Dialysis circuit clotting in critically ill patients with COVID-19 infection.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) infection has been associated with a hypercoagulable state with increased reports of thrombotic events. Acute kidney injury requiring dialysis is common in critically ill patients and circuit clotting compromises efficacy of treatment. This study aims to analyze the circuit life and circuit clotting during continuous kidney replacement therapy (CKRT) and intermittent hemodialysis in patients with and without COVID-19. METHODS: This is a single-center, retrospective cohort study in critically ill patients undergoing CKRT or intermittent hemodialysis between 1 February 2020 to 22 May 2020. Patients in the intensive care unit (ICU) with COVID-19 infection and contemporary controls who tested negative were included. Co-primary outcomes were functional circuit life for patients on CKRT and all circuit clotting events for patients on CKRT and/or intermittent hemodialysis. RESULTS: Seventy CKRT circuits and 32 intermittent hemodialysis sessions for 12 COVID-19 cases and 22 CKRT circuits and 18 intermittent hemodialysis sessions for 15 controls were analyzed. CKRT circuit clotting was more common in the COVID-19 group compared to the control group (64% vs 36%, p = 0.02), despite higher anticoagulation use in the COVID-19 group (41% vs 14%, p = 0.02). Functional CKRT circuit life was similar in COVID-19 patients and controls (median 11 vs 12 h, p = 0.69). On Cox regression analysis, circuit clotting was similar with hazard ratio (HR) 1.90 [95% confidence interval (CI): 0.89-4.04]; however, clotting was increased in COVID-19 patients after adjustment for anticoagulation use (HR: 3.31 [95% CI 1.49-7.33]). In patients with COVID-19, CKRT circuits with anticoagulation had a longer circuit life compared to CKRT circuits without anticoagulation (median 22 versus 7 h respectively, p <  0.001). Circuit clotting was similar in both groups undergoing intermittent hemodialysis. CONCLUSION: Dialysis clotting amongst COVID-19 patients is increased despite more anticoagulation use and the hazard for clotting is greater especially after adjusting for anticoagulation use. Circuit life was suboptimal in COVID-19 patients on circuits without anticoagulation and therefore routine use of anticoagulation amongst COVID-19 patients should be considered whenever possible.

Pyogenic liver abscesses in peritoneal dialysis patients: A single-centre retrospective case series.

Peritoneal dialysis (PD)-related infection rates have improved, but serious complications such as liver abscesses remain an issue, posing unique management challenges including safety of continuing PD versus early PD catheter removal. Current literature describing this is unfortunately limited. This study aims to describe the characteristics, management and outcomes of liver abscesses in PD patients from a retrospective review of prevalent PD patients on follow-up at Tan Tock Seng Hospital between 1st January 2016 and 30th June 2021. A total of 11/383 PD patients (2.9%) were treated for liver abscesses. Most were diabetic (n =10, 90.9%), with a median PD vintage of 541 days (interquartile range: 310-931 days). Fever (n = 7, 63.6%), bacteraemia (n = 7, 63.6%) and concomitant PD peritonitis (n = 7, 63.6%) were the most common presenting symptoms. Majority of patients underwent radiological aspiration of abscess in addition to antibiotics (n = 7, 63.6%). PD catheter was removed in eight patients (72.7%), with the most common indications being empirical removal due to intra-abdominal abscess (n = 5, 62.5%) followed by septic shock (n = 2, 25%) and refractory PD peritonitis (n = 1, 12.5%). Only three patients (37.5%) remained on PD, as they did not develop PD peritonitis during their course of treatment. The overall mortality remains high with three patients (27.3%) passing away within 6 months of presentation. Liver abscesses in PD patients is associated with poor technique and overall survival. Absence of PD peritonitis appears to be a good prognostic factor, but larger studies are required to guide the optimal management of liver abscesses in PD patients.

An Update on Current Therapeutic Options in IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) remains the leading cause of primary glomerular disease worldwide. Outcomes are poor with high rates of progressive chronic kidney disease and kidney failure, which contributes to global healthcare costs. Although this disease entity has been described, there were no disease-specific treatments until recently, with the current standard of care focusing on optimal supportive measures including lifestyle modifications and optimization of the renin-angiotensin-aldosterone blockade. However, with significant advances in the understanding of the pathogenesis of IgAN in the past decade, and the acceptance of surrogate outcomes for accelerated drug approval, there have been many new investigational agents tested to target this disease. As these agents become available, we envision a multi-pronged treatment strategy that simultaneously targets the consequences of ongoing nephron loss, stopping any glomerular inflammation, inhibiting pro-fibrotic signals in the glomerulus and tubulo-interstitium, and inhibiting the production of pathogenic IgA molecules. This review is an update on a previous review published in 2021, and we aim to summarize the developments and updates in therapeutic strategies in IgAN and highlight the promising discoveries that are likely to add to our armamentarium.

Genome sequence of Francisella tularensis subspecies holarctica strain FSC200, isolated from a child with tularemia.

Here we report the complete, accurate 1.89-Mb genome sequence of Francisella tularensis subsp. holarctica strain FSC200, isolated in 1998 in the Swedish municipality Ljusdal, which is in an area where tularemia is highly endemic. This genome is important because strain FSC200 has been extensively used for functional and genetic studies of Francisella and is well-characterized.

Large-insert genome analysis technology detects structural variation in Pseudomonas aeruginosa clinical strains from cystic fibrosis patients.

Large-insert genome analysis (LIGAN) is a broadly applicable, high-throughput technology designed to characterize genome-scale structural variation. Fosmid paired-end sequences and DNA fingerprints from a query genome are compared to a reference sequence using the Genomic Variation Analysis (GenVal) suite of software tools to pinpoint locations of insertions, deletions, and rearrangements. Fosmids spanning regions that contain new structural variants can then be sequenced. Clonal pairs of Pseudomonas aeruginosa isolates from four cystic fibrosis patients were used to validate the LIGAN technology. Approximately 1.5 Mb of inserted sequences were identified, including 743 kb containing 615 ORFs that are absent from published P. aeruginosa genomes. Six rearrangement breakpoints and 220 kb of deleted sequences were also identified. Our study expands the "genome universe" of P. aeruginosa and validates a technology that complements emerging, short-read sequencing methods that are better suited to characterizing single-nucleotide polymorphisms than structural variation.

Photosynthetic acclimation of Grammatophyllum speciosum to growth irradiance under natural conditions in Singapore.

Grammatophyllum speciosum, a native species to Singapore, have become extinct mainly due to habitat loss. Recently, Singapore has reintroduced G. speciosum into the natural environment under the orchid conservation programme. In this study, leaves of G. speciosum grown under low light (LL) under natural conditions had faster expansion rate and higher specific leaf area than leaves grown under intermediate light (IL) and high light (HL). All leaves had more than 95% midday relative water content. Although midday Fv/Fm ratios were lower in HL leaves than in IL and LL leaves, none of them exhibited chronic photoinhibition. HL leaves had upregulated their light utilization through higher photochemical quantum yield (ΔF/Fm') and greater electron transport rate. HL leaves also had higher non-photochemical quenching, indicating that they had higher capability to dissipate excess light as heat, which was supported by their lower chlorophyll but higher carotenoids content. Although there was a linear correction between leaf temperature and photosynthetic photon flux density (PPFD), no correlations were found between stomatal conductance (gs) and PPFD, gs and leaf temperature. Light-saturated photosynthetic CO2 assimilation rate (A sat ) was significantly higher in HL leaves than those of IL and LL leaves. However, all leaves had similar light-saturated stomatal conductance. Although LL leaves had higher leaf total reduced nitrogen that those of IL and HL leaves, none of them seemed to suffer from nitrogen deficiency during the experimental period. To conclude, G. speciosum is able to survive under different growth irradiances without watering and adding fertilizers.

Evolution of Burkholderia pseudomallei in recurrent melioidosis.

Burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable of causing severe acute infection with overwhelming septicemia leading to death. A high rate of recurrent disease occurs in adult patients, most often due to recrudescence of the initial infecting strain. Pathogen persistence and evolution during such relapsing infections are not well understood. Bacterial cells present in the primary inoculum and in late infections may differ greatly, as has been observed in chronic disease, or they may be genetically similar. To test these alternative models, we conducted whole-genome comparisons of clonal primary and relapse B. pseudomallei isolates recovered six months to six years apart from four adult Thai patients. We found differences within each of the four pairs, and some, including a 330 Kb deletion, affected substantial portions of the genome. Many of the changes were associated with increased antibiotic resistance. We also found evidence of positive selection for deleterious mutations in a TetR family transcriptional regulator from a set of 107 additional B. pseudomallei strains. As part of the study, we sequenced to base-pair accuracy the genome of B. pseudomallei strain 1026b, the model used for genetic studies of B. pseudomallei pathogenesis and antibiotic resistance. Our findings provide new insights into pathogen evolution during long-term infections and have important implications for the development of intervention strategies to combat recurrent melioidosis.

Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.

BACKGROUND: Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. CONCLUSION: The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.