Search

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Abstract Background Depression significantly impacts recovery and return to daily activities in cardiac surgery patients. Assessing and managing depressive symptoms before and after surgery are crucial for improving surgical outcomes and timely return to daily activities, including work. The objectives of this study were to examine differences in patients’ depression levels in relation to their return to daily activities in the early post-cardiac surgery period, and to assess predictors of delayed return to daily activities. Methods This single-centered study assessed return to independence, social participation, hobbies, and work in 100 cardiac surgical patients at 2 and 6 weeks post-surgery. Associations between depression levels and return to daily activities scores were evaluated. Results Higher Center for Epidemiologic Studies Depression Scale (CES-D) scores were significantly associated with delayed return to daily activities in all categories at both 2 and 6 weeks post-surgery. Specifically, higher depression score delayed return to independence and social participation at 2 weeks, and delayed return to independence, social participation, and return to work at 6 weeks. Conclusion Elevated depression scores are significantly associated with delayed return to daily activities post-cardiac surgery, indicating the importance of evaluating depression in cardiac surgical patients in the postend stage-operative period.

Abstract Objectives We aimed to evaluate the ability of the parasternal intercostal (PIC) thickening fraction during spontaneous breathing trial (SBT) to predict the need for reintubation within 48 h after extubation in surgical patients with sepsis. Methods This prospective observational study included adult patients with sepsis who were mechanically ventilated and indicated for SBT. Ultrasound measurements of the PIC thickening fraction and diaphragmatic excursion (DE) were recorded 15 min after the start of the SBT. After extubation, the patients were followed up for 48 h for the need for reintubation. The study outcomes were the ability of the PIC thickening fraction (primary outcome) and DE to predict reintubation within 48 h of extubation using area under receiver characteristic curve (AUC) analysis. The accuracy of the model including the findings of right PIC thickening fraction and right DE was also assessed using the current study cut-off values. Multivariate analysis was performed to identify independent risk factors for reintubation. Results We analyzed data from 49 patients who underwent successful SBT, and 10/49 (20%) required reintubation. The AUCs (95% confidence interval [CI]) for the ability of right and left side PIC thickening fraction to predict reintubation were 0.97 (0.88–1.00) and 0.96 (0.86–1.00), respectively; at a cutoff value of 6.5–8.3%, the PIC thickening fraction had a negative predictive value of 100%. The AUCs for the PIC thickening fraction and DE were comparable; and both measures were independent risk factors for reintubation. The AUC (95% CI) of the model including the right PIC thickening fraction > 6.5% and right DE ≤ 18 mm to predict reintubation was 0.99 (0.92–1.00), with a positive predictive value of 100% when both sonographic findings are positive and negative predictive value of 100% when both sonographic findings are negative. Conclusions Among surgical patients with sepsis, PIC thickening fraction evaluated during the SBT is an independent risk factor for reintubation. The PIC thickening fraction has an excellent predictive value for reintubation. A PIC thickening fraction of ≤ 6.5–8.3% can exclude reintubation, with a negative predictive value of 100%. Furthermore, a combination of high PIC and low DE can also indicate a high risk of reintubation. However, larger studies that include different populations are required to replicate our findings and validate the cutoff values.

AbstractAntibiotic-resistant pathogens are a growing global issue, leading to untreatable infectious diseases in both humans and animals. Personalized bacteriophage (phage) therapy, the use of specific anti-bacterial viruses, is currently a leading approach to combat antibiotic-resistant infections. The implementation of phage therapy has primarily been focused on humans, almost neglecting the impact of such infections on the health and welfare of companion animals. Pets also have the potential to spread resistant infections to their owners or the veterinary staff through zoonotic transmission. Here, we showcase personalized phage-antibiotic treatment of a cat with a multidrug-resistant Pseudomonas aeruginosa implant-associated infection post-arthrodesis surgery. The treatment encompassed a tailored combination of an anti-P. aeruginosa phage and ceftazidime, precisely matched to the pathogen. The phage was topically applied to the surgical wound while the antibiotic was administered intramuscularly. After two treatment courses spanning 7 and 3 weeks, the surgical wound, which had previously remained open for five months, fully closed. To the best of our knowledge, this is the first case of personalized phage therapy application in felines, which provides further evidence of the effectiveness of this approach. The successful outcome paves the way for personalized phage-antibiotic treatments against persistent infections therapy in veterinary practice.

BackgroundIn collaboration with local partners, we reviewed 18 national policy documents across two sub-Saharan African countries identified as pre-dividend nations by the World Bank in 2017: Nigeria and Tanzania. Our aim was to assess national policies in pre-dividend countries and to determine whether national strategies were primed to capitalize on changing demographic structures, maximally attain the demographic dividend, and augment socio-economic growth.MethodsWe conducted policy reviews by focusing on five key sectors of the Gates Institute Demographic Dividend Framework: Family Planning, Maternal and Child Health, Education, Women's Empowerment, and Labor Market. This framework was developed as a tool for countries to apply targeted policies for accelerating the demographic dividend based on their demographic structure. For each component we used a comprehensive list of indicators, defined via a systematic literature review, through which we assessed national policies aimed at maximizing the demographic dividend.ResultsBetween the two countries, we observed persistent gaps in policies targeting family planning. Although more comprehensive, policies addressing maternal and child health, education, women's empowerment, and labor market still lagged in their specificity and measurability. We identified specific policy amendments and alternatives that Nigeria and Tanzania could consider to mitigate these gaps. We also stress the importance of designing measurable policy initiatives across sectors.ConclusionsBased on these recommendations, as Nigeria, Tanzania, and other pre-dividend nations start experiencing rapid demographic changes, they may consider implementing routine policy reviews to strengthen policies across the five key sectors and harness the benefits of a demographic dividend.

Abstract Cell pH and Na+ homeostasis requires Na+/H+ antiporters. The crystal structure of NhaA, the main Escherichia coli Na+/H+ antiporter, revealed a unique NhaA structural fold shared by prokaryotic and eukaryotic membrane proteins. Out of the 12 NhaA transmembrane segments (TMs), TMs III–V and X–XII are topologically inverted repeats with unwound TMs IV and XI forming the X shape characterizing the NhaA fold. We show that intramolecular cross-linking under oxidizing conditions of a NhaA mutant with two Cys replacements across the crossing (D133C-T340C) inhibits antiporter activity and impairs NhaA-dependent cell growth in high-salts. The affinity purified D133C-T340C protein binds Li+ (the Na+ surrogate substrate of NhaA) under reducing conditions. The cross-linking traps the antiporter in an outward-facing conformation, blocking the antiport cycle. As many secondary transporters are found to share the NhaA fold, including some involved in human diseases, our data have importance for both basic and clinical research.

Abstract Introduction The objective of the study was to assess the effects of high-reliability system by implementing a command centre (CC) on clinical outcomes in a community hospital before and during COVID-19 pandemic from the year 2016 to 2021. Methods A descriptive, retrospective study was conducted at an acute care community hospital. The administrative data included monthly average admissions, intensive care unit (ICU) admissions, average length of stay, total ICU length of stay, and in-hospital mortality. In-hospital acquired events were recorded and defined as one of the following: cardiac arrest, cerebral infarction, respiratory arrest, or sepsis after hospital admissions. A subgroup statistical analysis of patients with in-hospital acquired events was performed. In addition, a subgroup statistical analysis was performed for the department of medicine. Results The rates of in-hospital acquired events and in-hospital mortality among all admitted patients did not change significantly throughout the years 2016 to 2021. In the subgroup of patients with in-hospital acquired events, the in-hospital mortality rate also did not change during the years of the study, despite the increase in the ICU admissions during the COVID-19 pandemic.Although the in-hospital mortality rate did not increase for all admitted patients, the in-hospital mortality rate increased in the department of medicine. Conclusion Implementation of CC and centralized management systems has the potential to improve quality of care by supporting early identification and real-time management of patients at risk of harm and clinical deterioration, including COVID-19 patients.

This comprehensive review examines the diverse range of uses of gold nanoparticles across numerous disciplines, focusing on their distinctive characteristics in catalysis, thermal conductivity, optical properties, electrical conductivity, and biological interactions. This work emphasizes the crucial significance of gold nanoparticles in the progression of cancer treatment, demonstrating their multifunctionality in the areas of drug transport, photothermal therapy, bioimaging, and diagnostic applications. Gold nanoparticles have demonstrated their utility in improving the accuracy and effectiveness of cancer treatments, presenting innovative approaches to address clinical obstacles. Nevertheless, the research also discusses notable challenges, including apprehensions over toxicity, the influence of nanoparticle size, and potential environmental repercussions. These issues emphasize the necessity of responsible administration to fully exploit the capabilities of gold nanoparticles in the context of cancer therapy. Notwithstanding these obstacles, the review ultimately underscores the profound influence of gold nanoparticles in diverse domains such as environmental monitoring, renewable energy, catalysis, renewable energy, healthcare, cosmetics, and biotechnology. This highlights their capacity to mold the future through inventive and adaptable means.

Summary: Phage therapy has re-emerged as a promising treatment for non-resolving infections. Given the lack of approved phage treatments, there is a need to establish a compassionate use pipeline. Here, we present a protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections. We describe steps for consultation and request implementation, evaluating and comparing different aspects of phage activity, and phage production. We then detail procedures for multidisciplinary meetings, ethics approvals, phage therapy, and follow-up.For complete details on the use and execution of this protocol, please refer to Onallah et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Introduction Sepsis alerts based on laboratory and vital sign criteria were found insufficient to improve patient outcomes. While most early sepsis alerts were implemented into smaller scale operating systems, a centralized new approach may provide more benefits, overcoming alert fatigue, improving deployment of staff and resources, and optimizing the overall management of sepsis. The objective of the study was to assess mortality and length of stay (LOS) trends in emergency department (ED) patients, following the implementation of a centralized and automated sepsis alert system. Methods The automated sepsis alert system was implemented in 2021 as part of a hospital-wide command and control center. Administrative data from the years 2018 to 2021 were collected. Data included ED visits, in-hospital mortality, triage levels, LOS, and the Canadian Triage and Acuity Scale (CTAS). Results Mortality rate for patients classified as CTAS I triage level was the lowest in 2021, after the implementation of the automated sepsis alert system, compared to 2020, 2019, and 2018 ( p

Abstract The vaginal microbiome plays a crucial role in our health. The composition of this community can be classified into five community state types (CSTs), four of which are primarily consisted of Lactobacillus species and considered healthy, while the fifth features non-Lactobacillus populations and signifies a disease state termed Bacterial vaginosis (BV), which is associated with various symptoms and increased susceptibility to diseases. Importantly, however, the exact mechanisms and dynamics underlying BV development are not yet fully understood, including specifically possible routes from a healthy to a BV state. To address this gap, this study set out to characterize the progression from healthy- to BV-associated compositions by analyzing 8026 vaginal samples and using a manifold-detection framework. This approach, inspired by single-cell analysis, aims to identify low-dimensional trajectories in the high-dimensional composition space. It further orders samples along these trajectories and assigns a score (pseudo-time) to each analyzed or new sample based on its proximity to the BV state. Our results reveal distinct routes of progression between healthy and BV states for each CST, with pseudo-time scores correlating with community diversity and quantifying the health state of each sample. Several BV indicators can also be successfully predicted based on pseudo-time scores, and key taxa involved in BV development can be identified using this approach. Taken together, these findings demonstrate how manifold detection can be used to successfully characterize the progression from healthy Lactobacillus-dominant populations to BV and to accurately quantify the health condition of new samples along the route of BV development.

Insulin pumps have transformed the way diabetes is managed by providing a more accurate and individualized method of delivering insulin, in contrast to conventional injection routines. This research explores the progression of insulin pumps, following their advancement from initial ideas to advanced contemporary systems. The report proceeds to categorize insulin pumps according to their delivery systems, specifically differentiating between conventional, patch, and implantable pumps. Every category is thoroughly examined, emphasizing its unique characteristics and capabilities. A comparative examination of commercially available pumps is provided to enhance informed decision making. This section provides a thorough analysis of important specifications among various brands and models. Considered factors include basal rate and bolus dosage capabilities, reservoir size, user interface, and compatibility with other diabetes care tools, such as continuous glucose monitoring (CGM) devices and so on. This review seeks to empower healthcare professionals and patients with the essential information to improve diabetes treatment via individualized pump therapy options. It provides a complete assessment of the development, categorization, and full specification comparisons of insulin pumps.