Biological and protective properties of immune sera directed to the influenza virus neuraminidase.

UNLABELLED: The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen. IMPORTANCE: The neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines.

Japanese encephalitis virus tropism in experimentally infected pigs.

Pigs are considered to be the main amplifying host for Japanese encephalitis virus (JEV), and their infection can correlate with human cases of disease. Despite their importance in the ecology of the virus as it relates to human cases of encephalitis, the pathogenesis of JEV in pigs remains obscure. In the present study, the localization and kinetics of virus replication were investigated in various tissues after experimental intravenous infection of pigs. The data demonstrate a rapid and broad spreading of the virus to the central nervous system (CNS) and various other organs. A particular tropism of JEV in pigs not only to the CNS but also for secondary lymphoid tissue, in particular the tonsils with the overall highest viral loads, was observed. In this organ, even 11 days post infection, the latest time point of the experiment, no apparent decrease in viral RNA loads and live virus was found despite the presence of a neutralizing antibody response. This was also well beyond the clinical and viremic phase. These results are of significance for the pathogenesis of JEV, and call for further experimental studies focusing on the cellular source and duration of virus replication in pigs.

Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection.

Age is not associated with intracranial haemorrhage in patients with mild traumatic brain injury and oral anticoagulation.

BACKGROUND: Patients admitted to emergency departments with traumatic brain injury (TBI) are commonly being treated with oral anticoagulants. In contrast to patients without anticoagulant medication, no guidelines, scores or recommendations exist for the management of mild traumatic brain injury in these patients. We therefore tested whether age as one of the high risk factors of the Canadian head CT rule is applicable to a patient population on oral anticoagulants. METHODS: This cross-sectional analysis included all patients with mild TBI and concomitant oral anticoagulant therapy admitted to the Emergency Department, Inselspital Bern, Switzerland, from November 2009 to October 2014 (n = 200). Using a logistic regression model, two groups of patients with mild TBI on oral anticoagulant therapy were compared - those with and those without intracranial haemorrhage. RESULTS: There was no significant difference in age between the patient groups with (n = 86) and without (n = 114) intracranial haemorrhage (p = 0.078). In univariate logistic regression, GCS (OR = 0.419 (0.258; 0.680)) and thromboembolic event as reason for anticoagulant therapy (OR = 0.486 (0.257; 0.918)) were significantly associated with intracranial haemorrhage in patients with mild TBI and anticoagulation (all p < 0.05). However, there was no association with age (p = 0.078, OR = 1.024 (0.997; 1.051)), the type of accident or additional medication with acetylsalicylic acid or clopidogrel ((both p > 0.05; 0.552 (0.139; 2.202) and 0.256 (0.029; 2.237), respectively). CONCLUSION: Our study found no association between age and intracranial bleeding. Therefore, until further risk factors are identified, diagnostic imaging with CCT remains necessary for mild TBI patients on oral anticoagulation of all ages, especially those with therapeutic anticoagulation because of thromboembolic events.

Chronological clinical and pathological documentation of porcine ulcerative dermatitis.

BACKGROUND: Porcine ulcerative dermatitis syndrome (PUDS) is a rare disease of breeding sows with an unknown pathogenesis. OBJECTIVE: To describe the evolution of clinical and histopathological lesions over the course of the disease and to elucidate the pathogenesis. ANIMAL: A 24-month-old, pluriparous, large white sow presented during gestation with ulcerations around the teats compatible with PUDS. METHODS AND RESULTS: Clinical and histopathological lesions were monitored over the course of the disease (i.e. during and after the subsequent pregnancy). A clear gestation-dependent flare of the lesions was observed with partial resolution occurring postpartum. The histological pattern presented as a lymphocytic interface dermatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: The findings in this case report link gestation with the development of clinical signs and histological changes. Multiparity appears to enhance severity and may finally result in a self-perpetuating disease. Therefore, it seems advisable to cull breeding sows after they have developed PUDS.

Anaphylaxis in a Swiss university emergency department: clinical characteristics and supposed triggers.

BACKGROUND: Anaphylaxis is the most severe form of acute systemic and potentially life-threatening reactions triggered by mast and basophilic cells. Recent studies show a worldwide incidence between 50 and 112 occurrences per 100,000 person-years. The most identified triggers are food, medications, and insect venoms. We aimed to analyze triggers and clinical symptoms of patients presenting to a Swiss university emergency department for adults. METHODS: Six-year retrospective analysis (01/2013 to 12/2018) of all patients (> 16 years of age) admitted with moderate or severe anaphylaxis (classification of Ring and Messmer ≥ 2) to the emergency department. Patient and clinical data were extracted from the electronic medical database of the emergency department. RESULTS: Of the 531 includes patients, 53.3% were female, the median age was 38 [IQR 26-51] years. The most common suspected triggers were medications (31.8%), food (25.6%), and insect stings (17.1%). Organ manifestations varied among the different suspected triggers: for medications, 90.5% of the patients had skin symptoms, followed by respiratory (62.7%), cardiovascular (44.4%) and gastrointestinal symptoms (33.7%); for food, gastrointestinal symptoms (39.7%) were more frequent than cardiovascular symptoms (36.8%) and for insect stings cardiovascular symptoms were apparent in 63.8% of the cases. CONCLUSIONS: Average annual incidence of moderate to severe anaphylaxis during the 6-year period in subjects > 16 years of age was 10.67 per 100,000 inhabitants. Medications (antibiotics, NSAID and radiocontrast agents) were the most frequently suspected triggers. Anaphylaxis due to insect stings was more frequently than in other studies. Regarding clinical symptoms, gastrointestinal symptoms need to be better considered, especially that initial treatment with epinephrine is not delayed.

Do all Emergency Room Patients With Influenza-like Symptoms Need Blood Cultures? A Retrospective Cohort Study of 2 Annual Influenza Seasons.

In this retrospective cohort study, we evaluated risk factors for bacteremia in emergency department patients presenting with influenza-like symptoms during influenza epidemic seasons. In patients without fever, chronic heart or chronic liver disease, blood culture collection might be omitted.

Retrospective Study of Tick Bites Associated with Neurological Disease in a Level Three University Hospital in Switzerland.

BACKGROUND: Ticks represent very important vectors of human and zoonotic pathogens, and tick-borne diseases (TBDs) are diagnosed with increasing frequency. Therefore, the aim of this retrospective study was to describe patients presenting with a complaint of tick bite in the emergency department (ED) of a large university hospital in Switzerland. METHODS: Data were collected by searching for keywords in the routine clinic database to identify cases from 1 July 2012 to 30 June 2020. The patients' data were screened for preexisting diseases and demographic and clinical characteristics. RESULTS: We included 415 patients collected over a period of 8 years, with highest admission frequencies from May to July. Of these, 82% were outpatients, 15.9% admitted to a hospital ward, and five to intensive care. The patients were allocated to three groups. The first group represented patients with erythema chronica migrans (ECM), which is pathognomonic for Lyme borreliosis (n = 45). Accordingly, 89% of cases in this group of patients were treated with antibiotics. The second group represented patients with other tick bite-associated erythema (n = 139). In this group, no particular clinical symptoms or laboratory findings were found. Finally, the largest group represented patients in which the tick bite was no longer visible (n = 201). This group of patients had significantly more evidence of neurological disorders (52%) and were treated at a higher rate with non-steroidal anti-inflammatory (29%) or antiviral (13%) drugs. Although the vaccination status for tick-borne encephalitis virus (TBEV) was not systematically evaluated, at least 10% of the latter group was vaccinated, indicating another source for neurological disease. Furthermore, only 14% of the tested patients were positive for IgM or IgG against TBEV. CONCLUSION: This retrospective study indicates the presence of many undiagnosed neurological diseases following tick bites that could be caused by TBEV or an unknown infectious agent. Taken together, although tick bites were not very frequently seen in the present tertiary ED, the frequent presence of neurological symptoms demands a more systematic assessment of vaccination status and TBEV serology as well as further diagnostic evaluations in patients that report tick bites and neurological symptoms.

Presentation and treatment of animal and human bite injuries at a Swiss tertiary emergency department: a cross-sectional study.

BACKGROUND: Animal and human bite injuries are a relevant health problem worldwide. With the increasing number of pets, bite injuries are becoming more frequent. Previous studies on animal and human bite injuries in Switzerland were completed several years ago. The aim of the present study was to provide a detailed overview of patients with bite injuries admitted to a tertiary emergency department in Switzerland in terms of demographics, injury patterns and treatment strategies. METHODS: A 9-year cross-sectional analysis of patients presenting to the emergency department of Bern University Hospital in the period January 2013 to December 2021 following an animal or human bite injury. RESULTS: A total of 829 patients with bite injuries were identified, including 70 for postexposure prophylaxis only. Their median age was 39 (IQR 27-54) years and 53.6% were female. Most patients were bitten by a dog (44.3%), followed by cats (31.5%) and humans (15.2%). Most bite injuries were mild (80.2%); severe injuries were mainly found in dog bites (28.3%). Most patients were treated within six hours after human (80.9%) or dog (61.6%) bites; after cat bites, patients often presented with a delay (74.5%) and signs of infection (73.6%). Human bite wounds were superficial in the majority of cases (95.7%), rarely showed signs of infection (5.2%) at the time of presentation and hospitalisation was never required. CONCLUSIONS: Our study provides a detailed overview of patients admitted to an emergency department of a tertiary Swiss University Hospital after an animal or human bite. In summary, bite injuries are common among patients who present to the emergency department. Therefore, primary and emergency care clinicians should be familiar with these injuries and their treatment strategies. The high risk of infection, particularly in cat bites, may warrant surgical debridement in the initial treatment of these patients. Prophylactic antibiotic therapy and close follow-up examinations are recommended in most cases.

Use of epinephrine in anaphylaxis: a retrospective cohort study at a Swiss university emergency department.

AIMS OF THE STUDY: Anaphylaxis is a medical emergency and requires prompt treatment to prevent life-threatening conditions. Epinephrine, considered as the first-line drug, is often not administered. We aimed first to analyse the use of epinephrine in patients with anaphylaxis in the emergency department of a university hospital and secondly to identify factors that influence the use of epinephrine. METHODS: We performed a retrospective analysis of all patients admitted with moderate or severe anaphylaxis to the emergency department between 1 January 2013 and 31 December 2018. Patient characteristics and treatment information were extracted from the electronic medical database of the emergency department. RESULTS: A total of 531 (0.2%) patients with moderate or severe anaphylaxis out of 260,485 patients admitted to the emergency department were included. Epinephrine was administered in 252 patients (47.3%). In a multivariate logistic regression, cardiovascular (Odds Ratio [OR] = 2.94, CI 1.96-4.46, p <0.001) and respiratory symptoms (OR = 3.14, CI 1.95-5.14, p<0.001) were associated with increased likelihood of epinephrine administration, in contrast to integumentary symptoms (OR = 0.98, CI 0.54-1.81, p = 0.961) and gastrointestinal symptoms (OR = 0.62, CI 0.39-1.00, p = 0.053). CONCLUSIONS: Less than half of the patients with moderate and severe anaphylaxis received epinephrine according to guidelines. In particular, gastrointestinal symptoms seem to be misrecognised as serious symptoms of anaphylaxis. Training of the emergency medical services and emergency department medical staff and further awareness are crucial to increase the administration rate of epinephrine in anaphylaxis.

Effects and utility of an online forward triage tool during the SARS-CoV-2 pandemic: a mixed method study and patient perspectives, Switzerland.

OBJECTIVE: To assess the effects (quantitatively) and the utility (qualitatively) of a COVID-19 online forward triage tool (OFTT) in a pandemic context. DESIGN: A mixed method sequential explanatory study was employed. Quantitative data of all OFTT users, between 2 March 2020 and 12 May 2020, were collected. Second, qualitative data were collected through key informant interviews (n=19) to explain the quantitative findings, explore tool utility, user experience and elicit recommendations. SETTING: The working group e-emergency medicine at the emergency department developed an OFTT, which was made available online. PARTICIPANTS: Participants included all users above the age of 18 that used the OFTT between 2 March 2020 and 12 May 2020. INTERVENTION: An OFTT that displayed the current test recommendations of the Federal Office of Public Health on whether someone needed testing for COVID-19 or not. No diagnosis was provided. RESULTS: In the study period, 6272 users consulted our OFTT; 40.2% (1626/4049) would have contacted a healthcare provider had the tool not existed. 560 participants consented to a follow-up survey and provided a valid email address. 31.4% (176/560) participants returned a complete follow-up questionnaire. 84.7% (149/176) followed the recommendations given. 41.5% (73/176) reported that their fear was allayed after using the tool. Qualitatively, seven overarching themes emerged namely (1) accessibility of tool, (2) user-friendliness of tool, (3) utility of tool as an information source, (4) utility of tool in allaying fear and anxiety, (5) utility of tool in medical decision-making (6) utility of tool in reducing the potential for onward transmissions and (7) utility of tool in reducing health system burden. CONCLUSION: Our findings demonstrated that a COVID-19 OFTT does not only reduce the health system burden but can also serve as an information source, reduce anxiety and fear, reduce potential for cross infections and facilitate medical decision-making.

Current Perspectives and Concerns Facing Hospital Evacuation: The Results of a Pilot Study and Literature Review.

OBJECTIVE: To analyze the evacuation preparedness of hospitals within the European Union (EU). METHOD: This study consisted of 2 steps. In the first step, a systematic review of the subject matter, according to the PRISMA flow diagram, was performed. Using Scopus (Elsevier, Amsterdam, Netherlands), PubMed (National Library of Medicine, Bethesda, MD), and Gothenburg University´s search engine, 11 questions were extracted from the review and were sent to representatives from 15 European Union (EU)- and non-EU countries. RESULTS: The findings indicate that there is neither a full preparedness nor a standard guideline for evacuation within the EU or other non-EU countries in this study. A major shortcoming revealed by this study is the lack of awareness of the untoward consequences of medical decision-making during an evacuation. Some countries did not respond to the questions due to the lack of relevant guidelines, instructions, or time. CONCLUSION: Hospitals are exposed to internal and external incidents and require an adequate evacuation plan. Despite many publications, reports, and conclusions on successful and unsuccessful evacuation, there is still no common guide for evacuation, and many hospitals lack the proper preparedness. There is a need for a multinational collaboration, specifically within the EU, to establish such an evacuation planning or guideline to be used mutually within the union and the international community.

Presentations with reported methamphetamine use to an urban emergency department in Switzerland.

AIMS OF THE STUDY: The stimulant methamphetamine (e.g., "crystal meth") is a commonly abused drug in many parts of the world and can cause significant health problems. The present study aims to describe presentations with reported methamphetamine use at an urban emergency department (ED) in Switzerland, to investigate prevalence, patterns and susceptible groups. METHODS: Retrospective study at the ED of the University Hospital of Bern, Switzerland. Cases from June 2012 to July 2019 were retrieved from the electronic patient database using full-text terms and were categorised into three groups based on patient history: "acute", if patients presented within 72 hours of last reported use, "chronic" in cases of regular use but not within the previous 72 hours, and "past" in cases of discontinued consumption. Cases with a positive methamphetamine urine drug screening test with no further information available were described separately. RESULTS: During the study period, 40 cases were categorised as "acute". Among those, the mean age was 29.5 years (standard deviation [SD] 8.7), 75% (n = 30) were male, and agitation (n = 11, 28%), hypertension (n = 11, 28%), tachycardia (n = 11, 28%), sleep disturbances (n = 10, 25%) and aggression (n = 8, 20%) were the most common symptoms. Most patients (n = 22, 55%) were medically discharged, but 35% (n = 14) were admitted to a psychiatric clinic. Most (n = 33, 82.5%) were polydrug users, with alcohol, cocaine and cannabis being the most frequent co-used substances. The "chronic" group included 37 cases. Those patients were mostly male (n = 26, 70%), with a mean age of 31 years (SD 11.0), and 46% (n = 17) presented because of psychiatric symptoms, such as psychosis, depression or aggression. Of the 45 cases in the "past" group (mean age of 30 years, SD 8.6), 69% (n = 31) were male, and 49% (n = 22) and 24% (n = 11), respectively, had medical and psychiatric symptoms as the reason for admission. Of 61 cases with a positive urine drug screening test as the sole indicator of methamphetamine use, 19 patients reported MDMA use (cross-reactivity with methamphetamine in the urine immunoassay used). In the 42 remaining cases, it was unclear if the positive result was due to unreported methamphetamine use or cross-reactivity. CONCLUSIONS: Most patients with reported methamphetamine use were young and male, with signs of sympathomimetic arousal and/or psychiatric symptoms. Although ED visits with reports of methamphetamine use appear to be uncommon, consumption-related health problems can require significant pre- and in-hospital resources.

Characterization of canine dendritic cells in healthy, atopic, and non-allergic inflamed skin.

Atopic dermatitis in humans and dogs is a chronic relapsing allergic skin disease. Dogs show a spontaneous disease similar to the human counterpart and represent a model to improve our understanding of the immunological mechanisms, the pathogenesis of the disease, and new therapy development. The aim of the study was to determine the frequency and phenotype of dendritic cells (DC) in the epidermis and dermis of healthy, canine atopic dermatitis lesional, and non-allergic inflammatory skin to further validate the model and to obtain insights into the contribution of DC to the pathogenesis of skin diseases in dogs. We first characterized canine skin DC using flow-cytometric analysis of isolated skin DC combined with an immunohistochemical approach. A major population of canine skin dendritic cells was identified as CD1c(+)CD11c(+)CD14(-)CD80(+)MHCII(+)MAC387(-) cells, with dermal DC but not Langerhans cells expressing CD11b. In the epidermis of lesional canine atopic dermatitis and non-allergic inflammatory skin, we found significantly more dendritic cells compared with nonlesional and control skin. Only in canine atopic dermatitis skin did we find a subset of dendritic cells positive for IgE, in the epidermis and the dermis. Under all inflammatory conditions, dermal dendritic cells expressed more CD14 and CD206. MAC387(+) putative macrophages were absent in healthy but present in inflamed skin, in particular during non-allergic diseases. This study permits a phenotypic identification and differentiation of canine skin dendritic cells and has identified markers and changes in dendritic cells and macrophage populations related to allergic and non-allergic inflammatory conditions. Our data suggest the participation of dendritic cells in the pathogenesis of canine atopic dermatitis similar to human atopic dermatitis and further validate the only non-murine spontaneous animal model for this disease.

Patient safety culture in a university hospital emergency department in Switzerland - a survey study.

Aim of the study: Poor safety culture, bad teamwork, non-functional inter-departmental working relationships and increased cognitive demands are associated with higher amounts of adverse events in hospitals. To improve patient safety, one of the first steps is to assess safety culture among health care providers in an institution. Considering the sparsity of studies addressing patient safety culture in Europe and Switzerland, the aim of the present study was to assess patient safety culture in the emergency department of a University Hospital in Switzerland. Methods: We employed the Hospital Survey On Patient Safety Culture, developed by the U.S. Agency for Healthcare Research and Quality. 140 questionnaires were distributed to nurses and physicians. Two weeks after the first questionnaire, we performed a sensitization campaign addressed to health care providers, and then repeated the survey. We calculated composite scores for each question category and percentages of positive responses for each dimension. For group comparisons such as possible differences relating to education and duration of employment and to compare results of the first and second survey we used T-tests. The results were compared to other published surveys outside of Switzerland. Results: Particularly positive assessments were found for the categories "nonpunitive response to errors", "teamwork within units", "supervisor/manager expectations and actions promoting patient safety" and, compared to other hospitals, also "staffing". The lowest average percent positive responses were found in the categories "frequencies of reported event", "teamwork across units" and "handoffs and transitions". Nurses and health care personnel with a longer employment history had an overall more negative assessment of patient safety culture, when compared to physicians and personnel with a shorter duration of employment, respectively. Conclusions: The present study has identified strengths and potential weaknesses in the safety culture of a large university hospital emergency department in Switzerland. The results provide opportunities for improvement of patient safety in particular in the reporting of adverse events, in interaction across units and patient transitions. Furthermore, as we employed a standardized self-assessment tool similar to previously published studies, the work contributes to the establishment of a benchmark for hospital safety culture at the national, European and international level.

Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

Several mosquito-borne Flaviviruses such as Japanese encephalitis virus (JEV), West Nile virus (WNV), Dengue Virus (DENV), and Zika virus (ZIKV) can cause severe clinical disease. Being zoonotic, Flaviviruses infect a wide variety of terrestrial vertebrates, which dependent of the virus-host interactions, can enhance ongoing epidemics and maintain the virus in the environment for prolonged periods. Targeted species can vary from amphibians, birds to various mammals, dependent on the virus. For many mosquito-borne flaviviruses the spectrum of targeted species is incompletely understood, in particular with respect to their contribution to the maintenance of virus in certain geographical regions. Furthermore, little is known about virus and host factors contributing to species tropism. The present study utilized human and porcine monocyte-derived dendritic cells (MoDC) as a cell culture model to better understand Flavivirus species tropism and innate immune responses. MoDC were selected based on their presence in the skin and their role as an early target cell for several Flaviviruses and their role as immune sentinels. While differences in viral infectivity and replication were minor when comparing porcine with human MoDC for some of the tested Flaviviruses, a particularly strong replication in human MoDC was found with USUV, while JEV appeared to have a stronger tropism for porcine MoDC. With respect to innate immune responses we found high induction of TNF and IFN-ß in both human and porcine MoDC after infection with JEV, WNV, and USUV, but not with DENV, ZIKV, and Wesselsbron virus. Spondweni virus induced these cytokine responses only in porcine MoDC. Overall, innate immune responses correlated with early infectivity and cytokine production. In conclusion, we demonstrate Flavivirus-dependent differences in the interaction with MoDC. These may play a role in pathogenesis but appear to only partially reflect the expected species tropism.

Corrigendum: Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

[This corrects the article DOI: 10.3389/fcimb.2019.00005.].

Heparin-Binding Protein as a Prognostic Biomarker of Sepsis and Disease Severity at the Emergency Department.

OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department. DESIGN: Prospective, international multicenter, convenience sample study. SETTING: Four general emergency departments at academic centers in Sweden, Switzerland, and Canada. PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: respiratory rate >25 breaths per minute; heart rate >120 beats per minute; altered mental status; systolic blood pressure <100 mm Hg; oxygen saturation <90% without oxygen; oxygen saturation <93% with oxygen; reported oxygen saturation <90%. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A total of 524 emergency department patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a noninfectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 h, 54 patients (10%) were admitted to an intensive care unit, and 23 patients (4%) died within 72 h. For the primary outcome, detection of infected-related organ dysfunction within 72 h, the area under the receiver operating curve (AUC) for HBP was 0.73 (95% CI 0.68-0.78) among all patients and 0.82 (95% CI 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 h) HBP had an AUC of 0.87 (95% CI 0.79-0.95) among all patients and 0.88 (95% CI 0.77-0.99) among patients confidently adjudicated to either infection or noninfection. CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.

An Accurate Diagnostic Pathway Helps to Correctly Distinguish Between the Possible Causes of Acute Scrotum.

OBJECTIVES: We sought to identify a simplified approach for the rapid differential diagnosis of patients presenting with acute scrotum. METHODS: A total of 440 patients referred to the emergency department of the University Hospital of Bern, Switzerland, with acute scrotum between 2003 and 2013 were retrospectively analyzed. Simple and multiple binary logistic regression analyses were used to evaluate clinical and laboratory parameters that may help to distinguish between genital/paragenital infection and acute testicular torsion. RESULTS: Over half (58.4%; 257/440) of the patients were diagnosed with genital/paragenital infection, 11.8% (52/440) with chronic testicular pain, 9.5% (42/440) with acute testicular torsion, 4.3% (19/440) with a testicular cancer, and 2.5% (11/440) with symptomatic distal ureterolithiasis. In multivariate analysis, a positive Prehn's sign was predictive of testicular torsion, whereas fever, dysuria, high leucocyte counts in blood and/or urine, high blood C-reactive protein, and burning pain were predictive of genital/paragenital infection. Color Doppler ultrasound did not help to distinguish between torsion and infection. CONCLUSIONS: An accurate diagnostic pathway helps to correctly distinguish between the possible causes of acute scrotum. However, none of the examinations performed could reliably distinguish between acute torsion and other causes of acute scrotum. Therefore, immediate surgical exploration of the testis is mandatory if torsion cannot be ruled out.