Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors

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Is Lockdown Effective in Limiting SARS-CoV-2 Epidemic Progression?—a Cross-Country Comparative Evaluation Using Epidemiokinetic Tools

BackgroundTo date, the risk/benefit balance of lockdown in controlling severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic is controversial.ObjectiveWe aimed to investigate the effectiveness of lockdown on SARS-CoV-2 epidemic progression in nine different countries (New Zealand, France, Spain, Germany, the Netherlands, Italy, the UK, Sweden, and the USA).DesignWe conducted a cross-country comparative evaluation using a susceptible-infected-recovered (SIR)-based model completed with pharmacokinetic approaches.Main MeasuresThe rate of new daily SARS-CoV-2 cases in the nine countries was calculated from the World Health Organization’s published data. Using a SIR-based model, we determined the infection (β) and recovery (γ) rate constants; their corresponding half-lives (t_1/2β and t_1/2γ); the basic reproduction numbers (R₀ as β/γ); the rates of susceptible S(t), infected I(t), and recovered R(t) compartments; and the effectiveness of lockdown. Since this approach requires the epidemic termination to build the (I) compartment, we determined S(t) at an early epidemic stage using simple linear regressions.Key ResultsIn New Zealand, France, Spain, Germany, the Netherlands, Italy, and the UK, early-onset stay-at-home orders and restrictions followed by gradual deconfinement allowed rapid reduction in SARS-CoV-2-infected individuals (t_1/2β ≤ 14 days) with R₀ ≤ 1.5 and rapid recovery (t_1/2γ ≤ 18 days). By contrast, in Sweden (no lockdown) and the USA (heterogeneous state-dependent lockdown followed by abrupt deconfinement scenarios), a prolonged plateau of SARS-CoV-2-infected individuals (terminal t_1/2β of 23 and 40 days, respectively) with elevated R₀ (4.9 and 4.4, respectively) and non-ending recovery (terminal t_1/2γ of 112 and 179 days, respectively) was observed.ConclusionsEarly-onset lockdown with gradual deconfinement allowed shortening the SARS-CoV-2 epidemic and reducing contaminations. Lockdown should be considered as an effective public health intervention to halt epidemic progression.KEY WORDS: COVID-19, epidemic, lockdown, modeling, pharmacokinetics, SARS-CoV-2     

Kinetic Slip Boundary Condition for Isothermal Rarefied Gas Flows Through Static Non-Planar Geometries Based on the Regularized Lattice-Boltzmann Method

The simulation of rarefied gas flows through complex porous media is challenging due to the tortuous flow pathways inherent to such structures. The Lattice Boltzmann method (LBM) has been identified as a promising avenue to solve flows through complex geometries due to the simplicity of its scheme and its high parallel computational efficiency. It has been proposed to model the stress-strain relationship with the extended Navier-Stokes equations rather than attempting to directly solve the Boltzmann equation. However, a regularization technique is required to filter out non-resolved higher-order components with a low-order velocity scheme. Although slip boundary conditions (BCs) have been proposed for the non-regularized multiple relaxation time LBM (MRT-LBM) for planar geometries, previous slip BCs have never been verified extensively with the regularization technique. In this work, following an extensive literature review on the imposition of slip BCs for rarefied flows with the LBM, it is proven that earlier values for kinetic parameters developed to impose slip BCs are inaccurate for the regularized MRT-LBM and differ between the D2Q9 and D3Q15 schemes. The error was eliminated for planar flows and good agreement between analytical solutions for arrays of cylinders and spheres was found with a wide range of Knudsen numbers.     

Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity.Outbreaks of 1997 avian influenza H5N1 and 2009 pandemic (p) H1N1 in humans have provided an opportunity to gain insight into cross-reactive immunity. The US military periodically collects and stores serum samples from service members linked to medical records.¹ We measured cross-reactive antibodies in stored serum to avian influenza H5N1 and 2009 pH1N1 from US military personnel and identified factors associated with presence of neutralizing antibodies.Two hundred archived serum samples were obtained from the US Department of Defense Serum Repository. They were representative of a wide cross-section of active military personnel at the times of collection, whereas specific geographic information was not available on the individual selected; the cohort represents the general US military population, which is deployed throughout the United States and globally. Fifty samples each were selected from four birth cohorts: (1) < 1949, (2) 1960–1965, (3) 1966–1971, and (4) 1972–1977. Within each cohort, 25 samples were collected in the year 2000 (before the introduction of intranasal live attenuated influenza vaccine [LAIV]), and 25 samples were collected in 2008 (where 51% of donors had received LAIV). It has been suggested that LAIV elicits cross-reactive immunity.^2,3 The samples were all collected before the outbreak of 2009 pH1N1, and there have not been any reported outbreaks of H5N1 in US military personnel.Assays used to measure antibodies included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay.⁴ Viral neutralization by antibodies against H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based (H5pp)⁵ and microneutralization assays, respectively. Electronic medical and vaccination records from the Defense Medical Surveillance System (DMSS), which captured records before the serum sample date, were linked to samples and compared with the in vitro results.¹The odds ratios (ORs) and 95% confidence intervals (95% CIs) of univariate and multivariate binary logistic regression analyses were used to determine the association between donor characteristics and positive antibody responses. A multiple logistic regression model was constructed, and it included independent variables with a P value of < 0.05 in univariate logistic regression. A P value of < 0.05 was considered to indicate statistical significance. SPSS 12.0 for Windows (SPSS Inc., Chicago, IL) was used to perform all statistical analysis.Cross-reactivity is summarized in 5 and 22.5% for the NI assay. H5pp and NI antibody titers to H5N1 were evenly distributed among birth cohorts and did not differ substantially based on history of vaccination or prior respiratory infections. Of those individuals with neutralizing antibodies to H5N1 (N = 28), 32.1% also had neutralizing antibodies to pH1N1, whereas 19.3% of those individuals with any H5N1-specific antibody response also had neutralizing antibodies to pH1N1 (

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

Purpose

Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO₂/FiO₂ ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.

Methods

We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.

Results

Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO₂ change was found according to oxygenation response or lung morphology.

Conclusions

In ARDS patients with a PaO₂/FiO₂ ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

     

Remodelling of vertebral endplate subchondral bone in scoliosis: A micro-CT analysis in a porcine model

Background

Disc degeneration has been correlated with alteration of bone density of adjacent vertebral bodies. Abnormal mechanical loading appears in scoliosis as compared to normal spines. How vertebral endplate was remodelled in scoliosis is not well understood.

Methods

We conducted a micro-CT analysis of subchondral bone of the vertebral endplate at the curve apex in a porcine scoliosis model. Two adjacent thoracic T₅–T₆ and lumbar L₁–L₂ levels were instrumented in six four-week-old pigs with a custom offset implant connected by a flexible stainless steel wire. Two months after implantation, three cylindrical specimens were harvested into the vertebral endplate of each of the scoliosis levels: centre, convexity and concavity, and from the dorsal T₉–T₁₀ vertebral units obtained from nine three-month-old non-instrumented pigs used as controls. Micro-CT analysis was carried out on each specimen.

Findings

In the concavity of the scoliotic spine, bone volume fraction, trabecular thickness, and trabecular separation significantly increased whereas in the convexity, only trabecular separation increased. Connectivity index and trabecular number decreased significantly.

Interpretation

This was the first micro-CT study of subchondral bone microarchitecture of the scoliotic vertebral end plate. At the curve apex, increased compression in the concavity induced an osteogenic process. In the convexity, diminished compression caused an osteolytic process with a local resorption. Clinically, the unbalanced tissue remodelling could play a role in the convective and diffusive transports into the end plate, which is of prime importance for the segment homeostasis in scoliosis treatment with or without surgery.