progression and improve patient outcomes.

A Specialised Antenatal Music Therapy (SAMT) programme for pregnant women with mental health conditions: A mixed-methods proof-of-concept study in Ireland

ABSTRACT Introduction Perinatal mental health has a long-term impact on maternal and infant well-being. Non-pharmacological treatment options are needed for pregnant women and emerging evidence has shown the potential of music therapy to improve perinatal mental health and antenatal attachment. However, research is lacking on individual music therapy for pregnant women with mental health conditions and formal music therapy services are currently absent within perinatal mental health care in Ireland. This mixed-methods, proof-of-concept study aimed to assess the feasibility and preliminary evidence on the effectiveness of a specialised antenatal music therapy (SAMT) programme for pregnant women attending the Specialist Perinatal Mental Health Service (SPMHS). Method Pregnant women between 25 and 33 weeks gestation with various mental health conditions were recruited through the SPMHS to receive six in-person or online sessions of SAMT. Feasibility outcomes included retention, adherence, and fidelity.\\ Assessment of participants’ wellbeing, anxiety, and antenatal attachment were conducted before and after SAMT and each session. Semi-structured interviews were conducted and analysed using thematic analysis. Results Twelve pregnant women were included and nine completed SAMT and assessments, demonstrating a 75% retention rate. High levels of adherence and fidelity were reported. Significant improvements were observed in participants’ wellbeing, anxiety levels, and antenatal attachment. Qualitative findings highlighted the therapeutic benefits, the accessibility and challenges of the online setting, distinctive therapeutic experiences, and participants’ recommendations. Discussion The findings suggest implementing SAMT within the Irish SPMHS is feasible and beneficial. The study offers insights into the therapeutic mechanisms of SAMT and supports the progression to a larger trial.

Clinical and patient reported treatment outcomes of livedoid vasculopathy: A systematic review

Abstract Livedoid vasculopathy (LV) is a rare condition affecting the lower extremities, often linked to hypercoagulable states or vascular disorders, and despite increasing treatment options, patients frequently experience suboptimal outcomes. Our systematic review of 44 studies, involving 216 patients, found that Rivaroxaban was the most common treatment, with complete (n=18, 31%) or partial (n=40, 68%) ulcer healing and complete pain resolution in the 19% reported, while IVIG also showed promise, though results were mixed. The review highlights the need for further research to identify optimal treatments for LV and establish a standard of care for future clinical trials.

Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials

BackgroundA multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies.MethodsA comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases’ inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results.ResultsThis comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19–0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44–0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines.ConclusionsThe clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

An economic model to understand the cost-effectiveness of olanzapine orally dispersible tablets (ODT) and olanzapine film coated tablets as a group compared with other oral atypical antipsychotics for treating schizophrenia in Morocco

BackgroundAntipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco.MethodsThe study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty.ResultsAccording to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings.ConclusionsThe model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations.

Evaluating the Impact of Filtering Techniques on Deep Learning-Based Brain Tumour Segmentation

Gliomas are a common and aggressive kind of brain tumour that is difficult to diagnose due to their infiltrative development, variable clinical presentation, and complex behaviour, making them an important focus in neuro-oncology. Segmentation of brain tumour images is critical for improving diagnosis, prognosis, and treatment options. Manually segmenting brain tumours is time-consuming and challenging. Automatic segmentation algorithms can significantly improve the accuracy and efficiency of tumour identification, thus improving treatment planning and outcomes. Deep learning-based segmentation tumours have shown significant advances in the last few years. This study evaluates the impact of four denoising filters, namely median, Gaussian, anisotropic diffusion, and bilateral, on tumour detection and segmentation. The U-Net architecture is applied for the segmentation of 3064 contrast-enhanced magnetic resonance images from 233 patients diagnosed with meningiomas, gliomas, and pituitary tumours. The results of this work demonstrate that bilateral filtering yields superior outcomes, proving to be a robust and computationally efficient approach in brain tumour segmentation. This method reduces the processing time by 12 epochs, which in turn contributes to lowering greenhouse gas emissions by optimizing computational resources and minimizing energy consumption.

A Rare Case of Pulmonary Artery Trunk Aneurysm.

Pulmonary artery trunk aneurysm (PATA) is a rare and complex vascular anomaly characterized by the abnormal dilation of the initial portion of the pulmonary artery, posing significant diagnostic and therapeutic challenges. This clinical case report aims to describe the follow-up of a patient with PATA, emphasizing the role of imaging in diagnosis and monitoring, as well as discussing potential associations with other conditions. The study is designed as a clinical case report, detailing the longitudinal follow-up of a single patient with PATA. The subject of this study is a 48-year-old female patient with a history of idiopathic hypertension who developed a PATA. Data Collection and/or Analysis: Since 2010, the patient underwent various imaging exams, including echocardiography, computed tomography, and catheter angiography, to detect and evaluate the aneurysm at different stages. The imaging results indicated a progression of the aneurysm over time, underscoring the importance of imaging in the early identification and monitoring of PATA. The report also explores the possible association of PATA with conditions such as pulmonary hypertension, Behçet's disease, and Hughes-Stovin syndrome, highlighting the diagnostic complexity. Imaging diagnosis is crucial for the detection, characterization, and monitoring of PATA, providing essential information for selecting appropriate treatment options and achieving a satisfactory prognosis. An individualized treatment approach, considering both medical and surgical options, is necessary based on the clinical characteristics of each patient.

Navigating the complexities of post-traumatic stress disorder and its variants

SUMMARY In this issue of BJPsych Advances Siddaway explores the challenges of assessing and treating post-traumatic stress disorder (PTSD) and complex PTSD. In this commentary I reflect on those challenges, not least of which is the need for a thorough understanding of different approaches to diagnoses. The very concept of diagnostic classification systems can be problematic, but when used sensitively they can aid communication, assessment and treatment. The relatively new diagnosis of complex PTSD may serve as a more accurate and more useful description of some psychological difficulties, leading to better treatment decisions. Good assessment, leading to accurate diagnosis, useful formulation and effective treatment takes time, and adequate resources should be allocated. Professionals can help patients to make well-informed choices about treatment options and they should offer evidence-based treatments without unnecessary delay.

Clinical and Radiological Profile of Nine Patients with Metachromatic Leukodystrophy

Introduction: Metachromatic leukodystrophy (MLD) is a rare, demyelinating, autosomal recessive lysosomal storage disease caused by a deficiency in the arylsulfatase A enzyme (ASA), which is encoded by ARSA gene. A lack of ASA activity results in an accumulation of sulfatides in the myelin sheaths of both the central and peripheral nervous systems, leading to developmental and neurocognitive progressive deterioration that can be observed in all age groups. Methods: We present a total of 9 patients with MLD with an average age of 61 months, whose clinical, laboratory and cranial magnetic resonance imaging findings were evaluated, and who underwent an ARSA gene molecular analysis. Results: Of the 9 patients, 7 had the late infantile form of the condition, 2 had the juvenile form, and 3 were identified through family screening. The median age at diagnosis was 30 months (min 3–max 73 months), the mean ASA activity value was 2 nmol/h/mgprt and the median cranial MR imaging severity score was 10 (min 5–max 18). The grey and white matter volumes of all patients, evaluated using volBrain software, were within the normal range. At an average age of 48 months, the late-infantile MLD patients were unable to control any body part. Conclusions: Hematopoietic stem cell transplantation (HSCT), a treatment option for both the juvenile and adult forms of MLD in asymptomatic or early symptomatic patients, was performed on two of the asymptomatic and early symptomatic patients, and post-HSCT ASA activity settled within the normal range and their developmental milestones stabilized. It is important to diagnose MLD in the asymptomatic period and newborn screening can support early diagnosis.

Polymyxin combined with Ocimum gratissimum essential oil: one alternative strategy for combating polymyxin-resistant Klebsiella pneumoniae.

Introduction. Multidrug-resistant infections present a critical public health due to scarce treatment options and high mortality. Ocimum gratissimum L. essential oil (O.geo) is a natural resource rich in eugenol known for its antimicrobial activity.Hypothesis/Gap Statement. O.geo may exert effective antimicrobial activity against polymyxin-resistant Klebsiella pneumoniae and, when combined with Polymyxin B (PMB), may exhibit a synergistic effect, enhancing treatment efficacy and reducing antimicrobial resistance.Aim. This study aims to investigate the antimicrobial activity of O.geo against polymyxin-resistant K. pneumoniae using in vitro tests and an in vivo Caenorhabditis elegans model.Methodology. The O.geo was obtained by hydrodistillation followed by gas chromatography. The MIC and antibiofilm activity were determined using broth microdilution. Checkerboard and time-kill assays evaluated the combination of O.geo and polymyxin B (PMB), whereas a protein leakage assay verified its action.Results. Eugenol (39.67%) was a major constituent identified. The MIC of the O.geo alone ranged from 128 to 512 µg ml-1. The fractional inhibitory concentration index (0.28) and time-kill assay showed a synergism. In addition, O.geo and PMB inhibited biofilm formation and increased protein leakage in the plasma membrane. The treatment was tested in vivo using a Caenorhabditis elegans model, and significantly increased survival without toxicity was observed.Conclusion. O.geo could be used as a potential therapeutic alternative to combat infections caused by multidrug-resistant bacteria, especially in combination with PMB.

Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells

BackgroundTriple-negative breast cancer (TNBC), known for its aggressiveness and limited treatment options, presents a significant challenge. Adoptive cell transfer, involving the ex vivo generation of antigen-specific T cells from peripheral blood mononuclear cells (PBMCs), emerges as a promising approach. The overexpression of mesothelin (MSLN) and nucleolin (NCL) in TNBC samples underscores their potential as targets for T cell therapy. This study explored the efficacy of multi-peptide pulsing of PBMCs to generate MSLN/NCL-specific T cells targeting MSLN+/NCL+ TNBC cells.MethodsTNBC patient samples were confirmed for both MSLN and NCL expression via immunohistochemistry. Synthesized MSLN and NCL peptides were combined and administered to activate PBMCs from healthy donors. The cancer-killing ability of the resultant T cells was assessed using crystal violet staining, and their subtypes and cytotoxic cytokines were characterized through flow cytometry and cytokine bead array.ResultsFindings showed that 85.3% (127/149) of TNBC cases were positive for either MSLN or NCL, or both; with single positivity rates for MSLN and NCL of 14.1% and 28.9%, respectively. MSLN and NCL peptides, with high binding affinity for HLA-A*02, were combined and introduced to activated PBMCs from healthy donors. The co-pulsed PBMCs significantly induced TEM and TEMRA CD3+/CD8+ T cells and IFN-γ production, compared to single-peptide pulsed or unpulsed conditions. Notably, MSLN/NCL-specific T cells successfully induced cell death in MSLN+/NCL+ MDA-MB-231 cells, releasing key cytotoxic factors such as perforin, granzymes A and B, Fas ligand, IFN-γ, and granulysin.ConclusionsThese findings serve as a proof-of-concept for using multiple immunogenic peptides as a novel therapeutic approach in TNBC patients.

THE ANALYSIS STUDY OF EVALUATING THE EFFICACY AND SAFETY OF PERCUTANEUS CORONARY INTERVENTION (PCI) VERSUS EDTA (CHELATION THERAPY) FOR CORONARY ARTERY DISEASE : A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Percutaneous coronary intervention (PCI) is a pivotal treatment for patients with stable coronary artery disease (CAD), yet its overall effectiveness remains limited. Despite technological advancements, only about 5% of patients receive PCI, comparable to the 5% who are treated with pharmacological therapies. The ongoing debate between PCI and optimal drug therapy (ODT) continues, with ethylenediaminetetraacetic acid (EDTA) emerging as a notable treatment alternative. This systematic review seeks to compare the outcomes of these interventions and offer guidance for clinical decision-making. Methods: Adhering to PRISMA 2020 guidelines, this review focused on full-text articles published in English from 2012 to 2024. To ensure the inclusion of high-quality studies, editorial pieces and review articles were excluded unless they included a DOI. A comprehensive literature search was performed across several reputable databases, including ScienceDirect, PubMed, and SagePub, to collect relevant research thoroughly. Result: The review analyzed over 800 publications from these databases. After an initial screening process, eight studies were selected for detailed examination. These selected studies underwent a rigorous review to ensure comprehensive and precise evaluation. Conclusion: While both EDTA and PCI represent advanced treatment options for CAD, their effectiveness is contested due to their complexity and high costs. The systematic review indicates that PCI may offer greater benefits for patients with chronic total occlusions (CTO), showing lower mortality and myocardial infarction (MI) rates. Future research should prioritize large-scale clinical trials to further elucidate the comparative efficacy of PCI and EDTA.

Case report: Manual carbon hemoperfusion for the treatment of meloxicam toxicity in a cat and suspected ibuprofen toxicity in a dog

Extracorporeal blood purification (ECBP) has become a popular treatment option for non-steroidal anti-inflammatory drug (NSAID) toxicity in small animals. However, challenges arise when using ECBP for small dogs and cats because the priming volume required by most machine-based ECBP platforms might be excessive, leading to cardiovascular instability if a blood prime is not used. This report describes the successful use of manual carbon hemoperfusion (MCHP) to reduce plasma meloxicam levels in a cat following an inadvertent overdose and its use in a dog following suspected ibuprofen ingestion. In both animals, MCHP reduced the circuit volume needed for ECBP from 125 mL with a machine-based therapeutic plasma exchange or 104 mL with an in-series carbon hemoperfusion on an intermittent hemodialysis platform to just 40–50 mL. In the cat, MCHP reduced plasma meloxicam levels by 44%, and in both animals, the use of MCHP in these pets was well-tolerated and safe. Due to pre-existing anemia, the cat required a blood transfusion but the dog did not. MCHP is technically simple and can be performed at any hospital with access to carbon filters and blood bank resources. This technique may represent a reasonable alternative to treat NSAID toxicities in animals that are too small for conventional extracorporeal decontamination methods using either machine-based platforms without using a blood prime or in locations where these machines are unavailable.