Project description:Background and objectiveNeuroblastoma (NB) is a common malignant tumor in children, and its treatment remains challenging. Precision medicine, as an individualized treatment strategy, aims to improve efficacy and reduce toxicity by combining unique patient- and tumor-related factors, bringing new hope for NB treatment. In this article, we review the evidence related to precision medicine in NB, with a focus on potential clinically actionable targets and a series of targeted drugs associated with NB.MethodsWe conducted an extensive search in PubMed, EMBASE, and Web of Science using key terms and database-specific strategies, filtered for time and language, to ensure a comprehensive collection of literature related to precision medicine in NB. The main search terms consisted of "neuroblastoma", "precision medicine", "pediatrics", and "targeting". The articles included in this study encompass those published from 1985 to the present, without restrictions on the type of articles.Key content and findingsALK inhibitors and MYCN inhibitors have been developed to interfere with tumor cell growth and dissemination, thereby improving treatment outcomes. Additionally, systematic testing to identify relevant driver mutations is crucial and can be used for diagnosis and prognostic assessment through the detection of many associated molecular markers. Furthermore, liquid biopsy, a non-invasive tumor detection method, can complement tissue biopsy and play a role in NB by analyzing circulating tumor DNA and circulating tumor cells to provide genetic information and molecular characteristics of the tumor. Recently, trials conducted by many pediatric oncology groups have shown the urgent need for new approaches to cure relapsed and refractory patients.ConclusionsThe purpose of this review is to summarize the latest advances in clinical treatment of NB, to better understand and focus on the development of promising treatment approaches, and to expedite the transition to the precision medicine clinical relevance in NB patients.
Project description:AbstractPneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.
Project description:PurposeWith the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field.MethodsTo pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust."ResultsThe participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence.ConclusionOngoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.
Project description:Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future.
Project description:Asthma affects more than 300 million people worldwide and poses a large socioeconomic burden, particularly in the 5% to 10% of severe asthmatics. So far, each entry of new biologics in clinical trials has led to high expectations for treating all severe asthma forms, but the outcome has only been successful if the biologic, as add-on treatment, targeted specific patient subgroups. Indeed, we now realize that asthma is a heterogeneous disease with multiple phenotypes, based on distinct pathophysiological mechanisms, called endotypes. Thus, asthma therapy is gradually moving to a personalized medicine approach, tailored to individual's asthma endotypes identified through biomarkers. Here, we review the clinical efficacy of antibody-related therapeutics undergoing clinical trials, or those already approved, for the treatment of severe type 2 asthma. Biologics targeting type 2 cytokines have shown consistent efficacy, especially in patients with evidence of type 2 inflammation, suggesting that the future of asthma biologics is promising.
Project description:Congenital human cytomegalovirus (HCMV) infection can result in severe and permanent neurological injury in newborns, and vaccine development is accordingly a major public health priority. HCMV can also cause disease in solid organ transplant (SOT) and hematopoietic stem-cell transplant (HSCT) recipients, and a vaccine would be valuable in prevention of viremia and end-organ disease in these populations. Currently there is no licensed HCMV vaccine, but progress toward this goal has been made in recent clinical trials. A recombinant HCMV glycoprotein B (gB) vaccine has been shown to have some efficacy in prevention of infection in young women and adolescents, and has provided benefit to HCMV-seronegative SOT recipients. Similarly, DNA vaccines based on gB and the immunodominant T-cell target, pp65 (ppUL83), have been shown to reduce viremia in HSCT patients. This review provides an overview of HCMV vaccine candidates in various stages of development, as well as an update on the current status of ongoing clinical trials. Protective correlates of vaccine-induced immunity may be different for pregnant woman and transplant patients. As more knowledge emerges about correlates of protection, the ultimate licensure of HCMV vaccines may reflect the uniqueness of the target populations being immunized.
Project description:The location of Ecuador-an equatorial nation-favors the multiplication and dispersal of the Leptospira genus both on the Pacific Coast and in the Amazon tropical ecoregions. Nevertheless, leptospirosis epidemiology has not been fully addressed, even though the disease has been recognized as a significant public health problem in the country. The purpose of this literature review is to update knowledge on the epidemiology and geographical distribution of Leptospira spp. and leptospirosis in Ecuador to target future research and develop a national control strategy. A retrospective literature search using five international, regional, and national databases on Leptospira and leptospirosis including humans, animals, and environmental isolations of the bacteria and the disease incidence in Ecuador published between 1919 and 2022 (103 years) with no restriction on language or publication date was performed. We found and analyzed 47 publications including 22 of humans, 19 of animals, and two of the environments; three of these covered more than one of these topics, and one covered all three (i.e., One Health). Most (60%) of the studies were conducted in the Coastal ecoregion. Twenty-four (51%) were published in international journals, and 27 (57%) were in Spanish. A total of 7342 human and 6314 other animal cases were studied. Leptospirosis was a frequent cause of acute undifferentiated febrile illness in the Coast and Amazon and was associated with rainfall. All three major clusters of Leptospira-pathogenic, intermediate, and saprophytic-were identified from both healthy and febrile humans, the environment, and animals; moreover, nine species and 29 serovars were recorded over the three Ecuadorian ecoregions. Leptospira infections were diagnosed in livestock, companion, and wild animals from the Amazon and the Coast regions along with sea lions from the Galápagos Islands. Microscopic-agglutination test was the diagnostic tool most widely used. Three reviews covering national data on outpatients and inpatients determined the varied annual incidence and mortality rate, with males being more commonly affected. No human cases have been reported in the Galápagos Islands. Genomic sequences of three pathogenic Leptospira were reported. No studies on clinical ground, antibiotic resistance, or treatment were reported, nor were control programs or clinical-practice guidelines found. The published literature demonstrated that leptospirosis was and still is an endemic disease with active transmission in the four geoclimatic regions of Ecuador including the Galápagos Islands. Animal infections, distributed in mainland and insular Ecuador, pose a significant health risk for humans. Nationwide epidemiological surveys-encouraging more research on the fauna and environment with appropriate sampling design on risk factors for human and animal leptospirosis, Leptospira genotyping, increased laboratory capability, and readily available official data-are required to improve our understanding of transmission patterns and to develop effective national intervention strategies with the intention of applying One Health approaches.
Project description:Lung cancer is the leading cause of cancer death worldwide, making it an attractive disease for chemoprevention. Although avoidance of tobacco use and smoking cessation will have the greatest impact on lung cancer development, chemoprevention could prove to be very effective, particularly in former smokers. Chemoprevention is the use of agents to reverse or inhibit carcinogenesis and has been successfully applied to other common malignancies. Despite prior studies in lung cancer chemoprevention failing to identify effective agents, we now have the ability to identify high-risk populations, and our understanding of lung tumour and premalignant biology continues to advance. There are distinct histological lesions that can be reproducibly graded as precursors of non-small-cell lung cancer and similar precursor lesions exist for adenocarcinoma. These premalignant lesions are being targeted by chemopreventive agents in current trials and will continue to be studied in the future. In addition, biomarkers that predict risk and response to targeted agents are being investigated and validated. In this Review, we discuss the principles of chemoprevention, data from preclinical models, completed clinical trials and observational studies, and describe new treatments for novel targeted pathways and future chemopreventive efforts.
Project description:Iron overload is becoming an increasing problem as haemoglobinopathy patients gain greater access to good medical care and as therapies for myelodysplastic syndromes improve. Therapeutic options for iron chelation therapy have increased and many patients now receive combination therapies. However, optimal utilization of iron chelation therapy requires knowledge not only of the total body iron burden but the relative iron distribution among the different organs. The physiological basis for extrahepatic iron deposition is presented in order to help identify patients at highest risk for cardiac and endocrine complications. This manuscript reviews the current state of the art for monitoring global iron overload status as well as its compartmentalization. Plasma markers, computerized tomography, liver biopsy, magnetic susceptibility devices and magnetic resonance imaging (MRI) techniques are all discussed but MRI has come to dominate clinical practice. The potential impact of recent pancreatic and pituitary MRI studies on clinical practice are discussed as well as other works-in-progress. Clinical protocols are derived from experience in haemoglobinopathies but may provide useful guiding principles for other iron overload disorders, such as myelodysplastic syndromes.
Project description:COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.