Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal ...replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
In critically ill patients receiving KRT, high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate ...current practices and evidence gaps related to fluid removal with KRT in critically ill patients.
This was a multinational, web-based survey distributed by seven networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39-question survey about fluid management practices on KRT. The survey was distributed from September 2021 to December 2021.
There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5- to 2-L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods ( i.e. , ultrasound, hemodynamic markers, and intra-abdominal pressure), while nephrologists were more likely to deploy cointerventions aimed at improving tolerance to fluid removal ( i.e. , osmotic agents and low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant.
We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. Most nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials.
To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas.
Gold nanoparticles approximately 11 nm ...in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays.
Gold uptake gave a 19:1 tumor to normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died.
Intravenously injected gold nanoparticles cross the blood-tumor barrier, but are largely blocked by the normal blood-brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers.
In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both ...are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.
The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 ...MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).
ABSTRACT
The Canada–France Imaging Survey (CFIS) will consist of deep, high-resolution r-band imaging over ∼5000 deg2 of the sky, representing a first-rate opportunity to identify recently merged ...galaxies. Because of the large number of galaxies in CFIS, we investigate the use of a convolutional neural network (CNN) for automated merger classification. Training samples of post-merger and isolated galaxy images are generated from the IllustrisTNG simulation processed with the observational realism code RealSim. The CNN’s overall classification accuracy is 88 per cent, remaining stable over a wide range of intrinsic and environmental parameters. We generate a mock galaxy survey from IllustrisTNG in order to explore the expected purity of post-merger samples identified by the CNN. Despite the CNN’s good performance in training, the intrinsic rarity of post-mergers leads to a sample that is only ∼6 per cent pure when the default decision threshold is used. We investigate trade-offs in purity and completeness with a variable decision threshold and find that we recover the statistical distribution of merger-induced star formation rate enhancements. Finally, the performance of the CNN is compared with both traditional automated methods and human classifiers. The CNN is shown to outperform Gini–M20 and asymmetry methods by an order of magnitude in post-merger sample purity on the mock survey data. Although the CNN outperforms the human classifiers on sample completeness, the purity of the post-merger sample identified by humans is frequently higher, indicating that a hybrid approach to classifications may be an effective solution to merger classifications in large surveys.
Purpose The purpose of this study was to investigate the indications for and outcomes of arthroscopic labral reconstruction in the hip by use of iliotibial band (ITB) autograft. Methods Between ...August 2005 and May 2008, the senior author (M.J.P.) performed 95 arthroscopic labral reconstructions using an ITB autograft in patients with advanced labral degeneration or deficiency. There were 47 patients who had undergone surgery at a minimum of 1 year previously and met the inclusion criteria. The modified Harris Hip Score (MHHS) and patient satisfaction were used to measure outcomes postoperatively. The labral autograft was harvested from the ITB through a separate incision. The graft was sutured to the intact labral remnant in the region of labral deficiency, re-establishing the suction seal of the hip joint. Results There were 32 men and 15 women. The mean age at the time of surgery was 37 years (range, 18 to 55 years). The mean time from the onset of symptoms to labral reconstruction was 36 months (range, 1 month to 12 years). Subsequent total hip arthroplasty was performed in 4 patients (9%). Follow-up was obtained in 37 of the remaining 43 patients. The mean time to follow-up was 18 months (range, 12 to 32 months). The mean MHHS improved from 62 (range, 35 to 92) preoperatively to 85 (range, 53 to 100) postoperatively ( P = .001). Median patient satisfaction was 8 out of 10 (range, 1 to 10). Patients who were treated within 1 year of injury had higher MHHSs than patients who waited longer than 1 year (93 v 81, P = .03). The independent predictor of patient satisfaction with outcome after labral reconstruction was age. Conclusions This study showed that patients who have labral deficiency or advanced labral degeneration had good outcomes and high patient satisfaction after arthroscopic intervention with acetabular labral reconstruction. Lower satisfaction was associated with joint space narrowing and increased age. Patients who waited longer than 1 year from the time of injury to surgery had lower function at follow-up than those treated in the first year. Level of Evidence Level IV, therapeutic case series.
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