Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Utility of Early Magnetic Resonance Imaging to Enhance Outcome Prediction in Critically Ill Children with Severe Traumatic Brain Injury.

BACKGROUND: Many children with severe traumatic brain injury (TBI) receive magnetic resonance imaging (MRI) during hospitalization. There are insufficient data on how different patterns of injury on early MRI inform outcomes. METHODS: Children (3-17 years) admitted in 2010-2021 for severe TBI (Glasgow Coma Scale [GCS] score < 9) were identified using our site's trauma registry. We used multivariable modeling to determine whether the hemorrhagic diffuse axonal injury (DAI) grade and the number of regions with restricted diffusion (subcortical white matter, corpus callosum, deep gray matter, and brainstem) on MRI obtained within 7 days of injury were independently associated with time to follow commands and with Functional Independence Measure for Children (WeeFIM) scores at the time of discharge from inpatient rehabilitation. We controlled for the clinical variables age, preadmission cardiopulmonary resuscitation, pupil reactivity, motor GCS score, and fever (> 38 °C) in the first 12 h. RESULTS: Of 260 patients, 136 (52%) underwent MRI within 7 days of injury at a median of 3 days (interquartile range [IQR] 2-4). Patients with early MRI were a median age of 11 years (IQR 7-14), 8 (6%) patients received cardiopulmonary resuscitation, 19 (14%) patients had bilateral unreactive pupils, the median motor GCS score was 1 (IQR 1-4), and 82 (60%) patients had fever. Grade 3 DAI was present in 46 (34%) patients, and restricted diffusion was noted in the corpus callosum in 75 (55%) patients, deep gray matter in 29 (21%) patients, subcortical white matter in 23 (17%) patients, and the brainstem in 20 (15%) patients. After controlling for clinical variables, an increased number of regions with restricted diffusion, but not hemorrhagic DAI grade, was independently associated with longer time to follow commands (hazard ratio 0.68, 95% confidence interval 0.53-0.89) and worse WeeFIM scores (estimate ß - 4.67, 95% confidence interval - 8.33 to - 1.01). CONCLUSIONS: Regional restricted diffusion on early MRI is independently associated with short-term outcomes in children with severe TBI. Multicenter cohort studies are needed to validate these findings and elucidate the association of early MRI features with long-term outcomes in children with severe TBI.

Epidemiology, causes, and morbidities of stroke in the young.

PURPOSE OF REVIEW: The purpose is to describe the latest research on epidemiology, causes, and morbidities of stroke in neonates and children. RECENT FINDINGS: The global incidence of childhood stroke is approximately 2 per 100 000 person-years, which is significantly lower compared to neonates (20-40 per 100 000 live births) and adults (80-90 per 100 000 person-years). Placental abnormalities are a risk factor for perinatal stroke, although cause is usually multifactorial. In children, nonatherosclerotic arteriopathies and arteriovenous malformations are major causes of ischemic and hemorrhagic strokes, respectively. The perinatal period confers a high risk of stroke and can lead to long-term disability, including motor delay, cognitive or speech impairment, and epilepsy. Recent studies suggest that at least 50% of survivors of perinatal stroke have abnormal neurodevelopmental scores in long-term follow up. Childhood stroke is associated with significant morbidity, including epilepsy, motor impairments, and behavioral disability. Recent studies have also identified an association between pediatric stroke and behavioral disorders, such as attention deficit hyperactivity disorder and autism. SUMMARY: Perinatal and childhood strokes are important causes of neurological morbidity. Given the low incidence of childhood stroke, prospective research studies on epidemiology, causes, and outcomes remain limited, highlighting the need for continued multisite collaborations.

An Approach to Modify 14-Membered Lactone Macrolide Antibiotic Scaffolds.

A ketolide derivative with (12R)-configuration was obtained via a novel ketene acetal in acidic conditions. The structure of this atypical ß-keto ketene acetal intermediate within the macrocyclic system has been determined by NMR and X-ray methods. The use of basic conditions at an elevated temperature yielded new, doubly α,ß-unsaturated ketone macrolide derivatives with (4E)-configuration as two conformational isomers of folded-in or folded-out conformations.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Diffuse Axonal Injury Grade on Early MRI is Associated with Worse Outcome in Children with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in children, but effective tools for predicting outcome remain elusive. Although many pediatric patients receive early magnetic resonance imaging (MRI), data on its utility in prognostication are lacking. Diffuse axonal injury (DAI) is a hallmark of TBI detected on early MRI and was shown previously to improve prognostication in adult patients with TBI. In this exploratory study, we investigated whether DAI grade correlates with functional outcome and improves prognostic accuracy when combined with core clinical variables and computed tomography (CT) biomarkers in pediatric patients with moderate-severe TBI (msTBI). METHODS: Pediatric patients (≤ 19 years) who were admitted to two regional level one trauma centers with a diagnosis of msTBI (Glasgow Coma Scale [GCS] score < 13) between 2011 and 2019 were identified through retrospective chart review. Patients who underwent brain MRI within 30 days of injury and had documented clinical follow-up after discharge were included. Age, pupil reactivity, and initial motor GCS score were collected as part of the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. Imaging was reviewed to calculate the Rotterdam score (CT) and DAI grade (MRI) and to evaluate for presence of hypoxic-ischemic injury (MRI). The primary outcome measure was the Pediatric Cerebral Performance Category Scale (PCPCS) score at 6 months after TBI, with favorable outcome defined as PCPCS scores 1-3 and unfavorable outcome defined as PCPCS scores 4-6. The secondary outcome measure was discharge disposition to home versus to an inpatient rehabilitation facility. RESULT: Of 55 patients included in the study, 45 (82%) had severe TBI. The most common mechanism of injury was motor vehicle collision (71%). Initial head CT scans showed acute hemorrhage in 84% of patients. MRI was acquired a median of 5 days after injury, and hemorrhagic DAI lesions were detected in 87% of patients. Each 1-point increase in DAI grade increased the odds of unfavorable functional outcome by 2.4-fold. When controlling for core IMPACT clinical variables, neither the DAI grade nor the Rotterdam score was independently correlated with outcome and neither significantly improved outcome prediction over the IMPACT model alone. CONCLUSIONS: A higher DAI grade on early MRI is associated with worse 6-month functional outcome and with discharge to inpatient rehabilitation in children with acute msTBI in a univariate analysis but does not independently correlate with outcome when controlling for the GCS score. Addition of the DAI grade to the core IMPACT model does not significantly improve prediction of poor neurological outcome. Further study is needed to elucidate the utility of early MRI in children with msTBI.

Synthesis and Antibacterial Activity of New N-Alkylammonium and Carbonate-Triazole Derivatives within Desosamine of 14- and 15-Membered Lactone Macrolides.

Desosamines of azithromycin (AZM) and clarithromycin (CLA) were modified by N-alkylation or nucleophilic substitution at the carbonyl/CuAAC sequence. Biological studies revealed a higher antibacterial potency of quaternary N-alkylammonium bromides of CLA as compared to AZM. SAR studies of CLA salts, including biological, conformation and molecular-docking analysis, enriched by physicochemical parameters, showed the importance of less bulky and unsaturated substituent for an efficient docking mode at the ribosomal tunnel and good antibacterial potency against clinical and standard Streptococcus pneumoniae and Streptococcus pyogenes strains (MICs 0.25 or 0.5 µg/mL). These CLA salts also have an at least threefold lower cytotoxicity than reference antibiotics at comparable antibacterial activity against the S. pneumoniae clinical strain. Differences in antibacterial effects noted for AZM and CLA salts bearing less bulky N-substituents can be better understood when their binding modes in the ribosomal tunnel are considered rather than their common low lipophilicity and excellent water solubility.

14- and 15-membered lactone macrolides and their analogues and hybrids: structure, molecular mechanism of action and biological activity.

Classical macrolides containing 14- or 15-membered aglycone lactone rings are basic and widely used antibacterial agents in clinical therapy. Macrolides exert antibacterial effects by blocking the exit peptide tunnel during translation at bacterial ribosomes. However, one macrolide occasionally manifests different docking modes or binding sites at ribosomes, which presents difficulties in designing macrolide modifications. In addition to their medical importance, lactone macrolides possess interesting chemistry driven by numerous intramolecular interactions or cascade transformations. Lactone macrolides are potent antibacterial/bactericidal agents, whereas derivatives of macrolactone antibiotics possess anti-malarial, anti-cancer, anti-inflammatory, and anti-leishmanial activity, and can regulate gastrointestinal motility. Hence, it is important to develop novel semi-synthetic and completely synthetic approaches for functionalising lactone cores of different macrolides and their structural analogues such as ketolides, fluoro-ketolides, acylides, and hybrids containing steroids, nucleosides, heterocycles, and peptides. Here, we discuss modifications that generate novel macrolides with enhanced biological potency and improved molecular mechanisms of action. The bibliography presented in this review contains references to articles and patents that were published and filed from 2009 to mid-2019.

Specific Interactions between Rifamycin Antibiotics and Water Influencing Ability To Overcome Natural Cell Barriers and the Range of Antibacterial Potency.

Rifamycins are a group of macrocyclic antibiotics mainly used for the treatment of various bacterial infections including tuberculosis. Spectroscopic studies of rifamycins evidence the formation of temperature- and solvent-dependent equilibria between A-, B-, and C-type conformers in solutions. The B- and C-type conformers of rifamycin antibiotics are exclusively formed in the presence of water molecules. A- and B-type conformers exhibit a hydrophilic and "open" ansa-bridge nature whereas the C-type conformer is more lipophilic due to the presence of a "closed" ansa-bridge structure. The involvement of the lactam moiety of the ansa-bridge in intramolecular H-bonds within rifapentine and rifampicin implicates the formation of a more hydrophilic A-type conformer. In contrast to rifampicin and rifapentine, for rifabutin and rifaximin, the "free" lactam group enhances conformational flexibility of the ansa-bridge, thereby enabling interconversion between A- and C-type conformers. In turn, an equilibrium between A- and C-type conformers for rifamycins improves their adaptation to the changing nature of bacteria cell membranes, especially those of Gram-negative strains and/or to efflux pump systems.

Synthesis, docking and antibacterial studies of more potent amine and hydrazone rifamycin congeners than rifampicin.

New rifamycin congeners (1-33) with incorporated amine and hydrazone substituents leading to lipophilic and/or basic nature and altered rigidity of modified C(3) arm were synthesized and structurally characterized in detail. NMR spectroscopic studies at different temperatures indicate two types of structures of rifamycin congeners that are realized in solution: zwitterionic and non-ionic forms in dependence of the basicity of modified C(3) arm. The presence of rifamycin congeners in these two possible forms has a significant impact on the physico-chemical parameters such as lipophilicity (clogP) and water solubility and different binding mode of the C(3) arm of antibiotic at RNAP binding pocket (molecular target) leading to different antibacterial potency. The highest antibacterial potency against S. aureus (including MRSA and MLSB strains) and S. epidermidis strains, even higher than reference rifampicin (Rif) and rifaximin (Rifx) antibiotics, was found for rifamycin congeners bearing at the C(3) arm relatively rigid and basic substituents (bipiperidine and guanidine groups). These modifications provide favorable docking mode and excellent water solubility resulting in high potency (MICs 0.0078 µg/mL what gives ∼ 8.5 nM), irrespective whether rifamycin congener is a tertiary amine (15) or hydrazone (29). In turn, for a higher antibacterial potency of rifamycin congeners against E. faecalis strain (MICs 0.5 µg/mL that is 0.6 µM) as compared to Rif and Rifx, the most crucial factors are: bulkiness and the lipophilic character of the end of the C(3) rebuilt arm.

Comparison of the effect of 5-grass pollen sublingual immunotherapy tablets and drops in children with rhinoconjunctivitis.

BACKGROUND: One of the most important aspects of sublingual immunotherapy (SLIT) is the regimen of administration. AIM: To find any differences in symptom-medication scores between the two groups of SLIT tablets and drops, given pre-coseasonally (starting 8 weeks before the pollen season) in children with rhinoconjunctivitis allergy to grass pollen. The secondary outcome were the differences in lung function and induction of T-regulatory forkhead box P3 (FOXP3) positive cells. METHODS: This was a retrospective, secondary analysis of pooled data obtained from our two prospective randomized placebo controlled trials that involved children who underwent SLIT. Forty-one children, ages 6-18 years, with allergic rhinitis (AR), sensitive to grass pollen, participated in the study. RESULTS: Treatment with both tablets and drops significantly reduced all symptoms (nasal, asthma, and ocular) within the groups; there was no significant difference between both groups. When compared with the tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score, but the difference was not statistically significant (p = 0.1036); there was no significant difference in asthma and nasal scores. We showed a significant decrease in the fractional exhaled nitric oxide level comparable in both immunotherapy groups. There were no differences between the groups in the induction of CD4+ CD25+ FOXP3+-positive cells in peripheral blood. CONCLUSIONS: Both protocols showed similar decreases in symptom-medication scores; however, when compared with tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score.

Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms.

INTRODUCTION: Markers of exhaled breath condensate (EBC) correlate with lung function impairment, airway remodeling and different aspects of the disease such as exercise-induced bronchoconstriction (EIB). Aim of the study was to determine the cytokine profile in EBC of children with asthma after an exercise treadmill challenge in order to obtain clinically useful information about mechanisms of EIB; also, to assess correlations between cytokine concentrations in EBC and clinical characteristics of the patients. MATERIAL AND METHODS: The study population consisted of 25 randomly selected children, aged 8 to 19 years, with asthma and EIB symptoms despite the use of control medications. Patients on the day of the study visit underwent fractional exhaled nitric oxide measurement (FeNO) and baseline spirometry, performed an exercise treadmill challenge (ETC), and EBC samples were obtained at the end of the ETC. RESULTS: In asthmatic children with positive ETC, monocyte hemotactic protein-1 (MCP-1) and IL-16 adjusted to pre-EBC forced expiratory volume in 1 s (FEV1) were significantly higher compared to children with negative ETC (p = 0.022 and p = 0.017 respectively). After adjustment to pre-EBC FEV1 other cytokines (IL-4, IL-5, IL-6, IL-8, MIG, TNF-α) were not related to post-exercise changes in FEV1. CONCLUSIONS: We observed a specific inflammatory profile in the airways of asthmatic children with bronchoconstriction induced by exercise. The concentration of cytokines in EBC depended on the post-exercise decrease in FEV1, which was measured by the area under the curve (AUC). MCP-1 and IL-16, adjusted to pre-EBC FEV1, were significantly higher in children with a positive exercise challenge compared to those with a negative one.

A Stem Cell Model of the Motor Circuit Uncouples Motor Neuron Death from Hyperexcitability Induced by SMN Deficiency.

In spinal muscular atrophy, a neurodegenerative disease caused by ubiquitous deficiency in the survival motor neuron (SMN) protein, sensory-motor synaptic dysfunction and increased excitability precede motor neuron (MN) loss. Whether central synaptic dysfunction and MN hyperexcitability are cell-autonomous events or they contribute to MN death is unknown. We addressed these issues using a stem-cell-based model of the motor circuit consisting of MNs and both excitatory and inhibitory interneurons (INs) in which SMN protein levels are selectively depleted. We show that SMN deficiency induces selective MN death through cell-autonomous mechanisms, while hyperexcitability is a non-cell-autonomous response of MNs to defects in pre-motor INs, leading to loss of glutamatergic synapses and reduced excitation. Findings from our in vitro model suggest that dysfunction and loss of MNs result from differential effects of SMN deficiency in distinct neurons of the motor circuit and that hyperexcitability does not trigger MN death.

16-Membered Macrolide Lactone Derivatives Bearing a Triazole-Functionalized Arm at the Aglycone C13 Position as Antibacterial and Anticancer Agents.

A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 µg mL(-1) ; 2.55-5.09 µm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 µm] potencies were those with the best aqueous solubility and bearing a saccharide-triazole arm at the C13 position of the aglycone. These derivatives preferentially bind at the ribosomal tunnel and show the most attractive selectivity indexes [SI; calculated relative to the human dermal fibroblast (HDF) cell line], even higher than that of the reference compound cytarabine. Results of molecular docking studies of this type of macrolide antibiotics at the ribosomal tunnel, together with experimentally determined lipophilicity and aqueous solubility values, as well as biological assay data revealed the importance of the introduced functional group at the aglycone C13 arm to the future design of anticancer and antibacterial drug candidates. Our results clearly indicate that the high antibacterial and anticancer activities of these types of macrolides do not necessarily depend on the presence of the aldehyde group at the aglycone lactone ring.

Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds.

Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases.

The function of human nervous system is critically dependent on proper interneuronal communication. Exosomes and other extracellular vesicles are emerging as a novel form of information exchange within the nervous system. Intraluminal vesicles within multivesicular bodies (MVBs) can be transported in neural cells anterogradely or retrogradely in order to be released into the extracellular space as exosomes. RNA loading into exosomes can be either via an interaction between RNA and the raft-like region of the MVB limiting membrane, or via an interaction between an RNA-binding protein-RNA complex with this raft-like region. Outflow of exosomes from neural cells and inflow of exosomes into neural cells presumably take place on a continuous basis. Exosomes can play both neuro-protective and neuro-toxic roles. In this review, we characterize the role of exosomes and microvesicles in normal nervous system function, and summarize evidence for defective signaling of these vesicles in disease pathogenesis of some neurodegenerative diseases.

Spirometry-Adjusted Fraction of Exhaled Nitric Oxide Allows Asthma Diagnosis in Children, Adolescents, and Young Adults.

BACKGROUND: Recently, it has been proved that fractional exhaled nitric oxide (FENO) results are in disagreement with other measurements of asthma control. The objective of this work is to present and validate new lung function/lung inflammation ratios. METHODS: This is a retrospective, cross-sectional study in which we evaluated data from medical documentation of 1,529 pediatric and adolescent subjects and a small number (2% of the studied population) of young adults, who presented symptoms suggestive of asthma (age range 4-24 y). We are the first to analyze results obtained in this manner (before the introduction of controlled medication): FENO, spirometry, specific resistance of the airways, diagnosis of allergic diseases, and allergen sensitization (specific immunoglobulin E results). RESULTS: Cut-off points for the new indicators allowed us to diagnose asthma in the study participants: for FVC/FENO ratio, 0.17 L/ppb; for FEV1/FENO ratio, 0.15 L/ppb; for forced expiratory flow during the middle half of the FVC maneuver (FEF25-75%)/FENO ratio, 0.16 L/s/ppb; for FENO/FVC ratio, 11.00 ppb/L; for FENO/FEV1 ratio, 12.53 ppb/L; and for FENO/FEF25-75% ratio, 11.81 ppb/L/s. Only the ratios described above were closely correlated with the diagnosis of asthma and with one another. They significantly differed between subjects with asthma and healthy subjects as well as between females and males. Only FEF25-75%/FENO and FENO/FEF25-75% values were significant predictors of any sensitization in the studied subjects. We found higher sensitivity than specificity and higher positive predictive value than negative predictive value for FVC/FENO, FEV1/FENO, and FEF25-75%/FENO and found a mirror image for reverse parameters. However, the positive predictive values and negative predictive values were not clearly convincing with respect to diagnostic accuracy in the case of the new parameters proposed. CONCLUSIONS: We propose new lung function/lung inflammation ratios by which it may become possible to diagnose asthma in children and adolescents on the basis of a subject's spirometry and FENO measurements. We believe that our ratios are only supportive of the universally used parameters in the process of diagnosing asthma. (ClinicalTrials.gov registration NCT01805635.).

Biochemical structure, symptoms, location and treatment of sialoliths.

BACKGROUND/PURPOSE: Sialolithiasis is the most common disease of the salivary glands, which can cause acute and chronic infections. More than 80% of sialoliths occur in the submandibular gland or its duct, 6% in the parotid gland, and 2% in the sublingual gland or minor salivary glands. Typical symptoms are recurrent swelling and pain in the involved gland, often associated with eating, due to obstructions of the draining duct. The aim of the study was to analyze biochemical structure, symptoms, size, and location of salivary stones as well as concomitance with nephrolithiasis. MATERIALS AND METHODS: This study was conducted targeting 46 patients with sialolithiasis who visited the Department of Oral Surgery, Medical University of Lodz, Poland in 2009-2015. Medical records containing patients' age, sex, position of the salivary stone, and symptoms were collected and analyzed. Stones were examined ultrastructurally with a scanning electron microscope and X-ray diffractometer. RESULTS: Multiple stones were found in 1% of patients. We observed that men had sialolithiasis about twice as often as women. The chemical structure of the stones varied but they mainly contained different traces of carbon, calcium, oxygen, phosphorus, and sulfur. Longitudinal sections of the stones revealed elongated, round, and irregular shapes. We noticed that nephrolithiasis was present in 11 (24%) patients. We observed the unilateral location of sialoliths with multilayer structures, mainly composed of inorganic material, such as hydroxyapatite. CONCLUSION: We found that the location of the stones influenced the symptoms, and concomitance of sialoliths and nephroliths was common.

Central giant cell granuloma located in the maxilla in a 8-year old boy.

UNLABELLED: Central giant cell granuloma is a rare occurring tumor-like lesion of the facial part of the skull, located more often in mandible (from 2:1 to 3:1), than in the maxilla. It accounts for 7% of all benign tumors of the jaws, whereas the brown tumor is a complication of a primary hyperparathyroidism and occurs in approximately 4.5%, or in 1.5%, when the tumor is a complication of secondary hyperparathyroidism. However, the brown tumor is significantly less often observed than the presented lesion. The authors describe a case of central giant cell granuloma of the maxilla, located in the area of premolar teeth. Pantomograhic x ray showed unilocular osteolytic bone loss of the maxilla with ectopic teeth. As a part of the One Day surgery procedures, the tumor has been removed with the margin and embedded teeth, and oroantral communication closure performed. In follow-up examination after 10 months and 2 years from the surgery, no recurrence of the tumor has been observed. CONCLUSION: In diferential diagnosis of tumors of face and skull, it is needed to consider the giant cell granuloma and also the brown bone tumor.

Total specific airway resistance vs spirometry in asthma evaluation in children in a large real-life population.

BACKGROUND: Total specific airway resistance (sRtot) has been introduced as an alternative technique to assess lung function with a particular application to younger children with asthma. OBJECTIVE: To establish a diagnostic value of the body plethysmographic parameter (sRtot) in asthma diagnosis in young children. METHODS: This was a prospective, noninterventional study. Children 4 to 18 year old with symptoms suggestive of asthma were included (n = 885). Subjects underwent body plethysmography and spirometry (when capable) with reversibility tests. Of 788 subjects who could perform spirometry in addition to body plethysmography, 578 were diagnosed with asthma. Subjects with asthma were treated for minimum of 6 months and then their asthma was confirmed or refuted. RESULTS: In 471 patients, asthma diagnosis was confirmed after 6 months of antiasthmatic treatment; 142 patients were 4 to 6 years old and 329 were 7 to 18 years old. Change in response to bronchodilator in children with asthma was significant for sRtot (P = .02) but not for forced expiration volume in 1 second (P = .21); sRtot was more sensitive and specific in identifying children with reversible obstruction than spirometry. There was a significant association between sRtot and asthma diagnosis in patients 4 to 6 years old (odds ratio 1.02, 95% confidence interval 1.01-1.03, P = .001); to differentiate subjects with asthma from those without asthma, the optimal cutoff point for sRtot was 174.5%. A sRtot value higher than 174.5% was associated with a positive prediction of an asthma diagnosis in patients 4 to 6 years old. A ratio of forced expiration volume in 1 second to forced vital capacity below 80% was not significantly associated with asthma. CONCLUSION: These data support the recommendation of performing sRtot rather than spirometry in young children as a fairly sensitive marker of asthma. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT01805635).