Improvement In Therapeutic Outcomes Research Articles

The Impact of Horse-Assisted Therapy on Socio-Emotional Behaviors in Children with Autism

Animal-assisted therapy for children with autism (ASD) is a form of complementary therapy, integrating methods from various other types of therapy. AAT, or animal-assisted therapy, is a series of interventions that are based on the behavioral traits of animals, especially dogs and horses, which are the most common in this context. These interventions can be integrated into conventional treatments such as behavioral therapy, play therapy, music therapy, occupational therapy, speech therapy, and art therapy, depending on the individual needs of patients. The objective of this study was to examine the effects of an already existing Equine Assisted Therapy (EAT) program on social communication skills, executive functions and motor skills in children diagnosed with autism spectrum disorders. The research adopted an observational design to analyze how often certain behaviors occur in the presence or absence of horses in a group intervention program. This research included 16 children diagnosed with autism spectrum disorder (ASD), aged between 9 and 14 years (12 boys and 4 girls), who were selected from an School Center for Inclusive Education. The conclusions drawn from our results showed that the horse-assisted therapy, implemented in our experiment, recorded a notable improvement in all the behavioral parameters analyzed. Improvements were observed in Attention in Activity (21.2%), Communication (18.3%) and Compliance (9.1%) during activities, Physical Movements, with a difference of 34.1%, Affective State (23.33%), Visual Control (45%), Functional Skills and Response to Command (46.66%), Social Attention (33.5%) and Dynamic Motor Skills (35.55%) during activities. And the biggest difference was observed in Vocalizations, with a difference of 53%. Our results strongly support the fact that complementary therapy of autism spectrum disorders with the help of horses is an effective form of intervention, which can bring substantial improvements in therapeutic outcomes.

Combining [177Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC. SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [177Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [177Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice. H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [177Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [177Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome. The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed.

Current Perspectives on Extensive Applications of Nanocochleates-based Drug Delivery

Abstract: Enhancing therapeutic efficacy stands as a pivotal concern across various medical conditions. Traditional therapeutic approaches have encountered limitations in addressing numerous issues. Over the recent years, the integration of nanotechnology has successfully overcome these obstacles, ushering in a new era of advanced treatment modalities. One notable stride has been the utilization of lipid-based nanocarriers, which have demonstrated substantial improvements in therapeutic outcomes. Among these innovative drug delivery systems (lipid-based), nanocochleates have emerged as the focal point for augmenting therapeutic potential and enabling targeted actions. Originally employed for vaccines, genes, and fungal infections, nanocochleates have evolved to address significant life-threatening diseases where conventional therapies fall short. The distinctive capability of nanocochleates lies in their ability to deliver drugs with enhanced precision in comparison with supplementary lipid-based systems, making them a promising novel carrier for improved efficacy. This piece of writing delves into the fundamentals of nanocochleates, exploring their safety and stability aspects, recent trends, and diverse applications. Notably, nanocochleates have shown promise in managing conditions such as diabetes mellitus, malaria, leishmaniasis, cancer, viral infections, and osteoporosis. By elucidating the unique attributes and potential of nanocochleates, this review aims to contribute valuable insights into their role as a cutting- edge drug delivery system across a spectrum of critical medical scenarios

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre.

Recombination activating genes (RAG)1 and RAG2 deficiency leads to combined T/B-cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1 and RAG2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. The male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0.5-2), 2 mo (1.25-5), and 14 mo (3.63-27), age at diagnosis was 4 mo (3-6), 4.5 mo (2.5-9.75), and 27 mo (14.5-70) in SCID (n = 25; 71.4%), OS (n = 5; 14.3%), and CID (n = 5; 14.3%) patients, respectively. Common clinical manifestations were recurrent sinopulmonary infections 82.9%, oral moniliasis 62.9%, diarrhea 51.4%, and eczema/dermatitis 42.9%. Autoimmune features were present in 31.4% of the patients; 80% were in CID patients. Lymphopenia was present in 92% of SCID, 80% of OS, and 80% of CID patients. All SCID and CID patients had low T (CD3, CD4, and CD8), low B, and increased NK cell numbers. Twenty-eight patients underwent hematopoietic stem cell transplantation (HSCT), whereas seven patients died before HSCT. Median age at HSCT was 7 mo (4-13.5). Survival differed in groups; maximum in SCID patients who had an HLA-matched family donor, minimum in OS. Totally 19 (54.3%) patients survived. Early molecular genetic studies will give both individualized therapy options, and a survival advantage because of timely diagnosis and treatment. Further improvement in therapeutic outcomes will be possible if clinicians gain time for HSCT.

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas.

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma (BCL) globally. Recently, its incidence has increased in Europe, the United States, and Asia, with the number of gastrointestinal FL cases expected to increase. Genetic abnormalities related to t(14;18) translocation, BCL2 overexpression, NF-κB pathway-related factors, histone acetylases, and histone methyltransferases cause FL and enhance its proliferation. Meanwhile, microRNAs are commonly used in diagnosing FL and predicting patient prognosis. Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted, resulting in a marked improvement in therapeutic outcomes for FL. Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options, FL treatment has become more complex, requiring combinatorial therapeutic regimens. However, optimal treatment combinations have not yet been achieved, highlighting the importance of a complete under-standing regarding the pathogenesis of gastrointestinal FL. Accordingly, this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations. Moreover, the results of clinical trials are summarized, with a particular focus on treating nodal and gastrointestinal FLs.

The master antioxidant defense is activated during EBV latent infection.

To our knowledge, this is the first report delineating the activation of the master antioxidant defense during EBV latency. We show that EBV-triggered reactive oxygen species production activates the Keap1-NRF2 pathway in EBV-transformed cells, and LMP1 plays a major role in this event, and the stress-related kinase TBK1 is required for NRF2 activation. Moreover, we show that the Keap1-NRF2 pathway is important for cell proliferation and EBV latency maintenance. Our findings disclose how EBV controls the balance between oxidative stress and antioxidant defense, which greatly improve our understanding of EBV latency and pathogenesis and may be leveraged to opportunities toward the improvement of therapeutic outcomes in EBV-associated diseases.

A 3D numerical model of controlled drug delivery to solid tumor by means of mild microwave hyperthermia-activated thermo-sensitive liposomes

A computational 3D analysis of liposomal drug delivery to investigate the effectiveness of this innovative therapy as an alternative to conventional chemotherapy is shown in this study. The temperature field evolution is obtained via the Local Thermal Non-Equilibrium (LTNE) bioheat model by including both variable porosity and blood vessels sizes to describe the local structure of the investigated tissue. Heating is induced by means of a microwave antenna directly inserted in tumor tissue, supplying a pulsating power to avoid tissue necrosis. Interstitial flow and drug diffusion are modeled by means of Darcy's law and convection-diffusion equations, respectively; Starling's law is included to simulate transcapillary exchange. After validating the model with available literature data, the results show that liposomal drug delivery leads to a 10% improvement in therapeutic outcomes (i.e., Fraction of Killed Cells, FKC). It is also proved that considering blood flow in the LTNE porous media model yields a more realistic evolution of drug diffusion and subsequent FKC, while severe tissue damage is avoided because of the pulsating power supply. This study highlights the potential benefits of using liposomal drug delivery in cancer chemotherapy via microwave-induced heating.

Delivery of Therapeutic RNA to the Bone Marrow in Multiple Myeloma Using CD38-Targeted Lipid Nanoparticles.

Multiple myeloma (MM) is a cancer of differentiated plasma cells that occurs in the bone marrow (BM). Despite the recent advancements in drug development, most patients with MM eventually relapse and the disease remains incurable. RNA therapy delivered via lipid nanoparticles (LNPs) has the potential to be a promising cancer treatment, however, its clinical implementation is limited due to inefficient delivery to non-hepatic tissues. Here, targeted (t)LNPs designed for delivery of RNA payload to MM cells are presented. The tLNPs consist of a novel ionizable lipid and are coated with an anti-CD38 antibody (αCD38-tLNPs). To explore their therapeutic potential, it is demonstrated that LNPs encapsulating small interference RNA (siRNA) against cytoskeleton-associated protein 5 (CKAP5) lead to a ≈90% decrease in cell viability of MM cells in vitro. Next, a new xenograft MM mouse model is employed, which clinically resembles the human disease and demonstrates efficient homing of MM cells to the BM. Specific delivery of αCD38-tLNPs to BM-residing and disseminated MM cells and the improvement in therapeutic outcome of MM-bearing mice treated with αCD38-tLNPs-siRNA-CKAP5 are shown. These results underscore the potential of RNA therapeutics for treatment of MM and the importance of developing effective targeted delivery systems and reliable preclinical models.

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma.

Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes. Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors. On the discovery cohort, the median age was 61years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33months, and overall survival was 45months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5years than those with two CYP2D6 copies (21%vs. 84%; p<.0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7-24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5years (56% vs. 87%; p=.02, HR=3.6; 95% CI, 1.1-5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV. Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients. Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.

Recent advances in immunotherapy and molecular targeted therapy for gastric cancer.

Our increasing understanding of the molecular biological characteristics of cancer and of cancer genomics is facilitating the development of immunotherapy and molecular targeted drugs for gastric cancer. After the approval of immune checkpoint inhibitors (ICIs) for melanoma in 2010, many different cancers have been shown to respond to such treatments. Thus, the anti-PD-1 antibody nivolumab was reported to prolong survival in 2017, and ICIs have become the mainstay of treatment development. Many clinical trials of combination therapies with cytotoxic agents and molecular-targeted agents, as well as combinations of immunotherapeutic agents acting via different mechanisms, are currently underway for each treatment line. As a result, further improvements in therapeutic outcomes for gastric cancer are anticipated in the near future.

Mental disorders and diabetes mellitus (Update 2023)

Psychiatric disorders and psychological problems are common in patients with diabetes mellitus. There is atwofold increase in depression which is associated with suboptimal glycemic control and increased morbidity and mortality. Other psychiatric disorders with ahigher incidence of diabetes are cognitive impairment, dementia, disturbed eating behavior, anxiety disorders, schizophrenia, bipolar disorders and borderline personality disorder. The coincidence of mental disorders and diabetes has unfavorable influences on metabolic control and micro- and macroangiopathic complications. Improvement of therapeutic outcome is achallenge in the modern health care system. The intentions behind this position paper are to rise awareness of this special set of problems, to intensify cooperation between involved health care providers and to reduce incidence of diabetes mellitus as well as morbidity and mortality from diabetes in this patient group.

A prognostic prediction model for ovarian cancer using a cross-modal view correlation discovery network.

Ovarian cancer is a tumor with different clinicopathological and molecular features, and the vast majority of patients have local or extensive spread at the time of diagnosis. Early diagnosis and prognostic prediction of patients can contribute to the understanding of the underlying pathogenesis of ovarian cancer and the improvement of therapeutic outcomes. The occurrence of ovarian cancer is influenced by multiple complex mechanisms, including the genome, transcriptome and proteome. Different types of omics analysis help predict the survival rate of ovarian cancer patients. Multi-omics data of ovarian cancer exhibit high-dimensional heterogeneity, and existing methods for integrating multi-omics data have not taken into account the variability and inter-correlation between different omics data. In this paper, we propose a deep learning model, MDCADON, which utilizes multi-omics data and cross-modal view correlation discovery network. We introduce random forest into LASSO regression for feature selection on mRNA expression, DNA methylation, miRNA expression and copy number variation (CNV), aiming to select important features highly correlated with ovarian cancer prognosis. A multi-modal deep neural network is used to comprehensively learn feature representations of each omics data and clinical data, and cross-modal view correlation discovery network is employed to construct the multi-omics discovery tensor, exploring the inter-relationships between different omics data. The experimental results demonstrate that MDCADON is superior to the existing methods in predicting ovarian cancer prognosis, which enables survival analysis for patients and facilitates the determination of follow-up treatment plans. Finally, we perform Gene Ontology (GO) term analysis and biological pathway analysis on the genes identified by MDCADON, revealing the underlying mechanisms of ovarian cancer and providing certain support for guiding ovarian cancer treatments.

Insight into Potential Biomedical Application of Mesoporous Materials.

The physicochemical properties of many drugs have a decisive impact on their bioavailability, as well as the pharmacokinetic efficiency in various disease therapeutics. That is why mesoporous materials have attracted a special interest in the drug delivery field, facilitating the loading of drugs into their pores due to their high surface area and porosity. The interfacial interactions established with drug molecules represent the driving force for efficient drug loading and controlled release kinetics. Moreover, these materials offer an optimal design for implantable local-delivery devices or for improving the accuracy of imaging techniques in clinical diagnosis. Their use is validated by improvements in therapeutic outcome and prevention of side effects. This review discusses the role of mesoporous materials in different biomedical applications.

PAP6 Surgery in the age of multimodal cancer therapy: Advances and the path to the future

Japan has produced world-class achievements in the surgical treatment of solid tumor cancers, both in short- and long-term outcomes. Up through the 1980s, standard surgical procedures were established in different areas of cancer for not only primary lesion resection but also preventive dissection of lymph nodes at risk of metastasis, resulting in the improvement of therapeutic outcomes. The 1990s saw the evolution and dissemination of these procedures as minimally invasive approaches through their combination with laparoscopy and thoracoscopy.

The role of nutritional support in non-small-cell lung cancer treatment

Scientific discoveries from recent years, along with rapid progress in clinical nutrition, are gradually changing the views of physicians around the world regarding the role of nutritional support in the treatment of patients with cancer. Nutritional support in the modern context is considered not only as part of basic care but also as a serious therapeutic tool in the treatment and rehabilitation of patients with cancer. The effectiveness of additional substrate provision in reducing the number of complications during specific treatment, as well as the ability of nutritional therapy to improve patients quality of life, has been proven.&#x0D; The present review is devoted to the problem of nutritional supplementation in patients with non-small-cell lung cancer.&#x0D; According to the current international clinical guidelines, the primary treatment for non-small-cell lung cancer is surgery, included as part of combination treatment, which aggravates nutritional status disorders. Against the background of metabolic disorders characteristic of the malignant process, anorexia-cachexia syndrome develops, accompanied by weight loss, which is extremely difficult to reverse. The metabolic response caused by surgical injury significantly accelerates catabolic processes and blocks anabolic ones, sharply increasing the patient's need for macronutrients and especially for protein, which, in the absence of exogenous intake, is extracted from muscle tissue. For the assimilation of this protein, an energy supply (carbohydrates and fats) is necessary, most of which is also derived from the patient's own tissues. With progressive weight loss in the preoperative period, protein and fat reserves in the postoperative period are not sufficient.&#x0D; The relationship between malnutrition and adverse treatment outcomes dictates the need for routine determination of nutritional status and correction of existing disorders in all patients with lung cancer. Nevertheless, most clinicians pay insufficient attention to the problem of nutritional status disorders in patients with non-small-cell lung cancer.&#x0D; To describe the necessity and safety of nutritional therapy in patients with non-small-cell lung cancer, an analysis of publications on the topic was carried out with a preliminary search in the medical databases PubMed and Medline. The data obtained show convincingly that patients with non-small-cell lung cancer often have anorexia-cachexia syndrome. In the perioperative period, nutritional support for non-small-cell lung cancer improves the immediate and long-term results of surgical treatment.&#x0D; Currently, nutritional therapy should be considered as an integral component of any anticancer treatment, as it contributes to the improvement of therapeutic results.

Cost Utility of Prasugrel in Postangioplasty Diabetic Patients

ObjectivesTo prevent thrombotic events after angioplasty, current guidelines recommend dual antiplatelet therapy with aspirin and thienopyridine. Clopidogrel is the only thienopyridine currently available in the Brazilian National Health System. The purpose of this study was to determine the cost-effectiveness of prasugrel, an alternative thienopyridine, compared with clopidogrel in patients with acute coronary syndrome and diabetes mellitus who underwent angioplasty. MethodsA state-transition Markov model was created to simulate the progression of diabetic patients after angioplasty. The model had a lifetime horizon and discounted outcomes at a 5% annual rate. The risks of myocardial infarction and death were calculated using data from the diabetes subgroup, and the risks of bleeding were calculated using data from the overall group from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38 trial. Direct costs were estimated using official Brazilian open data. Quality of life values were obtained through literature search. Univariate and multivariate sensitivity analyses were performed. ResultsPrasugrel was associated with more quality-adjusted life-years (QALYs) (5.03 vs 4.94) and higher costs (US$975.11 vs US$575.97), resulting in an incremental cost-utility ratio (ICUR) of US$4303.86/QALY. In one-way sensitivity analysis, the costs of prasugrel had the greatest impact on ICUR, followed by the initial age entering the cohort. In the probabilistic sensitivity analysis, all ICUR values simulations were less than one Brazilian gross domestic product per capita/QALY (US $5802.86). ConclusionsGiven the appealing economic profile, the clinical debate between reducing the risk of myocardial infarction and increasing the risk of bleeding may overcome economic concerns in the Brazilian National Health System.

Association between circulating MicroRNAs (hsa-miR-92a-1* and hsa-miR-454) and multiple sclerosis phenotypes and activity statu

Efficient diagnosis of multiple sclerosis (MS) disease along with early prediction of its progression will ultimately lead to better management, control of complications and improvement of therapeutic outcomes and patient’s well-being. Blood based biomarkers like circulating microRNAs represent a non- invasive, fast, and easily measured markers with a promising potential. This work intended to assess the relative expression of circulating hsa-miR-454 and hsa-miR-92a-1* as a diagnostic and prognostic tool among Egyptian MS patients in terms of correlation to disease type and severity. hsa-miR-454 and hsa-miR-92a-1* relative expression was measured in the plasma of 31 MS patients, relapsing remitting MS (RRMS, n=21) and progressive MS (PMS, n=10) and 20 age and sex matched normal controls by using reverse transcription followed by real time PCR. Disease severity assessment was done in the form of patient expanded disability status scale (EDSS) evaluation. Relative expression of hsa-miR-454 and hsa-miR-92a-1* did not show a statistically significant difference between MS cases and controls. However, hsa-miR-454 was significantly higher among RRMS patients in comparison to PMS patients (P = 0.04). Additionally, both markers showed a statistically significant upregulation among patients in disease exacerbation in comparison to patients in remission (P = &lt;0.01) and both showed a negative correlation with EDSS. In conclusion, microRNAs may represent potential valuable non-invasive biomarkers for assessment of MS type (RRMS vs PMS), as well as for prediction of disease activity and severity in MS patients.

Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: recent advancements, molecular effects, and future directions in the omics era.

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted attention in the biomedical field thanks to their ability to prompt hyperthermia in response to an alternated magnetic field. Hyperthermia is well known for inducing cell death, in particular in tumour cells, which seem to have a higher sensitivity to temperature increases. For this reason, hyperthermia has been recommended as a therapeutic tool against cancer. Despite the potentialities of this approach, little is still known about the effects provoked by magnetic hyperthermia at the molecular level, and about the particular cell death mechanisms that are activated. Nevertheless, in-depth knowledge of this aspect would allow improvement of therapeutic outcomes and favour clinical translation. Moreover, in the last few decades, a lot of effort has been put into finding an effective delivery strategy that could improve SPION biodistribution and localisation at the action site. The aim of this review is to provide a general outline of magnetic hyperthermia, focusing on iron oxide nanoparticles and their interactions with magnetic fields, as well as on new strategies to efficiently deliver them to the target site, and on recent in vitro and in vivo studies proposing possible cell death pathways activated by the treatment. We will also cover their current clinical status, and discuss the contributions of omics in understanding molecular interactions between iron oxide nanoparticles and the biological environment.

Infections Deaths in the PLATO Trial

Background Cardiovascular benefits of aggressive dual antiplatelet therapy may be associated with extra risks including bleeding, cancer, and infections discovered first for prasugrel in the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel (TRITON) trial. Ticagrelor in PLATO also caused slightly more infections but surprisingly less sepsis-related deaths (SRD) than clopidogrel. However, verified infection fatalities in PLATO were lacking from the public domain. We obtained the complete Food and Drug Administration (FDA)-issued primary causes death list, matched it with the few local site records dataset and analyzed the patterns of infections and deaths reported in PLATO. Methods Among infections, the FDA spreadsheet contains only two primary death codes for pneumonia (12–2) and SRD (12–8). We obtained local evidence for two pneumonia and two SRD and matched those with the FDA records. We assessed how SRD patterns were reported among nonvascular death's dataset. Results The FDA PLATO records indicate that clopidogrel caused numerically less ( n = 8) primary pneumonia deaths than ticagrelor ( n = 10) but over three times more SRD ( n = 23/7). Among matched verifiable outcomes, both pneumonia deaths were correct, but two clopidogrel SRD were incorrect. Of the remaining 21 clopidogrel SRD, 6 were reported as two separate closed paired entries in Brazil (lines 76 and 78 and 86 and 88) and India (lines 436 and 440), suggesting last minute addition of potentially incorrect SRD reports. Four ticagrelor SRD (lines 24,193,467 and 650) were “compensated” with close or next in line clopidogrel SRD entries (lines 22,195,468 and 651). Conclusion The FDA-issued evidence suggests no benefit of ticagrelor in preventing deaths from infections with slightly more pneumonia deaths, with possible misreporting of SRD in PLATO. These findings require an in-depth precise review of sepsis deaths in this trial.

Recent Advances in the Discovery of Biomarkers for Canine Osteosarcoma.

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.