Microbiota Predict Infections and Acute Graft-Versus-Host Disease After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.

Hemophagocytic lymphohistiocytosis-like toxicity (carHLH) after CD19-specific CAR T-cell therapy.

Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with significant toxicities secondary to immune activation, including a rare but increasingly recognised severe toxicity resembling haemophagocytic lymphohistiocytosis (carHLH). We report the development of carHLH in 14·8% of paediatric patients and young adults treated with CD19-specific CAR T-cell therapy with carHLH, occurring most commonly in those with high disease burden. The diagnosis and treatment of carHLH required a high index of suspicion and included multidrug immunomodulation with variable response to therapies. Compared to patients without carHLH, patients with carHLH had both reduced response to CAR T-cell therapy (P-value = 0·018) and overall survival (P-value = < 0·0001).

Exploring the multidimensional effects of human activity and land cover on fire occurrence for territorial planning.

The strong link between climate change and increased wildfire risk suggests a paradigm change on how humans must co-exist with fire and the environment. Different studies have demonstrated that human-induced fire ignitions can account for more than 90 % of forest fires, so human co-existence with wildfires requires informed decision making via preventive policies in order to minimize risk and adapt to new conditions. In this paper, we address the multidimensional effects of three groups of drivers (human activity, geographic and topographic, and land cover) that can be managed to assist in territorial planning under fire risk. We found critical factors of strong interactions with the potential to increase the likelihood of starting a fire. Our solution approach included the application of a Machine Learning method called Random Undersampling and Boosting (RUSBoost) to assess risk (fire occurrence probability), which was subsequently accompanied by a sensitivity analysis that revealed interactions of various levels of risk. The prediction performance of the proposed model was assessed using several statistical measures such as the Receiver Operating Characteristic curve (ROC) and the Area Under the Curve (AUC). The results confirmed the high accuracy of our model, with an AUC of 0.967 and an overall accuracy over test data of 93.01 % after applying a Bayesian approach for hyper-parameter optimization. The study area to test our solution approach comprised the entire geographical territory of central Chile.

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries.

BACKGROUND: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. METHOD/DESIGN: This is a prospective multi-centre observational study aiming to enrol 7-8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. DISCUSSION: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for "Integrated Management of Childhood Illness" used in dengue-endemic countries. TRIAL REGISTRATION: NCT01550016. Registration Date: March 7, 2012.

Barriers to the use of tests for early detection of colorectal cancer in Chile.

This study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.

Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies.

Chimeric antigen receptor (CAR) T-cell therapy is rapidly advancing, offering promising treatments for patients with hematological malignancy. However, associated infectious complications remain a significant concern because of their contribution to patient morbidity and non-relapse mortality. Recent epidemiological insights shed light on risk factors for infections after CAR T-cell therapy. However, the available evidence is predominantly retrospective, highlighting a need for further prospective studies. Institutions are challenged with managing infections after CAR T-cell therapy but variations in the approaches taken underscore the importance of standardizing infection prevention and management protocols across different healthcare settings. Therefore, the Infectious Diseases Special Interest Group of the American Society of Transplantation and Cellular Therapy assembled an expert panel to develop best practice considerations. The aim was to guide healthcare professionals in optimizing infection prevention and management for CAR T-cell therapy recipients and advocates for early consultation of Infectious Diseases during treatment planning phases given the complexities involved. By synthesizing current evidence and expert opinion these best practice considerations provide the basis for understanding infection risk after CAR T-cell therapies and propose risk-mitigating strategies in children, adolescents, and adults. Continued research and collaboration will be essential to refining and effectively implementing these recommendations.