Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

Quantification Quality Control Emerges as a Crucial Factor to Enhance Single-Cell Proteomics Data Analysis.

Mass spectrometry (MS)-based single-cell proteomics (SCP) provides us the opportunity to unbiasedly explore biological variability within cells without the limitation of antibody availability. This field is rapidly developed with the main focuses on instrument advancement, sample preparation refinement, and signal boosting methods; however, the optimal data processing and analysis are rarely investigated which holds an arduous challenge because of the high proportion of missing values and batch effect. Here, we introduced a quantification quality control to intensify the identification of differentially expressed proteins (DEPs) by considering both within and across SCP data. Combining quantification quality control with isobaric matching between runs (IMBR) and PSM-level normalization, an additional 12% and 19% of proteins and peptides, with more than 90% of proteins/peptides containing valid values, were quantified. Clearly, quantification quality control was able to reduce quantification variations and q-values with the more apparent cell type separations. In addition, we found that PSM-level normalization performed similar to other protein-level normalizations but kept the original data profiles without the additional requirement of data manipulation. In proof of concept of our refined pipeline, six uniquely identified DEPs exhibiting varied fold-changes and playing critical roles for melanoma and monocyte functionalities were selected for validation using immunoblotting. Five out of six validated DEPs showed an identical trend with the SCP dataset, emphasizing the feasibility of combining the IMBR, cell quality control, and PSM-level normalization in SCP analysis, which is beneficial for future SCP studies.

EGFR-T790M Mutation-Derived Interactome Rerouted EGFR Translocation Contributing to Gefitinib Resistance in Non-Small Cell Lung Cancer.

Secondary mutation, T790M, conferring tyrosine kinase inhibitors (TKIs) resistance beyond oncogenic epidermal growth factor receptor (EGFR) mutations presents a challenging unmet need. Although TKI-resistant mechanisms are intensively investigated, the underlying responses of cancer cells adapting drug perturbation are largely unknown. To illuminate the molecular basis linking acquired mutation to TKI resistance, affinity purification coupled mass spectrometry was adopted to dissect EGFR interactome in TKI-sensitive and TKI-resistant non-small cell lung cancer cells. The analysis revealed TKI-resistant EGFR-mutant interactome allocated in diverse subcellular distribution and enriched in endocytic trafficking, in which gefitinib intervention activated autophagy-mediated EGFR degradation and thus autophagy inhibition elevated gefitinib susceptibility. Alternatively, gefitinib prompted TKI-sensitive EGFR translocating toward cell periphery through Rab7 ubiquitination which may favor efficacy to TKIs suppression. This study revealed that T790M mutation rewired EGFR interactome that guided EGFR to autophagy-mediated degradation to escape treatment, suggesting that combination therapy with TKI and autophagy inhibitor may overcome acquired resistance in non-small cell lung cancer.

Benchmarking differential expression, imputation and quantification methods for proteomics data.

Data analysis is a critical part of quantitative proteomics studies in interpreting biological questions. Numerous computational tools for protein quantification, imputation and differential expression (DE) analysis were generated in the past decade and the search for optimal tools is still going on. Moreover, due to the rapid development of RNA sequencing (RNA-seq) technology, a vast number of DE analysis methods were created for that purpose. The applicability of these newly developed RNA-seq-oriented tools to proteomics data remains in doubt. In order to benchmark these analysis methods, a proteomics dataset consisting of proteins derived from humans, yeast and drosophila, in defined ratios, was generated in this study. Based on this dataset, DE analysis tools, including microarray- and RNA-seq-based ones, imputation algorithms and protein quantification methods were compared and benchmarked. Furthermore, applying these approaches to two public datasets showed that RNA-seq-based DE tools achieved higher accuracy (ACC) in identifying DEPs. This study provides useful guidelines for analyzing quantitative proteomics datasets. All the methods used in this study were integrated into the Perseus software, version 2.0.3.0, which is available at https://www.maxquant.org/perseus.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Bioproducts of Pseudomonas chlororaphis Suppress DMI Fungicide-Induced CsCYP51A and CsCYP51B Gene Expression in Colletotrichum siamense and Generate Synergistic Effects with Metconazole and Propiconazole.

Mixtures of fungicides with different modes of action are commonly used as disease and resistance management tools, but little is known of mixtures of natural and synthetic products. In this study, mixtures of metabolites from the rhizobacterium Pseudomonas chlororaphis strain ASF009 formulated as Howler EVO with below-label rates (50 µg/ml) of conventional sterol demethylation inhibitor (DMI) fungicides were investigated for control of anthracnose of cherry (Prunus avium) caused by Colletotrichum siamense. Howler mixed with metconazole or propiconazole synergistically reduced disease severity through lesion growth. Real-time PCR showed that difenoconazole, flutriafol, metconazole, and propiconazole induced the expression of DMI target genes CsCYP51A and CsCYP51B in C. siamense. The addition of Howler completely suppressed the DMI fungicide-induced expression of both CYP51 genes. We hypothesize that the downregulation of DMI fungicide-induced expression of the DMI target genes may, at least in part, explain the synergism observed in detached fruit assays.

Routine image-enhanced endoscopic surveillance for metachronous esophageal squamous cell neoplasms in head and neck cancer patients.

BACKGROUND: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy. METHODS: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed. RESULTS: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs. CONCLUSIONS: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.

Comparative Proteomics Reveals Prolonged Corneal Preservation Impaired Ocular Surface Immunity Accompanied by Fibrosis in Human Stroma.

Cornea transplantation is one of the most commonly performed allotransplantations worldwide. Prolonged storage of donor corneas leads to decreased endothelial cell viability, severe stromal edema, and opacification, significantly compromising the success rate of corneal transplantation. Corneal stroma, which constitutes the majority of the cornea, plays a crucial role in maintaining its shape and transparency. In this study, we conducted proteomic analysis of corneal stroma preserved in Optisol-GS medium at 4 °C for 7 or 14 days to investigate molecular changes during storage. Among 1923 identified proteins, 1634 were quantifiable and 387 were significantly regulated with longer preservation. Compared to stroma preserved for 7 days, proteins involved in ocular surface immunomodulation were largely downregulated while proteins associated with extracellular matrix reorganization and fibrosis were upregulated in those preserved for 14 days. The increase in extracellular matrix structural proteins together with upregulation of growth factor signaling implies the occurrence of stromal fibrosis, which may compromise tissue clarity and cause vision impairments. This study is the first to provide insights into how storage duration affects corneal stroma from a proteomic perspective. Our findings may contribute to future research efforts aimed at developing long-term preservation techniques and improving the quality of preserved corneas, thus maximizing their clinical application.

(Pro)renin receptor inhibition attenuated liver steatosis, inflammation, and fibrosis in mice with steatohepatitis.

The (Pro)renin receptor (PRR) is reportedly involved in hepatic lipid metabolism and hepatocyte PRR knockdown protects mice against hepatosteatosis. However, the impact of PRR inhibition on liver inflammation and fibrosis in nonalcoholic steatohepatitis (NASH) remains unclear. Herein, C57BL/6 mice were fed a normal chow diet or fast food diet (FFD) for 24 weeks. Lentivirus-mediated PRR short hairpin RNA (shRNA) or handle region peptide (HRP), a PRR blocker, was administered for PRR inhibition. Mouse primary hepatocytes were cultured with palmitic acid, prorenin, siRNA-targeted PRR, and HRP. In FFD-fed mice, PRR inhibition via lentivirus-mediated PRR knockdown or HRP significantly attenuated liver steatosis, inflammation, and fibrosis. Mechanistically, PRR knockdown or HRP decreased hepatic acetyl-CoA carboxylase (ACC) abundance and upregulated peroxisome proliferator-activated receptor-alpha (PPARα). HRP treatment also decreased hepatic PRR expression. In addition, intrahepatic oxidative stress, apoptosis and inflammatory cell recruitment were ameliorated by PRR knockdown or HRP treatment, along with suppression of proinflammatory cytokine expression. PRR inhibition downregulated the hepatic expression of profibrotic factors, as well as TGF-ß1/SMAD3 pathway. In primary mouse hepatocytes, PRR knockdown with siRNA or HRP downregulated cellular ACC and increased PPARα expression. In conclusion, our findings revealed that PRR inhibition attenuated hepatic steatosis, inflammation, and fibrosis in mice with NASH. Accordingly, targeting PRR signaling may serve as a potential treatment for NASH.

Predictors of technical success of percutaneous transhepatic common bile duct stone removal: is it only a matter of stone size?

OBJECTIVES: The common practice is to remove symptomatic common bile duct (CBD) stones in patients. This study aimed to investigate the factors affecting the percutaneous transhepatic removal of CBD stones. METHODS: We retrospectively analyzed the data of 100 patients (66 men and 34 women; age: 25-105 years, mean 79.1 years) with symptomatic CBD stones who underwent percutaneous transhepatic stone removal (PTSR) from January 2010 through October 2019. After balloon dilation of the ampulla of Vater or bilioenteric anastomosis, the stones were pushed out of the CBD into the small bowel with a balloon catheter. If failed, basket lithotripsy was performed. Technical success was defined as complete clearance of the bile ducts on a cholangiogram. RESULTS: The technical success rate was 83%, and achieved 90.2% in patients with altered gastroduodenal/pancreatobiliary anatomy. Multivariable analysis revealed that CBD diameter (odds ratio [OR]: 506.460, p = 0.015), failed ERCP (OR: 16.509, p = 0.004), Tokyo guidelines TG18/TG13 severity (grade III; OR: 60.467, p = 0.006), and left-sided transhepatic approach (OR: 21.621, p = 0.012) were risk factors for technical failure. The appropriate cutoff CBD size was 15.5 mm (area under the curve: 0.91). CBD stone size, radiopacity of stones, and CBD angle between retroduodenal and pancreatic portion did not influence technical success. CONCLUSIONS: PTSR is effective for CBD stone removal in older adults and individuals with altered gastrointestinal tract anatomy. The aforementioned risk factors for technical failure should be considered in preoperative evaluation before PTSR to improve the success rate. KEY POINTS: • PTSR is effective in symptomatic CBD stone management among older adults and individuals with altered anatomy. Investigating clinical /anatomic factors can guide radiologists toward a more comprehensive preoperative evaluation to maximize the success rate. • Our data indicate that dilated CBD (diameter ≥ 15.5 mm) and left-sided PTBDs reduce the technical success rate by 506-fold and 22-fold, respectively. • Clinical factors such as previous failed ERCP for stone removal and higher severity of acute cholangitis lessen the technical success rate.

Natural Drugs: A New Direction for the Prevention and Treatment of Diabetes.

Insulin resistance, as a common pathological process of many metabolic diseases, including diabetes and obesity, has attracted much attention due to its relevant influencing factors. To date, studies have mainly focused on the shared mechanisms between mitochondrial stress and insulin resistance, and they are now being pursued as a very attractive therapeutic target due to their extensive involvement in many human clinical settings. In view of the complex pathogenesis of diabetes, natural drugs have become new players in diabetes prevention and treatment because of their wide targets and few side effects. In particular, plant phenolics have received attention because of their close relationship with oxidative stress. In this review, we briefly review the mechanisms by which mitochondrial stress leads to insulin resistance. Moreover, we list some cytokines and genes that have recently been found to play roles in mitochondrial stress and insulin resistance. Furthermore, we describe several natural drugs that are currently widely used and give a brief overview of their therapeutic mechanisms. Finally, we suggest possible ideas for future research related to the unique role that natural drugs play in the treatment of insulin resistance through the above targets.

Xenograft-decellularized adipose tissue supports adipose remodeling in rabbit.

BACKGROUND: Decellularized adipose tissue (DAT) provides a suitable microenvironment for adipose stem cells (ADSCs) and promotes their adipogenic differentiation. Recent studies have focused on allogeneic DAT; however, insufficient adipose sources limit its wider application of allogeneic DAT. In this study, we compared the ability of allogeneic and xenogeneic DATs to induce adipose regeneration to explore the feasibility of xenogeneic DAT as an adjunctive material for tissue repair. METHODS: Decellularized adipose tissue from humans and rabbits was prepared using the Flynn's method. The proliferation, migration, and adipogenic functions of the allogeneic and the xenogeneic groups were compared. Rabbits were used to construct transplantation models: allogeneic (transplanted r-DAT) and xenogeneic groups (transplanted h-DAT). Comparison of DAT transplantation outcomes between the two groups. RESULTS: Xenogeneic DAT supports adipose regeneration. In vitro, adipose-derived stem cells cultured on xenogeneic DAT developed adipogenesis without media cues and were not statistically different from the effects of allogeneic DAT on cell migration, proliferation, and adipogenic capacity. In vivo, the animal model showed angiogenesis and adipogenesis, and the adipogenic ability of xenogeneic DAT was not statistically different from that of allogeneic DAT. CONCLUSION: Xenogeneic DATs can induce adipose regeneration, and its adipogenic ability has no statistical difference, compared with allogeneic DATs. Xenografts are expected to be useful for soft tissue repair.

The Efficacy of Mirabegron in Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis.

Background: This study aimed to assess the efficacy of mirabegron (50 mg daily) as a medical expulsive therapy for ureteral stones in adults. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 2021 to collect the clinical trials. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for the meta-analysis. Results: A total of four studies were included, involving 398 patients: 197 patients in mirabegron group and 201 patients in control group. The meta-analysis showed that the stone expulsion rate was higher in the mirabegron group than in the control group (OR: 2.12; 95% CI: 1.33 to 3.40; p=0.002). Subgroup analysis identified that the stone expulsion rate of patients with stone size <5/6 mm was significantly higher than that of patients with stone size ≥5/6 mm (OR: 0.31; 95% CI: 0.13 to 0.72; p=0.006). But no significant difference was identified between the mirabegron group and the control group for the stone expulsion interval (MD: -1.16, 95% CI: -3.56 to 1.24; p=0.35). In terms of pain episodes, the mirabegron group was significantly lower than that of the control group (MD: -0.34, 95% CI: -0.50 to 0.19; p < 0.0001). Conclusions: The medical expulsive therapy with mirabegron had a significant effect in improving the stone expulsion rate for patients with ureteral stones, especially in those whose stone size <5/6 mm. Mirabegron had no effect on the stone expulsion interval but did decrease the pain episodes.

Association between secondhand smoke and peripheral arterial disease: a meta-analysis of cross-sectional studies.

PURPOSE: The association between secondhand smoke (SHS) and peripheral arterial disease (PAD) was inconsistent and the studies were relatively scarce, hence, we conducted a meta-analysis of the association between SHS and PAD. MATERIALS AND METHODS: We systematically searched three electronic databases (PubMed, EMBASE, and Web of Science), and calculated the pooled prevalence risk ratio (RR) and estimated standard error by random effect model from the meta-analysis. Furthermore, we performed a subgroup meta-analysis according to the location of SHS exposure. RESULTS: We initially identified 502 articles from the electronic database, and 6 articles, cross-sectional data from 4 cross-sectional studies and 2 prospective cohort studies, were included in the meta-analysis. Among these six articles, two studies showed a significant correlation between SHS exposure and PAD, whereas no study showed a negative correlation between SHS exposure and PAD. In the meta-analysis, pooled prevalence showed a significant association between SHS exposure and PAD (RR = 1.23; 95% confidence interval [CI] 1.08-1.41; z = 3.02, p = 0.003). In the subgroup analysis based on location of SHS exposure, the prevalence RR of PAD at home was 1.30 (95% CI 1.14-1.49, Z-3.99, p < 0.0001). The prevalence RR in the subgroup of SHS exposure at work was not significant (RR = 0.89; 95% CI 0.55-1.44; z = 0.48, p = 0.63). CONCLUSION: Exposure to SHS was significantly and positively associated with PAD. Moreover, we found a significant association between exposure to SHS and PAD at home, but the association was not significant at work.

N-glycosylated GPNMB ligand independently activates mutated EGFR signaling and promotes metastasis in NSCLC.

Lung cancer is the leading cause of cancer-related death worldwide. As well as the identified role of epidermal growth factor receptor (EGFR), its association with driver mutations has improved the therapeutics for patients with lung cancer harboring EGFR mutations. These patients usually display shorter overall survival and a higher tendency to develop distant metastasis compared with those carrying the wild-type EGFR. Nevertheless, the way to control mutated EGFR signaling remains unclear. Here, we performed membrane proteomic analysis to determine potential components that may act with EGFR mutations to promote lung cancer malignancy. Expression of transmembrane glycoprotein non-metastatic melanoma protein B (GPNMB) was positively correlated with the status of mutated EGFR in non-small-cell lung cancer (NSCLC). This protein was not only overexpressed but also highly glycosylated in EGFR-mutated, especially EGFR-L858R mutated, NSCLC cells. Further examination showed that GPNMB could activate mutated EGFR without ligand stimulation and could bind to the C-terminus of EGFR, assist phosphorylation at Y845, turn on downstream STAT3 signaling, and promote cancer metastasis. Moreover, we also found that Asn134 (N134) glycosylation of GPNMB played a crucial role in this ligand-independent regulation. Depleting N134-glycosylation on GPNMB could dramatically inhibit binding of GPNMB to mutated EGFR, blocking its downstream signaling, and ultimately inhibiting cancer metastasis in NSCLC. Clarifying the role of N-glycosylated GPNMB in regulating the ligand-independent activation of mutated EGFR may soon give new insight into the development of novel therapeutics for NSCLC.

2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction.

Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents has become critical for lung cancer treatment. In this study, compound AS7128 was selected from a 2-million entry chemical library screening and identified as a candidate drug against non-small cell lung cancer in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and, thus, increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs through disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insight for using iASPP as a therapeutic target for non-small cell lung cancer treatment.

Anaerobic coverage as definitive therapy does not affect clinical outcomes in community-onset bacteremic biliary tract infection without anaerobic bacteremia.

BACKGROUND: Antibiotics with anaerobic coverage are widely used for the treatment of biliary tract infection (BTI), even in the absence of isolated anaerobes. The current study aimed to investigate the differences in clinical outcomes in patients with community-onset bacteremic BTIs without anaerobic bacteremia, treated with vs. without anti-anaerobic coverage. METHODS: A retrospective analysis was conducted at a medical center in Taiwan from September 2014 to March 2016. Patients with community-onset bacteremic BTIs without anaerobic bacteremia and who were treated with appropriate antibiotics were analyzed. The clinical outcomes were compared between patients treated with and without anti-anaerobic coverage as definitive therapy after the blood culture reports were available. Multivariable and propensity score-adjusted analysis were used to identify the risk factors associated with treatment failure. RESULTS: Among the enrolled 87 patients, 63 and 24 patients were treated with and without anaerobic coverage, respectively. Escherichia coli (55.2%) and Klebsiella pneumoniae (23.0%) were the most common organisms isolated from the blood cultures. The rate of treatment failure (relapse and 28-day mortality) was similar between the groups with and without anaerobic coverage (20.6% vs. 16.7%, p = 0.677). Propensity score-adjusted multivariable analysis revealed that definitive therapy without anaerobic coverage was not a predisposing factor for treatment failure (OR = 0.92, 95% CI 0.18-4.67, p = 0.916). CONCLUSIONS: Definitive therapy without anaerobic coverage does not affect the outcomes of patients with community-onset bacteremic BTIs without anaerobes isolated from blood. Our results might provide a possible target for antibiotic stewardship interventions in BTIs.

Fifteen-minute consultation: A child with a suspected drug allergy.

Adverse drug reactions are common in children, but true drug allergy is rare. It can be difficult to determine whether signs such as skin rashes are caused by the underlying illness or medications prescribed. Accurate diagnosis is important for patient safety and optimal treatment. We review the presentation of drug allergy and discuss current management options for children.