Risk of ankylosis of avulsed teeth immediately replanted or stored under favorable storage conditions before replantation: A long-term clinical study.

BACKGROUND/AIM: There are few long-term clinical follow-up studies on human teeth replanted immediately or after storage in a suitable storage medium prior to replantation. This study aimed to assess the risk of ankylosis in avulsed human teeth replanted immediately or after storage in physiological media for a short time. MATERIAL: Data from 116 patients with 145 replanted avulsed permanent teeth were selected from a comprehensive dental trauma database in Copenhagen University Hospital. The following teeth were selected: Group 1 comprised 36 teeth replanted immediately (dry time <6 min; wet time <6 min). Group 2 comprised 61 teeth replanted after physiologic storage media (saliva and saline) (dry time <6 min; wet time >5 min; wet time ranged from 7 to 170 min, and mean wet time was 59 min). Group 3 (control) included 48 teeth replanted after dry storage (dry time > 60 min). METHOD: Clinical and radiographic registrations were carried out according to a standardized protocol; follow-up ranged from 7 months to 23 years. Ankylosis was diagnosed by percussion test and radiographs and related to the conditions prior to replantation and stage of root development. RESULTS: The overall risk of ankylosis was 17.2% [95% CI: 4.61; 29.79] for immediately replanted teeth, 55.3% [95% CI: 42.54; 68.00] for teeth stored in physiologic media before replantation, and 85.7% [95% CI: 75.70; 95.73] for teeth stored dry more than 1 h. Mature teeth showed a significantly higher risk of ankylosis than immature teeth. CONCLUSION: This clinical long-term study has verified earlier experimental studies showing that immediate reimplantation has the lowest risk of ankylosis. Physiologic storage media are good alternatives that also reduce the risk of ankylosis compared to dry storage, where ankylosis is more likely although not always seen. Mature teeth are significantly more likely to develop ankylosis.

Risk of pulp necrosis and related complications in the permanent anterior teeth with lateral luxation: A systematic review and meta-analysis.

This systematic review aimed to evaluate the evidence related to the occurrence of pulp necrosis and related complications in permanent anterior teeth with lateral luxation. It was envisaged to address the ambiguity related to the recommendation for pulp extirpation in teeth with mature root apex. An a priori protocol was formulated as per the best practices of evidence-based medicine and registered in PROSPERO. A comprehensive search was performed electronically in PubMed, LILACS, Web of Science, EMBASE, Scopus, and Cochrane on July 10,2023 without any restriction of language or year of publication. The screening of titles and abstracts and later the full-text articles were performed. Later, the data extraction was performed by using a self-designed sheet, risk of bias (ROB) assessment was done, meta-analysis was performed, and the GRADE approach was used to assess the quality of evidence. The qualitative synthesis was performed on 13 studies done from 1985 to 2020 in hospital settings. There was variability in the minimum and total observation periods, sample sizes, and characteristics of the sample population. The overall pooled prevalence of pulp necrosis was found to be 57% (95% CI: 42, 72%). It was 12% (95% CI: 8%, 18%, I2 = 0%) in immature teeth, and 58% (95% CI: 42, 73%, I2 = 86%) in mature teeth. The pooled prevalence of EIRR was found to be 11% (95% CI: 4, 27%, I2 = 95%) with greater risk in teeth with mature root apex (RR: 1.26, 95% CI: 1.12, 1.42, I2 = 0%). The ROB was moderate or high in nine studies and the GRADE of evidence was very low in 14 of 15 outcomes. There are greater chances of pulp necrosis in teeth with lateral luxation, especially with mature apex. However, it can still be less than 60% in most cases with the prevalence of EIRR less than 20%. Hence, an absolute recommendation for endodontic intervention in mature teeth with lateral luxation must be interpreted with slight caution.

Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses.

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin ß1, only some integrin ß7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.

The risk of healing complications in primary teeth with root fractures: A retrospective cohort study.

BACKGROUND/AIM: Primary teeth are frequently affected by traumatic dental injuries. Root fractures are rare and have a reported incidence of 2% in the primary dentition. Hence, there is limited evidence on this topic. This study aims to evaluate the risk of healing complications in primary teeth with root fracture and to identify possible sequelae in the permanent dentition following root fracture in the primary dentition. MATERIALS AND METHODS: A retrospective analysis of a cohort of 53 patients with 74 root fractured primary teeth. The standard follow-up program included clinical and radiographic examination after 4 weeks, 8 weeks, 6 months, and 1 year after the trauma and when the patient was 6 years of age. The following complications were registered: pulp necrosis (PN), pulp canal obliteration (PCO), ankylosis with replacement root resorption (ARR), infection-related root resorption (IRR), premature tooth loss (PTL), and repair-related resorption (RRR). STATISTICS: The Kaplan-Meier and Aalen-Johansen estimators were employed. The level of significance was 5%. RESULTS: A total of 74 teeth were included. 42 teeth were extracted at the initial examination. Risks estimated after 3 years: PTL 45.9% [95% CI: 28.8-63.0], PCO 12.9% [95% CI: 2.3-23.4], PN 14.9% [95% CI: 3.9-25.9], RRR 2.6% [95% CI: 0.0-7.5]. No teeth showed ARR or IRR. All complications were diagnosed within the first year. Most common sequelae in the permanent dentition was demarcated opacities, with an estimated risk of 20% [95% CI: 8.2-41.3]. CONCLUSIONS: There is a low risk of healing complications following a root fracture in the primary dentition. Root fractures often result in early extraction of the coronal fragment. The remaining apical fragment will undergo a physiological resorption. Aside from opacities, there is a low risk of sequelae in the permanent dentition.

Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.

Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p < .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

RATIONALE: Asthma phenotyping requires novel biomarker discovery. OBJECTIVES: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). METHODS: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. RESULTS: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-ß and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. CONCLUSIONS: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

System dynamic modelling of healthcare associated influenza -a tool for infection control.

BACKGROUND: The transmission dynamics of influenza virus within healthcare settings are not fully understood. Capturing the interplay between host, viral and environmental factors is difficult using conventional research methods. Instead, system dynamic modelling may be used to illustrate the complex scenarios including non-linear relationships and multiple interactions which occur within hospitals during a seasonal influenza epidemic. We developed such a model intended as a support for health-care providers in identifying potentially effective control strategies to prevent influenza transmission. METHODS: By using computer simulation software, we constructed a system dynamic model to illustrate transmission dynamics within a large acute-care hospital. We used local real-world clinical and epidemiological data collected during the season 2016/17, as well as data from the national surveillance programs and relevant publications to form the basic structure of the model. Multiple stepwise simulations were performed to identify the relative effectiveness of various control strategies and to produce estimates of the accumulated number of healthcare-associated influenza cases per season. RESULTS: Scenarios regarding the number of patients exposed for influenza virus by shared room and the extent of antiviral prophylaxis and treatment were investigated in relation to estimations of influenza vaccine coverage, vaccine effectiveness and inflow of patients with influenza. In total, 680 simulations were performed, of which each one resulted in an estimated number per season. The most effective preventive measure identified by our model was administration of antiviral prophylaxis to exposed patients followed by reducing the number of patients receiving care in shared rooms. CONCLUSIONS: This study presents an system dynamic model that can be used to capture the complex dynamics of in-hospital transmission of viral infections and identify potentially effective interventions to prevent healthcare-associated influenza infections. Our simulations identified antiviral prophylaxis as the most effective way to control in-hospital influenza transmission.

Nonlinear Radiation Gauge for Near Kerr Spacetimes.

In this paper, we introduce and explore the properties of a new gauge choice for the vacuum Einstein equation inspired by the ingoing and outgoing radiation gauges (IRG, ORG) for the linearized vacuum Einstein equation introduced by Chrzanowski in his work on metric reconstruction (Chrzanowski in Phys Rev D 11:2042-2062, 1975) on the Kerr background. It has been shown by Price et al. (Class Quantum Gravity 24:2367-2388, 2007) that the IRG/ORG are consistent gauges for the linearized vacuum Einstein equation on Petrov type II backgrounds. In (Andersson et al. Stability for linearized gravity on the Kerr spacetime, 2019), the ORG was used in proving linearized stability for the Kerr spacetime, and the new non-linear radiation gauge introduced here is a direct generalization of that gauge condition, and is intended to be used to study the stability of Kerr black holes under the evolution generated by the vacuum Einstein equation.

Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation.

BACKGROUND: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. OBJECTIVE: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. METHODS: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. RESULTS: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). CONCLUSION: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.

NA0D - The new Traumatic Dental Injury classification of the World Health Organization.

An accurate, clear, and easy-to-use traumatic dental injury (TDI) classification and definition system is a prerequisite for proper diagnosis, study, and treatment. However, more than 50 classifications have been used in the past. The ideal solution would be that TDIs are adequately classified within the International Classification of Diseases (ICD), endorsed by the World Health Organization (WHO). TDI classification provided by the 11th Revision of the ICD (ICD-11), released in 2018, and previous Revisions, failed to classify TDIs satisfactorily. Therefore, in December 2018, a proposal was submitted by Dr's Stefano Petti, Jens Ove Andreasen, Ulf Glendor, and Lars Andersson, to the ICD-11, asking for a change of the existing TDI classification. Proposal #2130 highlighted the TDI paradox, the fifth most frequent disease/condition neglected by most public health agencies in the world, and the limits of ICD-11 classification. Namely, injuries of teeth and periodontal tissues were located in two separate blocks that did not mention dental/periodontal tissues; infraction, concussion, and subluxation were not coded; most TDIs lacked description; and tooth fractures were described through bone fracture descriptions (e.g., comminuted, compression, and fissured fractures). These limitations led to TDI mis-reporting, under-reporting, and non-specific reporting by untrained non-dental healthcare providers. In addition, no scientific articles on TDIs, present in PubMed, Scopus, and Web-of-Science, used the ICD classification. Proposal #2130 suggested to adopt the Andreasen classification, the most widely acknowledged classification used in dental traumatology. The Proposal was reviewed by two WHO teams, two scientific Committees, one WHO Collaborating Center, and the Department of Non-Communicable Disease Prevention at WHO headquarters, and it underwent two voting sessions. In March 2022, the Andreasen classification was accepted integrally. A new entity was generated, called NA0D, "Injury of teeth or supporting structures" (https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f1413338122). Hopefully, this will contribute to increasing the public awareness, and the dental profession's management, of TDIs.

Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019.

This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.

Comparable endemic coronavirus nucleoprotein-specific antibodies in mild and severe Covid-19 patients.

The severity of disease of Covid-19 is highly variable, ranging from asymptomatic to critical respiratory disease and death. Potential cross-reactive immune responses between SARS-CoV-2 and endemic coronavirus (eCoV) may hypothetically contribute to this variability. We herein studied if eCoV nucleoprotein (N)-specific antibodies in the sera of patients with mild or severe Covid-19 are associated with Covid-19 severity. There were comparable levels of eCoV N-specific antibodies early and during the first month of infection in Covid-19 patients with mild and severe symptoms, and healthy SARS-CoV-2-negative subjects. These results warrant further studies to investigate the potential role of eCoV-specific antibodies in immunity to SARS-CoV-2 infection.

Healthcare utilization and costs of psychiatric and somatic comorbidities associated with newly diagnosed adult ADHD.

BACKGROUND: Psychiatric and somatic problems in young adulthood have been found to be main drivers of costs in individuals with childhood ADHD. However, knowledge of the patterns of healthcare utilization and costs of comorbidities in middle-aged adults with newly diagnosed ADHD is very limited. METHOD: We studied individuals born 1966-1978 (from the Swedish Total Population Register) with newly diagnosed ADHD between the ages of 30-45 years and individuals without ADHD matched on birthdate, birth county, and sex. Healthcare utilization and expenditure for psychiatric and somatic disorders were obtained over four years (two years pre- and post-initial ADHD diagnosis). RESULTS: Middle-aged adults with newly diagnosed ADHD showed higher levels of healthcare utilization and costs (outpatient, inpatient, medications) for psychiatric and somatic comorbidities relative to adults without ADHD, both before and after the initial diagnosis. Females showed greater average group differences across the study period for medication prescriptions than males. Total incremental annual costs per capita were €2478.76 in adults with ADHD relative to those without, and costs were mainly driven by inpatient care. Psychiatric outpatient visits were statistically significantly higher the year before the ADHD diagnosis compared with two years before and after the diagnosis. CONCLUSION: This study demonstrates the substantial burden of psychiatric and somatic comorbidities in middle-aged adults newly diagnosed with ADHD. Psychiatric outpatient visits peaked in the year leading up to the ADHD diagnosis. Findings further suggested that females with ADHD may seek more treatment for comorbidities than males, which may reflect a general female tendency.

Jens Ove Andreasen, 1935-2020 Father of Dental Traumatology.

The life and professional contributions to dental traumatology of Dr. Jens Ove Andreasen are described in terms of his research, writing, teaching, and leadership.

The risks of ankylosis of 89 avulsed human teeth stored in saliva prior to replantation-A re-evaluation of a long-term clinical study.

BACKGROUND/AIM: The survival of an avulsed tooth highly depends on the emergency management. The aim of this study was to evaluate the risk of ankylosis for avulsed human teeth stored in saliva preceded by various dry storage conditions prior to replantation. MATERIAL AND METHODS: Data include 74 patients (54 male and 20 female) with 89 avulsed and replanted teeth (16 immature teeth, 73 mature teeth). Patient ages ranged from 6 to 36 years (median: 13.0 years). All teeth were stored in saliva before replantation. Treatment and follow-up were performed according to a standardized procedure. Follow-up periods ranged from 7 months to 20 years (mean 5.3 years). The risk of ankylosis over time was estimated by the Aalen-Johansen method in relation to the length of dry storage and the stage of root development. The effect of risk factors (root development and length of dry time) on the risk of ankylosis was analysed by Cox regression analysis. RESULTS: For mature teeth, dry storage for 5 min or less before saliva storage resulted in a 47.4% (95% confidence interval (CI): 32.8-60.7) ankylosis rate. When dry storage was >5 min and <20 min, the risk of ankylosis was 76.8% (95% CI: 45.7-91.5). When dry storage exceeded 20 min prior to saliva storage, ankylosis increased to 89.3% (95% CI: 68.0-96.7). Ankylosis also increased with increasing saliva storage time. Specifically, one additional minute of wet time increased the ankylosis hazard rate (HR) by approximately 1% (CI = [0%, 2%], p = .052). Teeth with mature root development were significantly more frequently affected by ankylosis than teeth with immature root development (HR: 2.4 (95% CI: 1.0-5.5), p = .04). CONCLUSION: Temporary storage in saliva should be encouraged if an avulsed permanent tooth cannot be immediately replanted or a suitable storage medium such as milk or saline is not immediately available at the place of the accident.

Comparison between Topical and Injection Anesthetics on Pain Related to Orthodontic Miniscrew Placement: A Split-mouth Study.

AIMS AND OBJECTIVES: The aims of this study were to compare the anesthetic effect of a lidocaine/prilocaine (L/P) topical anesthetic with placebo on pain from needle sticks and to compare the anesthetic effect of the L/P topical anesthetic with an infiltrative anesthetic on pain from orthodontic miniscrew placement. MATERIALS AND METHODS: Pain elimination was analyzed from two interventions: (a) needle stick and (b) miniscrew insertion. When assessing pain from needle stick, one side of the mandible received 2.5% lidocaine/2.5% prilocaine topical anesthetic, and the other side received placebo. When evaluating pain from miniscrew placement, one side of the mandible received L/P topical anesthetic and the other side received infiltrative anesthetic. The findings were recorded on a Visual Analogue Scale after needle stick and after miniscrew placement. Subjective assessment was analyzed by a questionnaire. RESULTS: The L/P topical anesthetic significantly eliminated the pain from needle stick (Mann-Whitney test of medians, 29.0 vs 0.0, respectively, p<0.001). However, the injection anesthetic eliminated the pain from the miniscrew placement better than the L/P topical anesthetic (Mann-Whitney test of medians, 0.0 vs 5.5, respectively, p<0.001). Eighty percent of the subjects felt more comfortable with L/P topical anesthetic than injection anesthetic. Pain from needle stick pain was reported to be the most uncomfortable part of the study. CONCLUSION: The L/P topical anesthetic efficiently eliminated pain from needle stick. The L/P topical anesthetic did not completely eliminate pain from miniscrew placement as the injection anesthesia, but it did reduce pain to tolerable levels. CLINICAL SIGNIFICANCE: L/P topical anesthetics can significantly eliminate pain from needle stick injections, and L/P topical anesthetics can reduce pain from orthodontic miniscrew placement to tolerable levels.

Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection.

BACKGROUND: Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital. METHODS: During the 2016-17 season, all hospitalized patients ≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care-associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included. RESULTS: We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P < .05). We identified 8 closely related clusters (involving ≥3 cases) and another 10 pairs of strains, supporting in-ward transmission. CONCLUSIONS: We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.

Pollen exposure weakens innate defense against respiratory viruses.

BACKGROUND: Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections. Our objective was therefore to assess whether pollen may interfere with antiviral immunity. METHODS: We combined data from real-life human exposure cohorts, a mouse model and human cell culture to test our hypothesis. RESULTS: Pollen significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co-exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to downregulation of type I and -III interferons in nasal mucosa. In a large patient cohort, numbers of rhinoviruspositive cases were correlated with airborne birch pollen concentrations. CONCLUSION: The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.

Serum neopterin levels in relation to mild and severe COVID-19.

BACKGROUND: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. METHODS: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. RESULTS: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. CONCLUSIONS: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.