Circulating IL-6 but not neutrophil extracellular traps levels can predict anakinra effectiveness in patients with severe COVID-19.

Added data on circulating IL-6 levels can predict COVID-19 severity and IL1RA efficiency.

What is the impact on work of osteoporotic fractures in active patients? A retrospective fracture-liaison-service study-Optiwork 1.

PURPOSE: Osteoporotic fractures have economic consequences and can alter the quality of life. Nevertheless, the direct impact on work has been infrequently reported. Our objective was to estimate the proportion of working patients resuming paid employment within the 3 months following an osteoporotic fracture, and to assess the consequences on their productivity and quality of life. METHODS: Patients aged between 45 and 64, screened by the Fracture Liaison Service of Hospital Paris Saint Joseph for a fragility fracture occurring between January 2017 and December 2018, and being paid employees at the time of the fracture, were included retrospectively. Medical data were extracted from electronic medical records. Self-reporting questionnaires concerning work activity and quality of life before and after the fracture were sent by post. RESULTS: Overall, 121 patients were included, with a mean age of 55.8; 82.6% of patients were female. Fracture of the lower extremity of the radius was the most frequent (38.2%), followed by the upper extremity of the humerus (23.1%). After the index fracture, 82.6% of the patients went back to work, including 76.0% within 3 months following the fracture. The median time to return to work was 2.2 months. Moreover, 19.8% of patients required adaptations of their current work. CONCLUSION: Osteoporotic fractures have a direct impact on work activity, causing work stoppages. Productivity at work and quality of life were also impacted. Further studies are needed to confirm these findings.

Resilience and livestock adaptations to demographic growth and technological change: A diachronic perspective from the Late Bronze Age to Late Antiquity in NE Iberia.

There are strong interactions between an economic system and its ecological context. In this sense, livestock have been an integral part of human economies since the Neolithic, contributing significantly to the creation and maintenance of agricultural anthropized landscapes. For this reason, in the frame of the ERC-StG project 'ZooMWest' we collected and analyzed thousands of zooarchaeological data from NE Iberia. By considering these data in comparison with ecological indicators (archaeobotanical remains) and archaeological evidence (settlement characteristics and their distribution) this paper seeks to characterize changes in animal production and the relationship between people, livestock, and their environment. These methods allow for an investigation of the topic at different scales (site, zone, territory) with a broad diachronic perspective, and for consideration of orography and cultural traditions alongside climatic factors. Through this integration of various streams of evidence, we aim to better understand the structure of ancient economic systems and the way they conditioned human decision-making on animal production. Results show a shifting relationship with the territory between the Bronze Age and Late Antiquity, in which market requirements and an economic model with a higher degree of integration increasingly influenced husbandry strategies. These processes are reflected in changes in land use and forms of territorial occupation, although along different rhythms and trajectories.

Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis.

BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.

Lumbar spinal stenosis and disc alterations affect the upper lumbar spine in adults with achondroplasia.

In achondroplasia, lumbar spinal stenosis arises from congenital dysplasia and acquired degenerative changes. We here aimed to describe the changes of the lumbar spinal canal and intervertebral disc in adults. We included 18 adults (age ≥ 18 years) with achondroplasia and lumbar spinal stenosis. Radiographs were used to analyze spinal-pelvic angles. Antero-posterior diameter of the spinal canal and the grade of disc degeneration were measured by MRI. Antero-posterior diameters of the spinal canal differed by spinal level (P < 0.05), with lower values observed at T12-L1, L1-2 and L2-3. Degrees of disc degeneration differed by intervertebral level, with higher degrees observed at L1-2, L2-3 and L3-4. A significant correlation was found between disc degeneration and thoraco-lumbar kyphosis at L2-3, between antero-posterior diameter of the spinal canal and lumbar lordosis at T12-L1 and L2-3, and between antero-posterior diameter of the spinal canal and thoraco-lumbar kyphosis at L1-2. Unlike the general population, spinal stenosis and disc degeneration involve the upper part of the lumbar spine in adults with achondroplasia, associated with thoraco-lumbar kyphosis and loss of lumbar lordosis.

Anakinra for severe forms of COVID-19: a cohort study.

BACKGROUND: Coronaviruses can induce the production of interleukin (IL)-1ß, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function. METHODS: The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death. The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). FINDINGS: From March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0·22 [95% CI 0·11-0·41; p<0·0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0·22 [95% CI 0·10-0·49]; p=0·0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group. INTERPRETATION: Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require controlled trials. FUNDING: Groupe Hospitalier Paris Saint-Joseph.