The Host Immune Response to Scedosporium/Lomentospora

Infections caused by the opportunistic pathogens Scedosporium/Lomentospora are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. Scedosporium/Lomentospora cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against L. prolificans. Moreover, a great number of Scedosporium/Lomentospora antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to Scedosporium/Lomentospora.This research was funded by the Basque Government, grant number IT1362-19. L.M.-S., M.A., and L.A.-F. were funded by the Basque Government

Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome

© 2020 The Authors.The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAPCD45) tumor and normal astrocytic cells, infiltrating myeloid cells —i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)— and tumor-infiltrating lymphocytes (TIL) —i.e. CD3T-cells and their TCD4, TCD8, TCD4CD8, and (CD25CD127) regulatory (T-regs) subsets, (CD19CD20) B-cells, and (CD16) NK-cells—. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4 (0.5% ± 0.7%) and TCD8 cells (0.6% ± 0.7%), together with lower numbers of TCD4CD8 T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and fondos FEDER, Grant/Award Number: CB16/12/00400 and ISCIII PI16/0476; Consejería de Sanidad Junta de Castilla y León, Gerencia Regional de Salud, Spain, Grant/Award Number: GRS2049/A/1

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Mikroorganismoek minbizia eragin dezakete?

Many studies have analyzed relationships between microorganisms and cancer, demonstrating that microorganisms are able to prevent the onset of cancer and, others to provoke it. Specifically, more and more scientific articles are publishing on microorganisms, linking them to the creation, implementation and dispersion of cancer. In fact, it is estimated that microorganisms cause 17.8% of all cancers. The cancer-causing viral capability is the most studied and, in consequence, many different viral mechanisms that can cause cancer have been described. The International Cancer Re-search Institute has categorized eight viruses for the first time as "carcinogenic to hu-mans", including a human papillomavirus, two herpesvirus and two hepatitis viruses. Regarding bacteria, among cancerous agents, Helicobacter pylori is the most studied in relation to stomach cancer. In addition, many other bacteria, such as Salmonella typhi, Chlamydia pneumoniae and Streptococcus bovis, have been directly related to cancer. Although relatively little research on the effect of fungi on cancer has been investi-gated, some of the toxins produced by these microorganisms have been shown to cause cancer. In addition, some mechanism for the generation and spread of cancer have been described in Candida albicans. Studies to date have shown the influence of microor-ganisms on the development and promotion of cancer. For this reason, to face cancer in the next future, deepen into the relationship between cancer and microorganisms will be essential; Ikerketa askok mikroorganismoen eta minbizien arteko erlazioak aztertu dituzte, eta erakutsi dute mikroorganismo batzuek minbiziaren agerpena saihesten dutela eta beste batzuek, aldiz, minbizia eragin dezaketela. Hain zuzen ere, gero eta artikulu zientifiko gehiago argitaratzen ari dira mikroorganismoak minbiziaren sortzearekin, ezarpenarekin eta sakabanaketarekin erlazionatuz. Izan ere, mikroorganismoek minbizi guztien % 17,8 eragiten dutela estimatu da. Minbizia sortzeko birusen gaitasuna da gehien ikertu dena eta, ondorioz, minbizia sor dezaketen mekanismo desberdin asko deskribatu dira. Minbizia Ikertzeko Nazioarteko Agentziak zortzi birus 1. mailako "gizakiontzat kartzinogeno"-tzat sailkatu ditu; haien artean, giza papiloma birusa, bi herpesbirus eta bi hepatitisaren birus aurkitzen dira. Bakterioei dagokienez, minbizi-eragileen artean, Helicobacter pylori da gehien ikertu dena urdaileko minbiziarekin erlazionatuta. Baina honetaz gain, beste hainbat bakterio, hala nola Salmonella typhi, Chlamydia pneumoniae eta Streptococcus bovis minbiziarekin zuzenki erlazionatu dira. Onddoek daukaten minbiziarekiko erlazioa oso gutxi ikertu den arren, mikroorganismo hauek sortutako toxina batzuek minbizia eragin dezaketela frogatu da. Horrez gain, Candida albicans onddoak minbiziaren sorrera eta hedapena eragin dezakeen hainbat mekanismo deskribatu dira. Orain arte egindako ikerketek mikroorganismoek minbiziaren garapenean eta sustapenean daukaten eragina agerrarazi dute. Hori dela eta, etorkizunean minbiziari aurre egiteko, minbiziaren eta mikroorganismoen arteko erlazioan sakontzea ezinbestekoa da

Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment

The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.This research was funded by the Basque Government, grant number IT1362-19. I.B., L.M.S. and L.A.F. received a predoctoral fellowship from the Basque Government

Toward an objective measure of functional disability in dysferlinopathy

Artículo de publicación ISIIntroduction: Understanding the natural history of dysferlinopathy is essential to design and quantify novel therapeutic protocols. Our aim in this study was to assess, clinically and functionally, a cohort of patients with dysferlinopathy, using validated scales. Methods: Thirty-one patients with genetically confirmed dysferlinopathy were assessed using the motor function measure (MFM), Modified Rankin Scale (MRS), Muscle Research Council (MRC) scale, serum creatine kinase (CK) assessment, baseline spirometry data, and echocardiographic and electrophysiologic studies. Results: MFM and MRC scores showed a significant negative correlation with disease duration and inverse correlation with MRS, but not with onset age, clinical phenotype, or CK levels. Percent forced vital capacity (% FVC) correlated negatively with disease duration and onset age. Eight known pathogenic mutations were identified recurrently, 4 of which accounted for 79% of the total. Conclusions: The results suggest that MFM is a reliable outcome measure that may be useful for longitudinal follow-up in dysferlinopathy. Recurrent mutations suggest a founder effect in the Chilean population

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. This was an observational retrospective study. A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures