Delayed Severe Gingivitis After Placement of Orthodontic Braces in an Atopic Teenager: A Case Report and Literature Review.

We report a case of a 15-year-old atopic patient presenting with delayed, severe ulcerative hypertrophic gingivitis after placement of orthodontic braces, which required removal of braces and restorative laser surgical procedures. Patch testing to multiple metals and chemicals showed weak positive reactions to steel bands and formaldehyde. The patient experienced urticarial, gingivitis, and other intraoral symptoms after patch testing and re-exposure to nickel-containing products. In contrast, nickel, cobalt, and cobalt-chromium (Co-Cr) bracket patch testing sites were negative. Nickel-caused contact dermatitis is Type IV delayed hypersensitivity reaction occurring at least 24 h after exposure. This reaction can result in intraoral blisters, ulcerations, eczematous and urticarial reactions of the face and more distant skin areas. This case illustrates the intraoral delayed response, symptom resolution after removing the braces, and brackets and local reactions upon subsequent nickel exposure, despite negative patch testing and lymphocyte stimulation test to nickel. This case further illustrates the difficulty associated with diagnosing nickel allergy.

Opinions, attitudes, and barriers to pediatric vaccination in Argentina.

In Argentina, vaccines included in the national calendar are mandatory, free of charge, and access to vaccination services with social equity for all stages of life are guaranteed by law. However, vaccination coverages are still suboptimal and have shown a constant decrease in the last five years. This study aimed to perform a survey to describe the parent's confidence, risk perception, sources of information and access barriers to vaccines and vaccination in Argentina. A survey was designed for parents in charge of children under 12 years of age to answer. The questionnaire was constructed based on validated questions of the international peer-reviewed literature adapted to our country's characteristics. The survey was performed on 1,202 respondents, covering all regions of Argentina, between 19th May and 18th June 2020. To highlight, 76.6 % were female and the mean age was 40.72 (±9.36 years). 9 % participants reported to assist to the private vaccination center, while 64 % and 23 % referred to take their children to the public vaccination point (primary care center and hospital, respectively). Additionally, respondents agreed that vaccines are safe (92 %), effective (94 %), and important for children to receive them (98 %). 48 % could identify-one or more barriers to vaccination, access and affordability were the most reported ones (74 %) being the lack of vaccine the main reason. In conclusion, this study showed that the great majority of parents trust in vaccines and health care teams but access and affordability reasons emerged as the main barriers to vaccination in our country.

Questioning Cause and Effect: Children with Severe Asthma Exhibit High Levels of Inflammatory Biomarkers Including Beta-Hexosaminidase, but Low Levels of Vitamin A and Immunoglobulins.

Asthma affects over 8% of the pediatric population in the United States, and Memphis, Tennessee has been labeled an asthma capital. Plasma samples were analyzed for biomarker profiles from 95 children with severe asthma and 47 age-matched, hospitalized nonasthmatic controls at Le Bonheur Children's Hospital in Memphis, where over 4000 asthmatics are cared for annually. Asthmatics exhibited significantly higher levels of periostin, surfactant protein D, receptor for advanced glycation end products and ß-hexosaminidase compared to controls. Children with severe asthma had lower levels of IgG1, IgG2 and IgA, and higher levels of IgE compared to controls, and approximately half of asthmatics exhibited IgG1 levels that were below age-specific norms. Vitamin A levels, measured by the surrogate retinol-binding protein, were insufficient or deficient in most asthmatic children, and correlated positively with IgG1. Which came first, asthma status or low levels of vitamin A and immunoglobulins? It is likely that inflammatory disease and immunosuppressive drugs contributed to a reduction in vitamin A and immunoglobulin levels. However, a nonmutually exclusive hypothesis is that low dietary vitamin A caused reductions in immune function and rendered children vulnerable to respiratory disease and consequent asthma pathogenesis. Continued attention to nutrition in combination with the biomarker profile is recommended to prevent and treat asthma in vulnerable children.

Examining the relationships between life satisfaction and alcohol, tobacco and marijuana use among school-aged children.

BACKGROUND: There are many known risk factors associated with youth substance use. Nonetheless, the impact of life satisfaction (LS) on the use of alcohol, tobacco and marijuana by adolescents still remains largely unknown. METHODS: The present analysis utilized data from the Health Behavior in School-Aged Children 2009-10 US study. Multilevel logistic regression models were used to assess the relationship between LS and individual substance use. Multilevel multinomial regression models examined the relationship with total number of substances used. RESULTS: After controlling for numerous variables associated with substance use, individuals reporting low LS were significantly more likely to ever use tobacco (OR = 1.34, 95% CI = [1.01, 1.78]), alcohol (OR = 1.45, 95% CI = [1.10, 1.92]) and marijuana (OR = 1.98, 95% CI = [1.39, 2.82]). Additionally, students with low LS were significantly more likely to use two substances (OR = 1.90, 95% CI = [1.15, 3.14]) and three substances concurrently (OR = 2.00, 95% CI = [1.27, 3.16]). CONCLUSIONS: The present study identified strong associations between LS and individual, as well as concurrent, substance use among adolescents. Interventions aiming to reduce adolescent substance use may benefit from incorporating components to improve LS.

Saccharomyces cerevisiae-Derived Mannan Does Not Alter Immune Responses to Aspergillus Allergens.

Severe asthma with fungal sensitization predominates in the population suffering from allergic asthma, to which there is no cure. While corticosteroids are the mainstay in current treatment, other means of controlling inflammation may be beneficial. Herein, we hypothesized that mannan from Saccharomyces cerevisiae would dampen the characteristics of fungal allergic asthma by altering the pulmonary immune responses. Using wild-type and transgenic mice expressing the human mannose receptor on smooth muscle cells, we explored the outcome of mannan administration during allergen exposure on the pathogenesis of fungal asthma through measurement of cardinal features of disease such as inflammation, goblet cell number, and airway hyperresponsiveness. Mannan treatment did not alter most hallmarks of allergic airways disease in wild-type mice. Transgenic mice treated with mannan during allergen exposure had an equivalent response to non-mannan-treated allergic mice except for a prominent granulocytic influx into airways and cytokine availability. Our studies suggest no role for mannan as an inflammatory regulator during fungal allergy.

Non-compliance with IDSA guidelines for patients presenting with methicillin-susceptible Staphylococcus aureus prosthetic joint infection is a risk factor for treatment failure.

OBJECTIVE: The long-term impact of treatment strategies proposed by the IDSA guidelines for patients presenting with methicillin-susceptible S. aureus (MSSA) prosthetic joint infection (PJI) is not well-known. PATIENTS AND METHODS: Retrospective (2000-2010) cohort study including patients presenting with MSSA hip or knee PJI. A univariate Cox analysis was performed to determine if the non-compliance with IDSA surgical guidelines was a risk factor for treatment failure. RESULTS: Eighty-nine patients with a mean follow-up of 2.8 years were included. Non-compliance with IDSA surgical guidelines was associated with treatment failure (hazard ratio 2.157; 95% CI [1.022-4.7]). The American Society of Anesthesiologists score, inadequate antimicrobial therapy, and a rifampicin-based regimen did not significantly influence patient outcome. CONCLUSION: Based on the IDSA guidelines, if a patient presenting with MSSA PJI is not eligible for implant retention, complete implant removal is needed to limit treatment failure.

Airway Epithelial Repair by a Prebiotic Mannan Derived from Saccharomyces cerevisiae.

In asthmatic airways, repeated epithelial damage and repair occur. No current therapy directly targets this process. We aimed to determine the effects of mannan derived from S. cerevisiae (SC-MN) on airway epithelial wound repair, in vitro. The presence of functional mannose receptors in bronchial epithelial cells was shown by endocytosis of colloidal gold-Man BSA via clathrin-coated pits in 16HBE cells. In primary normal human bronchial epithelial cells (NHBEC), SC-MN significantly facilitated wound closure. Treatment with SC-MN stimulated cell spreading as indicated by a significant increase in the average lamellipodial width of wound edge 16HBE cells. In addition, NHBEC treated with SC-MN showed increased expression and activation of Krüppel-like factors (KLFs) 4 and 5, transcription factors important in epithelial cell survival and regulation of epithelial-mesenchymal transition. We conclude that SC-MN facilitates wound repair in human bronchial epithelium, involving mannose receptors.

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models.

One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer.

SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3-4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.

[Advice for those that want to specialize in infectious diseases in Switzerland]. / Conseils à celles et ceux qui désirent embrasser une carrière d'infectiologue.

In Switzerland the specialty of Infectious Diseases attracts many young physicians. In this article we describe the place of infec- tious diseases in Switzerland. We review its usefulness for patients, the requirements to obtain a title of specialist, its different subs- pecialists and the potential job openings of this training.

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Methicillin-resistant Staphylococcus aureus (MRSA) infection continues to be a substantial global problem with significant associated morbidity and mortality. This review summarises the discussions that took place at the 4th MRSA Consensus Conference in relation to the current treatment options for serious MRSA infections and how to optimise whichever therapy is embarked upon. It highlights the many challenges faced by both the laboratory and clinicians in the diagnosis and treatment of MRSA infections.

Evaluation of B lymphocyte deficiencies.

The most common of the primary immunodeficiency diseases are those that involve inadequate antibody production. The characteristic presentation of these disorders is recurrent sinopulmonary infections. An arrest in B cell development at the pre-B cell stage leads to agammaglobulinemia and an insignificant number of B cells. X-linked agammaglobulinemia is the most common of these developmental arrests while the autosomal recessive agammaglobulinemias comprise a small minority of the total cases. Likewise, the most common form of the hyper-IgM syndromes (CD40 ligand deficiency) is X-linked. Of the autosomal recessive forms, CD40 deficiency is basically identical to the X-linked form in its clinical phenotype where, in addition to inadequate antibody production, there is defective T cell signaling through the CD40-CD40L interaction. Aside from CD40 deficiency, the other recessive forms of hyper-IgM syndrome have adequate T cell function. IgA deficiency is the most common and the most benign of the B cell disorders. Common variable immunodeficiency is diverse in its presentation and clinical course. The pathophysiology of this disease is multifactorial and frequently ill defined, often making it a diagnosis of exclusion. A working knowledge of identifiable PIDDs is essential in both recognizing when to suspect immunodeficiency and making a diagnosis.

Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection.

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively). Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis.

[Where are we in the treatment of chronic osteomyelitis?]. / Où en est-on dans le traitement médical des ostéomyélites chroniques?

Chronic osteomyelitis is a multifaceted bacterial infection with common features, which requires surgery for remission. The duration and modality of concomitant administration of antibiotic agents for adult patients is still based on expert opinions. The traditional recommendation of 6 to 12 weeks of antibiotic therapy with intravenous administration for at least the first 2 weeks is more and more challenged in favor of an oral antibiotic treatment with selected agents from the start. There is no evidence that the total duration of antibiotic therapy for more than 6-12 weeks improves outcome, when compared with shorter regimens. External advice from an expert team with combined surgeons and infectious disease physicians may help to reduce antibiotic consumption in a cost-effective way.

A 9-year-old boy with chronic urticaria and progressive spondyloarthritis.

A 9-year-old African American boy presented with chronic urticaria and progressive spondyloarthritis. Laboratory tests were abnormal for persistently positive antinuclear antibodies and undetectable total hemolytic complement (CH50) despite normal levels of complement C2, C3, and C4. Ultimately, further testing revealed an underlying deficiency in the immune system that may be associated with autoimmune disease and thus have a bearing on the patient's urticaria and spondyloarthritis. This is a unique presentation of a rare disease and underscores the importance of evaluating for systemic disease in the workup of chronic urticaria.

Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update.

Prevention of surgical site infection in orthopaedic surgery and bone trauma has some hallmarks not shared with other surgical disciplines: low inoculum for implant infections; pathogenicity of coagulase-negative staphylococci and other skin commensals; possible haematogenous origin; and long post-discharge surveillance periods. Only some of the many measures to prevent orthopaedic surgical site infection are based on strong evidence and there is insufficient evidence to show which element is superior over any other. This highlights the need for multimodal approaches involving active post-discharge surveillance, as well as preventive measures at every step of the care process. These range from preoperative care to surgery and postoperative care at the individual patient level, including department-wide interventions targeting all healthcare-associated infections and improving antibiotic stewardship. Although theoretically reducible to zero, the maximum realistic extent to decrease surgical site infection in elective orthopaedic surgery remains unknown.