Acute intestinal failure: international multicenter point-of-prevalence study

Background & aims: Intestinal failure (IF) is defined from a requirement or intravenous supplementation due to failing capacity to absorb nutrients and fluids. Acute IF is an acute, potentially reversible form of IF. We aimed to identify the prevalence, underlying causes and outcomes of acute IF. Methods: This point-of-prevalence study included all adult patients hospitalized in acute care hospitals and receiving parenteral nutrition (PN) on a study day. The reason for PN and the mechanism of IF (if present) were documented by local investigators and reviewed by an expert panel. Results: Twenty-three hospitals (19 university, 4 regional) with a total capacity of 16,356 acute care beds and 1237 intensive care unit (ICU) beds participated in this study. On the study day, 338 patients received PN (21 patients/1000 acute care beds) and 206 (13/1000) were categorized as acute IF. The categorization of reason for PN was revised in 64 cases (18.9% of total) in consensus between the expert panel and investigators. Hospital mortality of all study patients was 21.5%; the median hospital stay was 36 days. Patients with acute IF had a hospital mortality of 20.5% and median hospital stay of 38 days (P > 0.05 for both outcomes). Disordered gut motility (e.g. ileus) was the most common mechanism of acute IF, and 71.5% of patients with acute IF had undergone abdominal surgery. Duration of PN of ≥42 days was identified as being the best cut-off predicting hospital mortality within 90 days. PN ≥ 42 days, age, sepsis and ICU admission were independently associated with 90-day hospital mortality. Conclusions: Around 2% of adult patients in acute care hospitals received PN, 60% of them due to acute IF. High 90-day hospital mortality and long hospital stay were observed in patients receiving PN, whereas presence of acute IF did not additionally influence these outcomes. Duration of PN was associated with increased 90-day hospital mortality

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD

B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we found that BCR-NOTCH activation significantly increased the proximal BCR adapter protein BLNK. BCR-NOTCH activation also enabled persistent NOTCH2 surface expression, suggesting a positive feedback loop. Specific NOTCH2 blockade eliminated NOTCH-BCR activation and significantly altered NOTCH downstream targets and B-cell maturation/effector molecules. Examination of the molecular underpinnings of this “NOTCH2-BCR axis” in cGVHD revealed imbalanced expression of the transcription factors IRF4 and IRF8, each critical to B-cell differentiation and fate. All-trans retinoic acid (ATRA) increased IRF4 expression, restored the IRF4-to-IRF8 ratio, abrogated BCR-NOTCH hyperactivation, and reduced NOTCH2 expression in cGVHD B cells without compromising viability. ATRA-treated cGVHD B cells had elevated TLR9 and PAX5, but not BLIMP1 (a gene-expression pattern associated with mature follicular B cells) and also attained increased cytosine guanine dinucleotide responsiveness. Together, we reveal a mechanistic link between NOTCH2 activation and robust BCR responses to otherwise suboptimal amounts of surrogate antigen. Our findings suggest that peripheral B cells in cGVHD patients can be pharmacologically directed from hyperactivation toward maturity

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Insurance Rating of Patients with Inflammatory Bowel Disease: Report of a Conference on Morbidity and Mortality

Patient members reported to the Crohn’s and Colitis Foundation of Canada (CCFC) about their difficulties to obtain insurance. In 1991, the Lay Board of the CCFC requested its Medical Advisory Board (MAB) to investigate this problem. At that time, insurance ratings could be illustrated by the 1985 edition of Brackenridge’s monograph on life risks. The MAB found that data on mortality were outdated. A conference on morbidity and mortality of inflammatory bowel disease (IBD) was organized by the authors and held in May 1992. Based on questionnaires to patients, evidence provided by invited speakers and the results of small group conferences, it was concluded that patients with IBD have difficulties in obtaining insurance, even though the quality of life and mortality of IBD patients is not very different from that of the general population. However, the mortality rate of the healthy insured population is lower than that of the general population, and thus much lower than that of IBD patients. Patients have a better chance to obtain insurance if there is a close cooperation between the treating physician and the medical officer of the insurance company. Changes have occurred since the conference held in May 1992. The recent edition of Brackenridge’s text (1992) provides a better prognosis but unfortunately unchanged rating for patients with IBD than did the 1985 edition. Close cooperation between the Patient Advisory Committee of the CCFC and the Executives of the Canadian Life Insurance Medical Officers Association may further improve the insurance rating of patients with IBD

Enhancing the antibacterial activity of light-activated surfaces containing crystal violet and ZnO nanoparticles: investigation of nanoparticle size, capping ligand, and dopants

Healthcare-associated infections pose a serious risk for patients, staff, and visitors and are a severe burden on the National Health Service, costing at least £1 billion annually. Antimicrobial surfaces significantly contribute toward reducing the incidence of infections as they prevent bacterial adhesion and cause bacterial cell death. Using a simple, easily upscalable swell-encapsulation-shrink method, novel antimicrobial surfaces have been developed by incorporating metal oxide nanoparticles (NPs) and crystal violet (CV) dye into medical-grade polyurethane sheets. This study compares the bactericidal effects of polyurethane incorporating ZnO, Mg-doped ZnO, and MgO. All metal oxide NPs are well defined, with average diameters ranging from 2 to 18 nm. These materials demonstrate potent bactericidal activity when tested against clinically relevant bacteria such as Escherichia coli and Staphylococcus aureus. Additionally, these composites are tested against an epidemic strain of methicillin-resistant Staphylococcus aureus (MRSA) that is rife in hospitals throughout the UK. Furthermore, we have tested these materials using a low light intensity (∼500 lx), similar to that present in many clinical environments. The highest activity is achieved from polymer composites incorporating CV and ∼3 nm ZnO NPs, and the different performances of the metal oxides have been discussed

A Review of 50 Years of Study of Hydrology, Wetland Dynamics, Aquatic Metabolism, Water Quality and Trophic Status, and Nutrient Biogeochemistry in the Barataria Basin, Mississippi Delta—System Functioning, Human Impacts and Restoration Approaches

Here we review an extensive series of studies of Barataria Basin, an economically and ecologically important coastal basin of the Mississippi Delta. Human activity has greatly altered the hydrology of the basin by decreasing riverine inflows from leveeing of the river and its distributaries, increasing runoff with high nutrient concentrations from agricultural fields, and channelization of wetlands of the basin interior that has altered flow paths to often bypass wetlands. This has resulted in degraded water quality in the upper basin and wetland loss in the lower basin. Trophic state analysis found the upper basin to be eutrophic and the lower basin to be mesotrophic. Gross aquatic primary production (GAPP) was highest in the upper basin, lowest in the mid basin, and intermediate in the lower basin. Forested wetlands in the upper basin have degraded over the past several decades due to increased periods of flooding, while there has been massive loss of emergent wetlands in the lower basin due to increasing water levels and pervasive alteration of hydrology. Restoration will entail reconnection of waterways with surrounding wetlands in the upper basin, and implementation of river sediment diversions, marsh creation using dredged sediments and barrier island restoration. Findings from this review are discussed in terms of the functioning of deltas globally