Severe Spontaneous Hematomas in Patients Hospitalized with COVID-19.

Objective: To describe the epidemiological, clinical, laboratory, and radiological characteristics, medical treatment, and outcomes of a case series of severe spontaneous hematoma in COVID-19. Material and Methods. This retrospective study included patients hospitalized for COVID-19 who were diagnosed with severe spontaneous bleeding complications by following a standardized treatment protocol that included computed tomography angiography (CTA) from 1 March 2020 to 28 February 2022. The main outcomes were embolization and all-cause mortality. Baseline variables were analyzed for their association with mortality using bivariable logistic regression, and results were expressed as odds ratios (OR) and 95% confidence intervals (CI). Results: In total, 2450 adults were hospitalized for COVID-19 in our center during the study period. 20 patients presented severe and spontaneous intramuscular bleeding (8.1 per 1000 COVID-19 admission vs. 0.47 per 1000 non-COVID-19 admissions, p < 0.001); their median age was 68.5 years (interquartile range (IQR) 63, 80), they had high comorbidity (median Charlson comorbidity index 4.5), and 95% were receiving high doses of heparin. The median interval from COVID-19 symptoms to bleeding was 17 days (IQR 13, 24), and 70% reported cough as a previous symptom. Hypovolemic shock, hypotension, and abdominal pain were the most frequent symptoms of the hematoma. All presented decreased hemoglobin, and 95% required transfusion. Intramuscular hematoma occurred most frequently in the rectus sheath, iliopsoas compartment, and femoral-iliac compartment. All patients underwent embolization; mortality was 45%. We did not identify risk factors associated with an increased risk of death. Conclusion: Although severe bleeding is an uncommon complication of COVID-19, its prevalence is higher than in inpatients without COVID-19, it usually needs embolization, and it is associated with high mortality.

The effect of doping on low temperature growth of high quality GaAs nanowires on polycrystalline films.

The increasing demand for miniature autonomous sensors requires low cost integration methods, but to date, material limitations have prevented the direct growth of optically active III-V materials on CMOS devices. We report on the deposition of GaAs nanowires on polycrystalline conductive films to allow for direct integration of optoelectronic devices on dissimilar materials. Undoped, Si-doped, and Be-doped nanowires were grown at Ts  = 400 °C on oxide (indium tin oxide) and metallic (platinum and titanium) films. Be-doping is shown to significantly reduce the nanowire diameter and improve the nanowire aspect ratio to 50:1. Photoluminescence measurements of Be-doped nanowires are 1-2 orders of magnitude stronger than undoped and Si-doped nanowires and have a thermal activation energy of 14 meV, which is comparable to nanowires grown on crystalline substrates. Electrical measurements confirm that the metal-semiconductor junction is Ohmic. These results demonstrate the feasibility of integrating nanowire-based optoelectronic devices directly on CMOS chips.

Multisystem chronic illness prognostication in non-oncologic integrated care.

OBJECTIVES: To develop a mortality-predictive model for correct identification of patients with non-cancer multiple chronic conditions who would benefit from palliative care, recognise predictive indicators of death and provide with tools for individual risk score calculation. DESIGN: Retrospective observational study with multivariate logistic regression models. PARTICIPANTS: All patients with high-risk multiple chronic conditions incorporated into an integrated care strategy that fulfil two conditions: (1) they belong to the top 5% of the programme's risk pyramid according to the adjusted morbidity groups stratification tool and (2) they suffer simultaneously at least three selected chronic non-cancer pathologies (n=591). MAIN OUTCOME MEASURE: 1 year mortality since patient inclusion in the programme. RESULTS: Among study participants, 201 (34%) died within the 1 year follow-up. Variables found to be independently associated to 1 year mortality were the Barthel Scale (p<0.001), creatinine value (p=0.032), existence of pressure ulcers (p=0.029) and patient global status (p<0.001). The area under the curve (AUC) for our model was 0.751, which was validated using bootstrapping (AUC=0.751) and k-fold cross-validation (10 folds; AUC=0.744). The Hosmer-Lemeshow test (p=0.761) showed good calibration. CONCLUSIONS: This study develops and validates a mortality prediction model that will guide transitions of care to non-cancer palliative care services. The model determines prognostic indicators of death and provides tools for the estimation of individual death risk scores for each patient. We present a nomogram, a graphical risk calculation instrument, that favours a practical and easy use of the model within clinical practices.

Characterization of the migration of lung and blood T cells in response CXCL12 in a three-dimensional matrix.

The ability of T cells to microlocalize within tissues, such as the lung, is crucial for immune surveillance and increased T-cell infiltration is a feature of many inflammatory lung conditions. T-cell migration has mainly been studied in two-dimensional assays. Using three-dimensional collagen gels to mimic the extracellular matrix of lung tissue, we have characterized the migration of T lymphocytes isolated from peripheral blood (PBT) and lung (LT) in response to interleukin-2 (IL-2) and CXCL12. Freshly isolated PBT and LT showed a low degree of migration (blood 4.0 +/- 1.3% and lung 4.1 +/- 1.7%). Twenty-four hours of culture increased the percentage of migrating PBT and LT (blood 17.5 +/- 2.9% and lung 17.7 +/- 3.8%). The IL-2 stimulation modestly increased migration of PBT after 6 days (32.3 +/- 6.0%), but had no effect on the migration of LT (25.5 +/- 3.2%). Twenty-four hours of stimulation with anti-CD3/CD28 caused a small but significant increase in the migration of PBT (to 36.4 +/- 5.8%). In a directional three-dimensional assay, CXCL12 failed to induce migration of fresh PBT or LT. Twenty-four hours of culture, which increased CXCR4 expression of PBT 3.6-fold, significantly increased the migration of PBT in response to CXCL12. Migration of PBT to CXCL12 was blocked by pertussis toxin, but not by the phosphoinositide 3-kinase inhibitor wortmannin. Twenty-four-hour cultured LT did not respond to CXCL12. CD3/CD28-stimulation inhibited CXCL12-mediated migration of PBT. These results suggest that the migration pattern of PBT is distinct from that of LT.

Seismic data of a rockslide: Evaluation of noise levels, site effects, frequency content and identification of seismic phases.

Seismic data can provide information to deduce the occurrence of mass movement events, their release time, event location and dynamics characterization [1]. Nevertheless, the effect of local site amplifications, the level of seismic noise and the frequency content of the signals are important constraints to correctly identify and describe these types of events. In this article we provide data on: site effects, power spectral densities, polarization particle motion and spectrograms generated by a rockslide (∼450 m3) (hereinafter NR) recorded in two permanent seismic stations (EPOB and POBL) located ∼10 km from the source. Original data are available through the International Federation of Digital Seismograph Networks (FDSN, http://www.fdsn.org) for POBL and on request from Instituto Geográfico Nacional (IGN, http://www.ign.es) for EPOB. POBL and EPOB site effects analysis by means of Horizontal-to-Vertical spectral ratio (H/V) technique shows important signatures in POBL signal between 1 and 10 Hz, indicating strong amplification effects at these frequencies, not present in EPOB. For frequencies >1 Hz, Power Spectral Densities (PSD) are higher in POBL than in EPOB, indicating that POBL is noisier than EPOB. Based on the H/V and PSD analyzes, the EPOB station data was deemed preferable over the POBL, to conduct the research presented in the related article [1]. Particle polarization motion data enabled the identification of the arrivals of P, S, and superficial waves, confirming that Pg waves were correctly identified, providing necessary information for the event location in the research article [1]. Moreover, EPOB and POBL spectrograms together with the Fourier transform are included to analyze their content in the frequency domain showing that the expected high frequency phenomenon of the rockslide recorded at 10 km is attenuated and only the low frequency content between 1 and 15 Hz is recorded.

The chemokine CXCL16 is highly and constitutively expressed by human bronchial epithelial cells.

The chemokine receptor CXCR6 is highly expressed on lung-derived T cells compared to blood T cells, especially in inflammatory diseases characterised by T-cell migration to the lung. This suggests that CXCR6 is a candidate lung homing receptor. The sole ligand of CXCR6, CXCL16, has previously been shown to be expressed by alveolar macrophages. The authors hypothesized that also structural lung cells express CXCL16. CXCL16 expression was detected using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Chemotaxis assays were used to test functionality of the secreted protein. Human bronchial epithelial cells secreted relatively high basal levels of CXCL16 (> 1000 pg/mL). Interferon (IFN)-gamma, but not tumor necrosis factor (TNF)-alpha or interleukin (IL)-4, caused a modest but significant up-regulation in secretion. Airway smooth muscle and fibroblasts also expressed CXCL16, but at lower levels. Western blotting detected expression of the full-length (60-kDa) form of the chemokine in cell lysates, and the cleaved (35-kDa) form in culture supernatants. Concentrated supernatants from a bronchial epithelial cell line (BEAS-2B) were chemotactic for CXCR6 expressing T cells from blood. In conclusion, these results suggest that the bronchial epithelium is an important source of constitutively expressed CXCL16, which may be involved in T-cell recruitment to the lung in health and disease.

CXCR6 identifies a putative population of retained human lung T cells characterised by co-expression of activation markers.

Expressions of activation markers have been described on the surface of T cells in the blood and the lung in both health and disease. We have studied the distribution of activation markers on human lung T cells and have found that only certain populations exist. Importantly, the presence or absence of some markers appears to predict those of others, in particular cells which express CD103 also express CD49a and CD69, whereas cells which do not express CD69 also do not express CD49a or CD103. In view of the paucity of activation marker expression in the peripheral blood, we have hypothesised that these CD69+, CD49a+, and CD103+ (triple positive) cells are retained in the lung, possess effector function (IFNgamma secretion) and express particular chemokine receptors which allow them to be maintained in this environment. We have found that the ability of the triple negative cells to secrete IFNgamma is significantly less than the triple positive cells, suggesting that the expression of activation markers can highlight a highly specialised effector cell. We have studied the expression of 14 chemokine receptors and have found that the most striking difference between the triple negative cells and the triple positive cells is the expression of CXCR6 with 12.8+/-9.8% of triple negative cells expressing CXCR6 compared to 89.5+/-5.5% of triple positive cells. We propose therefore that CXCR6 may play an important role in the retention of T cells within the lung.

Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice.

Lactoferrin (Lf) is an iron-binding protein of external secretions and neutrophil secondary granules with antimicrobial and immunomodulatory activities. To further define these properties of Lf, we have investigated the response to Staphylococcus aureus infection in transgenic mice carrying a functional human Lf gene. The transgenic mice cleared bacteria significantly better than congenic littermates, associated with a trend to reduced incidence of arthritis, septicemia, and mortality. We identified two pathways by which S. aureus clearance was enhanced. First, human Lf directly inhibited the growth of S. aureus LS-1 in vitro. Second, S. aureus-infected transgenic mice exhibited enhanced Th1 immune polarization. Thus, spleen cells from infected transgenic mice produced higher levels of TNF-alpha and IFN-gamma and less IL-5 and IL-10 upon stimulation ex vivo with the exotoxin toxic shock syndrome toxin-1 compared with congenic controls. To confirm that these effects of Lf transgene expression could occur in the absence of live bacterial infection, we also showed that Lf-transgenic DBA/1 mice exhibited enhanced severity of collagen-induced arthritis, an established model of Th1-induced articular inflammation. Higher levels of stainable iron in the spleens of transgenic mice correlated with human Lf distribution, but all other parameters of iron metabolism did not differ between transgenic mice and wild-type littermates. These results demonstrate that human Lf can mediate both antimicrobial and immunomodulatory activities with downstream effects on the outcome of immune pathology in infectious and inflammatory disease.