Avacopan is an oral selective C5a receptor inhibitor. It received FDA approval in October 2021 for use with standard glucocorticoid therapy to treat antineutrophil cytoplasmic antibody-associated vasculitis. However, there are limitations to understanding adverse events (AEs) in clinical practice. In this study, we analyzed AEs related to avacopan by mining the FDA Adverse Event Reporting System (FAERS).

Adverse event reports associated with avacopan were retrieved from the FAERS database covering Q1-2022 to Q4 2024. After data standardization, reports exclusively involving avacopan were retained. Two disproportionality analysis methods, namely the reporting odds ratio and Bayesian confidence propagation neural network, were utilized to detect safety signals related to avacopan. A semi-quantitative scoring approach was employed to evaluate the clinical priority of the detected signals. Moreover, racial disparities in the occurrence risks of critical adverse event signals as well as temporal patterns of avacopan-related AEs were examined.

Among 1,128 avacopan-related reports, 33 adverse event signals were identified. These included label-listed AEs (nausea, fatigue, diarrhea, headache, rash, hypertension, blood creatinine increased, and abnormal liver function). Five new potential AEs were detected, including alopecia, increased appetite, hyperaesthesia teeth, oesophageal disorder, and muscle atrophy. Clinically, 0 were classified as high-priority signals, 2 as moderate-priority signals, and 31 as low-priority signals. Compared to American patients, Japanese patients exhibited a higher risk of liver dysfunction (p<0.001), while alopecia occurred exclusively in the American patient population. The median time to AE onset time for avacopan was 86.5 days(interquartile range [IQR] 27-236.75), with most occurring within the first month of treatment.

Avacopan exhibits favorable real-world safety with no high-priority AEs identified. Our findings may provide important evidence for future clinical research and the management of safety issues related to avacopan.

Antimicrobial stewardship programs (ASPs) are underrepresented in outpatient settings, where antibiotic use and overprescribing are common. Upper respiratory tract infections (URIs) account for 30% of outpatient antibiotic prescriptions, highlighting the need for enhanced ASP efforts. Rapid diagnostic testing (RDT) has important value in management of outpatient URIs, such as pharyngitis, and can lead to optimized prescribing practices and significant reductions in unnecessary antimicrobial use by facilitating accurate diagnoses. Implementation of outpatient RDTs is hindered by a lack of streamlined workflows, resources, and ASPs. These gaps often lead to suboptimal use of RDTs and misinterpretation of or failure to act on the results. Future RDT evaluations should include strategies to curtail unnecessary antibiotics and expand point-of-care testing (POCT) to additional settings to enhance antimicrobial stewardship. This paper reviews outpatient RDT initiatives, and specifically POCT, in URIs. Additionally, we highlight the need for more evidence demonstrating the impact on clinical outcomes and antibiotic prescribing with the implementation of RDTs.

Real-time polymerase chain reaction (PCR), the gold standard for viral diagnostics in children, is a sensitive but resource-intensive method. Viral antigen tests are cheaper and more rapid but have lower sensitivity. The clinical relevance of PCR positivity has been questioned because of its high sensitivity and detection in asymptomatic individuals. Thus, we hypothesized that antigen test positivity might be more indicative of active infection than PCR positivity. The aim of this study was to evaluate the antigen test mariPOC Respi test for the detection of 10 respiratory viruses versus PCR in relation to viral load, days of illness, and immunological viral response.

Children 1-59 months old with lower respiratory infections were prospectively enrolled at the emergency department, Sachs' Children and Youth Hospital, Stockholm, Sweden, between 2017 and 2019. Nasopharyngeal samples were collected from all cases (n = 314). The sensitivity and specificity of the mariPOC Respi test were assessed in children with and without an immunological viral response (defined as a blood myxovirus resistance Protein A level > 430 μg/L), using PCR as the reference standard.

The highest sensitivity for mariPOC Respi test was attained for respiratory syncytial virus (68%; 95% confidence interval: 63-73). Restricting the analysis to cases with a viral immunological response did not alter the results considerably.

These findings do not support the idea that mariPOC Respi test positivity to a higher degree than PCR correlates with clinical relevance, as indicated by an immunological viral response. The role of antigen tests in current clinical practice requires further discussion, particularly in the post-pandemic era.

ClinicalTrials.gov identifier: NCT03233516.

The forced oscillation technique (FOT) complements spirometry in assessing lung function, with higher sensitivity to small airway dysfunction. Systemic inflammation is thought to influence lung development and exercise-induced bronchoconstriction (EIB), but its relationship to circulating inflammatory proteins in adolescents is unclear.

To investigate associations between systemic inflammatory biomarkers and baseline lung function and post-exercise airway responses in adolescents.

In 143 adolescents (13-15 years) from a population-based cohort, baseline spirometry, FOT, and baseline blood samples were obtained. Participants completed an exercise challenge to assess EIB via changes in forced expiratory volume in 1 s (FEV₁), resistance at 5 Hz (R₅), and reactance at 5 Hz (X₅). Plasma protein levels were measured using the proximity extension assay technique (Olink Target Inflammation and Immune Response panels). Associations with lung function (FEV₁% predicted, R5, and X5 z-scores) and post-exercise responses (∆FEV₁, ∆R5, ∆X5) were analyzed using linear regression with false discovery rate correction. Interaction with atopy was also examined.

Higher plasma levels of C-C motif chemokine 19 (CCL19) were significantly associated with lower FEV₁% predicted and lower X₅ z-scores at baseline, indicating reduced lung function and impaired small airway function. No proteins were associated with post-exercise airway responses after correction. Five proteins showed significant interactions with atopy in relation to EIB.

Elevated CCL19 may reflect systemic inflammatory processes contributing to impaired lung function in early adolescence. The observed atopy-related interactions suggest the need to consider atopy in studies of systemic inflammation and airway physiology.

Chlamydia infection is a frequently reported notifiable condition in Queensland, with the highest prevalence observed among young people. Infection can occur in several sites including the anus, eye, pharynx, cervix/vagina, and urethra. Currently, historical trends in chlamydia by site of infection in Queensland are unknown.

A descriptive analysis of all chlamydia notifications in Queensland, 2000-2019, was performed. Queensland Health statewide notification data were classified as either anorectal, eye, genitourinary, upper respiratory tract, or other/unspecified. The number of chlamydia tests and proportion of tests positive for chlamydia were calculated using Medicare online testing data. Population denominator values were obtained from the Australian Bureau of Statistic's catalogues.

Over the 20-year period, chlamydia notifications increased, particularly among individuals aged 20-24 years. However, there was a noticeable decline in genitourinary notifications among those aged 15-19 years since 2010. Despite increased testing, the ratio of positive specimens to testing decreased among females aged 15-24 years.

Across the period of our study, there was a substantial and sustained decline in chlamydia notifications in those aged 15-19 years. Further research is required to understand factors that have contributed to this decrease and to guide programs for controlling chlamydia.

Neurological manifestations are sometimes seen in patients with multisystem inflammatory syndrome in children. Concurrent ataxia and papilledema are yet to be reported in patients with multisystem inflammatory syndrome in children.

A 13-year-old Iranian boy was transferred from a deprived area to the emergency department of Namazi Hospital (Shiraz, Iran) in May 2022 with fever, generalized skin rashes, palmar erythema, vomiting, and diarrhea. Severe conjunctivitis, photophobia, headache, and ataxia were also noted. His neurological manifestations improved following treatment with high-dose methylprednisolone and intravenous immunoglobulin. He was discharged 9 days later.

Physicians should be aware of ataxia and papilledema as extremely rare presentations of multisystem inflammatory syndrome in children.

Congenital Pulmonary Airway Malformation (CPAM) is a rare lung anomaly in pediatric patients, often diagnosed prenatally or postnatally. Although typically asymptomatic, CPAM can present with severe complications such as recurrent infections or lung abscesses. Thoracic ultrasound (LUS) is emerging as a valuable diagnostic tool, offering a non-invasive and radiation-free alternative to traditional imaging.

We present the case of a 2-year-old girl with persistent fever, cervical lymphadenopathy, and elevated inflammatory markers, initially raising suspicion for incomplete Kawasaki disease (KD). Despite the administration of intravenous immunoglobulin (IVIG), the fever persisted, prompting further investigations. Lung ultrasound revealed a 5.5 cm lesion with hyperechoic spots and vascularization, suggestive of a lung abscess associated with CPAM. Diagnosis was confirmed by chest CT, and the patient was successfully treated with targeted antibiotic therapy.

This case highlights the importance of considering CPAM as a differential diagnosis in pediatric patients with persistent fever of unknown origin. It also underscores the potential of lung ultrasound as a non-invasive diagnostic tool, complementing traditional imaging methods, in the management of complex pediatric conditions.

Asthma remains a highly prevalent and heterogeneous chronic respiratory disease in the pediatric population. Accumulating evidence has established a critical role of the gut-lung axis in the pathogenesis of asthma. Specifically, gut microbiota constituents such as Lactobacillus and Bifidobacterium species have been closely associated with childhood asthma. Current intervention strategies targeting the gut microbiota show considerable promise. Probiotic supplementation and short-chain fatty acids (SCFAs) have demonstrated the ability to restore microbial homeostasis and suppress type 2 inflammation. Additionally, phytogenic compounds exhibit potential in reshaping the gut microbial composition and ameliorating asthma symptoms. This review synthesizes clinical and mechanistic evidence from both human and animal studies, highlighting the translational potential of microbiota-targeted therapies. Future research should prioritize the development of personalized microbiota-based interventions to improve clinical outcomes in children with asthma.

Hypoxic pulmonary hypertension (HPH) lacks effective treatments. The research is designed to examine the effectiveness of Notoginsenoside R1 (NGR1) in addressing HPH and to explore its molecular mechanisms. Under hypoxic conditions, we created a rat model of HPH and treated the animals with NGR1. We assessed the therapeutic effects of NGR1 on HPH through hemodynamic measurements and pulmonary artery vascular remodeling. We employed transcriptomic analysis to evaluate gene expression changes in HPH rats. We conducted untargeted metabolomics to examine how NGR1 influences the metabolic profile of HPH rats. NGR1 treatment significantly improved hemodynamic parameters and ameliorated pulmonary artery vascular remodeling in HPH rats. Transcriptomic analysis identified Pck1 as the most significantly altered gene. NGR1 intervention significantly improved the expression of vascular remodeling-related proteins. NGR1 reversed the expression of glycolysis-related genes. NGR1 reduced the levels of glycolysis-related metabolites. Further analysis revealed that NGR1 treatment decreased PFKL, HK2, and LDHA protein expression and lowered lactate levels in lung tissue. Our findings demonstrate that NGR1 effectively alleviates the pathological features of HPH in rats. NGR1 inhibits hypoxia-induced glycolysis-mediated pulmonary artery remodeling, mitigates vascular endothelial damage, and suppresses the abnormal proliferation of smooth muscle cells and fibroblasts.

Controlling viral infections prior to solid organ transplantation is vital for successful engraftment and overall well-being of patients. One promising approach involves the deployment of viral antigen-specific cytotoxic T cells to eradicate viral pathogens. Although there have been attempts to develop anti-viral vaccines in the literature, the limited number of virus-specific cells which can be generated in vitro in the autologous system make it impracticable for autologous therapy.

We developed a straightforward and scalable method for the in vitro expansion of SARS-CoV-2 Spike S1 peptide-specific cytotoxic CD8⁺ T cells. This was achieved through combinatorial stimulation with S peptide-conjugated polystyrene microspheres in the presence of cytokines IL-2, IL-7, and IL-15 for 14 days.

Using A2/S₂₆₉-specific tetramers as markers, we compared induction of S-specific CD8⁺ T cells from patients awaiting kidney transplantation (n=67) with that of normal controls (n=65). We found that this method has the potential to achieve at least a 10-fold up to 200-fold increase in S-specific CD8⁺ T cells in 34.3% of kidney transplant candidates and 36.9% of normal controls, respectively. These SARS-CoV-2 specific CD8⁺ T cells released inflammatory cytokines, expressed effector-memory T cells markers, and killed target cells in a dose-dependent and antigen-specific manner.

Our study demonstrates that viral antigen-specific cytotoxic CD8⁺ T cells can be robustly enriched in vitro from peripheral blood mononuclear cells of both healthy individuals and patients with kidney diseases using peptide-conjugated microspheres. Our findings provide novel insights into a potential therapeutic approach, using autologous anti-viral CD8⁺ T cells for transplant recipients/candidates.