Background
In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I ...IFNs but rarely IFN-beta.
Objectives
We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.
Methods
We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain.
Results
The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (
p
= 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (
p
= 5.10e
−03
) and lower lymphocyte counts (
p
= 1.80e
−02
). No significant association with response to IFN-beta-1b therapy (
p
= 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%).
Conclusion
Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.
Gender as the "sociocultural role of sex" is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors' consequences and inequalities men/women. We ...aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both?
We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables.
We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term "gender" to define exposure. One article defined its "sex" exposure variable as gender-related mechanisms, and two articles used "sex" and "gender" interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors.
Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.
Abstract Inverse finite element-based analysis of soft biological tissues is an important tool to investigate their complex mechanical behavior and to develop physical models for medical simulations. ...Although there have recently been advances in dealing with the computational complexities of modeling biological materials, the collection of a sufficiently dense set of experimental data to properly capture their typically regionally varying properties still remains a critical issue. The aim of this work was to develop and test an optical system that combines 2D-Digital Image Correlation (DIC) and a novel Fringe Projection method with radial sensitivity (RFP) to test soft biological tissues under in vitro indentation. This system has the distinctive capability of using a single camera to retrieve the shape and 3D deformation of the whole upper surface of the indented sample without any blind measurement areas (with exception of the area under the indenter), with nominal depth and in-plane resolution of 0.05 mm and 0.004 mm, respectively. To test and illustrate the capabilities of the developed DIC/RFP system, the in vitro response to indentation of a homogeneous and isotropic latex foam is presented against the response of a slab of porcine ventricular myocardium, a highly in-homogeneous and anisotropic tissue. Our results illustrate the enhanced capabilities of the developed method to capture asymmetry in deformation with respect to standard indentation tests. This feature, together with the possibility of miniaturizing the system into a hand-held probe, makes this method potentially extendable to in vivo settings, alone or in combination with ultrasound measurements.
The effect of the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis on cell migration, the secretion of matrix metalloproteinases (MMPs) and the adhesion of human hepatoma ...cell lines has been investigated. A close correlation was observed between the expression of COX-2 under basal conditions and the secretion of MMP-2 and MMP-9. Cell migration in HuH-7 cells, which express high constitutive levels of COX-2 was significantly inhibited by selective inhibitors of COX-2 and enhanced by exogenous addition of PGE2. Hepatocellular carcinoma (HCC) cells expressed β1 and αVβ3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE2 increased the β1 integrin levels and adhesion on vitronectin in HuH-7 cells. Inhibitors of MEK/ERK, p38 MAPK, protein kinases A and C impaired the migration of HuH-7 cells induced by PGE2, indicating the involvement of multiple pathways in the process. Taken together, these results support the existence of a relationship between COX-2-derived PGE2 synthesis, and migration and adhesion through an integrin-dependent pathway in HCC cells.
Families with young children have faced serious challenges during the first lockdown as a result of the COVID-19 pandemic. In addition to remote working, parents have had to monitor their children's ...schoolwork and manage their daily lives. When one of the children also has neuro-developmental disorders, this results in an increased burden. We can therefore wonder how these families with one or more young children (under 6 years old) with special needs have experienced and dealt with this lockdown.
In this context, the "COVJEUNENFANT" study focused more specifically on the subjective experience, as a parent, of those who cared for children with special needs (i.e., with developmental disorders, neurodevelopmental disorders, proven disabilities or chronic health conditions) compared to the general population. We wished to see if the consequences of the health crisis were significantly different from those perceived by respondents in the general population (
= 490) and if the sociodemographic structure of these families differed from those of other respondents.
Ninety three French families with at least one child under 6 years old and one with developmental difficulties or a chronic illness, from a cohort of 490 control families, participated in a web-based survey during the first lockdown, from the 28th April 2020 to 29th May 2020.
After presenting the participants' sociodemographic characteristics, the results show that these French families (
= 93) are less wealthy than the control population "without special needs" (
= 397), have felt more pressures originating from their environment (families, friends, colleagues, media, social networks…), have suffered from more health issues (other than COVID-19), have taken more measures to protect themselves (social-distancing), and were less likely to feel happy. A significantly larger number of them lamented the lack of free time and voiced a larger need for information regarding children's education. However, their parental role was felt as being more satisfying and their family relations strengthened more than in the general population of participants.
It is apparent that urgent prioritisation is needed in order to support and care for these families by continuing to provide care for their children in one way or another, and by ensuring that their need to adapt again does not exceed their own abilities and resources, especially as young children, who have high levels of requirements, are present in the home.
Caveolae participate in several cellular processes such as vesicular transport, cholesterol homeostasis, regulation of signal transduction, integrin signaling, and cell growth. The expression and ...functional role of caveolin (Cav), the most abundant protein of caveolae, has been reported in liver and in different hepatocyte cell lines, in human cirrhotic liver, and in hepatocellular carcinomas. The role of Cav‐1 in liver regeneration after partial hepatectomy (PH) has been investigated as a model of liver proliferation in vivo. Our results show that Cav‐1 increases in liver after PH with a redistribution of the protein from the caveola‐enriched domain to the noncaveolar fraction. Moreover, the Cav‐1 located in the noncaveolar fraction is phosphorylated in tyrosine 14, even though the Cav‐1 gene is dispensable for liver regeneration after PH, as deduced from data obtained with commercially available animals lacking this gene. In addition to this, the proinflammatory stimulation of hepatocytes induces Cav‐1 translocation to a noncaveolar fraction and tyrosine 14 phosphorylation mainly through the activation of tyrosine kinases such as Src. Conclusion: These results support a dynamic role for Cav‐1 in liver proliferation both in vivo after PH and in vitro in cultured hepatic cell lines, but with minimal implications for the liver regeneration process. (HEPATOLOGY 2007.)
The objective of this retrospective study was to review the results of a 4-year audit performed on anesthetic machines and vaporizers used in veterinary clinics in Spain and Portugal. Data was ...collected between July 2016 and April 2020. Inspections were carried out by a team of seven veterinarians, using a human-modified system of checks that was adapted to a veterinary practice. The evaluation of each item was noted as "correct" or "incorrect". The vaporizers' performance was evaluated using a self-calibrating gas analyzer. The vaporizer was classified as "correct" or "incorrect" when the vaporization error was less than or equal to, or more than 20%, respectively. The anesthetic machine was classified as "conforming" if all its components were noted as "correct" and no leaks were detected, or as "non-conforming" if any of the components was noted as "incorrect" or if a leak was detected. If the inspector was able to repair on-site the item malfunctions detected and the machine was fit for use, they issued a final report as "conforming." On the contrary, if such malfunctions persisted, the final report was "non-conforming," and a recommendation to remove the machine from service until its final repair was provided. To perform statistical analysis, each inspected item was used as predictor, classification and regression trees were built, and a random forest analysis was performed. A total of 2,001 anesthetic machines and 2,309 vaporizers were studied. After inspection, 42.7 and 26.4% of the machines were non-conforming and conforming, respectively, whereas 30.9% could be repaired
. A total of 27.1% of the isoflurane vaporizers and 35.9% of the sevoflurane vaporizers were incorrect. Machine learning techniques showed that the most important variables in the classification of the anesthetic machines as conforming or non-conforming were mostly the scavenger system and the canister, followed some way behind by the APL valve, source of oxygen, reservoir bag, vaporizer, and connections.
Malaria in Equatorial Guinea remains a major public health problem. The country is a holo-endemic area with a year-round transmission pattern. In 2016, the prevalence of malaria was 12.09% and ...malaria caused 15% of deaths among children under 5 years. In the Continental Region, 95.2% of malaria infections were Plasmodium falciparum, 9.5% Plasmodium vivax, and eight cases mixed infection in 2011. The main strategy for malaria control is quick and accurate diagnosis followed by effective treatment. Early and accurate diagnosis of malaria is essential for both effective disease management and malaria surveillance. The quality of malaria diagnosis is important in all settings, as misdiagnosis can result in significant morbidity and mortality. Microscopy and RDTs are the primary choices for diagnosing malaria in the field. However, false-negative results may delay treatment and increase the number of persons capable of infecting mosquitoes in the community. The present study analysed the performance of microscopy and RDTs, the two main techniques used in Equatorial Guinea for the diagnosis of malaria, compared to semi-nested multiplex PCR (SnM-PCR).
A total of 1724 samples tested by microscopy, RDT, and SnM-PCR were analysed. Among the negative samples detected by microscopy, 335 (19.4%) were false negatives. On the other hand, the negative samples detected by RDT, 128 (13.3%) were false negatives based on PCR. This finding is important, especially since it is a group of patients who did not receive antimalarial treatment.
Owing to the high number of false negatives in microscopy, it is necessary to reinforce training in microscopy, the "Gold Standard" in endemic areas. A network of reference centres could potentially support ongoing diagnostic and control efforts made by malaria control programmes in the long term, as the National Centre of Tropical Medicine currently supports the National Programme against Malaria of Equatorial Guinea to perform all of the molecular studies necessary for disease control. Taking into account the results obtained with the RDTs, an exhaustive study of the deletion of the hrp2 gene must be done in EG to help choose the correct RDT for this area.
Mediterranean spotted fever (MSF) is a zoonotic disease caused by Rickettsia conorii. In Spain, deficiencies in the official reporting result in misreporting of this disease. This study aims to ...describe the clinical and temporal-spatial characteristics of MSF hospitalizations between 1997 and 2014.
We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD). All CMBD's hospital discharges with ICD-9 CM code 082.1 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed.
A total of 4,735 hospitalizations with MSF diagnosis were recorded during the study period, out of which 62.2% were male, mean age of 48. Diabetes mellitus, alcohol dependence syndrome, and chronic liver disease occurred in 10.8%, 2.4% and 2.8% hospitalizations, respectively. The median annual hospitalization rate showed a decreasing trend from a maximum of 12.9 in 1997 to a minimum rate of 3.1 in 2014. Most admissions occurred during the summer, showing a significant annual seasonal behavior. Important regional differences were found.
Although MSF hospitalization rates have decreased considerably, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance.
Objective
The main purpose of this work is to describe the sociodemographic and clinical characteristics of intensive care unit (ICU) patients in a second-level hospital in Madrid, Spain, focusing in ...those who underwent surgical tracheostomy during the coronavirus disease 2019 (COVID-19) pandemic. The surgical technique and associated complications are also detailed.
Study Design
Observational and historical cohort.
Setting
Single center.
Methods
Eighty-three intubated COVID-19 patients were analyzed. Thirty bedside surgical tracheostomies had been performed following our safety protocol.
Results
Data from 83 patients admitted to the ICU in Infanta Leonor University Hospital were collected; 74.7% were male. The average age was 59.7 years. The main comorbidities found were hypertension in 51.8%, diabetes mellitus in 25.3%, asthma in 7.2%, and chronic obstructive pulmonary disease in 3.6%. A surgical tracheostomy was carried out in 36.1% of patients who needed a prolonged intubation. The most frequent complication of the surgical procedure, bleeding, occurred in 30%, but the majority were mild and ceased with compression only. The most relevant complication was local infection, which occurred in 26.7% of patients. There were statistically significant differences in the time from the beginning of mechanical ventilation until weaning between tracheostomized and nontracheostomized patients. The mortality rate of patients who underwent tracheostomy was 56.7%. Despite severe acute respiratory syndrome coronavirus 2 being highly contagious and tracheostomy being considered a high-risk procedure, our rate of infected ear, nose, and throat specialists was only 11.8%.
Conclusion
In our experience, bedside surgical tracheostomy is a safe procedure in COVID-19 patients when safety protocols are followed.