Efficacy of a pediatric headache infusion center: A single-center experience.

OBJECTIVE: To evaluate the efficacy of a pediatric headache infusion center (HIC) in alleviating the symptoms and preventing future visits to the emergency department (ED). BACKGROUND: Headache is a common reason for visits to the pediatric ED. ED visits are associated with inordinate costs of care and are conceived by parents to be avoidable if adequate alternatives are available. An infusion center for acute treatment of intractable headache in children with chronic migraine may be an effective alternative to an ED visit. METHODS: This was a retrospective analysis of data from a single-center cohort of patients with a known history of chronic migraine, presenting to Dayton Children's HIC with an acute migraine from June 1, 2017 to June 1, 2020. Patients were treated according to established protocols divided into two pathways. Patient demographics, clinical characteristics, pre- and postinfusion pain scores, ED visits and inpatient admissions within 2 weeks of HIC visit, and ED visits 1 year prior and 1 year after the HIC visit were noted. RESULTS: A total of 297 HIC visits were analyzed from 201 patients. The HIC was effective in controlling symptoms with a significant reduction in pain score (median [interquartile range; IQR] 7.0 [2.0] preinfusion vs. 1.0 [2.0] postinfusion, p < 0.001). Only 25/297 (8.4%) patients came to the ED within 2 weeks of the HIC visit, and an even smaller number of patients (20/297, 6.7%) were admitted as inpatients within 2 weeks of the HIC visit. The number of ED visits was significantly reduced in the year after the HIC visit compared with the year prior (median [IQR] 1.0 [2.0] before vs. 0.0 [1.0] after, p < 0.001). CONCLUSION: A pediatric HIC is effective in alleviating the symptoms and preventing ED visits. These centers should be considered as standard of care at children's hospitals.

Activation of complement component 3 is associated with airways disease and pulmonary emphysema in alpha-1 antitrypsin deficiency.

INTRODUCTION: Alpha-1 antitrypsin (AAT) deficiency (AATD) is associated with early onset emphysema. The aim of this study was to investigate whether AAT binding to plasma constituents could regulate their activation, and in AATD, exploit this binding event to better understand the condition and uncover novel biomarkers of therapeutic efficacy. METHODS: To isolate AAT linker proteins, plasma samples were separated by size exclusion chromatography, followed by co-immunoprecipitation. AAT binding proteins were identified by mass spectrometry. Complement turnover and activation was determined by ELISA measurement of C3, C3a and C3d levels in plasma of healthy controls (n=15), AATD (n=51), non-AATD patients with obstructive airway disease (n=10) and AATD patients post AAT augmentation therapy (n=5). RESULTS: Direct binding of complement C3 to AAT was identified in vivo and in vitro. Compared with healthy controls, a breakdown product of C3, C3d, was increased in AATD (0.04 µg/mL vs 1.96 µg/mL, p=0.0002), with a significant correlation between radiographic pulmonary emphysema and plasma levels of C3d (R2=0.37, p=0.001). In vivo, AAT augmentation therapy significantly reduced plasma levels of C3d in comparison to patients not receiving AAT therapy (0.15 µg/mL vs 2.18 µg/mL, respectively, p=0.001). DISCUSSION: Results highlight the immune-modulatory impact of AAT on the complement system, involving an important potential role for complement activation in disease pathogenesis in AATD. The association between plasma C3d levels and pulmonary disease severity, that decrease in response to AAT augmentation therapy, supports the exploration of C3d as a candidate biomarker of therapeutic efficacy in AATD.

Lung involvement at presentation predicts disease activity and permanent organ damage at 6, 12 and 24 months follow - up in ANCA - associated vasculitis.

BACKGROUND: Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. RESULTS: 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p < 0.0001, rs = 0.5871). No differences between BVAS and VDI scores were seen for both groups, however in the lung-involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p = 0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p = 0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p = 0.027, p = 0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p < 0.001). CONCLUSION: AAV subjects with lung involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy.

Modified Brixia chest X-ray severity scoring system and correlation with intubation, non-invasive ventilation and death in a hospitalised COVID-19 cohort.

INTRODUCTION: There are few existing severity scoring systems in the literature, and no formally widely accepted chest X-ray template for reporting COVID-19 infection. We aimed to modify the chest X-ray COVID-19 severity scoring system from the Brixia scoring system with placement of more emphasis on consolidation and to assess if the scoring tool could help predict intubation. METHODS: A severity chest X-ray scoring system was modified from the Brixia scoring system. PCR positive COVID-19 positive patient's chest X-rays admitted to our hospital over 3 months were reviewed and correlated with; non-invasive ventilation, intubation and death. An analysis was performed using a receiver operating curve to predict intubation from all admission chest X-rays. RESULTS: The median score of all 325 admission chest X-rays was 3 (Interquartile range (IQR) 0-6.5). The median score of admission chest X-rays of those who did not require ICU admission and survived was 1.5 (IQR 0-5); and 9 (IQR 4.75-12) was median admission score of those requiring intubation. The median scores of the pre-intubation ICU chest X-rays was 11.5 (IQR 9-14.125), this increased from a median admission chest X-ray score for this group of 9 (P-value < 0.01). A cut-off score of 6 had a sensitivity of 77% and specificity of 73% in predicting the need for intubation. CONCLUSION: Higher chest X-ray severity scores are associated with intubation, need for non-invasive ventilation and death. This tool may also be helpful in predicting intubation.

Mechanism of olfactory deficit in neurotrauma and its related affective distress: A narrative review.

Traumatic brain injury (TBI) is among the leading causes of death and disability all over the globe. TBI is also commonly associated with clinical sequelae of posttraumatic depression, and reports of other subsequent affective distress are common. Similarly, posttraumatic changes in chemoreceptive sensory functions, primarily due to coup-contrecoup injury induced shearing of the olfactory nerve fibers, leading to anosmia and ageusia are also well documented in the literature. However, the current literature is limited in addressing the intersections between said variables. The aim of this study was to provide a focused narrative review of the literature, to address these intersections found in clinical sequelae of TBI. As chemoreceptive sensory deficits are also linked to significant affective distress of their own, this review addresses the bidirectionality between sensory deficit and affective distress. Prevalence, demographics, mechanisms, and clinical implications are presented. Previous research is presented and discussed, in an effort to highlight the importance of consideration for all factors in TBI patient care and future research.

95% prevalence of abnormality on hip MRI in elite academy level rugby union: A clinical and imaging study of hip disorders.

OBJECTIVES: To identify the prevalence of hip disorders in elite level academy rugby union players using clinical and radiological investigation comparing findings to active controls. DESIGN: Cross-sectional, controlled study. METHODS: Participants were assessed clinically using validated questionnaire (HAGOS) and physical testing procedures. Active ROM of all hip movements were measured using a goniometer and hip-specific clinical tests including the FABER and the Thomas test examined functional hip motion. Physical tests were compared to age, gender and activity matched controls. The rugby-playing participants underwent dedicated non-arthrographic 3T MRI imaging of the hip in axial oblique, sagittal and coronal planes to assess anatomical abnormality. RESULTS: The rugby cohort had significantly reduced ROM of internal/external rotation, extension and FABER scores compared to the controls. Symptoms were reported by 65% of rugby players (HAGOS symptom score <89.3) versus 15% in controls. There was a 95% prevalence of abnormality on MRI (19 of 20 players); 80% of the elite rugby players had labral pathology, 55% had a cam deformity (45% left sided 30% right-sided) and 25% had either unilateral or bilateral chondral wear. CONCLUSIONS: The prevalence of abnormality on MRI of the hip is high in rugby players at 95% of study participants. The percentage reporting symptoms was lower at 65% of the cohort although this was significantly higher than (non-rugby) matched controls at 15% of participants. Rugby players demonstrated significantly reduced ROM of the hip compared to controls. Further prospective research is required to investigate the long term sequelae of these findings.

A library-selected, Langerhans cell-targeting peptide enhances an immune response.

The ability to deliver antigens and immunomodulators specifically to Langerhans cells (LCs) in the skin could impact vaccine development. However, cell-specific targeting of therapeutic molecules remains a challenge in biomedicine. Using phage display technologies, we have developed a protocol that identifies peptides that mediate uptake into target cell types. Employing this approach, we have isolated a 20-mer peptide that mediates specific uptake by immunopotent LCs. The peptide is functional outside the context of the phage and is able to deliver a nanoparticle to LCs in vitro. Although selected on cells in vitro, the peptide is able to direct antigens and genes to LCs in vivo. Liposomes bearing the LC targeting peptide are able to deliver a transcriptionally active gene to LCs in a mouse model. Furthermore, we demonstrate that a low-dose injection into mice of phage bearing the LC-targeting peptide yields faster and higher immune responses against phage-associated antigens than control-phage injections.