Satisfaction of the Use of Telehealth and Access to Care for Veterans During the COVID-19 Pandemic.

Background: While many health care providers have shifted toward telehealth services in response to the COVID-19 pandemic, little is known about the perception and acceptance of such services, particularly among vulnerable populations. Veterans, who are at increased risk of physical and mental health needs, may benefit from the use and availability of telehealth services. Materials and Methods: Cross sectional survey data related to telehealth use, satisfaction, and access were collected through an online survey. Participants from previous research studies and veterans receiving care at a national veteran behavioral health organization were invited to participate. Results: A total of 404 veterans participated. Before the pandemic, many veterans had never used telehealth for physical (72%) or mental (76%) health care. Since the start of the pandemic, 62% of participants reported they received some care through telehealth services. Most participants found telehealth valuable and helpful (82%), indicated the technology was well explained (77%), and felt that issues were resolved quickly and easily (67%). Access to care was limited among participants who utilize massage therapy (64%), dental care (53%), routine checkups (50%), acupuncture (50%), and physical therapy (48%). Discussion: These findings showed an increase in the use of telehealth services and overwhelming satisfaction among veterans. Despite this, some veterans indicated barriers to receiving physical and mental health care. Conclusions: This provides an opportunity to expand the use of telehealth services to meet the health care needs of veterans. Barriers to care should be addressed to minimize the impact on the well-being of veterans.

The respiratory mechanics of the yacare caiman (Caiman yacare).

The structure and function of crocodilian lungs are unique compared with those of other reptiles. We examined the extent to which this and the semi-aquatic lifestyle of crocodilians affect their respiratory mechanics. We measured changes in intratracheal pressure in adult and juvenile caiman (Caiman yacare) during static and dynamic lung volume changes. The respiratory mechanics of juvenile caiman were additionally measured while the animals were floating in water and submerged at 30, 60 and 90 deg to the water's surface. The static compliance of the juvenile pulmonary system (2.89±0.22 ml cmH2O-1 100 g-1) was greater than that of adults (1.2±0.41 ml cmH2O-1 100 g-1), suggesting that the system stiffens as the body wall becomes more muscular and keratinized in adults. For both age groups, the lungs were much more compliant than the body wall, offering little resistance to air flow (15.35 and 4.25 ml cmH2O-1 100 g-1 for lungs, versus 3.39 and 1.67 ml cmH2O-1 100 g-1 for body wall, in juveniles and adults, respectively). Whole-system dynamic mechanics decreased with increasing ventilation frequency (fR), but was unaffected by changes in tidal volume (VT). The vast majority of the work of breathing was required to overcome elastic forces; however, work to overcome resistive forces increased proportionally with fR Work of breathing was higher in juvenile caiman submerged in water at 90 deg because of an increase in work to overcome both elastic and flow resistive forces. The lowest power of breathing was found to occur at high fR and low VT for any given minute ventilation (V̇E) in caiman of all ages.

Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity, Disproportional Reductions in White Matter Volume, and Microcephaly in Angelman Syndrome Model Mice.

Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. It is currently unclear how the consequences of this genetic insult unfold to impair neurodevelopment. We reasoned that by elucidating the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset, we would gain new insights into the mechanisms by which maternal UBE3A loss derails neurotypical brain growth and function. Detailed anatomical analysis of both male and female maternal Ube3a-null mice reveals that microcephaly in the AS mouse model is primarily driven by deficits in the growth of white matter tracts, which by adulthood are characterized by densely packed axons of disproportionately small caliber. Our results implicate impaired axon growth in the pathogenesis of AS and identify noninvasive structural neuroimaging as a potentially valuable tool for gauging therapeutic efficacy in the disorder.SIGNIFICANCE STATEMENT People who maternally inherit a deletion or nonfunctional copy of the UBE3A gene develop Angelman syndrome (AS), a severe neurodevelopmental disorder. To better understand how loss of maternal UBE3A function derails brain development, we analyzed brain structure in a maternal Ube3a knock-out mouse model of AS. We report that the volume of white matter (WM) is disproportionately reduced in AS mice, indicating that deficits in WM development are a major factor underlying impaired brain growth and microcephaly in the disorder. Notably, we find that axons within the WM pathways of AS model mice are abnormally small in caliber. This defect is associated with slowed nerve conduction, which could contribute to behavioral deficits in AS, including motor dysfunction.

Dependence of carbon nanotubes dispersion kinetics on surfactants.

Carbon nanotubes (CNTs) have been the subject of many studies due to their unique structure and desirable properties. However, the ability to solubilize and separate single CNTs from the bundles they form is still a challenge that needs to be overcome in order to extend their applications in the field of Nanotechnology. Covalent interactions are designed to modify CNTs surface and so prevent agglomeration. Though, this method alters the structures and intrinsic properties of CNTs. In the present work, noncovalent approaches to functionalize and solubilize CNTs are studied in detail. A dispersion kinetic study was performed to characterize the ability of different type of surfactants (non-ionic, anionic, cationic and biopolymer) to unzip CNT bundles. The dispersion kinetic study performed depicts the distinct CNTs bundles unzipping behavior of the different type of surfactants and the results elucidate specific wavelengths in relation with the degree of CNT clustering, which provides new tools for a deeper understanding and characterization of CNTs. Small angle x-ray scattering and transmission electron microscopy results are in agreement with UV-vis-NIR observations, revealing perfectly monodispersed CNTs for the biopolymer and cationic surfactant.

Validation of the German patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

BACKGROUND: Integrating the patient's perspective has become an increasingly important component of adverse event reporting. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). This instrument has been translated into German and linguistically validated; however, its quantitative measurement properties have not been evaluated. PATIENTS AND METHODS: A German language survey that included 31 PRO-CTCAE items, as well as the EORTC QLQ-C30 and the Oral Mucositis Daily Questionnaire (OMDQ), was distributed at 10 cancer treatment settings in Germany and Austria. Item quality was assessed by analysis of acceptability and comprehensibility. Reliability was evaluated by using Cronbach's' alpha and validity by principal components analysis (PCA), multitrait-multimethod matrix (MTMM) and known groups validity techniques. RESULTS: Of 660 surveys distributed to the study centres, 271 were returned (return rate 41%), and data from 262 were available for analysis. Participants' median age was 59.7 years, and 69.5% of the patients were female. Analysis of item quality supported the comprehensibility of the 31 PRO-CTCAE items. Reliability was very good; Cronbach's' alpha correlation coefficients were >0.9 for almost all item clusters. Construct validity of the PRO-CTCAE core item set was shown by identifying 10 conceptually meaningful item clusters via PCA. Moreover, construct validity was confirmed by the MTMM: monotrait-heteromethod comparison showed 100% high correlation, whereas heterotrait-monomethod comparison indicated 0% high correlation. Known groups validity was supported; PRO-CTCAE scores were significantly lower for those with impaired versus preserved health-related quality of life. CONCLUSION: A set of 31 items drawn from the German PRO-CTCAE item library demonstrated favourable measurement properties. These findings add to the body of evidence that PRO-CTCAE provides a rigorous method to capture patient self-reports of symptomatic toxicity for use in cancer clinical trials.

Outcome of patients with systemic diseases admitted to the medical intensive care unit of a tertiary referral hospital: a single-centre retrospective study.

OBJECTIVES: Systemic diseases form a rare heterogeneous group of diseases, with important morbidity caused by disease evolution and/or treatment. We describe the clinical features and outcome of patients with these diseases admitted to a referral hospital intensive care unit (ICU). METHOD: We conducted a retrospective case review of all patients with systemic diseases (n = 86) admitted to the medical ICU of Leuven University Hospital between May 2007 and September 2012. RESULTS: The most frequent diagnoses were systemic vasculitis (n = 31), sarcoidosis (n = 15), systemic sclerosis (n = 9), and systemic lupus erythematosus (SLE) (n = 7). The main reason for admission was infection (60%), followed by disease-related organ failure (48%). Respiratory failure was the most common organ dysfunction. The mean APACHE II (Acute Physiology and Chronic Health Evaluation II) score was 28 ± 10. Mortality was 19% during ICU admission, 39% during hospital stay, and 58% at the end of follow-up. Death was caused by infection in the majority of cases (56%), and by evolution of the underlying disease in 32%. Only age and APACHE II score were associated with mortality. CONCLUSIONS: The mortality of patients with systemic diseases admitted to an ICU is high, both during their stay in the ICU and afterwards. Age and APACHE II score, but not infection or immunosuppressive therapy, were associated with mortality.

Shigella flexneri serotype 1 infections in men who have sex with men in Vancouver, Canada.

OBJECTIVES: Outbreaks of shigellosis have been documented in men who have sex with men (MSM), associated with interpersonal transmission and underlying HIV infection. We observed a rise in Shigella flexneri isolates identified in a downtown tertiary-care hospital laboratory located within the city centre community health area (CHA-1) of Vancouver, Canada. The objectives of this study were to evaluate clinical outcomes of shigellosis cases among MSM admitted to hospital and to evaluate trends in Shigella cases within Vancouver, Canada. METHODS: Adult rates of shigellosis were analysed by gender and health region, from 2005 to 2011, followed by retrospective chart review of all hospital laboratory-identified S. flexneri cases from 2008 to 2012. Serotyping and pulsed-field gel electrophoresis (PFGE) were performed on these isolates. RESULTS: Although shigellosis rates in men within CHA-1 did not change from 2005 to 2011 (range 33.4-68.5 per 100 000; P = 0.74), they were significantly higher than in other regions within the city of Vancouver (P ≤ 0.001) and the province of British Columbia (P ≤ 0.001). Shigella flexneri rates in men within CHA-1 increased significantly (range 2.3-51.4 per 100 000; P < 0.001), starting in 2008, and were higher than in other regions within Vancouver (P ≤ 0.01). Seventy-nine isolates of S. flexneri from 72 patients were identified by a single hospital laboratory. All patients were male and predominantly MSM (91.7%) and HIV-infected (86.1%), with most (92.6%) demonstrating CD4 counts ≥ 200 cells/µL. In total, 38.0% required hospitalization. Most (87.3%) had S. flexneri serotype 1 infection, with 72.9% of these representing a single PFGE pattern. CONCLUSIONS: We identified high levels of transmission of a primarily clonal strain of S. flexneri serotype 1 in our local MSM population, resulting in a substantial burden of illness and health care resource use secondary to hospital admissions.

Signal enhancement in ultraflat electrochemical DNA biosensors.

The ability of holding back the undesired molecules, but at the same time to provide the right distribution and orientation of the bioreceptors, are critical targets to reach an efficient hybridization and enhanced detection in electrochemical DNA biosensors. The main actors responsible of these key functions are the substrate of the sensor and the interface auto-assembled on it. In this paper we present the annealing as a method to improve commercial gold evaporated substrates for biosensor applications. The restructuring of granulated gold surface by means of annealing heating treatment leads to the formation of ultraflat gold lamellar terraces. The formation of terraces was characterized with scanning tunneling microscopy and optical interferometry. The performance of the sensor sensitivity on granular substrates and ultraflat substrates was studied, concerning the orientation and surface coverage of the bioreceptor interface applied in electrochemical biosensor. The hybridization efficiency of ferrocene-labeled DNA amplified by PCR was characterized with surface plasmon resonance and electrochemistry. The experimental results demonstrate that annealing process, positive influence on optical and voltammetric readings, due to a structured organization of the bioreceptors on the flat substrate, gaining more efficient immobilization and DNA hybridization. The results suggest the annealing as a powerful tool for improving gold substrates in biosensors applications.

Reduction in community-onset methicillin-resistant Staphylococcus aureus rates in an urban Canadian hospital setting.

Community-onset methicillin resistant Staphylococcus aureus (CO-MRSA) became a prominent cause of infection in North America in 2003, with a peak in the epidemic noted by multiple groups in the USA between 2005 and 2007. We reviewed rates of MRSA in two hospitals in Vancouver, Canada, to observe changes in epidemiology from 2003 to 2011. Episodes of emergency department (ED) MRSA bacteraemia and wounds were extracted from the laboratory database, with rates calculated per 10,000 ED visits. All cases were assumed to be community onset, as they were diagnosed in the ED. A peak in ED MRSA bacteraemias occurred in 2005, at 7·8/10,000 ED visits. By 2011, rates of ED bacteraemia declined significantly to 3·3/10,000 ED visits (P

Cultural pathways to psychosis care: Patient and caregiver narratives from Puebla, Mexico.

The current study used the McGill Illness Narrative Interview (MINI) to explore patients' (n = 6) and caregivers' (n = 3) narratives about how they identified and sought care for psychosis. Participants were recruited from an outpatient clinic at the Hospital Psiquiátrico Dr. Rafael Serrano, a public psychiatric hospital in Puebla, Mexico. All participants consented to complete semi-structured interviews in Spanish. Thematic analyses were used to inductively identify common themes in participants' narratives. The results indicated that during the initial symptom onset, most participants noticed the presence of hallucinations but did not seek help for this hallmark symptom. Participants described seeking care only when they or their ill relative exhibited escalating aggressive behaviors or physical symptoms that were interpreted as common medical problems. As participants became connected to specialty mental health services, they began to develop a conceptualization of psychosis as a disorder of aggression. For some participants, this conceptualization of psychosis as an illness of aggression contributed to their ambivalence about the diagnosis. These results can be understood using a cultural scripts framework, which suggests that cultural norms are influenced by collective understandings of normalcy and valorization of behaviors. Implications for community campaigns are discussed.

Recruitment and Feasibility of Hair Cortisol Collection in a Sample of Ethnically and Sexually Diverse, Low-Income Adults: A Qualitative Community-Partnered Participatory Research Study.

The current study describes how a community-partnered participatory research (CPPR) model was used to enhance hair cortisol research engagement among low-income adults of diverse ethnicities and sexual and gender identities. Participants' reported motivations and concerns surrounding providing a hair sample are also described. Participants from a larger longitudinal study were invited to provide a hair sample and/or complete acceptability interviews. Results indicated that 71% of all persons (N=133) contacted participated in the current study, of whom 82% provided hair samples. Several themes emerged from the interviews indicating that participants were motivated to provide a hair sample due to internal and external factors; however, concerns about mistrust of research remained. Thus, collecting biospecimens in research with underserved groups requires careful consideration of benefits and risks to the individual and their communities. Our results provide guidelines for engaging low-income racially/ethnically and sexually diverse community members in biospecimen research to understand stress-health relationships.

Primary peritonitis due to group A Streptococcus in a previously healthy pediatric patient.

Primary peritonitis remains a rare disease in otherwise healthy children, with group A Streptococcus (GAS) being a particularly unusual cause. A case involving a 14-year-old girl, who presented with an 'acute abdomen' and was taken to the operating room for urgent laparoscopy, is reported. Abdominal and pelvic structures were only minimally inflamed, as was the appendix. Peritoneal fluid and blood cultures both grew pure cultures of GAS. The patient's course was complicated by streptococcal toxic shock syndrome. She fortunately made a full recovery. The present report highlights the diagnostic and treatment dilemmas associated with GAS primary peritonitis.

La péritonite primaire demeure une maladie rare chez un enfant autrement en santé, et le streptocoque du groupe A (SGA) en est une cause particulièrement inhabituelle. Les auteurs présentent le cas d'une fille de 14 ans qui a consulté en raison d'un « abdomen aigu ¼ et a dû subir une laparoscopie d'urgence en salle d'opération. Les structures abdominale et pelvienne, de même que l'appendice, étaient peu enflammées. Le liquide péritonéal et les prélèvements sanguins ont tous deux permis d'obtenir des cultures pures de SGA. L'évolution de la patiente a été compliquée par un syndrome de choc toxique streptococcique. Heureusement, elle s'est entièrement rétablie. Le présent rapport souligne les dilemmes diagnostiques et thérapeutiques associés à la péritonite primaire à SGA.

A Comprehensive Mixed Methods Approach for Studying the Quality of Life of Colombian Periodontists.

This study analyzed the association of the sociodemographic, labor, and health conditions on the quality of life (QOL) of the periodontists in Colombia. A mixed study (explanatory sequential design) was conducted. The first quantitative phase was carried out by a cross-sectional survey (n = 187; 60.4% females). Variables: sociodemographics, labor, and health conditions, QOL (WHOQOL-BREF). Normality tests, descriptive statistics, and bivariate analyzes were performed. Factors associated with QOL were established using multivariate linear regression. A second qualitative phase with two focus groups (FGs) delved into those aspects of relevance, through qualitative content analysis and triangulation of information. The multivariate linear regression analysis showed that the factors associated with the QOL scores were in the case of men and negatively (QOL decreases): having low social support (p < 0.001), reporting poor mental health (p < 0.01). For women, QOL scores were negatively associated with low social support (p < 0.001), reporting poor general and mental health (p < 0.01), having greater stress at work (p < 0.05), having a temporary contract (p < 0.05), and living in a medium or low socioeconomic status (p < 0.05). The analysis of the FG allowed us to understand how QOL is permeated by the social context. The specialization of periodontics has generated a change in living conditions, and an adaptation to the workplace that allows them to gain recognition and a higher QOL. In conclusion, the QOL of periodontists is defined in subjective terms (standards) and related to social and labor conditions. Follow-up and evaluation strategies of the general conditions of these clinical specialists in Colombia are required.

Offline exhaled nitric oxide in children: chemiluminescence vs. electrochemical devices.

Background: Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation that has been used in children, using the "offline" technique. To the extent of our knowledge, no article reported in literature compares the concordance and correlation between the two different technologies used to measure eNO at tidal volume offline. This study aimed to report the concordance and correlation of the eNO measured "offline" at tidal volume, using chemioluminiscence (cl) vs electrochemical devices (eq). Methods: A cross-sectional, observational, and prospective study was conducted in the National Institute of Respiratory Diseases (Instituto Nacional de Enfermedades Respiratorias), Mexico City. Healthy children and those with a lung disease between 1 and 11 years of age were included. The exhaled air sample at tidal volume was obtained by attaching a mask connected to a Mylar® bag. Results: We studied 36 children. The mean ± standard deviation (SD) age of the study population was 6 ± 2.6 years; 25% of the subjects included were healthy, and the rest had a lung disease. The concordance correlation coefficient between the two measuring devices was 0.98 (p < 0.001), with a mean difference of 1.46 ± 3.5 ppb and 95% limits of agreement from -5.3 ppb to 8.3 ppb. The linear regression model equation for the estimation of eNO was eNOcl = (eNOeq·1.0718) - 0.1343 (r2 = 0.97). Conclusions: The measurement of eNO at tidal volume by the offline method can be analyzed by electrochemical devices, and the results are interchangeable with those analyzed by chemiluminescence technology.

Introducción: El óxido nítrico exhalado (eNO) es un marcador no invasivo de inflamación de la vía aérea que se ha utilizado en niños mediante técnica «fuera de línea¼. Por lo que sabemos, en la literatura no existen reportes que comparen la concordancia y la correlación entre dos técnicas diferentes a volumen corriente. El objetivo de este trabajo es informar la concordancia y la correlación del eNO obtenido por la técnica fuera de línea a volumen corriente en los equipos de quimioluminiscencia (cl) y electroquímico (eq). Métodos: Se realizó un estudio transversal, observacional y prospectivo en el Instituto Nacional de Enfermedades Respiratorias, en Ciudad de México. Se incluyeron niños sanos y con enfermedad pulmonar de 1-11 años de edad. La muestra de aire exhalado se obtuvo a volumen corriente mediante una máscara con conexión a una bolsa de Mylar®. Resultados: Se estudiaron 36 niños. La edad promedio con su desviación estándar de la población de estudio fue de 6 ± 2.6 años. El 25% de los sujetos incluidos estaban sanos y el resto tenían alguna enfermedad pulmonar. El coeficiente de correlación de concordancia entre los dos equipos fue de 0.98 (p < 0.001), con una diferencia media de 1.46 ± 3.5 ppb y unos límites de concordancia del 95% de −5.3 a 8.3 ppb. La ecuación del modelo de regresión lineal del eNO fue eNOcl = (eNOeq·1,0718) − 0.1343 (r2 = 0.97). Conclusiones: La medición del eNO por el método fuera de línea a volumen corriente puede analizarse en dispositivos electroquímicos. Los resultados son intercambiables con los de quimioluminiscencia.

The effect of fluid bolus administration on cerebral tissue oxygenation in post-cardiac arrest patients.

PURPOSE: Fluid boluses (FB) are often used in post-cardiac arrest (CA) patients with haemodynamic instability. Although FB may improve cardiac output (CO) and mean arterial pressure (MAP), FB may also increase central venous pressure (CVP), reduce arterial PaO2, dilute haemoglobin and cause interstitial oedema. The aim of the present study was to investigate the net effect of FB administration on cerebral tissue oxygenation saturation (SctO2) in post-CA patients. METHODS: Pre-planned sub-study of the Neuroprotect post-CA trial (NCT02541591). Patients with anticipated fluid responsiveness based on stroke volume variation (SVV) or passive leg raising test were administered a FB of 500 ml plasma-lyte A (Baxter Healthcare) and underwent pre- and post-FB assessments of stroke volume, CO, MAP, CVP, haemoglobin, PaO2 and SctO2. RESULTS: 52 patients (mean age 64 ±â€¯12 years, 75% male) received a total of 115 FB. Although administration of a FB resulted in a significant increase of stroke volume (63 ±â€¯22 vs 67 ±â€¯23 mL, p = 0.001), CO (4,2 ±â€¯1,6 vs 4,4 ±â€¯1,7 L/min, p = 0.001) and MAP (74,8 ±â€¯13,2 vs 79,2 ±â€¯12,9 mmHg, p = 0.004), it did not improve SctO2 (68.54 ±â€¯6.99 vs 68.70 ±â€¯6.80%, p = 0.49). Fluid bolus administration also resulted in a significant increase of CVP (10,0 ±â€¯4,5 vs 10,7 ±â€¯4,9 mmHg, p = 0.02), but did not affect PaO2 (99 ±â€¯31 vs 94 ±â€¯31 mmHg, p = 0.15) or haemoglobin concentrations (12,9 ±â€¯2,1 vs 12,8 ±â€¯2,2 g/dL, p = 0.10). In a multivariate model, FB-induced changes in CO (beta 0,77; p = 0.004) and in CVP (beta -0,23; p = 0.02) but not in MAP (beta 0,02; p = 0.18) predicted post-FB ΔSctO2. CONCLUSIONS: Despite improvements in CO and MAP, FB administration did not improve SctO2 in post-cardiac arrest patients.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Community-acquired bacterial meningitis in adults: emergency department management protocol.

Acute bacterial meningitis (ABM) is a rare but disabling infectious condition that requires a performant multidisciplinary management approach. Between 70 and 90 adult patients are diagnosed with community-acquired ABM in Belgium annually, and reported case fatality rates range from 17 to 40%. The currently available guidelines provide evidence-based guidance on how to manage this disease. However, these guidelines do not translate the evidence to the daily practice at the emergency department in a Belgian healthcare context. We created a taskforce in University Hospitals Leuven consisting of experts with complementary expertise in managing this disease: neurology, neurosurgery, intensive care medicine, microbiology and infectious diseases. The taskforce agreed upon a flowchart containing seven management steps encompassing all relevant phases in emergency ABM management. In addition to the focus on timely and adequate initiation of antimicrobial treatment, the flowchart and protocol also provide guidance on practical hurdles such as how to assess the safety of performing a lumbar puncture and when to refer patients to the intensive care department. This protocol was implemented in University Hospitals Leuven and fosters inter-disciplinary coordination of ABM care.

Seroprevalence of Antitransglutaminase and Antiendomysium Antibodies in Adult Colombian Blood Bank Donors.

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten from wheat, barley, and rye in genetically susceptible individuals. The global prevalence of CD is 1.4%. However, most of the prevalence studies have been conducted in Caucasian populations; few studies have been performed in Latin America. The aim of this study is to determine the seroprevalence of auto-antibodies used as markers for CD in a Colombian cohort. In this cross-sectional study, the serum samples from Colombian donors of the National Red Cross Blood Bank were collected between June and September 2017 in Bogotá, Colombia. All sera were tested for IgA antitissue transglutaminase (TTG) by enzyme-linked immunosorbent assay. Seropositive sera were tested for IgA antiendomysium (EMA) using indirect immunofluorescence assay. The ancestral genetic composition was determined in donor samples with antibody assay reactivity. Those with two seroreactive assays were typed for HLA class II DQ2 and DQ8. In total, 228 blood donors participated in the study. Among them, 113 were females (49.56%) with an average age of 31.63 years (SD ± 12.99); males had an average of 34.71 years (SD ± 13.01). Only 3 (1.31%) donors reported chronic diarrhea and nonintentional weight loss; 11 (4.82%) had a family history of CD. For the serological assays, 11 donors (4.82%) were seroreactive to IgA anti-TTG: 3 had high reactivity and 8 had low reactivity. Of those seroreactive to IgA anti-TTG, 3 (1.32%) were also seroreactive to anti-EMA, and they were typed as HLA-DQ8 or HLA-DQ2. The baseline ancestral percentage of the seroreactive donors was higher for European and Native American than for African genes. The seroprevalence for anti-TTG and anti-EMA with the presence of HLA-DQ8 and HLA-DQ2 was 1.32%. Additionally, 4.82% donor participants were reactive only for anti-TTG. Compared with other studies, our findings suggest that Colombia has a high prevalence of CD markers.

A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study.

BACKGROUND: The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19. METHODS: In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily-or 75 IU anti-Xa twice daily for intensive care (ICU) patients-in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. DISCUSSION: In this trial, we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome. TRIAL REGISTRATION: The EU Clinical Trials Register 2020-001739-28 . Registered on April 10, 2020.