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Background and Objectives: Pyogenic spinal infections pose therapeutic challenges, with the optimal treatment approach remaining contentious. This study aimed to compare outcomes of conservative vs early surgical treatment (SuT) modalities in primary pyogenic spondylodiskitis through an international cohort analysis., Methods: A retrospective outcome analysis was conducted of 392 patients from the United Kingdom and Germany, treated between 2017 and 2022 with primary pyogenic spondylodiskitis. Patients were stratified by treatment modality. Propensity score matching, facilitated by a directed acyclic graph and principal component analysis, was used to balance risk factors between the compared patient cohorts. Primary outcome was mortality rate, while secondary outcomes included hospitalization duration, infection relapse, and neurological status at discharge., Results: The study included 95 patients undergoing conservative treatment, primarily treated in the United Kingdom, and 297 receiving SuT, predominantly in Germany. The mortality rate was notably higher in the conservative group (P < .001), while the surgical cohort experienced a shorter hospitalization duration (P < .01). After propensity score matching, 2 comparable cohorts of 95 patients each emerged. Subsequent analysis revealed a markedly increased mortality in the conservative group (24.2% for conservative treatment vs 4.2% for SuT, P < .001). Neither relapse nor neurological status at discharge showed significant differences between the groups., Conclusion: The study indicates that early surgical intervention may be more effective than conservative management in reducing mortality and hospital stay for patients with primary pyogenic spondylodiskitis. These findings highlight the need for prospective trials and more definitive treatment guidelines., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

High-throughput proteomics approaches have revolutionised the identification of RNA-binding proteins (RBPome) and RNA-binding sequences (RBDome) across organisms. Yet, the extent of noise, including false positives, associated with these methodologies, is difficult to quantify as experimental approaches for validating the results are generally low throughput. To address this, we introduce pyRBDome, a pipeline for enhancing RNA-binding proteome data in silico. It aligns the experimental results with RNA-binding site (RBS) predictions from distinct machine-learning tools and integrates high-resolution structural data when available. Its statistical evaluation of RBDome data enables quick identification of likely genuine RNA-binders in experimental datasets. Furthermore, by leveraging the pyRBDome results, we have enhanced the sensitivity and specificity of RBS detection through training new ensemble machine-learning models. pyRBDome analysis of a human RBDome dataset, compared with known structural data, revealed that although UV-cross-linked amino acids were more likely to contain predicted RBSs, they infrequently bind RNA in high-resolution structures. This discrepancy underscores the limitations of structural data as benchmarks, positioning pyRBDome as a valuable alternative for increasing confidence in RBDome datasets., (© 2024 Chu et al.)

RNA-binding proteins (RBPs) govern the lifespan of nearly all transcripts and play key roles in adaptive responses in microbes. A robust approach to examine protein-RNA interactions involves irradiating cells with UV light to form covalent adducts between RBPs and their cognate RNAs. Combined with RNA or protein purification, these procedures can provide global RBP censuses or transcriptomic maps for all target sequences of a single protein in living cells. The recent development of novel methods has quickly populated the RBP landscape in microorganisms. Here, we provide an overview of prominent UV cross-linking techniques which have been applied to investigate RNA interactomes in microbes. By assessing their advantages and caveats, this technical evaluation intends to guide the selection of appropriate methods and experimental design as well as to encourage the use of complementary UV-dependent techniques to inspect RNA-binding activity., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Background: Cancer and anti-cancer treatment (ACT) may be risk factors for severe SARS-CoV-2 infection and limited vaccine efficacy. Long-term longitudinal studies are needed to evaluate these risks. The Scottish COVID cancer immunity prevalence (SCCAMP) study characterizes the incidence and outcomes of SARS-CoV-2 infection and vaccination in patients with solid tumors undergoing ACT. This preliminary analysis includes 766 patients recruited since May 2020., Methods: Patients with solid-organ cancers attending secondary care for active ACT consented to the collection of routine electronic health record data and serial blood samples over 12 months. Blood samples were tested for total SARS-CoV-2 antibody., Results: A total of 766 participants were recruited between May 28, 2020 and October 31, 2021. Most received cytotoxic chemotherapy (79%). Among the participants, 48 (6.3%) were tested positive for SARS-CoV-2 by PCR. Infection rates were unaffected by ACT, largely aligning with the local population. Mortality proportion was not higher with a recent positive SARS-CoV-2 PCR (10.4% vs 10.6%). Multivariate analysis revealed lower infection rates in vaccinated patients regardless of chemotherapy (HR 0.307 [95% CI, 0.144-0.6548]) or immunotherapy (HR 0.314 [95% CI, 0.041-2.367]) treatment. A total of 96.3% of patients successfully raised SARS-CoV-2 antibodies after >2 vaccines. This was independent of the treatment type., Conclusion: This is the largest on-going longitudinal real-world dataset of patients undergoing ACT during the early stages of the COVID-19 pandemic. This preliminary analysis demonstrates that patients with solid tumors undergoing ACT have high protection from SARS-CoV-2 infection following COVID-19 vaccination. The SCCAMP study will evaluate long-term COVID-19 antibody trends, focusing on specific ACTs and patient subgroups., (© The Author(s) 2023. Published by Oxford University Press.)

Infected deep vein thrombophlebitis (i-DVT) in people who inject drugs (PWID) is a clinically challenging but poorly characterised disease. We undertook a retrospective observational study of 70 PWID presenting acutely with i-DVT to improve the clinical and microbiological characterisation of this disease. i-DVT was frequently associated with bacteraemia (59.1% patients with blood cultures obtained), groin abscesses (in 34.3%; of which 54.2% required surgical drainage), and septic pulmonary emboli (38.6%) requiring anticoagulation. Network analysis identified a cluster of patients presenting with respiratory symptoms but lacking typical DVT symptoms, more likely to have septic pulmonary emboli. A microbiologic diagnosis was frequently achieved (70%). Causative pathogens were predominantly gram-positive (S. aureus and streptococci, especially anginosus group), whereas gram-negative pathogens were identified very infrequently (in 6.1% of microbiological diagnoses). This suggests routine empiric therapy against gram-negative bacteria, though commonly administered, is not required. High rates of clinical cure (88.6%) were observed despite the complex nature of infections and independently of the highly variable intravenous and total antimicrobial durations received. There exists a rationale to devise pragmatic approaches to implement novel individualised treatment plans utilising oral antimicrobial therapy for i-DVT. Despite frequent healthcare interactions, opportunities to address HCV treatment and opioid substitution therapy were frequently missed during these acute admissions., (© 2021. The Author(s).)

Radiation therapy is a long-established and essential modality in the treatment of many cancers. It is well known that tissue within a field of radiation can suffer indiscriminate effects, leading to acute and chronic problems. The gastrointestinal tract may be adversely affected by radiation. From the mouth to the rectum, patients can experience troublesome symptoms that require the concerted input of specialist teams. Interventions range from nursing care, dietetic optimization, pharmacological management, and mechanical procedures through endoscopy and surgery. Quality evidence exists mainly for radiation induced effects in four distinct areas of the gastrointestinal tract: oral mucosa, esophagus, small bowel, and rectum. This review explores the experiences of oncology and gastrointestinal teams in managing the most common conditions and some of the different practices for radiation associated morbidity., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl - ) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl - to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl - to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.